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Pediatric Psychopharmacology: Regulations and Research
by Arline Kaplan
Every year, more than half of newly approved drugs and biologics considered likely to be prescribed for children lack labeling information on safe and effective use, reported the U.S. Food and Drug Administration (1998). Seeking to rectify this situation, the FDA recently issued final regulations (21 CFR Parts 201, 312, 314 and 601) requiring new drugs and biologics that are therapeutically important for children or will be commonly used in children to have labeling information on safe pediatric use (HHS, 1998).
This rule will also allow the FDA to require pediatric testing of already-marketed products in certain compelling circumstances, i.e., when a drug is commonly prescribed for use in children but the absence of adequate labeling could pose significant risks. The FDA (1999) has subsequently issued a written request for pediatric studies for buspirone (BuSpar), gabapentin (Neurontin) and lamotrigine chewable dispersible tablets (Lamictal), among other drugs.
The FDA's actions reflect growing concern over the substantial and increasing use of psychotropic medications in children and adolescents, and the extensive need for pediatric psychopharmacology research.
Both problems confronting pediatric psychopharmacology and prospects for positive change were delineated recently by John T. Walkup, M.D., during a presentation he co-prepared with Mark A. Riddle, M.D., a fellow colleague from the Division of Child and Adolescent Psychiatry at Johns Hopkins University in Baltimore.
Speaking at the American Academy of Child and Adolescent Psychiatry's 45th annual meeting in Anaheim, Calif., Walkup said that, "at least 10% of youngsters at any given time have a psychiatric disorder that would potentially respond to pharmacotherapy. The estimated prevalence of attention-deficit/hyperactivity disorder [ADHD] is 4%; of anxiety disorders, 2%; of major depressive disorder, 2%; of obsessive-compulsive disorder [OCD], 1%; and of other disorders, 1%." The prevalence estimate for the other disorders category could even be higher, Walkup noted, if it included bipolar disorder, psychotic disorders, the pervasive developmental disorders, such as autism and episodic aggression.
A significant dilemma in treating these disorders, according to Walkup, is that many of the medications prescribed for children are prescribed off-label (Riddle et al., 1998a; Vitiello and Jensen, 1997). As an example, he pointed to a list of the 10 drugs most prescribed to children off-label in 1994. Out of the 10, three were psychotropic medications: fluoxetine (Prozac), with 349,000 prescriptions to treat children and adolescents under age 16 suffering from depression and OCD; sertraline (Zoloft), with 248,000 prescriptions to treat children and adolescents suffering from depression; and methylphenidate (Ritalin), to treat children suffering from ADHD.
"Ritalin is approved for use in kids, but not approved for use in kids under age 6, yet there were 226,000 prescriptions for its use in children under age 6," Walkup said.
In explaining the lag in pediatric psychopharmacology research as compared to such research in adults, Walkup said that in the past it was viewed as a humanitarian and ethical principle not to do research studies on children, women of childbearing age or older adults. According to Walkup, it was not until 1979 that a pediatric-use section was developed for product information on drugs. Yet, medications that were originally tested on adult males and some females are increasingly being used on children and other populations.
"The risk of prescribing those medicines without information clearly outweighs the risk of studying them," he said. "Most medications used off-label to treat children and adolescents do not have adequate safety and efficacy data to support pediatric use."
Walkup discussed a comprehensive literature review of the efficacy of psychotropic medications in children (Riddle et al., 1998b).
"What we tried to do…was to look at all the medications available for use in child psychiatry, attempt to create our own list of medicines [and indicate] where there is enough data to support use and where there are some questions," he said. The researchers conducted an extensive literature search, even checking the chapters in psychopharmacology texts to identify more obscure studies. They then set standards as to what they would consider adequate trials.
"What we determined is that we wanted a sample size of greater than 40 in two studies or greater than 80 in one study. And by current industry standards, this is pretty small," he said. "What we found was that there were no controlled studies for any of these significant psychiatric disorders in childhood: anxiety disorders except for obsessive-compulsive disorder, bipolar disorder, bulimia, sleep disorders and substance use disorders."
There are, however, "some medications where we really do have sufficient data that actually support the FDA [pediatric use] indications these medicines currently carry," he said. He pointed to plenty of studies supporting the efficacy of methylphenidate, d-amphetamine (Dexedrine) and pemoline (Cylert) for treatment of ADHD in children age 6 and older.
For OCD, Walkup said there is good data on clomipramine (Anafranil) for use in children age 6 and older, fluvoxamine (Luvox), for children age 8 and older and sertraline, for children age 6 and older. For tic suppression, there is some data supporting pimozide's (Orap) use in young people age 12 and older. (Fluvoxamine was the first selective serotonin reuptake inhibitor [SSRI] approved by the FDA for OCD in children-Ed.)
"On the other hand, there are some medicines that we are currently using that have an FDA indication, but there really isn't any data that supports their use in children," he said.
A number of these medications were grandfathered in, according to Walkup. They were approved for use in the United States, and as a result, the indications were expanded to include children without sufficient supportive data. There are, for example, no current studies supporting the use of amphetamine salts (Adderall) in children 3 years of age or older, although there are some studies underway. Other FDA indications for use of drugs in children that lack sufficient supportive data, Walkup said, include d-amphetamine in young children ages 3 to 5 years; amitriptyline (Elavil) for depression in young people age 12 years or older; and chlorpromazine (Thorazine), thioridazine (Mellaril) and haloperidol (Haldol) for young children experiencing hyperactivity, behavior problems or pervasive developmental disorders.
"Again lithium compounds [Eskalith and Lithobid] have been grandfathered in for use in mania and bipolar disorder in kids over 12 years of age and…diazepam [Valium] for anxiety disorders in kids over 6 months of age," he said.
There are some medicines, not many, Walkup added, where there is no FDA pediatric use indication but where there is sufficient data to support such use. He cited some studies using bupropion (Wellbutrin) and imipramine (Tofranil) for ADHD in 6- to 12-year-olds, studies of desipramine (Norpramin) in children and adolescents and fluoxetine in children 8 years of age and older who are depressed (Emslie et al., 1997).
In addition, Walkup said, there are some interesting studies about the use of lithium for aggression in children over age 5 (Campbell et al., 1995) and naltrexone (ReVia) for hyperactivity in autism (Kolmen et al., 1997; Willemsen-Swinkels et al., 1996).
Long-term safety and efficacy data on the use of psychotropic medications in children is lacking, Walkup added.
"Mostly what we do are short-term studies. And in short-term studies, you really don't get a sense of how long the medicines work, whether they are continuously effective and whether any long-term side effects develop as a result," he said.
There are three long-term studies using methylphenidate for ADHD and a couple of studies looking at long-term use of SSRIs for treatment of OCD in children and adolescents that have yet to be published, Walkup said. Henrietta Leonard, M.D., at Rhode Island Hospital in Providence (Leonard et al., 1991) did a double-blind discontinuation trial.
Joseph Deveaugh-Geiss and colleagues (1992) conducted a multisite clomipramine trial and described in their article the results of their one-year open extension. Walkup added that he and colleagues are involved in collecting data for a one-year open extension of the fluvoxamine trial.
Beyond challenges of insufficient research data, Walkup also pointed out problems with an inadequate research infrastructure, difficulty in recruiting children and adolescents for studies, vocal opponents to pediatric pharmacology, and media sensationalism.
Pediatric psychopharmacology relies on an inadequate research infrastructure, according to Walkup. "I wasn't seriously trained in psychopharmacology, it was something I learned from other colleagues and on my own," he said, adding that the vast majority of divisions of child psychiatry in the country do not have a large psychopharmacology component.
"Once you have a research infrastructure, sometimes it is very difficult to recruit kids into pediatric psychopharmacology trials, especially if you are asking kids to undergo the traditional parallel-group, double-blind, placebo-controlled trials," he said. When asked up front to take the risk of having the child or adolescent go on active medicine or on placebo for an extended period of time, most families prefer to opt out of that choice and go to their local practitioner, according to Walkup.
Adding to these problems are a "number of opponents who are increasingly vocal regarding the use of pediatric psychopharmacologic agents," Walkup said.
"[Some] very prominent opponents [include] the Church of Scientology, which has waged a very active campaign…about Ritalin and more recently about fluoxetine, and some folks who are very outspoken. Peter Breggin, M.D., of the Center for Study of Psychiatry and Psychology in Maryland, has written a very controversial book, Talking Back to Ritalin: What Doctors Aren't Telling You About ADHD and Stimulant Drugs for Children." Media coverage of pediatric psychopharmacology, Walkup said, "is often sensationalized and quite misinformed." He drew attention to such statements in popular press as "we have replaced reading, writing, [and] arithmetic in our classrooms with reading, writing and Ritalin," and "overprescribing antidepressants to kids is a form of child abuse."
Despite these problems, Walkup said the prospects for the future of pediatric psychopharmacology are very promising. He pointed to the development of research units on pediatric psychopharmacology, the creation of training institutes at the American Academy of Child and Adolescent Psychiatry meetings, drug companies spending more money to support the "kinds of important studies that need to be done," and support from the American Academy of Pediatrics, the National Alliance for the Mentally Ill and the National Institute for Mental Health (NIMH).
"The National Institute of Mental Health has been very active [not only] in developing information through grants but also through setting up mechanisms for information dissemination like [the] ADHD consensus conference [held last November in Washington, D.C.], so that all practitioners and all families in [the] U.S. have the information we need to make decisions about treatment with psychotropic medicines," Walkup said.
The impetus for creating research units on pediatric psychopharmacology (RUPPs), according to Walkup, came from a 1995 conference cosponsored by the NIMH and the FDA (Vitiello and Jensen, 1997). The conference brought together more than 100 research experts, family and patient advocates and representatives of mental health professional associations.
"Out of that [conference] came a mandate to begin to study drugs that were currently available for which there was no information about their use in kids," according to Walkup.
To help bootstrap the field by providing the infrastructure for centers to complete the necessary safety, dose-ranging and efficacy studies in children and adolescents, the NIMH set up and funded the RUPPs. Currently, research units on pediatric psychopharmacology are at Columbia University College of Physicians/New York University; Johns Hopkins University School of Medicine in Baltimore; the University of Pittsburgh; Yale University; University of California, Los Angeles; Indiana University; and Ohio State University/Kennedy Krieger Institute. The last four RUPPs are funded under NIMH grants for pediatric psychopharmacology in treating autism and other pervasive disorders.
"Part of what we are supposed to be doing are systematic clinical trials, even including some open-label trials in an effort to collect information on whether medicines work and then moving on to efficacy trials, which are the traditional double-blind trials, and finally to effectiveness studies which are the use of medicines in a research design that is more exportable to clinicians' offices," Walkup said. "These studies all have different goals. The open trials, as I mentioned, are for finding new treatments, efficacy trials are to bring new medicines to the market…the effectiveness trials are really the comparison of treatments and creating designs that give you information about how to use the drug in your practice."
Although well-designed and well-conducted unmasked and uncontrolled clinical trials of psychotropic medications in children are needed, Walker believes that some publications standards should be imposed (Walkup et al., 1998). He also raised questions about other study designs. For example, would a period of open treatment, followed by a double-blind discontinuation, be acceptable to the FDA and other review bodies? In multisite trials, he said, "there is this tension between having a number of sites in order to complete the trial quickly, and having all the sites develop real expertise with the study, so it is conducted accurately." One of the problems with long-term studies, Walkup added, is that they are uncontrolled: "They tend to be used as an incentive for patients to enter double-blind trials, so that if you put in the time and effort to participate in a double-blind trial, at the end of the double-blind trial, you have an opportunity to get active medication for free for an extended period of time."
Effectiveness studies, Walkup said, often have complicated designs and are very costly. The Collaborative Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (the MTA) involved 576 children ages 7 to 9 years (Arnold et al., 1997). It was "a huge trial requiring multiple sites and a fair amount of financial support," Walkup said. He added that a similar multimodal treatment study will be conducted for children with depression and another for children with anxiety is in the planning stage.
Pediatric psychopharmacology research, Walkup believes, will soon move into "networks of university sites and private practitioners who work collaboratively and systematically to collect information about medication usage, usefulness and side effects."
Overall, "there are great prospects for pediatric psychopharmacology," Walkup said. "We continue to push forward, but every once in a while we do experience unfair criticism and blindsiding from the media. We really believe we are doing something that is worthwhile and needs to be supported. Over time, I believe, we will win out, but clearly there are some times when it is a tough fight."
References
Arnold LE, Abikoff HB, Cantwell DP et al. (1997), National Institute of Mental Health Collaborative Multimodal Treatment Study of children with ADHD (the MTA). Arch Gen Psychiatry 54(9):865-870.
Breggin PR (1998), Talking Back to Ritalin: What Doctors Aren't Telling You About ADHD and Stimulant Drugs for Children. Monroe, Maine: Common Courage Press.
Campbell M, Adams PB, Small AM et al. (1995), Lithium in hospitalized aggressive children with conduct disorder: a double-blind and placebo-controlled study. J Am Acad Child Adolesc Psychiatry 34(4):445-453.
DeVeaugh-Geiss J, Moroz G, Biederman J et al. (1992), Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder-a multicenter trial. J Am Acad Child Adolesc Psychiatry 31(1):45-49.
Emslie GJ, Rush AJ, Weinberg WA et al. (1997), A double-blind, randomized, placebo controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 54(11):1031-1037.
Health and Human Services (1998), Regulations requiring manufacturers to assess the safety and effectiveness of new drugs and biological products in pediatric patients; final rule. Federal Register. Available at: www.fda.gov/ohrms/dockets/98frl/120298c.pdf. Accessed March 20, 1999.
Kolmen BK, Feldman HM, Handen BL, Janosky JE (1997), Naltrexone in young autistic children: replication study and learning measures. J Am Acad Child Adolesc Psychiatry 36(11):1570-1578.
Leonard HL, Swedo SE, Lenane MC et al. (1991), A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. Arch Gen Psychiatry 48(10):922-927.
Riddle MA, Labellarte MJ, Walkup JT (1998a), Pediatric psychopharmacology: problems and prospects. J Child Adolesc Psychopharmacol 8(2):87-97.
Riddle MA, Subramaniam G, Walkup JT (1998b), Efficacy of psychiatric medications in children and adolescents. In: Psychiatric Clinics of North America Annual of Drug Therapy, Vol. 5, pp 269-285.
U.S. Food and Drug Administration (1998), FDA acts to make drugs safer for children. HHS News Nov. 27. Available at: www.fda.gov/bbs/topics/NEWS/. Accessed March 20, 1999.
U.S. Food and Drug Administration, Center for Drug Evaluation and Research (1999), Approved drug products in which FDA has issued a written request for pediatric studies under Section 505A of the Federal Food, Drug and Cosmetic Act. Jan. 25, 1999. Available at: www.fda.gov/cder/pediatric/wrlist.htm. Accessed March 20, 1999.
Vitiello B, Jensen PS (1997), Medication development and testing in children and adolescents. Current problems, future directions. Arch Gen Psychiatry 54(9):871-876.
Walkup JT, Labellarte MJ, Riddle MA (1998), Commentary: unmasked and uncontrolled medication trials in child and adolescent psychiatry. J Am Acad Child Adolesc Psychiatry 37(4):360-363.
Willemsen-Swinkels SH, Buitelaar JK, van Engeland H (1996), The effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study. Biol Psychiatry 39(12):1023-1031.
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DG DISPATCH - AACAP: Psychosocial Therapy Recommended For Major Depressive Disorder In Teens
By Lara Pullen
Special to DG News
CHICAGO, IL -- October 27, 1999 -- Approximately 2 percent of children and 6 percent of adolescents suffer from Major Depressive Disorder (MDD). A new study indicates that psychotherapy may be the treatment of choice for most of these children.
At the 46th annual meeting of the American Academy of Child and Adolescent Psychiatry, Dr. Boris Birmaher, of the University of Pittsburgh presented the results from the Pittsburgh Psychotherapy Trial. The study was designed to test the success rate of three different psychotherapies on children and adolescents: cognitive behavioral therapy, family therapy and supportive therapy.
The clinical outcome at the two-year follow-up showed no difference between the three types of psychotherapy. There was approximately 84 percent remittance and recovery from the index episode within one year after enrollment in the study. The rate of recurrence among those who recovered was approximately 30 percent and occurred on average 21 months after recovery. Thirty-eight percent of patients remained persistently depressed. These recovery and response rates for psychotherapy are similar to those reported in the literature for pharmacotherapy, Dr. Birmaher said.
He recommended an initial trial of psychosocial treatment for at least six to 12 weeks in those patients with an acute episode of MDD. If the patient does not respond to therapy or if the condition appears to be worsening, he then recommends the prescription of selective serotonin receptor inhibitors (SSRI’s).
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DG DISPATCH - AACAP: Bipolarity In Children And Adolescents Remains Largely Difficult To Treat

