Journal of Clinical Psychiatry最新文献

Objective: Both intravenous (IV) racemic ketamine and intranasal (IN) esketamine have emerged as rapid-acting antidepressants for treatment-resistant depression (TRD) and are increasingly used in clinical settings. Relatively few studies, however, have compared these interventions in larger, naturalistic cohorts. This study was conducted to assess the comparative efficacy and rapidity of response observed with repeated IV ketamine versus IN esketamine in a psychiatric neurotherapeutics specialty service. Through retrospective chart review, we conducted what is, to the best of our knowledge, among the larger such comparisons to date.

Methods: Data from 153 patients with severe TRD were reviewed (111 patients received IV ketamine and 42 patients received IN esketamine). In accordance with consensus criteria for TRD and validated objective criteria for illness severity, included patients failed a minimum of 2 adequate antidepressant treatment trials and demonstrated a preketamine treatment score of 16 or higher on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR₁₆). Severity of depression was subsequently reassessed with the QIDS-SR₁₆ prior to each ketamine and esketamine administration. A 2-way analysis of variance was used to compare changes in QIDS-SR₁₆ scores between the IV ketamine and IN esketamine treatment groups.

Results: With equivalent depression severity measured by QIDS-SR₁₆ at pretreatment baseline, the IV ketamine treatment group showed significantly greater decreases in QIDS-SR₁₆ scores compared to the IN esketamine group, as measured immediately before each treatment from the third to the eighth session (all P values < .05). Patients who received IV ketamine infusions demonstrated a 49.22% reduction in QIDS-SR₁₆ scores by the eighth treatment, while patients who received IN esketamine over the same induction period showed a 39.55% reduction. As expected, both IV ketamine and IN esketamine treatments resulted in significant decreases in QIDS-SR₁₆ scores. In the IV ketamine group, the decrease in QIDS-SR₁₆ scores reached significance after 1 treatment, while in the IN esketamine treatment group, the decrease in QIDS-SR₁₆ scores reached significance after the second treatment.

Conclusion: In this naturalistic sample of patients with similarly severe TRD treated in a ketamine subspecialty service over a 4-5-week induction period, treatment with IV racemic ketamine was associated with a more rapid response and greater overall efficacy than treatment with IN esketamine.

Background: Finasteride, widely prescribed for androgenetic alopecia, has long been suspected of causing severe neuropsychiatric reactions, including depression, anxiety, and suicidality, even after the drug is discontinued. This study systematically reviews evidence that supports this suspicion and analyzes the reasons for this delayed recognition.

Observations: Concerns about depression from finasteride were raised in several studies as early as 2002. Between the years 2017 and 2023, 4 independent analyses of adverse event reporting systems and 4 studies using data mining of healthcare records indicated a significant increase in the risk for depression, anxiety, and/or suicidal behavior with the use of finasteride. There has been, therefore, a two-decade delay in the realization of the incidences and the gravity of neuropsychiatric effects, allowing harm from a medicine prescribed for a cosmetic indication of hair loss.

Potential Harms and Implications: Over 20 years worldwide, hundreds of thousands may have endured depression, and hundreds may have died by suicide. According to the precautionary principle, such a risk from a cosmetic medication suggests a benefit-to-harm balance that justifies action to protect the public, and the burden of proving that the intervention is not harmful falls on manufacturers.

Causes for Delayed Risk Recognition: The long delay in recognizing the risks associated with finasteride exposure includes the manufacturer's failure to perform and publish simple pharmacovigilance studies using database analyses and regulators' failure to request such studies from the manufacturer or to perform them.

Conclusions and Relevance: Current evidence shows that finasteride use can cause depression and suicidality. A historical literature review discloses gaps between research evidence and regulatory steps. The lesson is that before approving a medication for the market, regulators should require manufacturers to commit to performing and disclosing ongoing postapproval analytical studies, and this requirement needs to be enforced.

