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

• Published in: Expert opinion on drug safety Vol. 14; no. 10; p. 1587
• Main Authors: Galling, Britta, Calsina Ferrer, Amat, Abi Zeid Daou, Margarita, Sangroula, Dinesh, Hagi, Katsuhiko, Correll, Christoph U
• Format: Journal Article
• Language: English
• Published: England 03-10-2015
• Subjects: Acute Disease; Adult; Antidepressive Agents - administration & dosage; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Depressive Disorder, Major - drug therapy; Drug Therapy, Combination; Humans; major depressive disorder; safety; antidepressant; tolerability; adverse effects; meta-analysis; co-treatment; depression; augmentation; combination
• DOI: 10.1517/14740338.2015.1085970
• EISSN: 1744-764X

Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common.
We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 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 ≥ 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, ≥ 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.
The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-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.