By Lara Pullen
Special to DG News
CHICAGO, IL -- October 25, 1999 -- Manic depression has only recently been recognized as a diagnosis in children and adolescents. In fact, a recent study suggests that only 50 percent of children suffering from biposal disorder are actually receiving appropriate treatment, suggesting that pediatricians do not easily recognize the symptoms of bipolarity as they are manifested in children.
Dr. Barbara Geller, of the Washington University School of Medicine, addressed these issues of pre-pubertal and early-adolescent bipolarity (PEA-BP) at the 46th annual meeting of the American Academy of Child and Adolescent Psychiatry, in Chicago, IL. She presented data from the ongoing National Institute of Mental Health study "Phenomenology and Course of Pediatric Bipolar Disorders."
The 93 children with PEA-BP enrolled in the study were on 25 different medications, including lithium, chlorpromazine and haloperidol. The study was unable to identify any statistical improvement for any of these 25 treatments or treatment combinations.
A preliminary look at the results two years after the start of the study shows that 70 percent of the patients had a bipolar episode during the past six-month timeframe, suggesting that PEA-BP is a chronic and recurrent disease, Dr. Geller said.
According to Dr. Geller, examples of manifestations of PEA-BP include giggling in class (elation), calling the principal to provide feedback on how a class is taught (grandiosity), and waking up in the middle of the night ready to dance (decreased need for sleep).
In the virtual absence of controlled, systematic studies of treatments for PEA-BP, physicians must rely on extrapolations from adult studies and their colleagues’ clinical experience in determining an appropriate approach to treatment.
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Brain Dysfunction May Explain Murderer's Crime

LOS ANGELES, CA. -- April 7, 1998 -- Dysfunctional brains - not dysfunctional families - may explain some murders, especially when the murderer comes from a "good" home, according to research published in the current issue of the journal Neuropsychiatry, Neuropsychology and Behavioral Neurology.
"If you're antisocial but you come from a good home, the reasons for your violent behavior may have more to do with biology than your upbringing," says University of Southern California psychophysiologist Adrian Raine, Ph.D., the article's lead author.
Murderers from relatively benign backgrounds are more likely to have reduced activity in two key brain areas than murderers from homes wracked by conflict, deprivation and abuse, Dr. Raine reports.
Raine directed a study in which scientists from USC and the University of California at Irvine used positron emission tomography (PET) to scan the brains of 38 men and women charged with murder. Some of the subjects had pleaded not guilty by reason of insanity, while the rest had been found incompetent to stand trial.
PET scans measure the uptake of blood sugar (glucose) in various brain areas during the performance of simple, repetitive tasks. (Glucose is the basic fuel that powers most cell functions. The amount used is related to the amount of cell activity.)
The researchers scoured court records, attorney interviews, medical and psychological records, and newspaper articles for evidence in the subjects' upbringing of physical or sexual abuse, neglect, extreme poverty, foster home placement, severe family conflict, a broken home or having a criminal parent-all environmental risks commonly associated with a propensity for violence.
The researchers then rated the severity of the risks they found on a five-point scale, with 0 representing no abuse, 1 minimal, 2 partial, 3 substantial and 4 extreme.
Of the 38 murderers, only 12 were found to have suffered significant psychosocial abuse and deprivation (ratings 2 to 4). The remaining 26 were found to have experienced minimal abuse and deprivation or none (ratings 0 - 1).
Compared to the subjects from bad homes, the 26 subjects from benign backgrounds averaged 5.7% less activity in the medial prefrontal cortex. More significantly, one particular part of the medial prefrontal cortex-the orbifrontal cortex on the right hemisphere-showed 14.2% less activity.
"Parents of violent kids think, 'What did I do wrong?'" says Raine, a professor of psychology in USC's College of Letters, Arts and Sciences. "When the kids come from a good home, the answer may be absolutely nothing. A biological deficit may be to blame."
Located just behind the forehead, the prefrontal cortex has been shown (in animal research) to be involved in inhibiting the functions of the limbic system, a far deeper area of the brain that gives rise to aggressive behavior.
Animal research also has shown that the right orbital frontal cortex is involved in fear conditioning-that is, in making a subconscious association between antisocial behavior and punishment. In humans, fear conditioning is thought to be the key to developing a conscience.
"Why doesn't everyone assault others or act violently?" Raine asks. "One reason is that most of us are good at fear conditioning and we've been punished in childhood for doing minor things like stealing or hitting friends. So we've learned the association between antisocial behavior and punishment and therefore feel fear when we even contemplate an antisocial act.
"But not everyone is able to form these conditioned responses with equal facility," Raine says. "While some people have biological systems that make it easy, others have biological systems that make it hard. If you are an individual whose right orbital cortex is not functioning well, you're biologically disadvantaged in developing a conscience."
Outside of any effect they may have in predisposing an individual to violence, such brain deficits can only be detected through such relatively new functional brain imaging techniques as PET scans.
Raine says the USC-UCI study sheds light on a long-standing mystery in crime and punishment-how some criminals appear so clearly to be a product of their background, while others seem to defy their seemingly benign upbringing.
"It may help explain the difference between Robert Alton Harris, who was battered from pillar to post all his life, and Jeffrey Dahmer, who by all accounts came from a good home. Brain dysfunction may have played a relatively greater role with Dahmer."
Raine says that further research is needed to discover causes of the reduced brain activity detected in the USC-UCI study.
"If reduced activity in the two areas of the prefrontal cortex in fact predisposes an individual to homicide, then tackling the causes of the brain dysfunction would help reduce violence," says Raine, the author of "The Psychopathology of Crime: Criminal Behavior as a Clinical Disorder" (Academic Press, 1993).
Past research has established an increased propensity for aggressive behavior among individuals with lower function in areas of the brain that can sustain damage during birth or other obstetrical complications. However, research has never estab- lished a vulnerability to obstetrical complications in either the medial prefrontal cortex or the right orbital frontal cortex.
Deficits in both the right and the left orbital prefrontal cortex have been linked in the past to head injuries. In Raine's study, however, the murderers from good homes had experienced no higher rate of head injuries than the murderers from bad homes.
This, says Raine, suggests that individuals are born with this sort of brain dysfunction. The differences in brain activity also did not appear related to age, sex, ethnicity, handedness, schizophrenia or generalized brain dysfunction.
The findings are consistent with a 1981 English study that linked deficits in fear conditioning to antisocial behavior, but only among individuals from apparently good homes. Raine replicated those findings in a 1997 study of 1,795 toddlers living in Mauritius, an island in the Indian Ocean.
Given the homogeneity of the current study sample, the USC- UCI findings cannot be generalized to other violent populations, Raine says. For the same reason, measuring activity levels in the medial prefrontal cortex or the right orbital frontal cortex cannot yet be used as a test to determine whether someone is a likely murderer.
The findings do, however, help to substantiate the dual role of nature and nurture in predisposing an individual to crime. Raine's earlier research found that individuals who suffered both birth complications and maternal rejection are more than twice as likely to become criminals in adulthood, compared with individuals who suffered only one or the other of these risk factors.
"Research continues to illustrate the critical importance of integrating biological with social measures in understanding how violence develops," Raine says.
The USC-UCI research was funded by the National Institute of Mental Health.
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Copyright © 1997 The Seattle Times Company
Sunday, Aug. 10, 1997
Prozac-type drugs being given to kids
by Barbara Strauch
New York Times
The Long Island girl is nearly 15 years old and she has been taking Prozac since she was 5.
Before Prozac, she was a mess. She could not be left alone, even for minutes. Strangers terrified her and she was obsessed by thoughts that her parents were dying or burglars were breaking into her house. Conventional therapy failed, said the girl's mother, who spoke on the condition that she and her daughter not be identified.
But after taking Prozac, the girl was transformed. Today, she is in her school's honors program.
In the decade the girl has taken Prozac - now in its 10th year on the market and the most popular antidepressant ever in the United States - the drug was never approved for children. No antidepressant has ever been formally cleared for children or adolescents.
But that could be about to change. The drug company that makes Prozac, Eli Lilly, recently submitted data on the drug to the Food and Drug Administration in an effort to have it approved for children. The agency has asked for more information.
Companies making similar new antidepressants, most of which regulate mood by adjusting the brain chemical serotonin, are gathering information and conducting pediatric studies in hopes of getting federal approval for use of their drugs in children.
SmithKline Beecham is analyzing results from two large studies of its drug, Paxil, on adolescents. Bristol-Myers Squibb Co. is doing a trial of Serzone and American Home Products Corp. is testing Effexor.
FDA approval is, in fact, not necessary. Once the agency approves a drug for sale, doctors can prescribe it to anyone for any purpose. So the new medications have quietly flowed into the children's market. But the agency's approval of an antidepressant for children would be a tremendous marketing lift for the drug.
Last year, nearly 600,000 children and adolescents were prescribed Prozac, Paxil or Pfizer's Zoloft, according to IMS America Ltd., a research concern. Prozac prescriptions for those 13 to 18 years old increased 46 percent last year.
Over all, Prozac sales totaled $1.73 billion in the United States in 1996, Eli Lilly said.
But the adult market for the drugs has become saturated. New adult prescriptions for Prozac fell 5 percent last year and 2.7 percent the year before, after increasing 13 percent in 1994. Companies are looking for customers.
Mint and orange flavors
Formal FDA clearance of antidepressants for children would mean companies could directly market them for use by children.
"It would be a positive," said Barbara Ryan, managing director of Alex. Brown & Sons, which analyzes the pharmaceutical industry. "The companies are looking for expanded markets."
Critics worry, though, that not enough is known about how antidepressants work on the growing brain, or that cost-conscious insurance companies will turn too quickly to drugs, rather than costly conventional psychotherapy. Others fear that formal approval could encourage excessive prescriptions of the drugs or even accidental overdoses, especially since some companies are already preparing them in mint and orange-flavored liquid versions.
"Depressed kids need all the help we can give them," said Dr. Leon Eisenberg, professor of social medicine at Harvard Medical School. "But even a good drug can be abused."
Marsha Levy Warren, a Manhattan clinical psychologist, said that she was worried that FDA approval of antidepressants for the young might mean teen-agers would be medicated just for acting like teen-agers and that by promoting drugs without counseling, children would get the wrong message.
"If we are giving them medication to stabilize their moods," Warren said, "they may not be able to handle the ebb and flow of emotion that is part of life."
But for the mother of the Long Island girl, FDA approval would be a long-awaited vindication.
"It's scary enough to give your child medication," said the mother, a social worker, "but to give something that isn't approved is even scarier. There was no research and I was against medication. But now I'm a believer."
Her daughter's psychiatrist, Dr. Harold Koplewicz, a professor of clinical psychiatry at New York University School of Medicine, has had dozens of children on the new antidepressants. The author of "It's Nobody's Fault," a book on brain disorders in children, he acknowledges that depression is difficult to diagnose in children and counseling should be tried first.
But, Koplewicz said, children's depression remains undertreated and underdiagnosed and medication can be lifesaving. He says treating depression with medicine can "keep kids from medicating themselves with feel-good drugs" that are illegal.
"If a child truly has depression, medication should be considered as part of the treatment," Koplewicz said. "This is no Prozac party; these drugs only work if you need them."
"A Satanic mix"
Dr. Peter Jensen, chief of the child- and adolescent-disorders research branch of the National Institute of Mental Health, said rates of both adolescent depression and suicide have risen over the last decade, with the teen-age suicide rate now equaling that of adults. "We don't want to leave these kids as therapeutic orphans," Jensen said. "This is an urgent public health concern."
Even after 10 years of Prozac, however, the psychiatric field remains divided. Counseling is considered crucial, but there are worries that doctors are being pushed to prescribe drugs too quickly for a growing variety of ailments from depression and obsessive-compulsive disorders to even extreme shyness. Already, many complain about pressure from health maintenance organizations in favor of relatively low-cost drugs over counseling and hospital stays.
"But a drug that works coupled with the financial crunch on a health provider could be a problem," Eisenberg said. "Managed care and psychotropic drugs are a Satanic mix."
5 percent suffer depression
Drug companies have been reluctant to try earlier antidepressants on children because of their more severe side effects, like heart irregularity. The few studies that had been done on the early antidepressants and children showed that the drugs were no better than dummy pills.
And until about 15 years ago, no one thought children could suffer depression. Now, experts estimate it afflicts about 4 million American children - or 5 percent.
Lately, researchers have begun studying how children respond to the newer drugs, called selective serotonin reuptake inhibitors, or SSRIs. Prozac, the first of the new class, was initially criticized for possibly inducing suicide in adults.
Those concerns have eased and researchers say there have not been any documented cases of newer antidepressants pushing children to suicide. Some studies have suggested that all the SSRIs can sometimes cause restlessness and impulsive behavior or even mania. But because they have less effect on the heart, there is less fear of a lethal overdose.
FDA officials say that so far they have not received reports from doctors that would have raised a red flag about the use of Prozac by children.
Doctors like Donna Moreau, director of the children's anxiety and depression clinic at Columbia Presbyterian Medical Center, see clear results with drugs like Prozac. About 50 percent of severely depressed children get better with six weeks of psychotherapy, Moreau said. But for the rest, drugs, usually given along with counseling, seem to help, she said, adding, "I'm convinced it's the medication working."

Permission to repost or reprint any material on this site must be obtained by contacting Barbara Davis at The Seattle Times, (206) 464-2310, bdav-new@seatimes.com
http://www.seattletimes.com/extra/browse/html97/altdrug_081097.html

INTERNATIONAL COALITION FOR DRUG AWARENESS
ADDRESSING AMERICA'S THIRD LEADING CAUSE OF DEATH -- PRESCRIPTION MEDICATIONS
The International Coalition For Drug Awareness is a private, non-profit group of physicians, researchers, journalists and other concerned citizens. Our primary focus is to address the world's most pervasive and subtle drug problem - prescription drugs. We are dedicated to educating the people of the world regarding the potential harmful and life threatening short and long term effects of these drugs. As the cause of an estimated 200,000 deaths per year in America, drug reactions are now the third leading cause of death! The most dangerous period of time for a drug is upon market introduction. At that point physicians and their patients only have information on adverse reactions present in the controlled environment of a clinical trial, and are unaware of the potential adverse reactions of these new drugs when dispensed to the general public. We feel there is a need to track and report patient reactions more carefully and more rapidly than what is presently being done, which should result in lower medical costs for the patients and doctors as well. This better tracking might also begin to breech the gap that is beginning to form between well-meaning doctors and maltreated patients. By keeping prescribing physicians and their patients abrest of recent adverse reaction reports we hope to cut the number of unnessesary deaths due to drug reactions and interactions and lessen the number of malpractice suits filed against physicians as a result of those reactions. Beyond this public education process it is our intention is to serve as an watch dog group in relationship with the FDA and equivilent organizations around the world, encouraging them to remove drugs which demonstrate high numbers of dangerous adverse reactions and threaten the public safety. Originally Phen-Fen Redux were thought to be so safe that 18 million people took the drugs. Now we know that they were so dangerous that those who took even one pill have been advised to have their hearts checked. If these drugs could be among the most popular on the market and touted as "the thing" for weight management for a two year period, leaving a backlash of victims that attorney's offices cannot even begin to handle, what other mistakes will we wake up to tomorrow? What are you taking right now that could be just as dangerous as these diet pills? What do you know about the medications you are currently taking? What do you know about the dangers of taking the drugs you are taking in combination with one another? Even more frightening to ask is "What does your doctor know or not know about the answers to these questions?"Prescription drugs are now the third leading cause of death in America killing 200,000 every year. Do you know that you have a seven times greater chance of dying by walking into your doctor's office than you do in getting behind the wheel of your car? Every year 200,000 die from prescription drug reactions and another 80,000 die from medical malpractice, while 41,000 die in auto accidents. What is wrong with our focus on the "drug war" when 200,000 die each year from prescription drugs, yet approximately only 20,000 die as a result of illegal drug use? Billions of dollars go into illegal drug issues in this country every year even though FAR MORE are dying from legal drugs. Everyone is asking, "Where is the FDA?" Perhaps we should look to see if they are hiding in the pockets of the large pharmaceutical giants. Yes, the pharmaceutical companies where so many FDA officials go to work when they finish their posts at the FDA. Some of the most popular drugs on the market today are those that increase serotonin levels like the diet pills that were just pulled from the market. Drugs like Prozac, Zoloft, Paxil, Luvox, Effexor, Serzone, Anafranil, etc. are some of the biggest money makers ever for the pharmaceutical companies.Yet are you aware that the use of Prozac among children from ages 6 - 12 went from 41,000 in 1995 to 203,000 in 1996. The number of new prescriptions written increased almost 400% in just one year?!! This is a very powerful mind-altering drug that has not been approved for use in children and yet our children are popping it like candy! Just Prozac's affect upon cortisol levels alone should frighten parents to death. One 30mg dose has been shown to CLEARLY DOUBLE the level of cortisol! Increased cortisol is impairs the development and regeneration of the liver, kidneys and muscles. It also retards linear growth. How many parents are given that information? How many doctors are aware of it themselves?The study being used to gain FDA approval of this medication demonstrates that the rate of mania (a terrible form of insanity including symptoms of sexual compulsions, criminal behavior, alcohol cravings, rages leading to domestic violence, delusions of grandeur -- often mistaken for increased self confidence, wild spending and varied types of criminal behavior) among children taking Prozac in this study was three times higher than it is for adults - three out of 100 had to drop out of the study due to this devastating complication! Why do this to our children when there are many safer natural options?
Even the developers of these meds are speaking out. In the October 20, 1997 issue of TIME magazine Dr. Candace Pert, who is one of the two developers of the serotonin binding process which made the serotonergic medications possible stated, "I AM ALARMED AT THE MONSTER that Johns Hopkins neuroscientist Solomon Snyder and I created when we discovered the simple binding assay for drug receptors 25 years ago. Prozac and other antidepressant serotonin-receptor-active compounds may also cause cardiovascular problems in some susceptible people after long-term use, which has become common practice despite the lack of safety studies." "The public is being misinformed about the precision of these selective serotonin-uptake inhibitors when the medical profession oversimplifies their action in the brain and ignores the body as if it exists merely to carry the head around! In short, these molecules of emotion regulate every aspect of our physiology. A new paradigm has evolved, with implications that life-style changes such as diet and exercise can offer profound, safe and natural mood elevation." (Dr. Candace B. Pert is a research professor at Georgetown University Medical Center in Washington, D.C.)
http://members.aol.com/atracyphd/mission.htm
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Creating a 'Generation Rx' as more kids are drugged for behavior problems

