title: Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis.
abstract: BACKGROUND
  Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a 1 The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks, NY, USA +1 71 84 70 48 12 ; +1 71 83 43 16 59 ; ccorrell@lij.edu.
authors.forename: Britta
authors.initials: B
authors.lastname: Galling
authors.affiliation: b 2 Institut d'Ássistència Sanitària, Hospital de Santa Caterina , Salt, Spain.
authors.forename: Amat
authors.initials: A
authors.lastname: Calsina Ferrer
authors.affiliation: c 3 Vanderbilt Psychiatric Hospital , Nashville, TN, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Abi Zeid Daou
authors.affiliation: a 1 The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks, NY, USA +1 71 84 70 48 12 ; +1 71 83 43 16 59 ; ccorrell@lij.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Sangroula
authors.affiliation: a 1 The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks, NY, USA +1 71 84 70 48 12 ; +1 71 83 43 16 59 ; ccorrell@lij.edu.|d 4 Dainippon Sumitomo Pharma Co, Ltd , Osaka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hagi
authors.affiliation: a 1 The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks, NY, USA +1 71 84 70 48 12 ; +1 71 83 43 16 59 ; ccorrell@lij.edu.|e 5 Hofstra North Shore LIJ School of Medicine , Hempstead, NY, USA.|f 6 The Feinstein Institute for Medical Research , Manhasset, NY, USA.|g 7 Albert Einstein College of Medicine , Bronx, NY, USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000208:Acute Disease; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans
chemical_list: D000928:Antidepressive Agents
keywords: adverse effects; antidepressant; augmentation; co-treatment; combination; depression; major depressive disorder; meta-analysis; safety; tolerability