Journal of Clinical Psychopharmacology最新文献

Purpose: Somatic symptoms are commonly seen in major depressive disorder (MDD) with postpartum onset and can be similar to side effects of antidepressant medications. The aim of this study is to determine whether the decline in depressive symptoms measured by the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) is significantly associated with the decrease in somatic symptoms identified by the Asberg scale.

Methods: A secondary analysis of data from a randomized controlled trial was conducted. The original 8-week trial included 62 participants and assessed the efficacy of sertraline versus estradiol transdermal patches and their respective placebos for MDD with postpartum onset. The SIGH-ADS scale was used to assess depression severity and the Asberg scale was used to evaluate treatment emergent side effects, defined as an increase of ≥2 from baseline measures. Correlation analyses were performed between total scale scores. The scales were compared to establish symptoms, which overlapped across scales versus symptoms, which were unique to each scale.

Results: Positive correlations were observed between the SIGH-ADS and Asberg scales and across the 8-week trial in all 3 treatment groups (correlation coefficient range 0.468-0.712). Headache was the most frequent treatment emergent side effect (10 occurrences). Fourteen symptoms were found to overlap between the 2 scales.

Conclusions: These findings underscore the importance of reviewing somatic symptoms before administering medication to discern true treatment emergent side effects, especially in populations recovering from labor and delivery. Somatic symptoms decline in parallel with depressive symptom scores during treatment, suggesting they are indicative of underlying illness rather than side effects.

Purpose/background: Clozapine-induced hypersalivation is one of the most common bothersome adverse reactions of clozapine. The management strategies for this condition remain inadequately studied and understood. The objective of the study is to compare the effectiveness and tolerability of (1) trihexyphenidyl 5 mg/d, (2) clonidine 0.15 mg/d, or (3) a reduction of clozapine dosage by 25 to 50 mg/d for managing clozapine-induced hypersalivation.

Methods/procedures: A randomized, open-label, non-placebo-controlled clinical trial was conducted from December 2023 to May 2024. Eligible patients were randomly assigned to 1 of 3 groups. Primary outcomes were assessed using the Drooling Severity and Frequency Scale (DSFS) and the Nocturnal Hypersalivation Rating Scale (NHRS) at baseline, week 4, and week 8. Quality of life assessed using the pharmaceutical therapy for quality of life short version and adverse drug reactions were recorded as secondary outcomes.

Findings/results: A total of 67 patients were randomly assigned to 1 of 3 treatment groups. By week 8, significant reductions in DSFS and NHRS scores were observed in all groups, with clonidine showing the greatest improvement. Trihexyphenidyl was also effective, whereas reducing clozapine dose resulted in more modest improvements. Quality of life improved significantly across all groups, with the greatest improvement observed in the clonidine group. The most common adverse effects were dry mouth, constipation, drowsiness, and dizziness.

Implications/conclusions: Clonidine and trihexyphenidyl appear to be more effective options for managing clozapine-induced hypersalivation compared to clozapine dose reduction.

Background: Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but is often discontinued due to adverse effects. This study compared early clozapine discontinuation rates and reasons in patients with mood and psychotic disorders.

Methods: Data from all individuals with mood or psychotic disorders who initiated clozapine for the first time at the inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 and 2022 were retrospectively analyzed. Early clozapine discontinuation, defined as discontinuation within 90 days of initiation, was the primary outcome. Cox proportional hazards regression was used to assess factors associated with discontinuation.

Results: Of 83 patients (mood group n = 37, psychosis group n = 46), those in the mood group were older ( P = 0.022) and more likely to be nonsmokers ( P = 0.034). The overall 90-day clozapine discontinuation rate was 45.7%. Early discontinuation was significantly higher in the mood group than in the psychosis group (hazard ratio = 2.41, 95% confidence interval = 1.26-4.64, P = 0.008). Other factors associated with early discontinuation were female sex ( P = 0.033), older age ( P = 0.026), and nonsmoking ( P = 0.001). In multivariable analysis, smoking status was the only factor significantly inversely associated with early clozapine discontinuation (hazard ratio = 0.47, 95% confidence interval = 0.22-0.99, P = 0.048), while diagnostic group, sex, and age did not show significant associations (all P > 0.05). Discontinuations were primarily due to adverse drug reactions in both groups.

