Psychopharmacology bulletin最新文献

Background: Acute alcoholic hallucinosis (ICD-10 F10.52) necessitates urgent antipsychotic treatment but carries high risks of adverse drug reactions (ADRs). While pharmacogenetic clinical decision support systems (CDSS) show promise, their utility is limited by static genotyping and incomplete biomarker integration.

Purpose: This study aimed to develop and validate a multi-omics framework integrating pharmacogenetic testing, CYP phenotyping, and microRNA biomarkers to personalize antipsychotic therapy and improve outcomes in acute alcoholic hallucinosis.

Material and methods: In this three-arm study, 300 Russian inpatients with acute alcoholic hallucinosis underwent: 1) Randomized pharmacogenetic-guided vs. standard therapy (n = 100); 2) CYP2D6/CYP3A4 phenotyping via urinary pinoline/cortisol ratios (n = 100); and 3) microRNA quantification (miR-27b, miR-370-3p; n = 100). Efficacy (PANSS) and safety (UKU) were assessed over 6 days.

Results: Pharmacogenetic guidance significantly reduced ADRs (UKU day 6: 5.0 [3.0 - 8.0] vs. 12.0 [10.0 - 16.0], p < 0.01) with comparable efficacy (PANSS≈1.0). Phenotyping identified 28% CYP2D6 poor metabolizers (vs. 15% by genotyping), exhibiting 40% higher haloperidol levels (r = 0.72, p < 0.001). Baseline miR-27b inversely correlated with day-3 PANSS (r = - 0.54, p < 0.001), while miR-370-3p predicted poorer day-6 response (ΔPANSS r = 0.48, p < 0.001) and higher UKU scores (r = 0.52, p < 0.001). Integrating microRNAs with phenotyping improved ADR prediction accuracy by 22% versus single modalities.

Conclusion: A multi-omics approach synergistically optimizes antipsychotic therapy by addressing genotyping limitations through dynamic phenotyping and microRNA-based prognostication, significantly enhancing safety in this high-risk population.

Introduction: Drug-assisted interviews have been used in psychiatry for about a century. The use of barbiturates for this purpose has declined, and the use of lorazepam has gained popularity over time for conducting drug-assisted interviews, given a better safety profile. However, the evidence for the use of lorazepam for drug-assisted interviews is fragmented and anecdotal, and mostly in the form of case reports. The current review aims to synthesize available evidence on the use of lorazepam-assisted interviews in psychiatry.

Methods: For this narrative review, a literature search was conducted using PubMed, Scopus, and Google Scholar. Peer-reviewed articles on the use of lorazepam for drug-assisted interviews for psychiatric patients were identified, and data were manually extracted and synthesized.

Results: Eleven case reports and one case series on lorazepam-assisted interviews were identified. Dissociative disorder was the common diagnosis where it was used, with most studies reporting significant improvement after the interviews. Adverse events, though rare, included excessive sedation, disinhibition, agitation, and emotional lability. Interview protocols varied among the studies, with doses ranging from 2 to 18 mg, administered through intravenous routes either as boluses or infusion (rates ranging from 0.05 mg/min to 0.1 mg/min). Most studies involved single sessions, with a maximum of 12 sessions in one case report.

Conclusion: Lorazepam-assisted interview may hold potential clinical utility in appropriate cases. Future studies are needed to establish efficacy and safety and to evaluate interview protocols.

Background: Clozapine and olanzapine are associated with clinically relevant weight gain and metabolic risk.

Objective: To compare the risk of obesity (BMI ⩾ 30) between clozapine and olanzapine and to develop a parsimonious prediction model with performance and clinical-utility evaluation.

Methods: We fit a multivariable logistic regression on complete cases using index drug, daily dose, prolactin (PRL), cortisol, free thyroxine (FT4), and HDL. Discrimination (AUC), probability accuracy (Brier score), calibration (intercept/slope and deciles), and decision-curve analysis (DCA) were reported.

Results: In the classification cohort, obesity counts were equal for clozapine (9/19) and olanzapine (9/19). The model achieved strong internal discrimination (AUC 0.869) with good calibration (slope 1.00; intercept -0.00) and Brier 0.123. DCA indicated net benefit at practical thresholds (∼5-15%), supporting low-harm preventive actions.

Conclusions: Drug-related risk can be individualized with a lean model using routine variables. External validation and unit harmonization-especially for HDL-are recommended before broad deployment.

