A. Lack of stimulants’ long-term efficacy as a treatment for ADHD
1. NIMH collaborative multisite multimodal treatment study of ADHD. Richters, J. Journal of the American Academy of Child and Adolescent Psychiatry 34 (1995):987-1000.
In the 1990s, the NIMH mounted a long-term study of ADHD treatments. As it did so, researchers acknowledged that the “long-term efficacy of stimulant medication has not been demonstrated for any domain of child functioning.” The MTA trial would be the “first major clinical trial” that the NIMH had ever conducted of a “childhood mental disorder.”
2. 3-year followup of the NIMH MTA Study. Jensen, P. Journal of the American Academy of Child and Adolescent Psychiatry 46 (2007):989-1002.
At the end of 14 months, core ADHD symptoms were reduced more in the children treated with stimulants than with behavioral therapy. However, at the end of three years, “medication use was a significant marker not of beneficial outcome, but of deterioration. That is, participants using medication in the 24-to-36 month period actually showed increased symptomatology during that interval relative to those not taking medication.”
3. Mta at 8 years. Molina, B. Journal of the American Academy of Child and Adolescent Psychiatry 48 (2009):484-500.
At the end of six years, medication use was “associated with worse hyperactivity-impulsivity and oppositional defiant disorder symptoms,” and with greater “overall functional impairment.”
B. Lack of antidepressants’ short-term efficacy in children and adolescents
4. Selective serotonin reuptake inibitors in childhood depression. Whittington, C. The Lancet 363 (2004):1341-5.
In 2003, the Medicine and Healthcare Regulatory Authority Agency (MHRA) in the United Kingdom essentially banned the use of SSRI antidepressants, except for fluoxetine, in patients under 18 years old. It did so because it found that the drugs did not offer a favorable risk-benefit profile in this age group. In this Lancet review of the available trial data, the researchers announced they supported “the conclusions reached by the MHRA.”
5 . Depressing research. Editorial, The Lancet 363 (2004):1335.
The Lancet editors concluded that all SSRIs, other than fluoxetine, “were both ineffective and harmful in children.”
6. Efficacy and safety of antidepressants for children and adolescents. Jureidini, J. British Medical Journal 328 (2004):879-83.
After reviewing the outcomes literature, researchers concluded that clinical trials did not provide evidence that SSRIs, including fluoxetine, were safe and effective in children and adolescents. As such, “recommending (any antidepressant) as a treatment option, let alone as first-line treatment, would be inappropriate.”
C. Use of stimulants and antidepressants often leads to juvenile bipolar illness
Up until the 1990s, bipolar illness was rarely diagnosed in teenagers and virtually never in prepubertal children. But once psychiatrists began prescribing stimulants and antidepressants to children and adolescents, many began experiencing psychotic and manic reactions. These youth were then diagnosed with bipolar disorder.
7. Psychotic side effects of stimulants. Cherland, E. Canadian Journal of Psychiatry 44 (1999):811-3.
Within 21 months, 11 percent of children treated with a stimulant for ADHD developed “psychotic symptoms.”
8. Prior stimulant treatment in adolescents with bipolar disorder. DelBello, M. Bipolar Disorders 3 (2001):53-57.
Two-thirds of the adolescent patients hospitalized for mania at the University of Cincinnati Medical Center had been on stimulants “prior to the onset of an affective episode.” Stimulants, the researchers concluded, may “precipitate depression and/or mania in children who would not have otherwise developed bipolar disorder.”
9. Attention-deficit hyperactivity disorder and juvenile mania. Biederman, J. Journal of the American Academy of Child and Adolescent Psychiatry 35 (1996):997-1008.
Eleven percent of children diagnosed with ADHD and treated with stimulants developed bipolar symptoms within four years.
10. Pediatric-onset bipolar disorder. Faeeda, G. Harvard Review of Psychiatry 3 (1995):171-95.
Twenty-five percent of children and adolescents diagnosed with depression and treated with antidepressants convert to bipolar illness within four years. “Antidepressant treatment may well induce switching into mania, rapid cycling or affective instability in the young, as it almost certainly does in adults.”
11. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Geller, B. American Journal of Psychiatry 158 (2001):125-7.
Nearly half of prepubertal children treated for depression converted to bipolar within 10 years.
Prior stimulant and antidepressant usage in all juvenile bipolar patients
12. Antidepressant exposure in bipolar children. Cicero, D. Psychiatry 66 (2003):317-22.
In a study of 79 juvenile bipolar patients, 62% had been treated with a stimulant or an antidepressant prior to becoming manic.
13. Pediatric bipolar disorder. Faedda, G. Bipolar Disorders 6 (2004):305-13.
Eighty-four percent of the children treated for bipolar illness at a mood disorders clinic in New York City between 1998 and 2000 had been exposed to psychiatric drugs prior to their being diagnosed as bipolar. “Strikingly, in fewer than 10% (of the cases) was diagnosis of bipolar disorder considered initially.”
D. Diagnosis and drug treatment lead to severe chronic illness
In adults diagnosed with bipolar illness, the worst outcomes are seen in those with “mixed state” and “rapid cycling symptoms.” Those symptoms were virtually never seen in adults prior to the psychopharmacology era, but rather are associated with exposure to antidepressants. These are the very symptoms that afflict the overwhelming majority of juvenile bipolar patients, which suggests that they will have very poor long-term outcomes.
14. Treatment-emergent mania in pediatric bipolar disorder. Faedda, G. Journal of Affective Disorders 82 (2004):149-58.
Two-thirds of the juvenile bipolar patients treated at a mood disorders clinic in New York City were “ultra, ultra rapid-cyclers,” and another 19% suffred from rapid cycling only a little bit less extreme. “In contrast to a biphasic, episodic and relatively slow cycling course in some adults with bipolar disorder, pediatric forms usually involve mixed mood states and a sub-chronic, unstable, and unremitting course.”
15. Long-term implications of early onset in bipolar disorder. Perlis, R. Biological Psychiatry 55 (2002):875-81.
In the NIMH’s STEP-BD study, researchers conclude that pre-adult onset (of bipolar illness) is “associated with greater rates of comorbid anxiety disorders and substance abuse, more recurrences, shorter periods of euthymia, and greater likelihood of suicide attempts and violence.”
16. Course and outcome of bipolar spectrum disorder in children and adolescents_ A review of the existing literature. Birmaher, B. Development and Psychophathology 18 (2006):1023-35.
Early onset bipolar patients are symptomatic about 60% of the time and shift polarity–from depression to mania or vice versa–an astonishing 16 times a year. The prepubertal patients were “two times less likely that those with postpubertal onset bipolar to recover,” and will likely be “poor responders to treatment when they become adults.”
17. Twelve-month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode. DelBello, M. American Journal of Psychiatry 164 (2007):582-90.
Only 41% of adolescents hospitalized for a first bipolar episode functionally recovered within one year.
18. Psychosocial functioning among bipolar youth . Goldstein, T. Journal of Affective Disorders 114 (2009):174-83.
In juvenile bipolar patients, functional impairment worsens after the first year (with continued drug treatment.)
19. Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype. American Journal of Psychiatry 159 (2002):927-33.
Lithium, antidepressants and mood stabilizers all failed to help bipolar youth fare better at the end of two years. Juvenile bipolar patients treated with an antipsychotic medication, which is a standard treatment, “were significantly less likely to recover than those who did not receive a neuroleptic.”
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