Copyright © 1997 Nando.net
Copyright © 1997 Reuter Information Service
CHICAGO (July 8, 1997 4:27 p.m. EDT) - Eric's mind was wandering and his grades were down, but rather than changing 8-year-old Eric's world, everyone suggested changing Eric -- with a drug.
Ritalin was prescribed for the Indianapolis boy, based on a teacher's recommendation, four hours of tests, 20 minutes with a psychologist and a diagnosis of attention deficit-hyperactive disorder.
With few questions, Eric's parents gave their son the drug -- given annually to millions of children in the United States -- and waited.
"I had high hopes for Ritalin, I really did ... This was supposed to be the magic stuff," said Eric's mother, who asked that their real names not be used. After three weeks, Eric was miserable and showed no improvement, she said.
"He told me when he was on the medicine he didn't feel like a whole person, that he felt weird," said his mother, who took him off the drug, reordered her family's priorities and started a home-schooling program.
"He's my kid again ... It's going great. His attention span is unbelievable. It's just a matter of someone giving him a few minutes," she said.
Stories like Eric's are becoming more common as busy parents, overcrowded schools and cost-conscious healthcare providers look increasingly to drugs for quick, cheap help in coping with an age group becoming known as Generation Rx.
Ritalin -- known as "the shutup-and-sit-down drug" -- was prescribed for three million children and teen-agers in this country last year, up from 2.1 million in 1993, according to IMS America Ltd., a market research firm in Pennsylvania.
Nearly 700,000 American children and adolescents between 6 and 18 years old got prescriptions last year for Prozac, Zoloft or Paxil -- the three top-selling antidepressants.
That was up from just over 300,000 prescriptions in 1993, IMS reported.
No studies have determined the long-term health effects of these drugs on childrens' growing brains and bodies and most of the antidepressants are being prescribed without official pediatric approval from the U.S. Food and Drug Administration.
"It's an incredible commentary on our society that instead of addressing the basic needs of our kids we drug them," said Dr. Peter Breggin, director of the Center for the Study of Psychiatry in Bethesda, Md.
"Instead of addressing their needs for better family life, better education, more spiritual direction, safer environments, better television and videos, instead of addressing all of that, we're simply drugging them," he added.
Mood-altering drugs, used by millions of U.S. adults, are seen by some in medicine as a major boon to child psychiatry.
"Drugs like ... Prozac are extremely helpful in treating depression and related disorders in children," said Dr. Peter Stokes, professor of psychiatry and medicine at Cornell Medical College in New York and author of a soon-to-be-published review of research in the field.
Even advocates, however, express concern about overuse of the drugs in children.
"There's a real sense that these kids have lots of problems and need much more than just the medicine," said Dr. Graham Emslie, professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas.
Emslie headed a landmark study being published this month that was the first to show that Prozac works in treating childhood depression, at least compared with placebos.
Backed by such studies, the world drug industry is marching cautiously into the juvenile mental health market, seen by Wall Street analysts as a growth area for products that are saturating the adult population.
"The market potential is huge ... Kids get depressed about pimples, grades, who knows what," said independent drug industry analyst Hemant Shah.
The FDA is evaluating mountains of data submitted last year by drug firms answering the agency's appeal for better information on pediatric use of the drugs. Several drugmakers are awaiting or about to seek FDA clearance to sell antidepressants as federally approved treatments for children.
The medical diagnoses are diverse -- oppositional-defiant disorder, clinical depression, separation anxiety, conduct disorder and obsessive-compulsive disorder. Precise symptoms for some of these problems, especially the newer ones, vary, but estimates of sufferers run to the millions.
Pharmacia & Upjohn Inc. and marketing partner Solvay Pharmaceuticals Inc. of Belgium won FDA approval in March to sell Luvox as a treatment for obsessive-compulsive disorder in children.
Pfizer Inc. has submitted an FDA application for Zoloft, a drug similar to Prozac, as a treatment for pediatric obsessive-compulsive disorder, a spokesman said.
SmithKline Beecham Plc is analyzing data from a recent study of Paxil, an antidepressant, in 12- to 18-year-olds and plans to apply for FDA clearance, a spokeswoman said.
Eli Lilly and Co., maker of Prozac, has submitted pediatric data to the FDA, too.
Dr. Joe Woolston, director of childrens' psychiatric in-patient services at Yale-New Haven Hospital in Connecticut, said overuse of these drugs in children is a problem sometimes compounded by overlapping prescriptions.
"Every week I see at least one child who is on a regimen of something like Ritalin, Depakote, Haldol and Zoloft. It's just a ridiculous medication regimen," he said.
"This is a brand-new chapter" in child psychiatry, Woolston said. "The problem is, people are using medications instead of doing full evaluation and treatment. Medication should be part of intervention, but it can't be stand-alone."
By KEVIN DRAWBAUGH, Reuter
http://www4.nando.net/newsroom/ntn/health/070897/health21_12606.html

http://www.nandotimes.com/healthscience/
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PSYCHIATRIC STIGMA
follows you everywhere you go
for the rest of your life
a warning from
Lawrence Stevens, J.D.

A problem you should think about before consulting a mental health professional, or encouraging someone else to do so, is the stigma of having received the so-called therapy. If you seek counseling or "therapy" from a psychiatrist or psychologist, how are you going to answer questions on job applications, applications for occupational or professional licenses, a driver's license, applications for health or life insurance, and school and college applications, such as "Have you ever had psychiatric or psychological therapy?" When you apply for a job or occupational license or a driver's license or apply for an insurance policy or admission to an educational program you will often be required to answer this or a similar question. When you answer such questions candidly and admit having received psychiatric or psychological "help", the result often will be loss of important opportunities: Answering yes to such questions often results in rejection for employment or licensure or admission to college or other educational program or denial of insurance coverage. Sometimes you will be forced to ask your "therapist" to breach the confidentiality of your communications with him or her by making a report on you in order for you to get a job, license, insurance coverage, or admission to school. If you conceal your experience of psychiatric or psychological "therapy" by answering "no", thereafter you will have to be careful to watch what you say and to whom, and you may with good reason worry about being found out - since you run the risk of being fired from a job or expelled from school or suffering revocation of licensure if your deception is ever discovered. You may eventually find the insurance policy you have been paying premiums on for many years is valueless because of what you concealed on the application for the policy years earlier.
In his book The Powers of Psychiatry, Jonas Robitscher, J.D., M.D., Professor of Law and Behavioral Sciences at Emory University's Schools of Law and Medicine, pointed out that "Applicants for the state of Georgia bar examination, like applicants in many other states, are required to state...whether they have ever received diagnosis of...emotional disturbance, nervous or mental disorder, or received regular treatment for any of these conditions. Although there is no known instance of this information having been used to keep an applicant from taking the examination or being admitted to the Georgia bar, there are instances of denying applicants in other jurisdictions" (Houghton Mifflin Co., 1980, p. 234).
In the same book Dr. Robitscher described the case of a medical school applicant who had graduated from college magna cum laude, who was admitted to Phi Beta Kappa, and who scored in the upper ninety-ninth percentile in the Medical College Admission Test - but who was denied admission to medical school because she had sought psychiatric treatment (pp. 238-239). He said this is typical of "prejudicial policies of not admitting or readmitting students who have had or are undergoing psychotherapy" (p. 239).
An airline pilot told me he was grounded for seven months by the Federal Aviation Administration because he revealed he had been seeing a psychiatrist (for so-called outpatient psychotherapy) on the medical history questionnaire he was required to fill out as part of his routine periodic medical examinations required of airline pilots and which involved criminal penalties (a fine of up to $10,000 and/or up to five years imprisonment) for concealing the requested information. He told me he enjoyed seeing the psychiatrist but that the hassle which resulted from his doing so, because of the questions it created about his job qualifications, out-weighed whatever benefit came from seeing the psychiatrist. He said that all factors considered, "It wasn't worth it." When taking physical examinations, pilots in the United States are required to "List all visits in the last three years to a physician, physician assistant, nurse practitioner, psychologist, clinical social worker, or substance abuse specialist for treatment, evaluation, or counseling. Give date, name, address, and type of health professional consulted, and briefly state reason for consultation. ... Routine dental, eye, and FAA periodic medical examinations may be excluded" (FAA Form 8500-8, italics added). This suggests that, contrary to what some people think, anyone consulting a psychologist or clinical social worker is considered suspect. That is, stigma attaches to anyone consulting not only psychiatrists, but also psychologists or social workers. Routine dental or eye examinations involve no stigma or suspicion of disqualification and therefore are not required to be reported.
The 1988 Democratic Party Presidential nominee, Massachusetts Governor Michael Dukakis, in the words of Newsweek, "was accused of having received psychiatric treatment" ("The High Velocity Rumor Mill", Newsweek, August 15, 1988, p. 22. See also, Andrew Rosenthal, "Dukakis Releases Medical Details To Stop Rumors on Mental Health", The New York Times, August 4, 1988, p. 1). The accusations proved to be false, but the impression given by the news reports about this story is that Dukakis' presidential campaign would have been doomed by this one fact alone if the claim he had ever consulted a psychiatrist or psychologist had proven to be true. In 1972 U.S. Senator Thomas Eagleton was nominated for Vice-President of the United States at the Democratic National Convention but subsequently was removed from the ticket by the Democratic National Committee when it became known he had undergone psychiatric treatment, including hospitalization and electric shock treatment.
Bruce Ennis, an ACLU attorney who has represented people deprived of employment because of psychiatric stigma, argues that "In the job market, it is better to be an ex-convict than an ex-mental patient." He says "very few employers will knowingly hire an ex-mental patient." He points out that "Almost all public employers and most large companies ask job applicants if they have ever been hospitalized for mental illness" and that "If the answer is yes, the applicant will almost certainly not get the job". Mr. Ennis also points out that "if the applicant lies and says no, he runs the risk of eventual discovery". On this basis Mr. Ennis argues that "It is time for psychiatrists and judges to face the brutal facts. When they commit a person to a mental hospital, they are taking away not only his liberty, but also any chance he might have for a decent life in the future." On the basis of his experience as an attorney for people saddled with psychiatric stigma he observes that "Even voluntary hospitalization creates so many problems and closes so many doors that an old joke takes on new truth - a person has to be crazy to sign himself into a mental hospital" (Bruce J. Ennis, Prisoners of Psychiatry: Mental Patients, Psychiatrists, and the Law, Harcourt Brace Jovanovich, 1972, pp. 143-144). Mr. Ennis wrote those remarks in 1972, but if anyone is inclined to think psychiatric stigma substantially diminished during the 1970s and 1980s, consider once again the reaction of the press and public in 1988 to the apparently false allegation that presidential candidate Governor Michael Dukakis had previously consulted a psychiatrist. That it should be such a headline grabbing issue shows how stigmatizing is any experience as a psychiatric "patient". This public reaction is particularly noteworthy in light of the fact that Governor Dukakis was accused only of consulting a psychiatrist in his office, not psychiatric hospitalization.
