Balancing benefits and harms of treatments for acute bipolar depression

作者：Ketter Terence A^*; Miller Shefali; Dell'Osso Bernardo; Calabrese Joseph R; Frye Mark A; Citrome Leslie

来源：Journal of Affective Disorders, 2014, 169: S24-S33.

DOI：10.1016/s0165-0327(14)70006-0

• Antidepressants
• Antipsychotics
• Olanzapine plus fluoxetine
• Quetiapine
• Lurasidone
• Lamotrigine
• Antidepressants
• Armodafinil
• Bipolar depression
• Bipolar disorder
• Mood stabilizers
• Number needed to harm
• Number needed to treat

Background: Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.
Methods: Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.
Results: The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.
Limitations: NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.
Conclusions: For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.

• 出版日期2014-12