International Clinical Psychopharmacology最新文献

This 6-month open-label extension (OLE) period of a Phase 3 placebo-controlled study (NCT02600494) examined the safety of lumateperone in patients with bipolar I or bipolar II depression. Eligible patients completing the placebo-controlled period received lumateperone 42 mg once daily up to 175 days. The primary endpoint was safety and tolerability, assessed by adverse events (AEs) and clinical laboratory evaluations analyzed by imputing missing data using a last observation carried forward approach. The secondary endpoint was efficacy measured by Montgomery-Åsberg Depression Rating Scale (MADRS) total and Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) scores. Of 127 patients in the OLE, 58.3% completed treatment, and 42.5% experienced a drug-related treatment-emergent AE (TEAE); the most common TEAEs were headache (20.5%), dry mouth (11.8%), dizziness (10.2%), and nausea (10.2%). The majority (92%) of TEAEs were of mild or moderate severity. There were no notable changes in extrapyramidal symptom scores, cardiometabolic parameters, or body morphology. MADRS total score (mean change, -8.9, nominal P < 0.0001), CGI-BP-S total score (-2.3, nominal P < 0.0001), and CGI-BP-S depression subscore (-1.3, nominal P < 0.0001) improved over time, from baseline to Day 175. Overall, 6-month lumateperone 42 mg was generally well tolerated, and depressive symptoms based on MADRS total score and CGI-BP-S improved over time.

Semaglutide (SEM), a long-acting glucagon-like peptide-1 receptor agonist, affects neural circuits regulating food intake and satiety, and it provides neuroprotective effects; however, SEM may influence psychological functioning, possibly leading to psychopathological symptoms. This review examines studies on SEM, focusing on its effects on mental health and potential neuropsychiatric side effects. A systematic search in PubMed and Google Scholar was conducted for studies up to March 2025, yielding 342 papers, of which 37 met the eligibility criteria. The selected studies included cohort studies, pharmacovigilance research, open-label studies, and randomized-controlled trials. Findings show that SEM is effective and well-tolerated in various psychiatric populations, with potential benefits in managing binge eating disorder (BED), metabolic disturbances in psychotic disorders, and alcohol use disorder; however, these drugs are also linked to depressive symptoms and suicidal ideation, alongside potential antidepressant effects, though this evidence is preliminary. SEM showed to be of great interest in the treatment of BED, acting not only on weight decrease but also on cognitive symptoms linked to the disease. Similar findings, though preliminary, have been observed for the treatment of alcohol and substance use disorder. The use of SEM in mood disorders, in particular depression, is still controversial.

This systematic review and meta-analysis included randomized controlled trials (RCTs) to compare the efficacy, (treatment-emergent) suicidality, tolerability, and acceptability of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) against placebo in treating children and adolescents with anxiety disorders. We searched multiple electronic databases on July 15 2024. The outcomes included anxiety reduction (efficacy), suicidality rate, dropout rate because of adverse effects (tolerability), and overall dropout rate (acceptability). This study included 15 trials involving 2083 participants (median age = 11.61 years), investigating five SSRIs and two SNRIs. SSRIs/SNRIs significantly reduced anxiety symptoms [14 trials, standardized mean difference = -0.49, 95% confidence interval (CI): -0.65 to -0.33, I2 = 60%], with no significant difference between the two classes. Compared with placebo, they showed a higher risk of suicidal ideation [eight trials, risk ratio = 3.51, 95% confidence interval (CI): 1.51-8.16, I2 = 0%], greater acceptability (15 trials, risk ratio = 0.86, 95% CI: 0.75-0.99, I2 = 0%), and similar tolerability (14 trials, risk ratio = 1.30, 95% CI: 0.68-2.46, I2 = 35%). SSRIs and SNRIs effectively reduce anxiety symptoms in children and adolescents, with good tolerability and acceptability; however, they may increase the risk of suicidal ideation.

Depression has a high prevalence and increasing incidence in the USA. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are the most commonly used treatments. To be effective, SSRIs must be taken consistently. This study evaluated adherence and persistence among veterans diagnosed with major depressive disorder (MDD) who initiated SSRI monotherapy within 90 days of diagnosis. Using Veterans Affairs healthcare data from 2000 to 2023, we identified veterans with MDD who filled a prescription for one of the five most common SSRIs: citalopram, escitalopram, fluoxetine, paroxetine, or sertraline. Adherence was measured as the proportion of days covered during the first year, with greater than or equal to 80% considered adherent. Persistence was measured as time to discontinuation, defined as a 90-day gap in supply. Among 300 628 eligible patients, 29.3% were adherent and 49.6% persisted on treatment for more than 180 days. Escitalopram, fluoxetine, and sertraline had significantly higher adherence and lower discontinuation hazards compared with citalopram and paroxetine. These results suggest that escitalopram, fluoxetine, and sertraline support better long-term adherence and persistence in veterans with MDD. Enhanced understanding of these dynamics can improve patient education and support systems that address specific adherence barriers, including side effects and lack of information about treatment duration and expectations.

This Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of lumateperone to treat bipolar depression. Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1:1 to 6-week lumateperone 28 mg ( n  = 183), lumateperone 42 mg ( n  = 185), or placebo ( n  = 186). Primary and key secondary endpoints were change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total score and time to first sustained response (≥50% reduction from baseline in MADRS Total score), respectively. Safety assessments included adverse events, extrapyramidal symptoms (EPS), laboratory evaluations, and vital signs. Neither dose of lumateperone achieved significant improvement vs. placebo ( P > 0.05) in the primary endpoint (MADRS Total score, least squares mean difference vs. placebo: 28 mg, 0.9; 42 mg, -1.0) or in the key secondary endpoint (MADRS Total time to first sustained response hazard ratio vs. placebo: 28 mg, 1.00; 42 mg, 0.93), likely due to a high placebo response. Both lumateperone doses were well tolerated, with low EPS risk and minimal changes in weight, prolactin, and cardiometabolic or endocrine parameters. While study efficacy objectives were not met, both doses of lumateperone were generally safe and well tolerated in patients with bipolar depression.

This multicenter, 6-month naturalistic observational study investigated the time from as-needed (PRN) administration of psychotropic medications to the onset of calming in patients with acute psychotic disorders. Newly admitted patients exhibiting moderate to marked agitation on the Agitation-Calmness Evaluation Scale (ACES) and requiring PRN treatment were included, and 170 first agitation episodes were analyzed. The primary outcome was time to onset of effect, defined as achieving ACES = 3. Medication refusal at baseline was far more frequent in patients with injectable formulations than those with oral or sublingual agents (65.5% vs. 4.3%). Kaplan-Meier estimates showed mean onset times (minutes) for oral/sublingual drugs as follows: asenapine sublingual, 30.0; olanzapine orally disintegrating tablet, 31.9; quetiapine, 46.6; and risperidone oral solution, 34.5. Using Cox proportional hazards models with asenapine as reference, quetiapine demonstrated a significantly lower hazard of achieving calming (hazard ratio 0.39), while risperidone showed a nonsignificant trend. For injectable antipsychotics, mean onset times were: olanzapine intramuscular, 36.3; haloperidol intramuscular, 47.5; and haloperidol intravenous, 45.0, with no significant differences among them. No serious adverse events were observed. The findings suggest that asenapine sublingual may offer faster calming in patients without refusal, and that future studies with shorter assessment intervals are warranted.

Treatment of obsessive-compulsive disorder (OCD) symptoms in patients with bipolar disorder (BD) is challenging. In this research, the therapeutic effects of risperidone on OCD symptoms in patients with BD are investigated. Forty-two patients with concurrent BD and OCD symptoms were randomly assigned to receive risperidone or a placebo in a blinded randomized placebo-controlled trial. The patients of both groups were in the euthymic phase of BD. OCD symptoms were measured by the Yale-Brown Obsessive Compulsive Behavior Scale (YBOCS) before the study initiation and at the 4 th ,8 th , and 12 th weeks in each group. All the patients completed the trial with no dropouts. At the initial evaluation, the risperidone and placebo groups did not differ significantly regarding their YBOCS scores. After 12 weeks of treatment, the OCD symptoms were significantly lower in the risperidone group compared to the placebo group [YBOCS: 5(3) vs. 11(6.5), P -value < 0.001]. The number of patients with more than 35% reduction in YBOCS was significantly higher in the risperidone group compared to the placebo group [20/21 (95.23%) vs. 10/21 (47.61%), P -value = 0.001]. Risperidone could effectively reduce OCD symptoms in BD patients. The treatment was safe and well tolerated.

There is a growing concern about the inappropriate use of prescription drugs in correctional facilities because of the impact on mental and physical health, drug interactions, risk of overdoses, and drug-related deaths. This study systematically examines the prevalence of abuse and misuse of prescription medications in correctional facilities and factors associated among adult individuals who are incarcerated. A systematic search was performed including articles in English, up to 31 August 2024. Fourteen relevant studies were included. The most reported prescription drugs in custodial settings were opioid substitution treatments, opioid and non-opioid analgesics, and gabapentinoids. Inappropriate use of benzodiazepines resulted also to be relevant. Inconsistency in the definition of abuse and misuse as well as the important heterogeneity in population characteristics and study designs prevent us to draw definitive conclusions as regards the prevalence of abuse and misuse of prescription treatments in custodial settings. Few and inconsistent correlations emerged from available literature. Monitoring inappropriate use of prescription medicines in correctional facilities is warranted. In particular, institutions, policy-makers, and healthcare professionals should jointly provide appropriate intervention strategies. Future research should be taken into account the important limitations of the existing literature.