The presumption of unreliability, untrustworthiness, and emotional instability which flows from having ever sought psychiatric or psychological "therapy" doesn't haunt only people with responsibilities like doctors, lawyers, airline pilots, and Presidential/Vice-Presidential candidates: In his book, Prisoners of Psychiatry, ACLU attorney Bruce Ennis reports many cases of people who have been denied taxi driver licenses because of past psychiatric treatment even though "Most of them had never been hospitalized" and had never done anything to suggest they were dangerous (p. 160).
In a book she wrote, Eileen Walkenstein, M.D., a psychiatrist, says "A psychiatric diagnosis is like a jail sentence, a permanent mark on your record that follows you wherever you go" (Don't Shrink To Fit! A Confrontation with Dehumanization in Psychiatry and Psychology, Grove Press, 1975, p. 22). If you consult a mental health professional, you will probably get some kind of "diagnosis". In at least some states, professional licensing laws require mental health professionals, including psychologists, to keep a written record of "diagnosis" and "treatment".
In 1992, Commenting on the Americans with Disabilities Act (ADA), Peter Manheimer, chairperson of the Commission for the Advancement of the Physically Handicapped, said "It is most appropriate that the ADA protects recovering drug addicts, alcoholics, persons with AIDS, and persons who have mental and psychological disabilities, as they form the most misunderstood and feared portion of the disability community. They suffer the greatest discrimination" (Peter Manheimer, "Reporting on persons with disabilities", letter to the editor, Miami Herald, July 24, 1992, p. 16A - italics added).
And "a study by the National Institute of Mental Health in 1993 found that even ex-convicts rank above former mental patients in social acceptance" (Chi Chi Sileo, "Rip-offs Depress Mental Health Care", Insight magazine, January 24, 1994, p. 14.) This article quotes a psychiatric hospital patient saying "The stigma is incredible...Forget telling an employer! Sometimes they find out anyway, and all of a sudden you're unfit to work there" (ibid). In his autobiography, Kenneth Donaldson said after he had been committed to a psychiatric hospital, people "accepted a psychiatric diagnosis which forever rent the fabric of my life. Thereafter, not only society at large but members of my family would not see Ken the son and father and friend, but Ken the mental patient. From this would flow unimagined misery, a fog which would envelop all our lives. And our situation would be, of course, representative of millions. The fog would seep into my employment, my relations with doctors, my access to lawyers and the courts. Every enterprise in which I would engage would be poisoned by the label. It haunted me and frightened others" (Insanity Inside Out, Crown Pub., 1976, p. 321).
In his book The Powers of Psychiatry, Emory University professor Jonas Robitscher, J.D., M.D., said: "Psychiatrists have been so criticized for the errors or vagueness in their labeling procedures because the label produces a new disability, which often remains as a burden long after the symptoms that led to the label have departed. ... A study of the attitudes in a small town indicates that fellow townspeople reject other members of the community in a direct relationship to the professionalization and specialization of the source of help, with the least rejection when help is sought from a clergyman, increasing percentages of rejection for those seeking psychiatric help from physicians and psychiatrists, and the most rejection for those who get mental hospital help. A study of work supervisors shows that the knowledge that an employee is seeing a psychiatrist would be likely to rule out a promotion even if the employee is doing good work...The harm and potential harm done to mental patients and former mental patients is not only confined to those who have had serious illnesses, those who have been hospitalized or who have had to interrupt careers or schooling. Psychiatrists know that many people who consult them as outpatients are much less 'sick' than many or most of the general population. If these people had decided not to be patients but instead to be clients or parishioners and had taken their problems to a social worker, a pastoral counselor, or a faith healer, they would have incurred no stigma. ... The ubiquitous questionnaires that ask, 'Have you ever consulted a physician for a physical or emotional or mental condition?' do not take account of those who should have and haven't, or those who are able to answer no because they have taken their problems to an encounter group, a sensitivity-training session, an est seminar, or a consciousness- raising group, and so have escaped the discriminatory effect of seeking help" (pp. 230, 232, 233).
The difficulty of getting a health insurance policy after having sought psychiatric or psychological "therapy" or even marriage counselling was mentioned in the August 1990 issue of Consumer Reports in an article titled "The Crisis in Health Insurance": "Virtually no commercial carriers and only a handful of Blue Cross and Blue Shield plans will sell policies to anyone who has had heart disease, internal cancer, diabetes, strokes, adrenal disorders, epilepsy, or ulcerative colitis. Treatment for alcohol and substance abuse, depression, or even visits to a marriage counselor can also mean a rejection. If you have less serious conditions, you may get coverage, but on unfavorable terms" (p. 540 - italics added).
The stigma involved in obtaining psychiatric "therapy" was discussed in an article by columnist Darrell Sifford titled "Should You Lie About Psychiatric Care?" appearing in The Charlotte Observer (Charlotte, N.C.) on June 10, 1990. A mother wrote to Mr. Sifford asking whether her teenage son, who was about to apply for admission to college, should answer truthfully the questions about psychiatric treatment, which he had had at the age of 15. She wrote: "Many of these [college application] forms request information regarding any psychiatric treatment. And once he is out in the real world, most job application forms ask for the same information ... Have we [by insisting he get psychiatric care] doomed him to a future of lying on application forms for fear of losing the position or college being applied for? What should we do?" The newspaper columnist realized the woman's question is what he called "a serious question. Very Serious." He shared the woman's letter with Paul Fink, immediate past president of the American Psychiatric Association. This was Dr. Fink's advice: "I would tell them to lie on the forms ... The stigma is there, and to deny it and sacrifice yourself by telling the truth makes no sense. ... With the public at large I work to decrease stigma, but with individual patients I impress on them how widespread and deeply rooted the stigma is. ... If two people who are equal in credentials apply for a job and one has had psychiatric treatment, that person will be discriminated against, and he'll be the loser in the competition for the job. ... Even if the person with treatment had better credentials, he most likely still would lose out to the other person. That's how deeply rooted the stigma is. ... I will not encourage anybody to acknowledge that they had treatment" (p. 4E).
Do you want to go through life with this kind of secret? How do you feel about lying on applications for the rest of your life? If it is your rebellious adolescent or troubled spouse for whom you're considering psychiatric "treatment", ask yourself this question: Do you really hate your rebellious teenager or spouse enough to impose this kind of problem on him or her? Is it really the right thing to do? The problems motivating you to impose so-called therapy on a member of your family are probably temporary, but psychiatric stigma is forever.
The Americans with Disabilities Act (ADA), is unlikely to help much, despite its aim of eliminating discrimination in employment against people with disabilities, including alleged psychiatric disabilities. As Jonas Robitscher, J.D., M.D., said in his book The Powers of Psychiatry prior to the enactment of the ADA: "The disclosure that one is or has been mentally ill can lead to rejection, and other reasons for the rejection can always be found. ... Forcing private employers to hire the disabled would raise issues of invasion of privacy and problems of enforcement. Stigmatization will continue to be a problem, and discrimination will continue to exist" (p. 241-242). In areas covered by the ADA, availing oneself of its protection will probably require large amounts of time spent in litigation and a lot of money paid in lawyer's fees, with uncertain results.
And there are many areas of stigmatization and discrimination the ADA and other laws don't cover. One example is colleges and universities that do not receive federal funds. Another is the effect of psychiatric stigma on personal relationships: Keeping secrets conceals parts of who you are and prevents emotional intimacy of the sort most people want with friends and especially with one's spouse; but sharing this secret leaves you open to blackmail or similar kinds of pressure. Concealing psychiatric "treatment" from an employer (as is often necessary to get a job) but revealing it to one's spouse or a friend gives the spouse or friend knowledge that can be used against you if your relationship turns sour. Should you be put in a position where you must lie to your spouse or a friend to keep secret your history of so-called psychiatric or psychological "therapy" (e.g., if he or she should ask), you introduce deception into a relationship where probably you wish you could be honest and sincere. Even if you don't tell your spouse or someone you are thinking about marrying, divorce now occurs in close to a majority of marriages, and in a divorce - especially if you get into a dispute over child custody or even visitation rights - your spouse's attorney will probably ask you, under oath when you are subject to the penalties of perjury, if you have ever had psychiatric or psychotherapeutic "treatment" - perhaps confronting you with the choice of committing perjury or jeopardizing your employment by telling the truth. Whether you admit having had psychiatric or psychological "therapy" or it is discovered some other way, the resulting stigma may result in losing your children in a custody battle, and threats to reveal it to your employer may be used to pressure you to agree to property division or alimony (or lack of it) or an amount of child support that is not appropriate. You may have to consider these problems when contemplating the wisdom of getting married or divorced - problems you could have avoided by simply avoiding having received "therapy". You are likely to face a similar dilemma if you are ever called for jury duty, since during the jury selection phase of the trial potential jurors are often asked, under oath, if they have ever had psychiatric "treatment". Another time you will probably be asked about past psychiatric "treatment" is if your job requires you to get a security clearance or bonding.
If the so-called therapy helped enough, it might be worth the problems created by the stigma of having had psychiatric or psychological "help". However, the benefit assumed to come from psychiatric and psychological "therapy" (itself a questionable assumption) is vastly outweighed by the stigma that comes from receiving it. The stigma that results from seeing psychiatrists, psychologists, or psychiatric social workers is a strong argument in favor of instead consulting friends, family, or nonprofessional counselors whose expertise comes from life rather than from "professional" training, or simply working at solving your problems yourself.

