"Although some might argue that the precise relative risk of antidepressant-induced mania or hypomania is unknown (eg, considering intervening factors such as the natural illness course), recent literature suggests that the emergence of mania or hypomania can be reasonably attributed to antidepressant use in no more than 10% to 25% of patients with bipolar disorder"
"One large randomized trial showed comparable antidepressant efficacy with a mood stabilizer plus adjunctive venlafaxine (43%) vs sertraline (55%) vs bupropion (49%) over 10 weeks,14 but the lack of a mood stabilizer monotherapy comparison group limits the ability to anticipate whether adjunctive antidepressants increase response or remission rates more than mood stabilizers alone. Adjunctive imipramine,13 paroxetine,12,13,15 and bupropion12 yield no greater improvement in depressive symptoms than is seen with optimally dosed mood stabilizers alone."
"The largest dataset on this topic—the randomized controlled data from Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)12—found that the risk for treatment-emergent manic switch with paroxetine or bupropion was almost identical (about 10%) with or without an FDA-approved antimanic agent.
In a retrospective study, Henry et al6 found that cotherapy with lithium but not divalproex or carbamazepine protects against antidepressant-induced mania, and that switch rates to mania were the same whether or not an antidepressant was taken with an anticonvulsant. In a naturalistic retrospective study (n=158), Bottlender et al24 revealed that mood stabilizers (lithium, carbamazepine, or divalproex) prevented switches from depression to mania during treatment with TCAs but not SSRIs or MAOIs.
I favor incorporating lithium or other antimanic agents in the regimens of patients with bipolar depression not primarily to guard against antidepressant-induced mania but more for pharmacodynamic synergy—complementary mechanisms of action that collectively may produce more substantial antidepressant effects—especially when the patient’s illness course has included manic or hypomanic features in the preceding year."
"Wehr et al25 reported that antidepressants may accelerate cycling frequency (ie, inter-episode durations become shorter) in a small subgroup (N=10) of patients. By contrast, use of TCAs was not more likely in the weeks preceding shifts from depression to mania or hypomania in a 14-year follow-up study of bipolar rapid cycling from the NIMH Collaborative Depression Study.26 In fact, rapid-cycling patients spent more weeks depressed when taking lithium without a TCA than with."
Antidepressants in bipolar disorder: 7 myths and realities
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