Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression?

Med Hypotheses. 2005;65(1):39-43. doi: 10.1016/j.mehy.2005.02.010.


While antidepressants have been demonstrated to be a safe and effective treatment for unipolar major depressive disorder (MDD) in adults, the use of antidepressants to treat children and adolescents is controversial. There is a paucity of evidence to suggest that antidepressants are effective when used to treat children and adolescents and some recent placebo-controlled evidence has suggested that antidepressant treatment increases suicidality in this population. MDD is a very broad construct, and includes many clinical subtypes. Bipolar Disorder (BD) has an earlier age of onset than MDD. The initial polarity of illness in bipolar disorder is frequently depression. Patients are more likely to first present for treatment during the depressive phase of the illness than during manic or hypomanic phases. It is probable that a substantial portion of depressed children and adolescents may not suffer from unipolar MDD but may have a bipolar spectrum disorder. There are few trials supporting the efficacy of antidepressants in bipolar disorder, and some evidence that they may induce rapid cycling, switching and mania. Antidepressant induced mania is often mixed, with admixtures of manic and depressive features. An increased suicide risk is a particular feature of mixed states, potentially explaining why suicidal ideation can emerge with antidepressant treatment. Antidepressants are unlikely to somehow act differently in children than they do in adults. A more plausible explanation is that incipient bipolar disorder is often not diagnosed early in children and adolescents and the differential effects of antidepressants in this group is a result of differing diagnostic casemixes.

MeSH terms

  • Adolescent
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / parasitology
  • Child
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / parasitology
  • Diagnosis, Differential
  • Drug Resistance
  • Humans
  • Models, Biological
  • Suicide, Attempted / psychology*


  • Antidepressive Agents