THE AUTHOR, Lawrence Stevens, is a lawyer whose practice has included representing psychiatric "patients". His pamphlets are not copyrighted. You are invited to make copies for distribution to those who you think will benefit.
http://www.antipsychiatry.org/stigma.htm

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Commentary:
Against Biologic Psychiatry
by David Kaiser, M.D.
December 1996 (abridged)
As a practicing psychiatrist, I have watched with growing dismay and outrage the rise and triumph of the hegemony known as biologic psychiatry. Within the general field of modern psychiatry, biologism now completely dominates the discourse on the causes and treatment of mental illness, and in my view this has been a catastrophe with far-reaching effects on individual patients and the cultural psyche at large. It has occurred to me with forcible irony that psychiatry has quite literally lost its mind, and along with it the minds of the patients they are presumably supposed to care for. Even a cursory glance at any major psychiatric journal is enough to convince me that the field has gone far down the road into a kind of delusion, whose main tenets consist of a particularly pernicious biologic determinism and a pseudo-scientific understanding of human nature and mental illness.
The purpose of this piece is not to attempt a full critique or history of this occurrence, but to merely present some of the glaring problems of this movement, as I believe significant harm is being done to patients under the guise of modern psychiatric treatment. I am a psychiatrist trained in the late 1980s and early 1990s, and I use both psychotherapy and medications in my approach to patients. I state these facts to make it clear that this is not an antipsychiatry tract, and I am speaking from within the field of psychiatry, although I find it increasingly impossible to identify with this profession, for reasons which will become clear below.
Biologic psychiatrists as a whole are unapologetic in their view that they have found the road to the truth, namely that mental illnesses for the most part are genetic in origin and should be treated with biologic manipulations, i.e., psychoactive medications, electroconvulsive treatment (which has made an astounding comeback), and in some cases psychosurgery. Although they admit a role for environmental and social factors, these are usually relegated to a secondary status. Their unquestioning confidence in their biologic paradigms of mental illness is truly staggering.
In my opinion, this modern version of the ideology of biologic/genetic determinism is a powerful force that demands a response. And when I use the word ideology here, I mean it in it's most pernicious form, i.e., as a discourse and practice of power whose true motivations and sources are hidden to the public and even to the practitioners themselves, and which causes real harm to the patients at the receiving end.
Biologic psychiatry as it exists today is a dogma that urgently needs to be unmasked. One of the surest signs that dogmatists are at work here is that they rarely question or attempt to problemitize their basic assumptions. In fact, they seem blissfully unaware that there is a problem here. They act in seeming unawareness that they are caught up in larger historical and cultural forces that underwrite their entire scientific edifice.
These forces include the medicalization of all public discourse on how to live our lives, a growing cultural denial of psychic pain as inherent in living as human beings, the well-known American mixture of ahistoricism and belief in limitless scientific progress, and the growing power of the pharmaceutical and managed care industries. These self-proclaimed visionaries, oblivious to all of this, boast of real scientific progress over what they consider to be the dogma of psychoanalysis, which had up until recently reigned as psychiatry's premier paradigm.
Now, it is not my intention to defend psychoanalysis, which had its own unfortunate excesses, although I do use psychoanalytic principles in the kind of psychotherapy I do. However, it is quite clear to me that the grandiose claims of biologic psychiatry are wildly overstated, unproved and essentially self-serving. ... in reality, i.e., the reality of treating patients, medications have profound limitations. I know that if the only tool I had in treatment was a prescription pad, I would be a poor psychiatrist. The center of treatment will always need to be listening to and speaking with the patients coming to me. This means listening seriously to what they say about their lives and history as a whole, not merely listening for which symptoms might respond to medications. Although it seems astounding that I would have to state this, biologic psychiatrists as a whole really only listen to that portion of the patient's discourse that corresponds to their biologic paradigms of mental illness. It is the nature of dogma that its practitioners hear only what they want to hear.
So what are the limitations of biologic psychiatry? First of all, medications lessen symptoms, they do not treat mental illness per se. This distinction is crucial. Symptoms by definition are the surface presentation of a deeper process. This is self-evident. However, there has been a vast and largely unacknowledged effort on the part of modern (i.e., biologic) psychiatry to equate symptoms with mental illness.
For example the illness major depression is defined by its set of specific symptoms. The underlying cause is presumed to be a biologic/genetic disturbance, even though this has never been proven in the case of depression. The errors in logic here are clear. A set of symptoms is given a name such as major depression, which defines it as an illness, which is then treated with a medication, despite the fact that the underlying cause of the symptoms remains completely unknown and essentially untreated. I have seen repeatedly that, for example, in the case of depression, once medications lessen the symptoms, I am still sitting across from a suffering patient who wants to talk about his unhappiness. This process of equating symptoms with illnesses has been repeated with every diagnostic category, culminating in perhaps one of the greatest sophistries psychiatry has pulled off in its illustrious history of sophistries, namely the creation of the Diagnostic and Statistical Manual (currently in its fourth incarnation under the name DSM-IV), the bible of modern psychiatry.
In it are listed all known mental disorders, defined individually by their respective symptom lists. Thus mental illnesses are equated with symptoms. The surface is all there is. The perverse beauty of this scheme is that if you take away a patient's symptoms, the disorder is gone. For those who do serious work with patients, this manual is useless, because for me it is simply irrelevant what name you give to a particular set of symptoms. It is an absolute myth created by modern psychiatry that these disorders actually exist as discrete entities that have a cause and treatment. This is essentially a pseudo-scientific enterprise that grew out of modern psychiatry's desire to emulate modern medical science, despite the very real possibility that psychic pain, because of its existential nature, may always elude the capture of modern medical discourse and practice.
Despite its obvious limitations, the DSM-IV has become the basis for psychiatric training and research. ... Patients are suffering from far more than symptoms. Symptoms are the signs and clues to direct us to the real issues. If you take away the symptoms too quickly with medications or suggestion, you lose the opportunity to help a patient in a more profound way. ... Modern psychiatry now foists on patients the view that their deepest and most private ills are now medical problems to be managed by physician-psychiatrists who will take away their symptoms and return them to normal functioning. This is more than a bit malignant.
One of the dominant discourses that runs through the DSM-IV and modern psychiatry in general is the equating of mental health with normal functioning and adaptation. There is a barely concealed strain of a specific form of Utopianism here which blithely announces that our psychic ills are primarily biologic and can be removed from our lives without difficulty, leaving us better adapted and more productive.
What is left completely out, of course, are any notions that our psychic ills are a reflection of cultural pathology. In fact, this new biologic psychiatry can only exist to the extent it can deny not only the truths of psychoanalysis, but also the truths of any serious cultural criticism. It is then no surprise that this psychiatry thrives in this country presently, where such denials are rampant and deeply embedded.
I am constantly amazed by how many patients who come to see me believe or want to believe that their difficulties are biologic and can be relieved by a pill. This is despite the fact that modern psychiatry has yet to convincingly prove the genetic/biologic cause of any single mental illness. However, this does not stop psychiatry from making essentially unproven claims that depression, bipolar illness, anxiety disorders, alcoholism and a host of other disorders are in fact primarily biologic and probably genetic in origin, and that it is only a matter of time until all this is proven. This kind of faith in science and progress is staggering, not to mention naive and perhaps delusional.
As in any dogma, there is no perspective within biologic psychiatry that can effectively question its own motives, basic beliefs and potential blind spots. And thus, as in any dogma, there is no way for the field to curb its own excesses, or to see how it might be acting out certain specific cultural fantasies and wishes. The rise and fall of biologic determinism in a culture likely has complicated and interesting causes, which are beyond the scope of this paper. ...
I would be remiss if I left out the obvious economic factors in psychiatry's movement toward the biologic. Pharmaceutical corporations now contribute heavily to psychiatric research and are increasingly present and a part of psychiatric academic conferences. There has been little resistance in the field to this, with the exception of occasional token protest, despite its obvious corrosive and corrupting effects.
It is as if psychiatry, long marginalized by science and the rest of medicine because of its soft quality, is now rejoicing in its new found legitimacy, and thus does not have the will to resist its own degradation. The fact that drug companies embrace and fund this new psychiatry is cause enough for alarm. Equally telling is a similar embrace by the managed care industry, which obviously likes its quick-fix approach and simplistic approach to complicated clinical problems.
When I talk to a managed care representative about the care of one of my patients, they invariably want to know what medications I am using and little else, and there is often an implication that I am not medicating aggressively enough. There is now a growing cottage industry within psychiatry in advocating ways to work with managed care, despite the obvious fact that managed care has little interest in quality care and realistic treatment approaches to real patients. This financial pressure by managed care contributes added pressure for psychiatry to go down a biologic road and to avoid more realistic treatment approaches.
What this means in real terms is that psychotherapy is left out. There has thus been a triple partnership created between this new psychiatry, drug companies and managed care, each part supporting and reinforcing the other in the pursuit of profits and legitimacy. What this means to the patients caught in this squeeze is that they are increasingly overmedicated, denied access to psychotherapy and diagnosed with fictitious disorders, leaving them probably worse off in the long run.
It is quite depressing to listen to the discourse of modern psychiatry. In fact, it has become embar- rassing to me. One gets the strong impression that patients have become abstractions, black boxes of biologic symptoms, disconnected from the narratives of their current and past lives. This pseudo-scientific discourse is shot through with insecurity and pretension, creating the illusion of objectivity, an inevitable march of progress beyond the hopeless subjectivity of psychoanalysis. Psychotherapy is dismissed and relegated to nonmedical therapists.
I actually have no objections to real science in the field, if, for example, it can help me make better medication decisions or develop newer and better medications. But in general biologic psychiatry has not delivered on its grandiose and utopian claims, as today's collection of medications are woefully inadequate to address the complicated clinical issues that come before me every day. This is all not terribly surprising given what I have outlined in this piece. There will be no substitute for the difficult work of engaging with patients at the level of their lived experience, of helping patients piece together meaning and understanding in the place of their pain, fragmentation and confusion.
Patients these days are not suffering from biologic illnesses. What I generally see is patients suffering from current or past violence, traumatic loss, loss of power or control over their lives and the effects of cultural fragmentation, isolation and impoverishment that are specific to this culture at this time. How this manifests in any individual is absolutely specific; therefore, one should resist any attempt to generalize or classify, as science forces us to do. Once you go down the route of generalization, you have ceased listening to the patient and the richness of their lived experience.
Unfortunately what I also see these days are the casualties of this new biologic psychiatry, as patients often come to me with many years of past treatment. Patients having been diagnosed with chemical imbalances despite the fact that no test exists to support such a claim, and that there is no real conception of what a correct chemical balance would look like. Patients with years of medication trials which have done nothing except reify in them an identity as a chronic patient with a bad brain. This identification as a biologically-impaired patient is one of the most destructive effects of biologic psychiatry. ... At the level of individual patients this means a growing number of overdiagnosed, overmedicated and disarticulated people less able to define and control their own identities and lives. ... If psychiatry is to regain any semblance of legitimacy and integrity, it must strip itself of false and hubristic scientific claims and humbly submit itself to the urgent task of listening to individual patients with patience and intelligence. Only then can we have any real sense of what to say back to them. ...
Anyone who dissents by choice or nature slips into the realm of the disordered or pathologic, is then located as such by medical science and is then subject to social management and control.
Now, psychiatry has always provided this social function, as admirably shown by Foucault and others. I would submit, however, that modern psychiatry, under the guise of medical and scientific authority and legitimacy, has surpassed all past attempts by psychiatry to identify and control dissent and individual difference. It has done this by infiltrating the cultural psyche, a psyche already vulnerable to any kind of medical discourse, to the point where it is a generally accepted cultural notion now that, say, depression is an illness caused by a chemical imbalance.
Now when a person becomes depressed, for example, they are less able to read it or interpret it as a sign that there may be a problem in their life that needs to be looked at or addressed. They are less able to question their life choices, or question for example the institutions that surround them. They are less able to fashion their own personal or cultural critique which could potentially lead them to more fruitful directions. Instead they identify themselves as ill and submit to the correction of a psychiatrist, who promises to take away the depression so they can get back to their lives as they are. In short, the very meanings of unhappiness are being redefined as illness. In my view this is a dismaying cultural catastrophe. I do not mean to suggest that psychiatry is solely to blame for this, given how wide a cultural shift this is. However, I do think that psychiatry has not only not resisted its role here, but actually has fulfilled it with considerable hubris. ...
I am increasingly astonished about how unable the average patient is now to articulate reasons for their unhappiness, and how readily they will accept a medical diagnosis and solution if given one by a narrow-minded psychiatrist. This is a cultural pathologic dependence on medical authority. Granted, there are patients who do fight this kind of definition and continue to search for better explanations for themselves which are less infantilizing, but in my experience this is not common. There is a frightening choking off of the possibility for dissent and creative questioning here, a silencing of very basic questions such as what is this pain? or what is my purpose? Modern psychiatry has unconscionably participated in this pathology for its own gain and power. It is a moral, not scientific issue at stake here, and in my view this is why many astute Americans rightfully distrust this new psychiatry and its Utopian claims about happiness through medical progress. ... When one reads psychiatric journals now, one senses a dangerous giddiness about the field's discoveries and progress, which in my view are wildly and irresponsibly overstated. ...
Having said this, what I am advocating is a psychiatry which devotes itself humbly to the task of listening to patients in a way that other medical practitioners cannot. This means paying close attention to a patient's current and past narrative without attempting to control, manipulate or define it. From this position a psychiatrist can then assist the patient in raising relevant questions about their lives and pain. ... Diagnosis should play a secondary and small role here, given that little is known about what these diagnoses actually mean. ...
A more humane psychiatry, if it is even possible in today's cultural climate, must recognize the powerful potential of the uses and abuses of power if it is not to become a tool of social control and normalization. As I have outlined in this piece, these abuses of power are by no means always obvious and self-evident, and their recognition requires rigorous thought and self-examination. The psychiatrist plays a particular role in cultural and individual fantasies, and an intelligent psychiatrist must be aware of the complexity of these fantasies if he is to act in a position outside these projections and fantasies. This requires real moral awareness on the part of a psychiatrist who wishes to act intelligently. What I am advocating for in outline form as stated previously are the minimal requirements necessary for the field of psychiatry to reverse its current degradation. What is essential at this time is for psychiatrists and other clinicians to speak out against the ideology known as biologic psychiatry.

Dr. Kaiser is in private practice in Chicago and is affiliated with Northwestern University Hospital.
http://www.antipsychiatry.org/kaiser.htm
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PEDIATRIC PHARMACOTHERAPY
A Monthly Review for Health Care Professionals of the Children's Medical Center
Volume 1 Number 2, February 1995

News from the FDA
The following drugs were approved by the FDA at the end of 1994:
Abciximab (ReoPro®) - antiplatelet therapy designed to reduce complications following angioplasty
Dalteparin (Fragmin®) - another low-molecular weight heparin for preventing/minimizing
DVTDorzolamide (Trusopt®) - for treatment of open-angle glaucoma
Fluvoxamine (Luvox®) - a serotonin reuptake inhibitor for treatment of depression and obsessive-compulsive disorder, similar to Prozac®
Lamotrigine (Lamictal®) - an anticonvulsant for partial seizures, data available on pediatric use
Metformin (Glucophage®) - oral antihyperglycemic for treatment of Type II diabetes
Nefazodone (Serzone®) - an antidepressant
Rimexolone (Vexol®) - for treatment of uveitis
Spirapril (Renormax®) - another ACE inhibitor for hypertension
Vinorelbine (Navelbine®) - chemotherapy for non-smallcell lung cancer
In addition, there are a number of new medications that are candidates for approval during 1995 that may be useful in pediatric patients. The following is a partial list of agents which have been recommended for approval by one of the FDA advisory committees:
Amiodarone (Cordarone IV®) - will be available for intravenous use
Cefaclor (Ceclor CD®) - a longer-acting preparation for twice daily dosing
Cefipime (Maxipime®) - an anti-Pseudomonal cephalosporin
Dirithromycin (Dynabac®) - another macrolide antibiotic
Hepatitis A vaccine (Harvix®)
Ipratropium/Albuterol (Combivent®)
Tuberculosis vaccine (Mycobax®)
Varicella vaccine (Varivax®) - finally?
After the patent on a medication expires, generic formulations can be marketed. The following agents became available in generic form during 1994:
Bumetanide (injection)
Cefaclor (oral suspension)
Cimetidine (injection, oral solution, and tablets)
Cromolyn (inhalation)
Etoposide (injection)
Flurbiprofen (tablets)
Glipizide (tablets)
Lorazepam (injection)
Naproxen (oral suspension)
Triazolam (tablets)
Verapamil (sustained-release tablets)
http://hsc.virginia.edu/cmc/pedpharm/v1n2.html

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Selective Serotonin Reuptake Inhibitors (SSRIs) in Children
From issue No. 241 (November, 1997) of Medical Sciences Bulletin
Drugs mentioned:
fluoxetine
(Prozac)
fluvoxamine
(Luvox)

