💊 Antidepressant Use in Bipolar Depression: A Clinical Controversy

Antidepressants are frequently prescribed for bipolar disorder in clinical practice, despite poor scientific evidence supporting their efficacy for bipolar depression. Depressive episodes in bipolar disorder are particularly challenging due to their high prevalence, greater impairment in psychosocial and cognitive functioning, increased risk of suicide, and complex treatment. While a systematic review and network meta-analysis by Yildiz et al. suggested antidepressants might be an efficacious drug class, the overall evidence is weak, based on small trials with low to moderate effect sizes. Furthermore, other meta-analyses conclude that adjunctive second-generation antidepressants offer only a small magnitude of benefit and do not increase clinical response or remission rates. For acute bipolar depression, drugs like quetiapine, olanzapine, lurasidone, and cariprazine have shown greater efficacy with moderate confidence in the evidence.

A major concern with using antidepressants for bipolar depression is the risk of switching to mania or hypomania. Antidepressant use has been identified as a pharmacotherapy trigger for manic/hypomanic episodes, particularly tricyclic antidepressants and, to a lesser extent, selective serotonin-reuptake inhibitors (SSRIs). The overall risk of mania in patients with antidepressant exposure averaged 12.5%, compared to 7.5% without. This risk is heightened in patients presenting with subtle manic symptoms during the depressive episode (e.g., distractibility, racing thoughts, psychomotor agitation). National register-based studies suggest that combining an antidepressant with a mood stabiliser may mitigate the risk of mania.

The official clinical guidelines from the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the International Society for Bipolar Disorders (ISBD) recommend quetiapine, lithium, lamotrigine, and lurasidone as first-line treatments for bipolar depression, specifically not recommending antidepressants. The paper ultimately recommends prioritizing lithium as the basic treatment, combined with an atypical antipsychotic (like quetiapine, lurasidone, or cariprazine), or lamotrigine as an alternative. If an antidepressant is added, it should never be used without a mood stabiliser, and SSRIs are preferred due to their low switch rate. These recommendations emphasize avoiding antidepressants in patients with signs of subtly increased psychomotor tempo or racing thoughts and prioritizing drugs like lithium, which have proven effects across all phases of bipolar disorder.

https://ugeskriftet.dk/dmj/use-antidepressants-bipolar-disorder-controversy-between-science-and-clinical-practice