Journal of Clinical Psychiatry最新文献

Cannabis use during pregnancy is increasing; the study of adverse outcomes in cannabis-exposed pregnancies is therefore important. Previous articles in this series described increased risks of maternal adverse outcomes, fetal adverse outcomes, birth defects in newborns, and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in childhood. This article examines neuropsychiatric adverse outcomes in offspring gestationally exposed to cannabis. Currently available research suggests that prenatal cannabis exposure is associated with increased risks of ASD, ADHD, psychosis proneness, psychotic like experiences, internalizing problems, externalizing problems, attention problems, thought-related problems, social problems, impaired executive function, and observed aggression. There is insufficient study of prenatal cannabis exposure and offspring IQ. Shortcomings in the existing literature are discussed; as examples, many outcomes were determined by screening rather than by formal assessment, prenatal cannabis exposure was ascertained retrospectively in some studies, childhood adverse experiences and exposures were seldom included as covariates, and details about cannabis use (source, potency, frequency, reasons) were unavailable. Curiously, the findings of adverse outcomes were inconsistent, and the effect sizes were small. Possible explanations are that women who use cannabis during pregnancy may not admit it and their pregnancy outcomes may then be misclassified into the control group, assessment of outcomes at too young an age or with insufficient accuracy may blur differences between exposed and unexposed groups, and adjustment for covariates may mask the full effects of cannabis. A last observation is that the studies reviewed were based on exposures that occurred decades ago. Given the increasing potency of currently available cannabis and the limitations of the existing research, it is possible that the available findings underestimate the breadth and severity of the risks. Cannabis is not a necessary substance for use during pregnancy, and so women who consider it safe might do well to guard against complacency and unnecessary exposure.

Objective: To evaluate weight change with a combination of olanzapine and samidorphan (OLZ/SAM) versus olanzapine by pooling data across clinical studies.

Methods: This study was an individual patient data (IPD) meta-analysis of clinical trial data.

Data Sources and Study Selection: EMBASE, MEDLINE, and PsycInfo were searched for randomized clinical trials (≥12 weeks) in adults with schizophrenia or bipolar I disorder in which weight change from baseline was the primary or secondary end point. Search results were reviewed for eligible studies.

Participants: Patients receiving daily OLZ/SAM (olanzapine 5-20 mg + samidorphan 10 mg) or olanzapine (5-20 mg) who underwent ≥1 postbaseline weight assessment by week 12 were included.

Outcomes: The primary outcome was percent change in body weight at week 12. Secondary outcomes were proportions of patients with ≥7% or ≥10% weight gain from baseline at week 12.

Results: Overall, 1063 patients from 3 studies conducted between June 2013 and December 2021 were analyzed. At week 12, OLZ/SAM treatment was associated with a lower least squares mean (LSM) percent change in body weight from baseline (3.68%) vs olanzapine (5.43%) (LSM [SE] difference=-1.75% [.41]; 95% CI, -2.55 to -0.94). Fewer patients treated with OLZ/SAM gained ≥7% (23.9% vs 34.6%; odds ratio [OR] = 0.58; 95% CI, 0.043-0.79) or ≥10% (13.7% vs 20.4%; OR = 0.60; 95% CI, 0.42-0.88) of their baseline body weight at week 12.

Conclusion: In this IPD meta-analysis, OLZ/SAM treatment was associated with less weight gain and reduced risk of reaching ≥7% or ≥10% gain in body weight versus olanzapine over 12 weeks.

Objective: We compared substance use disorder (SUD) prevalence among adult inflammatory bowel disease (IBD) hospitalizations with non-IBD controls from the 2016-2018 National Inpatient Sample, assessing correlations with demographics, socioeconomic status, geographic regions, depression, and anxiety.

Methods: The primary aim focused on SUD, defined as substance abuse or dependence (International Statistical Classification of Diseases, Tenth Revision [ICD-10]: F10-F19) excluding unspecified use or remission, among hospitalizations documenting IBD (Crohn's disease or ulcerative colitis; ICD-10: K50-51) as one admitting diagnosis (IBD-D). The prevalence of SUD among hospitalizations with and without IBD was compared. The secondary aim further characterized factors influencing SUD among hospitalizations with IBD as the primary diagnosis (IBD-PD). Multivariable logistic regression was performed to estimate the adjusted odds ratios (ORs) for SUD including associated covariates.

Results: SUD prevalence was 20.9% for IBD-D and 20.8% for non-IBD controls (P = .38). After adjustments, there was less SUD (OR 0.92, 95% CI, 0.90-0.93) but more opioid use disorder (OUD) (OR 1.20, 95% CI, 1.15-1.24) among IBD-D; other substances were less likely among IBD-D. Among IBD-PD hospitalizations, SUD significantly associated with Crohn's disease (75.1% vs 58.8%, P < .001), Medicaid (30.4% vs 15.8%, P < .001), lowest-income quartile (32.8% vs 23.8%, P < .001), depression (19.1% vs. 12.5%), and anxiety (24.7% vs. 14.9%). These factors were also associated with OUD. Notably, certain geographic regions and urbanization levels correlated with both elevated SUD and OUD among IBD-PD hospitalizations.

Conclusions: We comprehensively characterized SUD prevalence among adult IBD hospitalizations, identifying demographic, socioeconomic, geographic, and mental health risk factors for SUD and OUD in IBD. These findings inform efforts to decrease SUD among IBD patients by improving health care delivery through reducing health care disparities and improving psychiatric care.

Objective: Pharmacotherapy plays a crucial role in treating attention-deficit/ hyperactivity disorder (ADHD). However, current medications for ADHD have limitations and potential adverse effects. Glutamate, a neurotransmitter that directly and indirectly modulates dopamine neurotransmission, is considered a new therapeutic target for ADHD. We conducted a systematic review to determine the efficacy and safety of memantine, an uncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, in both pediatric and adult patients with ADHD.

Data Sources: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for articles on memantine use in ADHD patients published up to August 31, 2023, using terms related to ADHD and memantine.

Study Selection: Studies selected according to PRISMA guidelines. We included both randomized and nonrandomized trials for a comprehensive review. We excluded non-English publications, review articles, and studies without full text.

Data Extraction: Two authors extracted data using the data extraction form designed for this review. Independent authors conducted a risk of bias assessment using risk of bias 2 (RoB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I).

Results: Six studies met the inclusion criteria, 3 on pediatric populations, and 3 on adults. Three studies were conducted in the United States (2 in adults) and 3 in Iran (1 in adults). Memantine showed potential benefits in managing ADHD symptoms and had a favorable safety profile. However, most studies involved small patient groups at single institutions, and their quality was low.

Conclusions: Memantine has the potential to be a relatively safe alternative or adjunctive treatment for ADHD, but more refined studies with larger populations are needed.

J Clin Psychiatry 2025;86(1):24r15507.

Author affiliations are listed at the end of this article.

Background: Treatment of attention-deficit/ hyperactivity disorder (ADHD) in patients with a substance use disorder (SUD) and comorbid ADHD (SUD +ADHD) may have positive effects on the outcome of both conditions, but controversy exists regarding the preferred ADHD treatment in these patients. Little is known about the treatments that are provided for these patients in routine addiction care practice and the factors that are associated with treatment provision.

Objective: To describe the treatments provided in everyday clinical practice and to explore factors associated with ADHD treatment provision in patients with SUD +ADHD.

Methods: An international multicenter observational prospective cohort design was employed. Patients with moderate to severe SUD and comorbid ADHD according to DSM-5 were invited to participate at the start of a new SUD treatment episode between June 2017 and May 2021. Clinical and sociodemographic data were collected at 12 study sites in 9 countries through patient interviews, interviews with treatment providers, and patient files. Treatment variation across studies was described, and mixed-effect logistic regression was used to identify factors associated with ADHD treatment provision.

Results: A total of 578 treatment-seeking patients with SUD +ADHD (274 inpatients, 303 outpatients, and 1 unknown) were recruited. About two thirds received some kind of ADHD treatment (62.8%), with 54.0% receiving pharmacologic, 34.0% receiving psychological treatment, and 25.1% receiving combined pharmacologic and psychological treatment. The treatment site explained more of the variation in ADHD treatment provision than individual patient factors. In addition, higher ADHD symptom severity and sobriety at intake were associated with receiving ADHD treatment.

Conclusion: These findings suggest that treatment of SUD +ADHD patients is suboptimal even in specialized centers with substantial practice variation. Further research is needed to better understand the barriers to implement treatment guidelines for ADHD + SUD and, thus, to improve quality of care.

Trial Registration: ISRCTN: 15998989 20/12/2019 (https://doi.org/10.1186/ISRCTN15998989).

Up to 10% of women may use cannabis during pregnancy; this is of concern because constituents of cannabis cross the placental barrier and potentially influence neurodevelopment by acting on cannabinoid receptors in the developing fetal brain. In this context, a recent meta analysis of 13 observational studies found that gestational exposure to cannabis was associated with a small increase in the risk of autism spectrum disorder (ASD; relative risk [RR], 1.30) and with an even smaller increase in the risk of attention deficit/hyperactivity disorder (ADHD; RR, 1.13); the latter finding was probably supported by publication bias. In this meta-analysis, 4 studies provided information on ASD (pooled N = 178,565) and 10 on ADHD (pooled N = 203,783). In a large (n = 222,534) retrospectively ascertained cohort study published after the meta-analysis, cannabis use disorder (CUD) recorded before pregnancy, during pregnancy, and during pregnancy plus the year after delivery were associated with closely similar increased risks of ASD (RRs, 3.02-3.21). The risks were smaller in smokers (RRs, 1.74-1.87) than in nonsmokers (RRs, 4.55-4.83) but differed little between male (RRs, 3.01-3.06) and female (RRs, 2.71-2.85) offspring. Although the cohort study had many strengths, its limitations permitted only the conclusion that peri-pregnancy exposure to CUD is associated with a large increase in the risk of ASD in offspring; it remained possible that much of the risk was driven by genetic, environmental, or behavioral variables. The field is nascent; the total number of cannabis exposed pregnancies (with ASD and ADHD as the outcomes) in world literature is small. However, cannabis use during pregnancy is, at the very least, a clear marker for adverse neurodevelopmental outcomes, besides the adverse maternal, fetal, and neonatal outcomes identified in other studies. Healthcare providers who manage women who use cannabis during pregnancy need to be aware of these adverse outcomes.

Objective: Evaluate long-term safety, tolerability, and durability of the effect of olanzapine/samidorphan (OLZ/SAM) for up to 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I).

Methods: This phase 3, multicenter, open-label, long-term extension (conducted June 2017-September 2023) assessed OLZ/SAM in patients completing the ENLIGHTEN clinical program. Patients received ≥2-4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. The durability of the effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale.

Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform disorder, and 48 (9%) had BD-I. Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients eligible for 4 years, 109 (32.5%) received it. The most common AEs were weight increased (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and weight decreased (5.7%). At 2 years, mean (SD) body weight change was 0.84 (6.84) kg; waist circumference change was -0.56 (6.24) cm. At 4 years, mean (SD) body weight change was 2.65 (8.12) kg; waist circumference change was 1.37 (8.65) cm. Changes in lipid/glycemic parameters were minimal. CGI-S scores remained stable.

Conclusion: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies.

Trials Registration: ClinicalTrials.gov identifier: NCT03201757.