This case report presents a complex psychiatric profile of a 19-year-old female with diagnoses of Fetal Alcohol Syndrome (FAS), Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), mild intellectual disability, and mood dysregulation, complicated by trauma history, psychotic features, and repeated hospitalizations. Her neurodevelopmental and psychiatric disorders have contributed to persistent high-risk behaviors, legal involvement, and challenges with independent living, ultimately necessitating group home placement. This case highlights the unique relationship between FAS and coexisting neurodevelopmental conditions, emphasizing the poor long-term outcomes frequently associated with FAS and ultimately the importance of comprehensive, multidisciplinary care in managing such patients. We review the current literature on co-occurrence of ASD and FAS, prognosis, and clinical management challenges posed by these overlapping conditions.

Over the last twenty years, the development of antipsychotic medications has progressed from simple dopamine receptor antagonism to more complex, multi-receptor strategies. This evolution reflects an effort to improve therapeutic effectiveness, reduce side effects, and address a broader spectrum of psychiatric symptoms. Traditional first-generation antipsychotics primarily block dopamine D₂ receptors, which often results in motor-related side effects and limited benefits for cognitive and negative symptoms. Second-generation agents introduced the combination of dopamine and serotonin receptor modulation, improving outcomes in emotional and social functioning with fewer extrapyramidal side effects. This class represented a significant improvement in tolerability and addressed a wider range of symptoms. Third-generation antipsychotics further refined this approach by acting as partial agonists at dopamine D₂/D₃ receptors while continuing to influence serotonergic pathways. These medications offer more balanced dopaminergic activity, improved cognitive and mood effects, and reduced metabolic and motor risks. The latest developments, referred to as fourth-generation antipsychotics, signal a major shift in psychopharmacology. These agents, which include novel compounds with minimal direct dopamine activity, act on receptors such as 5-HT₂A, TAAR1, muscarinic, glutamate, and sigma. This receptor diversity allows for greater effectiveness in managing negative symptoms and cognitive impairments, while substantially lowering the risks of endocrine disturbances and movement disorders. These emerging agents hold promise for better overall patient outcomes. This review highlights the clinical relevance of third- and fourth-generation antipsychotics and supports the growing trend toward targeted, receptor-specific treatments in managing psychotic disorders.

Background: Cannabidiol (CBD), a non-intoxicating compound derived from Cannabis sativa, has gained widespread popularity for its proposed therapeutic effects in conditions such as anxiety, insomnia, and chronic pain. Unlike tetrahydrocannabinol (THC), CBD is often perceived as safe, with minimal psychoactive properties. However, its psychiatric safety profile, particularly in relation to mood disorders, remains poorly understood.

Case presentation: We report the case of a 31-year-old male with no prior psychiatric history who developed a manic episode characterized by irritability, decreased need for sleep, hyperactivity, and aggression. These symptoms emerged after three months of escalating daily CBD use via vaping, reaching high doses shortly before admission. Toxicology screening was negative for other substances, and the patient showed clinical improvement with mood stabilizers and antipsychotics following the discontinuation of CBD.

Discussion: This case raises concerns about the potential of high-dose CBD to induce manic symptoms in certain individuals. While CBD has been proposed to have anxiolytic and antipsychotic effects, its influence on mood regulation may be complex and dose-dependent. The variability in commercial CBD product composition, including possible contamination or mislabeling, further complicates risk assessment. Current evidence from clinical trials on CBD's effects in mood disorders is limited and inconclusive.

Conclusion: Clinicians should remain alert to the psychiatric effects of CBD, particularly in patients presenting with new-onset mood symptoms. This report underscores the need for controlled studies to assess the safety of CBD in psychiatric populations and calls for stricter regulation of cannabinoid products.

Background: Methadone is a long-acting opioid utilized in the management of chronic pain and opioid dependency. Given its unique pharmacokinetics and potential for both therapeutic benefit and risk, understanding prescribing patterns is essential. This study aimed to evaluate methadone utilization at a single academic university over a one-year period as well as discuss important considerations of methadone pharmacology.

Methods: A retrospective review was conducted using electronic medical records to assess the number of methadone prescriptions issued across the institution between January 1, 2024, and December 31, 2024. The total number of prescriptions was analyzed and categorized into four quarters. In Q1 (January-March), 96 prescriptions were issued, followed by 109 in Q2 (April-June), 120 in Q3 (July-September), and 145 in Q4 (October-December).

