Meta-analysis: Risk of dry mouth with second generation antidepressants

Objective: The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth.

Data sources and study selection: A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD.

Data extraction: A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth.

Results: 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR)=2.24, 95% Confidence Interval (CI): 1.95-2.58, z=11.2, p<0.001) were associated with a significantly greater risk of dry mouth (test for subgroup differences χ²=7.6, df=1; p=0.006) compared to placebo than SSRIs (RR=1.65, 95% CI: 1.39-1.95, z=5.8, p<0.001). There was a significant difference found in the risk of dry mouth between diagnostic indications within the SNRI class (test for subgroup differences χ²=9.63, df=1; p=0.002). Anxiety diagnoses (RR=2.78, 95% CI: 2.29-3.38, z=10.32, p<0.001) were associated with a greater risk of dry mouth compared to depression (RR=1.80, 95% CI: 1.48-2.18, z=5.85, p<0.001). Decreased affinity for Alpha-1 (PE=0.18, 95% CI: 0.07-0.28, z=3.26, p=0.001) and Alpha-2 (PE=0.49, 95% CI: 0.22-0.75, z=3.64, p<0.001) receptors and SERT (PE=0.07, 95% CI: 0.01-0.14, z=2.10, p<0.05) was significantly associated with increased risk of dry mouth.

Conclusions: The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs.