A number of recent studies have examined the safety and tolerability of antidepressant co-treatment, with results suggesting that some combinations are less advisable than others.
A database analysis compared the effect on body-mass index (BMI) of antidepressant monotherapy versus combination therapy administered for at least six months (Ravindran et al. Ther Adv Psychopharmacol 2015;5:158-165). The drugs included were SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), the SNRI duloxetine, and bupropion. All of the SSRI/SNRI agents were associated with significant increases in BMI, with a similar impact when used as monotherapy or in combination. The highest weight gain was seen with the combination of escitalopram and bupropion.
Weight gain was also common with bupropion combination therapy in a one-year trial of treatment-resistant depression (Clayton et al. BMC Res Notes 2014;7:459). Study subjects received either the combination of bupropion + aripiprazole, or an SSRI or SNRI + aripiprazole. Mean change in body weight at one year was 3.1 kg with the bupropion combination versus 2.4 kg with the SSRI/SNRI. The SSRI/SNRI + aripiprazole combination was associated with a higher incidence of fasting glucose abnormalities (17.4% vs. 8.3%), and elevated total cholesterol levels (34.7% vs. 25.0%).
A systematic review examined data for 23 short-term trials (mean 6.6 weeks) comparing antidepressant monotherapy and combination therapy (Galling et al. Expert Opin Drug Saf 2015;14:1587-1608). Antidepressant + antidepressant co-treatment was associated with a higher risk of weight gain (relative risk 2.17) and significant (>7%) weight gain (RR 3.15). There was also an increased risk of tremor (RR 1.55) and sweating (RR 1.95) with combination therapy. The authors noted that the combination of an SSRI with either a TCA or NaSSA (noradrenergic and specific serotonergic antidepressant) agent was associated with more adverse effects, and this approach should be used with caution.
Recent studies have also highlighted the problem of obesity in women on antidepressant regimens (Grundy et al. PLoS One 2014;9:e99780. Noordam et al. J Clin Psychiatry 2015;76:e745-51), and SSRI-associated weight gain in overweight adolescents (Cockerill et al. Innov Clin Neurosci 2014;11:14-21).