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Balancing benefits and harms of treatments for acute bipolar depression.

Journal of affective disorders (2014-12-24)
Terence A Ketter, Shefali Miller, Bernardo Dell'Osso, Joseph R Calabrese, Mark A Frye, Leslie Citrome
ABSTRACT

Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments. 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. 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. NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Sigma-Aldrich
Carbamazepine, powder
Supelco
Lamotrigine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Lamotrigine, ≥98%, powder
Lamotrigine for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Lamotrigine, United States Pharmacopeia (USP) Reference Standard
Lamotrigine for peak identification, European Pharmacopoeia (EP) Reference Standard
Lamotrigine, European Pharmacopoeia (EP) Reference Standard
Supelco
Lamotrigine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Fluoxetine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®