Objective: In treatment-resistant depression (TRD), augmentation with aripiprazole (A-ARI) or combination therapy by adding bupropion (C-BUP) has been reported as more effective than switching to bupropion (S-BUP), but C-BUP risks falls in older adults, and A-ARI risks weight gain and tardive dyskinesia (TD). The aim of this study was to clarify whether the enhanced effectiveness outweighs such risks.

Methods: In this risk-benefit decision analysis, lifetime quality-adjusted life-years (QALYs) following 1 year of A-ARI or C-BUP vs S-BUP treatment were simulated in a health-state transition model tracking depression remission, falls, weight gain, and TD, in age and baseline body mass index (BMI) subgroups, using data from the VAST-D and OPTIMUM trials and other literature. QALYs were converted to depression-free day-equivalents (DFDs), the QALYs gained from 1 day of remitted versus active depression.

Results: Simulated adults aged 18-64 years experienced a net benefit of C-BUP over S-BUP of 20.7 DFDs, equivalent to about 3 weeks of faster remission of depressive symptoms. In older adults, especially those aged 85+ years, this benefit over S-BUP was partially but not fully offset by a risk of falls. In adults aged 18-64 years, A-ARI was estimated to offer only 8.0 DFDs after subtracting the expected harms from TD, and this was further reduced to -22.8 DFDs once metabolic harms were considered, in those overweight at baseline. Overall, C-BUP was preferred over A-ARI in all subgroups except ages 85-89 years with BMI<25, in whom A-ARI was preferred.

Conclusion: In our model, C-BUP better balanced efficacy and tolerability in TRD in adults under 85 years than did S-BUP or A-ARI. A-ARI was least-preferred in overweight adults. These results may inform shared decision-making and clinical guidelines.

Background: Short-term studies have demonstrated antisuicidal effects of ketamine/esketamine for patients with treatment-resistant depression (TRD). However, long-term data and their impact in reducing suicidality-related health care utilization are limited. This 6-month mirror-image study compares suicidality-associated emergency department (ED) visits before and after acute treatment with ketamine/esketamine in a TRD cohort.

Method: This study included adults with TRD evaluated at Mayo Clinic Depression Center (Rochester, Minnesota) from May 2018 to May 2024, who received an acute series of intravenous (IV) ketamine or intranasal (IN) esketamine treatments. The primary outcome measure was the number of suicidality-associated ED visits in the 6 months before and after treatment. Negative binomial mixed-effects model was utilized to analyze suicidality-associated ED visits per person, estimating incidence rate ratios (IRRs) and 95% confidence intervals for the change between pre-and posttreatment periods.

Results: Of 124 eligible individuals, 27 were excluded due to unavailable data, leaving 97 for analysis. The cohort was 69% female, with a median age of 48.9 years; 97% had major depressive disorder, and most (75%) received IV ketamine. After the acute treatment phase, ED visits for suicidal ideation decreased by 84% (IRR=0.16, 95% CI, 0.06-0.46, P=.001), and total ED visits for suicidality decreased by 63% (IRR=0.37, 95% CI, 0.18-0.77, P=.007).

Conclusions: Ketamine and esketamine reduced long-term ED visits for suicidality in individuals with TRD. Further longer-term follow-up research is encouraged to ascertain if these benefits on suicidality reduction are mood state dependent or reflect an independent mechanism.

Objectives: Posttraumatic stress disorder is a significant public health concern in the US, with military veterans disproportionately affected. Although younger veterans exhibit a higher prevalence of posttraumatic stress disorder (PTSD) compared to their older counterparts, the mechanisms driving this age-related difference remain unclear. This study examined sociodemographic, trauma-specific, and psychosocial factors that may contribute to the elevated prevalence of PTSD in younger (age <50) vs older (age 50 and older) veterans.

Methods: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US military veterans (n=4,069).