The safety and effectiveness of most drugs are generally not as well established during clinical trials in children as in adults. Consequently, there is limited controlled research on the use of SSRIs in children for the treatment psychoactive disorders. This limited experience makes it difficult to determine whether SSRIs are appropriate therapies in children, and if so, at what dose and for what length of therapy. However, an increasing base of experience is being developed to answer these questions. DeVane et al (see References) have reviewed some of the studies that provide evidence for the safe and effective use of these drugs in young patients, and some of these are described here briefly.
In one study reviewed, 40 adolescents participated in a placebo-controlled, double-blind study of fluoxetine in major depression. A total of 32 patients were available for interview after the 8 weeks of treatment. The investigators concluded that there was a greater improvement in the fluoxetine group than in the control group; however, this difference was not statistically significant. Side effects were mostly mild, and the most frequent side effects were headache, vomiting, insomnia, and tremor.
Another study was conducted in 15 adolescents with major depression. After the treatment period with SSRIs was over, it was noted that 64% of the children showed a greater than 50% change on the Hamilton Rating Scale for Depression (HAM-D) and 73% showed improvement by the Clinical Global Impression (CGI) scale.
The use of fluvoxamine has been evaluated in 6 young patients for the treatment of major depressive disorders. All patients showed a significant decrease in Beck Depression Inventory (BDI) scores.
Fluvoxamine was assessed in 14 adolescents with a diagnosis of OCD by Apter et al. Y-BOCS scores improved significantly after 6 weeks of active treatment. Side effects included nausea, agitation, and insomnia. Treatment had to be discontinued in 4 patients because of side effects.
While doing chart reviews of 31 inpatient children, investigators in another study found that 74% of the patients showed improvement as rated using the CGI following treatment with fluoxetine at doses that ranged from 20-80 mg/day for 7-89 days. However, 43% had minimal improvement or no change.
A randomized, double-blind, placebo-controlled, fixed dose (20 mg/day) trial of fluoxetine in 14 patients with obsessive compulsive disorder (OCD) whose age ranged from 8-15 years showed that fluoxetine was safe and effective for the short-term treatment of children with OCD. Scores on the Yales-Brown Obsessive Compulsive Scale (Y-BOCS) decreased 44% after fluoxetine treatment compared with a 27% decrease after placebo treatment. Side effects were mild.
Another study evaluated the use of fluoxetine in 11 boys with a diagnosis of Tourette's syndrome. An improvement was found in terms of tic severity, attention abilities, and social functioning. However these differences were not statistically significant.
Fluoxetine appears to be effective in treating eating disorders such as anorexia and bulimia. However, in the studies reviewed by DeVane et al., either the patient population was small or the study design was poor. Hence, a definitive conclusion can not be drawn.
SSRIs have also been studied in the treatment of attention-deficit/hyperactivity disorder (ADHD). In one study, fluoxetine was shown to cause a moderate improvement in 58% of patients evaluated. However, 42% had minimal improvement.
The side effects caused by SSRIs in adolescents varied widely. Some trials suggest that they are mild whereas others concluded that the side effects were significant. Some of these side effects include motor restlessness, sleep disturbances, social disinhibition, mania or hypomania, and psychosis. The most common side effects that were experienced include hypomania-like symptoms, irritability, gastrointestinal upset, and insomnia.
The use of SSRIs in children at present is supported by preliminary findings. There are case reports and other small studies that suggest that they may be useful. However, as indicated by the study conducted by Simeon et al, which was well-designed, there was no statistically significant improvement with the use of SSRIs. Recent initiatives by manufacturers of SSRIs to better define the value of these drugs in pediatric indications have, in fact, resulted in the approval of at least one of these drugs (fluvoxamine) for the treatment of childhood obsessive-compulsive disorder (see Fluvoxamine for Childhood OCD ). As physicians gain experience with the use of SSRIs in clinical practice, and as the results of larger, well-designed controlled clinical studies become available, a more comprehensive understanding of the role of these drugs in childhood psychiatric disorders will emerge.

References

Constantino JN, Liberman M, Kincaid M. Effects of serotonin reuptake inhibitors on aggressive behavior in psychiatrically hospitalized adolescents: results of an open trial. J Child Adolesc Psychopharmacol. 1997;7:31-44.
DeVane CL, Sallee FR. Serotonin selective reuptake inhibitors in child and adolescent psychopharmacology: A review of published experience. J Clin Psychiatry 1996;57:55- 66.
http://webmaster@pharminfo.com/pubs/msb/ssri_child241.html
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Pediatric Pharmacotherapy
A Monthly Review for Health Care Professionals of the Children's Medical Center
Volume 2, Number 10, October 1996
The Use of Selective Serotonin Re-uptake Inhibitors in Children and Adolescents

In 1988, fluoxetine (Prozac®) was approved by the FDA for use in the United States.1 With its introduction came a new era in the treatment of depression and obsessive-compulsive disorders. Compared to the non-specific receptor binding of the heterocyclic (tricyclic and tertiary) antidepressants previously available, fluoxetine offered fewer major adverse effects and relative safety after overdose.

Fluoxetine and its successors (Table 1) differ from the heterocyclic antidepressants in that they inhibit serotonin reuptake, with little or no effect on other receptor sites.1,2 As a result of this specificity, these agents are referred to as selective serotonin reuptake inhibitors (SSRIs). Their clinical efficacy is believed to be the result of an initial increase in serotonin concentrations (inhibition of reuptake) in the synaptic cleft followed by desensitization of serotonin autoreceptors and increasing serotonin release. The latter effect is likely the most significant in treating symptoms of depression. Similar to the heterocyclic antidepressants, the full effect of SSRI therapy does not occur until two to three weeks after the initiation of treatment.1,2

Table 1: SSRIs Currently Availablea
Fluoxetine HCL (Prozac®) b Fluvoxamine maleate (Luvox®) Paroxetine HCl (Paxil®) Sertraline HCL (Zoloft®)
a all products are on formulary at UVA
b available in an oral liquid
Differences among the SSRIs consist primarily of relative receptor site specificity and pharmacokinetic characteristics. For example, paroxetine has the greatest affinity for serotonin receptors, but also shows mild binding at muscarinic receptors, resulting in its greater likelihood to cause anticholinergic adverse effects such as dry mouth.
Pharmacokinetic differences are reflected in bioavailability, protein binding, and elimination of parent compound and active metabolites. Bioavailability ranges from 44% with sertraline to 80-95 % with fluoxetine and fluvoxamine. With the exception of fluvoxamine, these agents are highly protein bound. All SSRIs undergo hepatic metabolism. Fluoxetine and sertraline have active metabolites with long elimination half-lives, resulting in prolonged effects even after the discontinuation of therapy. Genetic polymorphism resulting in the presence or absence of hepatic enzyme CYP2D6 greatly influences the rate of elimination of both fluoxetine and paroxetine.1

Use in Children and Adolescents
In children and adolescents, SSRIs have been used in the treatment of depression, obsessive-compulsive disorders (OCD), anxiety and panic disorders, eating disorders, attention deficit/hyperactivity disorder (ADHD), Tourette's syndrome, trichotillomania, mental retardation, Prader-Willi syndrome, Lesch-Nyhan syndrome, enuresis, and autism.3-4 As might be expected from the relative infrequency of some of these conditions, there are few controlled clinical trials with SSRIs in children.
Four trials involving SSRIs in children with depression have been conducted, including one controlled study, two unblinded trials, and one retrospective review.3 Simeon and colleagues5 conducted a placebo-controlled, double-blinded study in 32 children between the ages of 13 and 18 years. Half were given fluoxetine and the others received a placebo. Fluoxetine was initiated at a dosage of 20 mg per day and increased to 60 mg per day during the second week of treatment.
At the end of a two-month treatment period, symptoms had improved in the treated patients in all areas of the rating scales except sleep disturbance. These differences, however, were not statistically significant. Adverse effects included headache, vomiting, insomnia, weight loss, and tremor, but were considered mild and transient. The authors concluded that approximately 2/3 of their sample population responded well to fluoxetine, but cautioned that most children still required significant assistance with psychosocial functioning.
Fluoxetine has also been studied in children with OCD, using dosages of 10 to 80 mg per day. Two trials, one open label and one placebo-controlled, have been published, as well as several case reports and a retrospective review.3,6 In 1992, Riddle7 and colleagues from the Yale Child Study Center conducted a placebo-controlled, double-blinded, cross-over study of fluoxetine in a group of 14 adolescents between 8 and 15 years of age. Patients were randomized to either placebo or a standard dosage of fluoxetine (20 mg per day) for a period of 8 weeks then were changed to the other treatment for a period of 12 weeks.
During fluoxetine treatment, the patients showed a significant improvement over their baseline scores on rating scales of obsessive ideation and compulsive activities. Switching to placebo administration resulted in a return to near baseline values. Adverse effects included insomnia, fatigue, nausea, and worsening of tic severity. One patient experienced suicidal ideation while receiving fluoxetine. While serum fluoxetine concentrations did not correlate with degree of disease response, adverse effects were associated with higher concentrations. The authors concluded that fluoxetine is generally a safe and effective therapeutic alternative for the treatment of children and adolescents with OCD.
Although the majority of studies and case series have utilized fluoxetine in the pediatric population, there are open trials and case reports demonstrating the efficacy of fluvoxamine (100-300 mg/day) and sertraline (75 mg/day). In addition, some reports describe the use of combination therapy with an SSRI and clomipramine or buspirone in children with OCD, and with methylphenidate in children with ADHD. In the few comparison trials that have been conducted with heterocyclic antidepressants, SSRIs appear to be as efficacious as the older "standard" therapies.3

Adverse Effects
Compared with older heterocyclic antidepressants, SSRIs cause less sedation, weight gain, anticholinergic and cardiovascular adverse effects. Although the SSRIs are associated with a long list of adverse effects, in most patients they are mild and transient, rarely requiring discontinuation of therapy.
In adults, the most frequent adverse effects reported include: GI upset (nausea, vomiting, and diarrhea) reported in 10-30% of patients, CNS effects (insomnia, headache, and nervousness) reported in approximately 15% of patients, sexual dysfunction, diaphoresis, rash, and tremor (each occurring in up to 10% of patients). 1,2 Similar results have been reported in pediatric studies.3,5-7 These effects are typically dose-related, and most patients respond to a lower dose without loss of clinical benefit.
Differences in adverse effects among SSRIs may be the result of receptor specificity. Sertraline and fluoxetine are more frequently associated with diarrhea due to their greater specificity for serotonin receptors, while paroxetine has a lower incidence because of its antimuscarinic effects. The highly selective agents are also more frequently associated with insomnia and agitation, while less selective agents may be more likely to cause somnolence.1
Numerous other adverse reactions have been reported in isolated cases. The development of extrapyramidal symptoms has been reported in patients receiving fluoxetine and paroxetine.1,8 These symptoms, including dystonic reactions, akathisia, and motor tics, are likely to be the result of an indirect effect on dopaminergic receptors and typically resolve upon discontinuation of therapy.
In addition, suicidal ideation has been reported in both children and adults receiving SSRIs, although this is difficult to assess apart from the underlying illness. In a retrospective review of 42 children between the ages of 10 and 17 years treated with fluoxetine, King et al9 found six children with self-injurious ideation and behavior. Four of the children had a positive history, but worsened on therapy. All patients responded to discontinuation of fluoxetine and management with other medications.
Death associated with overdose appears to be rare. Feierabend10 described the case of a 4 year old child who ingested approximately 35 (20 mg) fluoxetine capsules. The patient exhibited signs of agitation followed by a period of unresponsiveness. A serum fluoxetine concentration taken on admission was 3,080 ng/ml (usual values in adults receiving treatment are 40-500 ng/ml). The patient's symptoms resolved without treatment. As in this case, most patients recover without sequelae. Other signs of toxicity include: agitation, drowsiness, vomiting, diarrhea, coma, hypotension, arrhythmias, and seizures. There is no antidote for SSRI overdose; therapy consists of supportive measures.1,2

Drug Interactions
The SSRIs have a number of significant pharmacokinetic drug interactions as a result of protein binding or induction of hepatic metabolism of other substances (Table 2). The degree of metabolism through the CYP2D6 pathway influences the degree of severity of many of these drug interactions.2 Patients should be instructed not to take any medications, including over-the-counter preparations, until they have checked with their doctor or pharmacist for potential drug interactions.
a change in serum concentration of object drug
In summary, SSRIs offer the advantages of fewer significant adverse effects and safety in overdose compared to older antidepressants. Their role in the treatment of psychiatric conditions in children and adolescents is just beginning to be explored. Selection of a specific agent should incorporate differences in receptor specificity, pharmacokinetic characteristics, and adverse effect profiles, in order to optimize therapy for the individual patient.

