Antidepressants in Bipolar Disorder 7 Myths and Realities (2010)

Few topics are as controversial as the role of antidepressants for patients with bipolar disorder. Although depression usually is the predominant, most enduring mood state in bipolar disorder, clinicians often face uncertainty about using antidepressants because of concerns about safety and efficacy. Whether and when to use antidepressants for bipolar depression hinges on complex parameters that preclude any single, simple rule. Rather than asking if antidepressants are useful or detrimental for depressed patients with bipolar disorder, a more practical question might be: Under what circumstances are antidepressants likely to be beneficial, deleterious, or ineffective for an individual patient? Because real world patients often have idiosyncrasies that defy practice guidelines' generic treatment recommendations, clinicians who practice in the proverbial trenches need strategies to tailor treatments to each patient that are informed--but not dictated--by evidence-based research. [ILLUSTRATION OMITTED] Early suspicions Concerns that antidepressants might precipitate mania were first described with tricyclic antidepressant (TCA) use in Europe in the 1960s. After bupropion and selective serotonin reuptake inhibitors (SSRIs) emerged, some clinicians believed they posed a lesser risk for this phenomenon compared with TCAs (1), (2) or monoamine oxidase inhibitors (MAOIs). (3) [ILLUSTRATION OMITTED] Antidepressants' potential to induce short-term mania/hypomania following acute exposure has been weighed against the longer-term risk for worsening illness course by increasing frequency of subsequent episodes (so-called cycle acceleration). In the 1980s, some researchers suggested that rapid cycling might--at least in some instances--represent an iatrogenic phenomenon caused by long-term antidepressant use. These issues remain controversial, but more than 20 years of research suggest that antidepressants induce mania or accelerate cycling in a smaller minority of bipolar disorder patients than was once thought. Table 1 and Table 2 (page 44) summarize findings from randomized controlled studies that have examined antidepressants' efficacy for acute bipolar depression. Except for a study of fluoxetine plus olanzapine, (4) no large-scale placebo-controlled trial has demonstrated superior antidepressant response to a mood stabilizer plus antidepressant compared with a mood stabilizer alone. Table 1 Antidepressants for bipolar depression: SSRIs and SNRIs * Acute efficacy Reported switch risk Fluoxetine (SSRI) 86% response rate after 3 weeks in 0% 6-week double-blind randomized comparison with imipramine or placebo (a) 38% response rate after 8 weeks of 0% placebo-controlled monotherapy in bipolar II or NOS subjects (b) 56% response rate over 8 weeks in 6% combination with olanzapine; significantly better than placebo plus olanzapine (30%) (c) Paroxetine (SSRI) Same as placebo when added to an 10.1 % (reported only jointly for antimanic drug (STEP-BD) for up to paroxetine or bupropion) 26 weeks (d) 36% response rate (no different 7% from placebo) when coadministered with therapeutically dosed lithium over 10 weeks (e) Same as divalproex plus lithium 0% when coadministered with divalproex or lithium over 6 weeks (actual response rates not reported) (f) 43% response (coadministered with 3% (not statistically lithium, divalproex, or significantly different from carbamazepine) over 6 weeks (g) venlafaxine comparison arm) Sertraline (SSRI) 41 % improved (comparable to rates 12% seen with bupropion [33%] or venlafaxine [36%] when coadministered with a mood stabilizer over 10 weeks (h) Venlafaxine (SNRI) 3 6% improved (comparable to rates 6% seen with bupropion [33%] or sertraline [41 %]) when coadministered with a mood stabilizer over 10 weeks (h) 48%o response (coadministered with 13% (not statistically lithium, divalproex, or significantly different from carbamazepine) over 6 weeks (9) paroxetine comparison arm) * No data are available for citatopram, desvenlafaxine, duloxetine, escitalopram, fluvoxamine, or milnacipran NOS: not otherwise specified; SNRI: serotonin/norepinephrine reuptake inhibitor; SSRI: selectiveserotonin reuptake inhibitor; STEP-BD: Systematic Treatment Enhancement Program for Bipolar Disorder Source: For reference citations, see this article at CurrentPsychiatry. …