Results: Younger veterans were 3 times more likely to screen positive for PTSD compared to older veterans (weighted 14.7% vs 4.9%, P<.001). Mediation analysis revealed that 90% of the association between younger age and PTSD was indirectly mediated by psychosocial and trauma-specific factors. Psychosocial difficulties contributed the most to accounting for this association (42.9%), followed by loneliness (23.6%), avoidance coping (9.7%), adverse childhood experiences (9.5%), and combat exposure severity (4.2%). Secondary analyses identified interpersonal relationship challenges, substance use and self-blame coping strategies, and childhood physical abuse as key mediators of this association.

Conclusion: Psychosocial and trauma-specific factors may mediate the link between younger age and higher rates of PTSD among US military veterans. These findings underscore the importance of targeted interventions designed to address psychosocial challenges, strengthen social connections, and promote adaptive coping strategies among younger veterans who are at risk for or currently living with PTSD.

Objective: This study examined the relationships between body fat mass percentage and mental health (depression and anxiety symptoms) during pregnancy, while assessing the moderating effects of physical activity and diet quality.

Methods: A prospective cohort of 219 pregnant women was recruited for a longitudinal study of maternal health during pregnancy and offspring outcomes. Pregnant participants were assessed at ∼12 and ∼36 weeks of pregnancy. Body composition was measured using air displacement plethysmography, physical activity was measured with ActiGraph wearables, and diet was measured using the National Institute of Health Diet History Questionnaire-III. Depression and anxiety symptoms were also evaluated using the Beck Depression Inventory-II and State-Trait Anxiety Inventory, respectively, at each study visits. Multivariable mixed linear models adjusted for demographic and socioeconomic factors were used to analyze relationships among these parameters. The study period is from October 2019 to August 2024.

Results: Higher body fat mass percentage was significantly associated with increased depression (β= 0.246, P=.014) and anxiety scores (β= 0.241, P=.002). Physical activity moderated the effect of body fat on depression (interaction β=-0.001, P=.017), while diet quality moderated the effect of body fat on anxiety (interaction β=-0.002, P=.047).

Conclusion: Higher body fat mass during pregnancy is associated with more symptoms of depression and anxiety. However, increased physical activity and adherence to high-quality diets can attenuate these effects, indicating that lifestyle interventions during pregnancy may improve mental health of pregnant women, particularly for those with obesity.

Objective: The objective of this study was to investigate potential associations between bariatric surgery and new onset mental health diagnoses and emergent psychiatric care utilization.

Methods: This was an observational retrospective cohort study. Patients without a history of mental health diagnoses who underwent bariatric surgery between 2010-2016 were matched to patients who were eligible for but did not undergo bariatric surgery on demographic, body mass index (BMI), and comorbidity burden at baseline (date of surgery for cases and matching date for controls). Outcomes of new onset mental health diagnoses after baseline and emergent care utilization were measured in 2-year increments between baseline (ranged from 2010 to 2016) until the end of follow-up (December 31, 2021) to assess changes in risk over time.

Results: The surgical group had lower risk of a new onset mental health diagnosis in the first 2 years (hazard ratio [HR]: 0.82, 95% CI, 0.76-0.88) and approximately 20% higher risk in years 4-8 of follow-up than the control group (years 4-6 HR: 1.22, 95% CI, 1.09-1.36; years 6-8 HR: 1.19, 95% CI, 1.03-1.39). However, emergent psychiatric service utilization did not differ between the groups during follow-up. Utilization was associated with a higher BMI (HR: 1.03, 95% CI, 1.02-1.04) and higher comorbidity burden (HR: 1.43, 95% CI, 1.37-1.49) at baseline.

Conclusions: Bariatric surgery may have a delayed impact on new onset mental health diagnoses, with surgical patients having higher risk of diagnoses than their nonsurgical counterparts 4-8 years following surgery. Despite these increases, there was no change in emergent psychiatric service utilization.