The researchers also noted an increased risk of treatment-emergent mania or hypomania with prolonged use so they advise that these medications should be used only in the short term.
According to a commentary, these data are consistent with advice of the International Society for Bipolar Disorders Task Force on antidepressant use in bipolar disorder and with guidelines by the British Association of Psychopharmacology, but inconsistent with findings from the STEP-BD study, which reported antidepressants to be inefficacious but safe with regards to switch to mania or hypomania. The commentators suggest that these current findings make more clinical sense, because in their clinical experience, adjunctive antidepressants usually work and sometimes do cause switch to mania or hypomania. They note that adjunctive antidepressants have a number needed to treat of 15 and number needed to harm of 19 meaning that the efficacy is limited and the tolerability is good, even if there might be a small (but again significant) risk of affective switch in some patients over the long term. They therefore advise the provision of psychoeducation to all patients with bipolar disorder to caution them about the risk of switch, independently of whether it is spontaneous or drug induced. They add that the meta-analysis did not address side-effects other than switch to mania or hypomania, and therefore clinicians should keep in mind the overall tolerability profile of modern antidepressants and that of the alternatives when considering benefits and risks. They conclude overall “we now know better what many of us suspected for a long time—that antidepressants work (but not very well) in bipolar depression. The precise place of antidepressants in the treatment algorithm should be elucidated in head-to-head studies against other alternatives.”