August 2010

The Generic Medication Question
Variability in the bioavailability of generic medications can affect efficacy and tolerability in some patients.

Anticonvulsants and Suicide Risk
Findings from a recent study support the US Food and Drug Administration's 2008 conclusion that anticonvulsants increase the risk of suicidal ideation and behavior.

Antidepressant-Induced Mania?
Evidence from a meta-analysis of controlled and open trials suggests that antidepressants increase the risk of a switch from depression into hypomania or mania in patients with bipolar disorder and in those with major depression.

Medications to Reduce Antipsychotic-Induced Weight Gain
The overall effect of medications as antidotes to antipsychotic-induced weight gain is modest; diet and exercise should be the first-line strategy.

In Brief
Veterans with PTSD Have Greater Risk of Dementia; Bupropion Safe and Effective Aid for Smoking Cessation in Schizophrenia

Smoking and Clozapine Levels
Elevations in plasma clozapine (Clozaril and others) concentrations following smoking cessation can be dramatic and potentially lead to serious toxicity.

Antidepressant-Induced Mania?

August 2010

Do antidepressants increase the likelihood that a patient will develop mania? Most clinicians believe they do, but data are sparse and contradictory. Recently, Tondo and associates conducted a comprehensive computerized literature search for studies addressing this issue.1

The authors reviewed all available controlled and open trials since "the dawn of the antidepressant era in the late 1950s" that pertained to this topic. They identified 73 reports involving 109 trials, which included well over 100,000 adult patients. Just over half of the studies were randomized and controlled; the remainder were open.

Antidepressants did, in fact, increase the risk of a switch into mania. The overall proportion of manias was 12.5% with and 7.5% without antidepressants—a 1.7-fold increase (P = .04). As expected, new episodes of mania occurred much more frequently in patients with bipolar disorder than in those with major depressive disorder (MDD). But the relative increase in risk of mania from antidepressant treatment was much higher in MDD patients than in bipolar patients: nearly five-fold versus one-fold. Tricyclic antidepressants appeared to cause a greater risk of a switch into mania than modern antidepressants. Monoamine oxidase inhibitors carried the lowest risk among the major categories of antidepressants. Mood stabilizers had little preventive effect against mood elevation during antidepressant treatment.

The authors appropriately warn that their meta-analytic findings should be viewed cautiously because the studies included were very heterogeneous. However, they believe their research provides strong support for the hypothesis that antidepressants do, in fact, increase the risk of a switch from depression into hypomania or mania. The absolute risk of developing mania is greater in patients with bipolar disorder who take antidepressants (especially tricyclics), but MDD patients also are at risk. Even though their study did not find a protective benefit from mood stabilizers, the authors recommend using mood stabilizers in bipolar disorder patients who must take an antidepressant.

1Tondo L, Vázquez G, Baldessarini RJ: Mania associated with antidepressant treatment: Comprehensive meta-analytic review. Acta Psychiatr Scand 2010;121:404-414.