Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review Long-term lithium treatment has been associated with reduced risk of suicide and suicide attempts in patients with bipolar disorder (BPD) or other major affective disorders (1-8). In a previous meta-analysis that included only 22 studies reporting on completed suicides, we found an 82% Objectives: To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term lithium treatment.Methods: Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off lithium by metaanalytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). Results:In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among lithium-treated subjects than among those not treated with lithium (RR ¼ 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with lithium-treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size.Conclusions: Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.

Bipolar (manic-depressive) disorder is a common and severe illness. It is also potentially fatal as a result of accidents and increased mortality associated with comorbid substance use and medical illnesses, but its highest lethality results from suicide. Suicide rates, averaging 0.4% per year in men and women diagnosed with bipolar disorder, are >20-fold higher than in the general population. Suicidal acts often occur early in the illness course and in association with severe depressive and dysphoric-agitated mixed phases of illness, especially following repeated, severe depressions. Systematic consideration of risk and protective factors enhances assessment of potentially suicidal patients. Short-term interventions employed empirically to manage acute suicidality include close clinical supervision, rapid hospitalisation and use of electroconvulsive treatment. Several plausible therapeutic interventions have limited evidence of long-term effectiveness against mortality risks associated with any psychiatric disorder, including antidepressant, antimanic, antipsychotic and electroconvulsive, as well as psychosocial, treatments. However, in bipolar disorder and other major affective disorders, lithium maintenance treatment is a notable exception, with strong and consistent evidence that it reduces suicidal risk. The growing range of drugs being introduced to treat acute and long-term phases of bipolar disorder, including antiepileptic drugs, atypical antipsychotics and relatively safe, modern antidepressants, require research assessment for their ability to limit premature mortality from suicide and other causes. For now, however, more can be done to improve treatment in major affective illnesses by application of current knowledge in a systematic fashion, with close and sustained clinical follow-up of patients at risk, hopefully with a resulting reduction of mortality rates.