Optimizing patient expectancy in the pharmacologic treatment of major depressive disorder.

BACKGROUND: Patient expectancy is an important source of placebo effects in antidepressant clinical trials, but all prior studies measured expectancy prior to the initiation of medication treatment. Little is known about how expectancy changes during the course of treatment and how such changes influence clinical outcome. Consequently, we undertook the first analysis to date of in-treatment expectancy during antidepressant treatment to identify its clinical and demographic correlates, typical trajectories, and associations with treatment outcome. METHODS: Data were combined from two randomized controlled trials of antidepressant medication for major depressive disorder in which baseline and in-treatment expectancy assessments were available. Machine learning methods were used to identify pre-treatment clinical and demographic predictors of expectancy. Multilevel models were implemented to test the effects of expectancy on subsequent treatment outcome, disentangling within- and between-patient effects. RESULTS: Random forest analyses demonstrated that whereas more severe depressive symptoms predicted lower pre-treatment expectancy, in-treatment expectancy was unrelated to symptom severity. At each measurement point, increased in-treatment patient expectancy significantly predicted decreased depressive symptoms at the following measurement (B = -0.45, t = -3.04, p = 0.003). The greater the gap between expected treatment outcomes and actual depressive severity, the greater the subsequent symptom reductions were (B = 0.49, t = 2.33, p = 0.02). CONCLUSIONS: Greater in-treatment patient expectancy is associated with greater subsequent depressive symptom reduction. These findings suggest that clinicians may benefit from monitoring and optimizing patient expectancy during antidepressant treatment. Expectancy may represent another treatment parameter, similar to medication compliance and side effects, to be regularly monitored during antidepressant clinical management.

Meta-analysis: Risk of hyperhidrosis with second-generation antidepressants.

BACKGROUND: Our goal was to quantify the risk of hyperhidrosis associated with commonly used antidepressant agents and examine the impact of medication class, pharmacodynamics, and dose on risk of hyperhidrosis. METHODS: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of second-generation antidepressant medications in the treatment of adults with a depressive disorder, anxiety disorders, or obsessive-compulsive disorder. We used a random-effects meta-analysis to examine the pooled risk ratio of hyperhidrosis reported as a side effect in adults treated with second-generation antidepressants compared to placebo. We used stratified subgroup analysis and metaregression to examine the effects of medication type, class, dosage, indication, and receptor affinity profile on the measured risk of hyperhidrosis. RESULTS: We identified 76 trials involving 28,544 subjects. There was no significant difference in the risk of hyperhidrosis between serotonin-norepinephrine reuptake inhibitors (SNRI) [risk ratio (RR) = 3.17, 95% CI: 2.63-3.82] and selective serotonin reuptake inhibitors (SSRI) (RR = 2.93, 95% CI: 2.46-3.47) medications compared to placebo. All antidepressant medications were associated with a significantly increased risk of hyperhidrosis except fluvoxamine (RR = 0.56, 95% CI: 0.12-2.53), bupropion (RR = 1.23, 95% CI: 0.57-2.67), and vortioxetine (RR = 1.35, 95% CI: 0.79-2.33). The dose of SSRI/SNRI medications was not significantly associated with the risk of hyperhidrosis. Increased risk of hyperhidrosis was associated with increased affinity of SSRI/SNRI medications to the dopamine transporter. CONCLUSION: Risk of hyperhidrosis was significantly increased with most antidepressant medications but was associated with dopamine transporter affinity.

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.