Results: A total of 470 methadone prescriptions were issued during the study period, demonstrating a steady increase over the year. The percentage increase in methadone prescriptions from Q1 to Q4 was approximately 51%. Notably, this analysis did not differentiate between prescriptions for chronic pain versus opioid dependency treatment. The rise likely reflects prescribing for pain management, as methadone for OUD is typically dispensed through regulated clinics not captured in this data. However, some prescriptions may reflect dual management by addiction medicine providers within our institution.

Conclusions: This study highlights a consistent rise in methadone prescriptions at this particular institution, underscoring the need for further investigation into prescribing patterns, patient demographics, and clinical indications. Future research should stratify prescriptions by primary indication to better understand the drivers of methadone utilization and its impact on patient outcomes.

Purpose of study: This retrospective review aimed to evaluate the prevalence of tetrahydrocannabinol (THC)-positive urine drug screens (UDS) in patients undergoing chronic opioid therapy (COT) for chronic pain at a single academic institution. With a growing national trend toward cannabis legalization and increased public access to marijuana for medical and recreational purposes, understanding the intersection between THC use and opioid prescribing practices is essential. The presence of THC on UDS has clinical, legal, and ethical implications, especially in regions where cannabis remains illegal. This study sought to quantify the prevalence of THC positivity in patients receiving COT for chronic pain.

Findings: A total of 244 UDS results were reviewed from January 1, 2024, to December 31, 2024. Among these, 24 patients (9.8%) tested positive for THC. Documentation and clinical responses to positive results varied, with some providers documenting patient counseling, while others did not acknowledge the result in the medical record. In a small subset of cases, positive THC findings contributed to changes in opioid therapy, including tapering or discontinuation.

Conclusion: THC-positive UDS results are relatively common among patients receiving chronic opioid therapy, highlighting the increasing prevalence of cannabis use in this population. These findings align with prior literature and reinforce the need for individualized, non-punitive approaches to care. Routine screening, consistent documentation, and open communication about cannabis use are essential components of effective opioid risk stratification, safe prescribing practices, and informed treatment planning. These considerations are critical in regions where recreational marijuana remains illegal, which may further influence provider decision-making regarding ongoing opioid therapy.

Psychogenic voice disorder, often a manifestation of conversion disorder, is characterized by a sudden impairment of voice following a stressful event or other psychological cause. This case report presents a patient with a psychogenic voice disorder featuring the atypical ability to sing despite losing conversational voice. Few case reports exist on psychogenic speech and voice disorders, and no cases in the current literature examine the loss of conversational voice with preservation of singing voice. In this case, the patient experienced sudden onset stuttering which progressed to complete loss of voice in all settings while retaining the ability to sing. Despite extensive medical, psychiatric, and speech-language evaluations, including psychotherapy and speech therapy, the symptoms persisted, highlighting the diagnostic and treatment challenges in psychogenic voice disorders. This case underscores the complex interplay between psychological stressors and physical symptoms in psychogenic voice disorders, and highlights the lack of effective, evidence-based therapies for psychogenic voice disorders.

Purpose: Individuals with Bipolar II disorder (BD-II) face high rates of depression and have limited FDA-approved treatments, leading to treatment delays and poor functioning. Although not commonly recommended, monoaminergic antidepressants are prescribed to 50% of patients. This review updates the evidence for second-generation antidepressant (SGAD) monotherapy in treating acute BD-II depression.

Methods: We searched Ovid MEDLINE, Embase, CENTRAL, PsycINFO, Scopus, and Web of Science from March 2021 to February 2025 and included five studies published before 2021. Randomized controlled trials (RCTs) evaluating SGAD monotherapy in adults with acute BD-II depression. Primary outcomes were response, remission, treatment-emergent affective switch (TEAS), dropouts owing to adverse events (AEs), and overall discontinuations.

Results: Of 949 records identified, 12 studies were selected for full-text assessment, and six were included in our systematic review. The final dataset comprised four double-blind RCTs (n = 533), one open-label RCT (n = 83), and one triple-blind RCT (n = 40). Venlafaxine and sertraline produced short-term benefits, with response rates 60.4%-73.3% and remission rates 44.2%-58.5%. TEAS risk was ⩽ 19.9% and did not differ from lithium in head-to-head comparisons. AEs withdrawals were similar; SGADs often had comparable or better all-cause discontinuation than comparators.

Conclusions: Limited short-term evidence indicates that SGAD monotherapy in acute BD-II depression is well-tolerated and has similar response rates to lithium, without increasing switch risk. Nevertheless, the evidence base is small and heterogeneous. Larger and longer RCTs are needed to confirm efficacy, characterize maintenance benefits, and inform personalized treatment decisions.