Safety and tolerability of antipsychotic-mood stabilizer co-treatment in the management of acute bipolar disorder: results from a systematic review and exploratory meta-analysis

Introduction: Mood stabilizer (MS) plus antipsychotic (AP) co-treatment is common in patients with acute bipolar disorder (BD), but adverse effects (AEs) of this strategy have not been systematically reviewed. Areas covered: We conducted a systematic review searching PubMed/MEDLINE and PsycINFO on April 1, 2015 for randomized trials in \u3e= 20 adults with acute manic/mixed or depressed BD comparing MS or AP monotherapy with their combination that reported quantitative AE data. Pooled together, MS+AP versus MS monotherapy (studies = 18, n = 4419) was associated with significantly higher burden regarding 21/53 (39.6%) individual AEs, particularly weight gain-related (5/5 = 100%), extrapyramidal (5/12 = 41.7%) and glucose/lipid-related AEs (3/8 = 37.5%). AP+MS versus AP monotherapy (studies = 3, n = 397) was associated with significantly higher burden regarding 4/21 (19.0%) individual AEs (\u3e= 1 AE, tremor, sedation/somnolence, vomiting). Expert opinion: Efficacy advantages of AP+MS co-treatment versus monotherapy should be balanced with its greater AE burden. AE risk is higher for adding AP to MS (17 additional AEs) than adding MS to an AP, including the particularly concerning cardiometabolic AEs. More data are needed, as only one or two studies provided data for 21/21 (100%) AEs of MS augmentation of AP, and 13/53 (24.5%) AEs of AP augmentation of MS, and as sparse data suggest clinically relevant AE differences across individual AP+MS combinations

Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis

INTRODUCTION: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common. AREAS COVERED: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in \u3e/= 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 - 1.10) and frequency of \u3e/= 1 AE (RR = 1.19, 95% CI = 0.95 - 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, \u3e/= 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs. EXPERT OPINION: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-a-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed