Journal of Clinical Psychiatry最新文献

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population.

Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes.

Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year (P < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P < .001 and +0.12%, P = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg (P = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month (P = .004), whereas a trend was observed for women (+0.40%, P = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period.

Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

Objective: Data are lacking on the neurodevelopmental outcomes of children prenatally exposed to second-generation antipsychotics (SGAs). The objective of this study is to examine neurodevelopmental outcomes of children exposed in utero to SGAs compared to those unexposed in a cohort of mothers with psychiatric morbidity.

Methods: We conducted a cross-sectional assessment of preschool-aged children whose mothers were enrolled in the National Pregnancy Registry for Psychiatric Medications. Two validated, parent-report developmental and behavioral screening assessments, the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Preschool Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5), respectively, were delivered electronically to eligible participants. Outcomes of children exposed in utero to SGAs were compared to those unexposed to SGAs in a cohort of mothers with a history of psychiatric illness. Exposure to other psychotropic medications during pregnancy was not an exclusion criterion for either group.

Results: From January 2, 2018, to February 2, 2021, 520 children were eligible, and 352 responses were collected (67.7%), including 178 children in the SGA-exposed group (mean age = 2.6 years) and 174 children in the unexposed comparison group (mean age = 2.1 years). No significant differences between groups were detected (OR = 1.24, 95% CI, 0.74-2.09) with respect to developmental outcomes assessed by the ASQ-3. Similarly, for behavioral outcomes, adjusted analysis showed no significant differences in odds of an abnormal "clinical" score on the CBCL/1½-5 composite scales.

Conclusions: The current study is the first to examine neurobehavioral outcomes of preschool-aged children exposed prenatally to SGAs. No significant differences in overall development or behavior were detected in the exposed versus unexposed group. These preliminary findings are an important step in delineating neurodevelopmental effects of prenatal SGA exposure.

Objective: Self-stigma, a phenomenon wherein individuals internalize self-directed negative stereotypes about mental illness, is associated with negative outcomes related to recovery. This randomized controlled study assessed the efficacy of a brief social contact-based video intervention in reducing self-stigma in a large sample of individuals ages 18-35 endorsing an ongoing mental health condition. We hypothesized that the brief video would reduce self-stigma.

Methods: In January and February 2023, we recruited and assigned 1,214 participants to a brief video-based intervention depicting a young individual living with mental illness sharing his personal story or to a non-intervention control. In the 2-minute video, informed by focus groups, a young individual described struggles with mental illness symptoms; this was balanced with descriptions of living a meaningful and productive life. Self-stigma assessments (Stereotype Endorsement, Alienation, Stigma Resistance, Perceived Devaluation Discrimination, Secrecy, and Recovery Assessment Scale) were conducted pre- and post-intervention and at 30-day follow-up.

Results: A 2 ✕ 3 group-by-time analysis of variance showed that mean self-stigma scores decreased in the intervention arm relative to control across 5 of 6 self-stigma domains: Stereotype Endorsement (P = .006), Alienation (P < .001), Stigma Resistance (P = .004), Secrecy (P < .001), and Recovery Assessment Scale (P < .001). Cohen d effect sizes ranged from 0.22 to 0.46 for baseline to post-intervention changes. Baseline and 30-day follow-up assessments did not significantly differ.

Conclusions: A 2-minute social contact-based video intervention effectively yielded an immediate but not a lasting decrease in self-stigma among young individuals with ongoing mental health conditions. This is the first study to examine the effect of a video intervention on self-stigma. Future trials of self-stigma treatment interventions should explore whether combining existing interventions with brief videos enhances intervention effects.

Trial Registration: NCT05878470.

Background: Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL_NCD) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications.

Methods: This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment.

Results: Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively.

Conclusions: No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using AL_NCD plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using AL_NCD plus 30-mg oral aripiprazole.

Trial Registration: ClinicalTrials.gov identifier: NCT03345979.

Objective: Adolescent suicide is a major public health problem, and risk of suicide is higher among those with major depressive disorder (MDD), which may be linked to alterations in mitogen- and stress-activated kinase 1 (MSK1) and to defects in executive function. Here, we aimed to investigate the potential impacts of executive function and MSK1 methylation on suicidal ideation in adolescents with MDD.

Methods: The study enrolled 66 drug-naive adolescents who were experiencing their first episode of MDD from February 2019 until October 2020. After 6 weeks of receiving antidepressant treatment, 65 participants remained in the study. Suicidal ideation and depressive severity were assessed using the Hamilton Depression Rating Scale, while executive function was evaluated using the Cambridge Neuropsychological Test Automated Battery. MSK1 methylation was measured using bisulfite DNA analysis.

Results: Among the 66 adolescents with MDD, 43 (65.15%) reported suicidal ideation, while 23 (34.85%) did not. Individuals with suicidal ideation had worse executive function and higher MSK1 methylation than those without suicidal ideation. The MSK1 methylation percentage may predict suicidal ideation in adolescents with MDD (odds ratio [OR] 1.227, 95% CI [1.031 to 1.461]). Improvement in executive function was significantly associated with reduced suicidal ideation during antidepressant treatment (β = -0.200, 95% CI [-0.877 to -0.085]).

Conclusions: Our results strengthen the evidence for a link among MSK1 methylation, executive function, and suicidal ideation in adolescent MDD.

Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033402.

Objective: Given the high rate of comorbid posttraumatic stress disorder (PTSD) and cannabis use, it is critical that further research be conducted to address the associated benefits and risks of cannabis use in this population. This systematic review evaluated evidence on the effects of cannabis and cannabinoids on PTSD symptoms and PTSD clusters.

Data Sources: A systematic search of PubMed, PsycINFO, and EMBASE databases was performed using terms related to cannabis, cannabinoids, and PTSD. Peer-reviewed studies available online in English and published from January 1990 through February 2023 were considered.

Study Selection: Included studies were experimental or observational in design, were conducted in cannabis-using patients with PTSD, used validated measures of PTSD, and were published in English.

Data Extraction: Extracted information included study aims, study design, sample size and sex, comparator group, cannabis-related characteristics, psychometric instruments, and relevant clinical findings regarding overall PTSD symptoms and cluster symptoms.

Results: Fourteen studies were included, 3 in a comorbid PTSD and cannabis use disorder (CUD) sample and 11 in a non-CUD sample. Of the 10 studies examining overall PTSD symptoms in a non-CUD sample, 5 suggested benefits associated with cannabis use and 5 suggested no effect or worsening of symptoms. Four studies reported benefits of cannabis for cluster B- and E-related symptoms in a non-CUD sample. All 3 studies in cannabis-using patients with a comorbid PTSD and CUD diagnosis reported risks for worsening of overall symptoms.

Conclusions: This review did not find major benefits of cannabinoids in improving overall PTSD symptoms. Some benefits with regard to cluster B and E symptoms were observed. Some risks with regard to worsening suicidal ideation and violent behavior were also reported. Individuals with a comorbid CUD diagnosis may be at greater risk for negative cannabis-related PTSD outcomes. More experimental studies are needed to determine the causal effects of cannabis and cannabinoids in PTSD.

Sedentary behaviors are leisurely behaviors that occur during waking hours performed while lying down or seated; examples are relaxing, conversing, using a smartphone, watching television, traveling in private or public transport, and thinking or working at a desk. Sedentary behaviors are common in everyday life; the average person spends 9-10 h/d sedentary. Findings from meta-analyses show that higher levels of physical activity are associated with a reduced risk of dementia and that near-absence of moderate to vigorous physical activity is associated with an increased risk of dementia. Sedentariness is a clearly defined construct that is more than just low levels of physical activity. Sedentariness, therefore, merits independent study. In this context, a recent cohort study, conducted in elderly subjects (mean age, 67 years) who were followed for a mean of 6.7 years, found that sedentariness, independent of current levels of moderate to vigorous physical activity, was associated in a dose-dependent fashion with the risk of incident dementia; the finding held true when reverse causation was addressed through the exclusion of subjects who developed dementia within 4 years of follow-up. The adjusted 10-year risk of dementia rose from about 8% with sedentariness at 10 h/d to about 23% with sedentariness at 15 h/d; the difference is clinically meaningful. Limitations of studies in the field are that residual confounding cannot be excluded, and that no randomized controlled trials exist upon which guidance may be based. Nevertheless, it could be prudent to decrease sedentary behaviors if only because these have also been associated with other adverse physical and mental health outcomes. Additional subjects explained in this article include reverse causation and how it may be dealt with during research design and data analysis, individual participant data meta-analysis, and making sense of results that are reported in terms of "per 1,000 person-years."