Conclusions: Nearly half of the patients discontinued clozapine early, with higher rates in the mood group. Studies should further explore potential pharmacodynamic and pharmacokinetic factors associated with discontinuation, including the influence of smoking. Careful monitoring and personalized management of side effects are crucial for optimizing clozapine therapy and improving treatment outcomes.

Background: This randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifer NCT04285515) evaluated efficacy and safety of lumateperone to treat major depressive episodes (MDEs) associated with major depressive disorder (MDD) or bipolar depression with mixed features.

Procedures: Patients (18-75 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-defined MDD with mixed features (n = 185) or bipolar disorder with mixed features (n = 200) and experiencing an MDE were randomized 1:1 to 6-week placebo (n = 195) or lumateperone 42 mg (n = 193). Primary and key secondary endpoints were change from baseline to day 43 in Montgomery-Åsberg Depression Rating Scale Total and Clinical Global Impression Scale-Severity (CGI-S) scores in 3 populations with combined MDD/bipolar depression, individual MDD, and individual bipolar depression. Safety included adverse events (AEs), extrapyramidal symptoms, and laboratory parameters.

Results: Lumateperone met the primary endpoint, significantly improving Montgomery-Åsberg Depression Rating Scale total score at day 43 in populations with combined MDD/bipolar depression (least squares mean difference vs placebo [LSMD], -5.7; 95% confidence interval [CI], -7.60,-3.84; effect size [ES], -0.64; P < 0.0001), MDD (LSMD, -5.9; 95% CI, -8.61,-3.29; ES, -0.67; P < 0.0001), and bipolar depression (LSMD, -5.7; 95% CI, -8.29,-3.05; ES, -0.64; P < 0.0001). Lumateperone significantly improved CGI-S and Young Mania Rating Scale total scores at day 43 in these populations. Lumateperone was well-tolerated. Treatment-emergent AEs (≥5%, twice placebo) in the combined population were somnolence (placebo, 1.6%; lumateperone, 12.5%), dizziness (placebo, 2.1%; lumateperone, 12.0%), and nausea (placebo, 1.6%; lumateperone, 9.9%). There were no mania/hypomania treatment-emergent AEs with lumateperone and minimal extrapyramidal symptoms or metabolic risk.

Conclusions: Lumateperone 42 mg significantly improved depression symptoms and disease severity and was generally safe and well-tolerated in patients with MDD or bipolar depression with mixed features.

Purpose: To evaluate the risk of bleeding associated with the simultaneous administration of antidepressants (ADs) and direct oral anticoagulants (DOACs).

Methods: PubMed, Embase, and Scopus databases were searched for papers that focused on the concomitant administration of ADs and DOACs and presented data on the bleeding outcomes. The comparator group of interest was subjects who received only DOACs. Besides the overall pooled analysis, irrespective of the primary disease condition, we were also interested in studies involving patients with atrial fibrillation (AF). We therefore included studies with relevant comparisons (AD with DOACs, compared to DOACs alone), regardless of the reported underlying condition. Thereafter, we conducted a sensitivity analysis to refine estimates specific to AF. Clinical trials and observational studies were eligible. Pooled effect sizes were reported as relative risk (RR) for studies with cohort design and as odds ratio (OR) for case-control studies.

Results: Ten studies were included. Overall pooled analysis showed that treatment with both DOAC and selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) was associated with significantly higher risk of major bleeding (cohort: RR 1.25, 95% CI: 1.07-1.47; case-control: OR 1.40, 95% CI: 1.15-1.69). The risk of intracranial bleeding was found to be increased when cohort studies were pooled (RR 1.44, 95% CI: 1.24-1.66), but not with pooling of case-control studies (OR 1.58, 95% CI: 0.43-5.75). The risk of gastrointestinal bleeding and transient ischemic attack (TIA)/ischemic stroke was comparable between the 2 groups (DOAC + SSRI/SNRI vs DOAC only group).

Conclusions: Our results indicate that combined SSRIs/SNRIs and DOAC treatment may be associated with increased incidence of major and intracranial bleeding, further emphasizing the importance of caution when considering their concomitant use.