References
Finley PR. Selective serotonin reuptake inhibitors: Pharmacologic profiles and potential therapeutic distinctions. Ann Pharmacother 1994;28:1359-69.
Antidepressants. In: Olin BR ed. Drug Facts and Comparisons. St. Louis: Facts and Comparisons, Inc. 1996:264d-r.
DeVane CL, Sallee FR. Serotonin selective reuptake inhibitors in child and adolescent psychopharmacology. J Clin Psychiatry 1996;57:55-66.
Campbell M, Cueva JE. Psychopharmacology in child and adolescent psychiatry: A review of the past seven years. Part II. J Am Acad Child Adolesc Psychiatry 1995;34:1262-72.
Simeon JG, Dinicola VF, Ferguson HB. Adolescent depression: A placebo-controlled fluoxetine treatment study and follow-up. Prog Neuro-Psychopharmacol Biol Psychiat 1990;14:791-5.
Geller DA, Biederman J, Reed ED et al. Similarities in response to fluoxetine in the treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1995;34:36-44.
Riddle MA, Scahill L, King RA et al. Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1992;31:1062-9.
Eisenhauer G, Jermain DM. Fluoxetine and tics in an adolescent. Ann Pharmacother 1993;27:725-6.
King RA, Riddle MA, Chappell PB et al. Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment. J Am Acad Child Adolesc Psychiatry 1991;30:179-86.
Feierabend HR. Benign course in a child with a massive fluoxetine overdose. J Fam Pract 1995;41:289-91.
Contributing Editor: Marcia Buck, Pharm.D. Editorial Board: Robert J. Roberts, MD, PhD Anne E. Hendrick, PharmD Dave Rogers, PharmD Production Managers: Stephen M. Borowitz and Sharon L. Estes If you have comments, questions, suggestions, or would like to be included on our mailing list, please send a note to Marcia Buck, Pharm.D., Box 274-11 Children's Medical Center at the University of Virginia, Charlottesville, VA 22908 or e-mail to mlb3u@virginia.edu Fax: 804-982-1682 Office: 804-982-0921

http://www.med.virginia.edu/cmc/pedpharm/v2n10.htm#adverse effects
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George Mason University
A College Student's Guide to Psychopharmacology
Introduction
This guide is designed to help you understand some of the medications that are prescribed by psychiatrists. It is by no means a complete compendium of all medications. It briefly touches upon the categories of medication used for treating common psychological disorders, describing the indications for medication, an overview of how the medications work, and the potential for addiction and adverse effects.
It is also important to remember the following points:
1. Medication is frequently given for a period of time rather than indefinitely. This will depend upon the psychological disorder and the medication.
2. When considering whether to take medication or while taking medication, it is important to ask questions of your doctor and to carefully monitor symptoms.
3. Medication is most often taken in conjunction with counseling in order to receive comprehensive assistance.
Depression
Depression is a medical illness like any other medical illness. Common symptoms of depression include problems with sleep and appetite, loss of concentration and memory, lack of interest, low energy and a low mood. There also may be tearfulness, indecisiveness, a sense of helplessness, hopelessness, and guilt. These symptoms, of a pervasive nature, affect mood, thinking, and behavior for a period of ten days to two weeks or more. Major depression often requires treatment with drugs. The diagnosis may be obscured by anxiety, insomnia, substance abuse, or multiple somatic or physical complaints that frequently accompany depression. Many drugs including oral contraceptives, high blood pressure medication, long-term benzodiazepine use, and illegal substances such as cocaine can also cause depression. Moreover, a very common substance, alcohol may (with long-term use) cause depression or worsen a depression already in existence.
It has been estimated that approximately one of five people in this country is depressed at any given time. The good news, however, is that depression is very treatable. Many antidepressants are available to treat this common disorder. At least 80% of people will recover on the first antidepressant that they try. The remainder usually recover with different antidepressants or a combination of medications.
The older antidepressants are called tricyclics because of their chemical structure which includes a three ring component. They are very effective and much research has been done with these substances, More well known compounds in this class include Elavil (amitriptyline), Tofranil (imipramine), Pamelor (nortriptyline), and Norpamin (desipramine). They have gone somewhat out of favor because of their broad side effect profile which may include sedation, weight gain, dry mouth, blurred vision, and constipation. MAO inhibitors have also been used to treat depression. However, these have gone somewhat out of favor as well because of their restrictions on dietary intake and over-the-counter medications.
Wellbutrin (bupropion) is another medication that is effectively used. It requires two daily doses. It may also be helpful with attention deficit disorder.
The newer antidepressants are called selective serotonin re-uptake inhibitors (SSRIs) because of their specific action on a neurochemical called serotonin. In this class of medication are Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Luvox (fluvoxamine), and Celexa (citalopram). They seem to be very well tolerated because of their low side effect profile and low lethality. These medications take three to six weeks to work as they cause a subtle re-regulation of neurotransmitter systems.
Effexor, also known as Venlafaxine, is another antidepressant alternative that may be effective for some patients. Trazadone, another antidepressant, is helpful as a second drug for patients with sleep disturbance. Some antidepressants, particularly the serotonin re-uptake inhibitors may be energizing and worsen a sleep disorder. Low doses of trazadone in addition to these can improve sleep. Serzone, a medication similar to trazadone, is particularly helpful in treating depression which is accompanied by anxiety. It does not cause weight gain but may cause sleepiness.
The most common side effects with serotonin re-uptake inhibitors include nausea, headache, nervousness and insomnia. However, they do not usually cause the weight gain that is more common with tricyclic antidepressants. Agitation and increased anxiety may occur in the first weeks of treatment and subside later. All serotonin re-uptake inhibitors may cause some incidences of delayed orgasm or inorgasmia in men and women. This is a totally reversible side effect which may be improved by decreasing the dose. Wellbutrin may cause agitation and rarely seizures but fewer of the other side effects of tricyclic antidepressants. Effexor is generally similar to the serotonin re-uptake inhibitors in its adverse effects, but it has been associated in a small number of people with a sustained increase in blood pressure. Therefore, blood pressure monitoring is essential.
Anxiety
Anxiety is generally defined as an overwhelming sense of uneasiness or discomfort. It may be related to a precipitating condition or situation (i.e. an upcoming examination) though at times the cause may not be readily discernible.
There are many medications that can be used to treat anxiety disorders. Benzodiazepines are one of the more common classes of medication used. Benzodiazepine medications have been around for a long time and have many uses; among them muscle relaxation, induction of sleep, and rapid relief against common forms of anxiety. Medications in the class include valium, librium, xanax, klonopin, ativan, and serax. Benzodiazepines act by increasing GABA, an inhibitory neurotransmitter in the brain. While the clinical effects for all benzodiazepines are similar, they differ in the way in which the body may metabolize them. Some medications are more long acting and are more useful in treating anxiety that tends to be fairly consistent, prevalent and interferes with sleep as opposed to a brief episode of anxiety (i.e. anxiety that might be experienced prior to test situations) which might do better with a short-acting drug. All the benzodiazepines have a potential for abuse and one may develop tolerance to them; however under the supervision of a psychiatrist, this is unlikely to occur. Another medication, Buspar, is a non-benzodiazepine antianxiety drug. It does not cause sedation and has no potential for abuse; however it may take as long as four weeks to act.
Sedation is the most common adverse effect of the benzodiazepines. It may be more severe in the elderly and increase the risk of falls. Anterograde amnesia, inability to remember a period of hours after taking the drug, has occurred in some patients. Overdoses of benzodiazepines are rarely lethal, but they can be dangerous if taken with alcohol, barbiturates, opiates, or other drugs that depress the central nervous system. For this reason, patients on benzodiazepines are usually encouraged to avoid alcohol. Physical dependence may develop with chronic use. Withdrawal symptoms including insomnia, nausea, vomiting, twitching, sweating, and muscle cramping can develop when these drugs are abruptly discontinued, especially after prolonged or excessive use. Gradual tapering of dosage, sometimes over weeks or months, is recommended in order to avoid this potential side effect. With some benzodiazepines that have longer half-lives (i.e. those that last longer in your body) withdrawal symptoms and rebound anxiety may be less frequent and milder. Benzodiazepines are usually, although not always, used for short-term treatment of anxiety (potentially for a few days to weeks).
Obsessive Compulsive Disorder
Obsessive compulsive disorder is a form of anxiety disorder that affects approximately 2% of the population. The main features of this disorder are obsessions, intrusive thoughts that one cannot control, and/or repetitive behaviors called compulsions that are also out of ones control and that one must engage in to reduce anxiety. This disorder can be very disabling and disturbing. Fortunately, many medications are available that are effective in treating both the obsessions and compulsions. In this country Anafranil, and the serotonin re-uptake inhibitors are most commonly used. The side effects of Anafranil are very similar to the side effects described above for the tricyclic antidepressants.
Mania
Mania is a sense of euphoria often associated with a decreased need for sleep, increased appetite, increased energy, and a sense of overwhelming well being, almost grandiosity. Some self-destructive behaviors including increased spending, sexual promiscuity, and substance abuse may also occur. Mania occurs as part of bipolar disorder also known as manic-depression which includes periods of highs and lows in cycles. The common drugs used to treat mania include lithium, and some newer medications including Valproate, Tegretol, Neurontin and lamictal. Lithium, the most common treatment, may take two to four weeks to have a full therapeutic effect. Lithium requires laboratory studies to check baseline functions of red and white blood cells, as well as thyroid and kidney capacity. Lithium can be given safely if serum concentrations are monitored.
Nausea and fatigue may occur in the first weeks of treatment with Lithium even when the serum concentrations are in the recommended range. Tremors, thirst, increased urination, fluid retention and weight gain can persist for the duration of treatment. Lithium induced tremor, which is a very minor trembling generally of the upper extremities can be treated by lowering the dose or by adding Inderal, which is a form of an antihypertensive or high blood pressure medication.
For patients who cannot tolerate Lithium or with a specific form of mania, Valproate, Tegretol, Neurontin or lamictal may be reasonable alternatives. Some recent research has also suggested that fish oil or flax oil may benefit some patients as well.
Attention Deficit/Hyperactivity Disorder
Attention deficit/hyperactivity disorder is a condition characterized by difficulties in inattention and/or hyperactivity-impulsivity. These difficulties must first be present in childhood, although they may not have been recognized then. Approximately one third of children diagnosed with attention deficit disorder in childhood will have residual symptoms as adults. Medications more commonly used to treat this condition include stimulants such as Ritalin, Dexedrine, Adderall and Pemoline as well as many of the antidepressants previously mentioned in the discussion on depression.
Psychosis
Psychosis is a state in which one has difficulty determining reality from unreality. This can be acute or long term. Psychosis may be caused by a variety of factors including drug intoxication, head trauma, overwhelming infections or a biologically based psychological disorder.
Antipsychotics are the drug of choice to treat this condition. Among the well known antipsychotics are Haldol, Stelazine, Trilafon, Mellaril, and Thorazine. Side effects include sedation, dry mouth, blurred vision, and perhaps change in blood pressure. They tend to work quickly and do not require the three to six weeks to reach the maximum effect as do the antidepressants.
Newer antipsychotics with a generally more favorable set of side effects and better effectiveness include Zyprexa, Risperidone, and Seroquel.
Summary
The above descriptions are by no means a complete or exhaustive survey of all the psychiatric conditions seen by psychiatrists. However they give a brief review of the more common conditions seen in a college setting. This material is provided to you as a means to help you to understand both some of the terms that your counselor at the Counseling Center may use and what might be expected should you be referred to a psychiatrist. For more information, please consult your counselor at the Counseling Center or if you have not seen a counselor, call 993-2380 to discuss your concerns and questions.
Prepared by Susan Trachman, M.D., Consulting Psychiatrist, George Mason University Counseling Center, and Cynthia Cohen, M.D., Psychiatrist.
Spring 1999
For more information about Counseling Center, call 703-993-2380.
Send comments or questions to pagemaster Diane Knight at dknight@gmu.edu . Created on July 1, 1995. Updated March 25, 1998
http://web.gmu.edu/departments/csdc/pharcolo.html
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Vital Information About Ritalin, Attention Deficit-Hyperactivity Disorder and the Politics Behind the ADHD/Ritalin Movement
Summarized from Talking Back to Ritalin by Peter R. Bre