Treatment options are limited for depressive episodes in patients with bipolar II disorder. This post hoc analysis evaluated the efficacy of lumateperone in three pooled short-term, Phase 3 studies in patients with a major depressive episode (MDE) associated with bipolar II disorder.

This post hoc analysis pooled data from patients (18–75 years) with DSM-5 diagnosed bipolar II disorder experiencing an MDE in randomized, double-blind, placebo-controlled studies of lumateperone 42 mg monotherapy (Study 401, Study 404) and adjunctive therapy to lithium or valproate (Study 402). Primary and key secondary outcomes were change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total and Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) scores. Safety was also assessed.

Lumateperone significantly improved MADRS Total score at Day 43 in the bipolar II population (placebo, n = 87; lumateperone, n = 87; least squares mean difference vs. placebo [LSMD], −4.0; P < .05). In the bipolar II population, lumateperone significantly improved CGI-BP-S Total (LSMD, −1.0; P < .05), Depression (LSMD, −0.5; P < .05), and Overall Bipolar Illness scores (LSMD, −0.5; P < .05) compared with placebo at Day 43. No new safety signals were identified, with minimal risk of extrapyramidal symptoms, cardiometabolic abnormalities, or prolactin elevation.

Lumateperone 42 mg monotherapy or adjunctive therapy significantly improved symptoms of depression and disease severity in patients with bipolar II disorder across Phase 3 studies. Lumateperone was generally well tolerated. These results support lumateperone 42 mg to treat MDEs associated with bipolar II disorder.

Much work has been done on the role of trauma in obsessive–compulsive disorder (OCD), but the relationship between stressful life events (SLEs) and the onset of OCD remains poorly studied. This study aims to summarize the evidence about the association between SLEs and OCD development.

For this systematic review, we searched PubMed, Web of Science, Scopus, and PsycINFO databases for studies published from the database’s inception to December 12, 2024. We included studies investigating the prevalence of SLEs among individuals diagnosed with OCD compared to other psychiatric disorders or healthy controls.

Seven studies met the inclusion criteria and were incorporated. Two studies found that OCD patients suffered more SLEs than healthy controls in the year before the onset of OCD. Two of the included studies showed a higher occurrence of SLEs across the patients’ lifetime before the onset of OCD. Three studies were comparable and, therefore, meta-analyzable. Together, they revealed that SLEs in the year before the onset of OCD were associated with a small yet positive pooled effect size.

Our review suggests that SLEs may be highly represented among people with OCD both in the year preceding the disorder’s onset and throughout their lifetime.

Obsessive-compulsive disorder (OCD) is a significantly disabling and difficult-to-treat psychiatric disorder. Non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been increasingly used in the management of OCD. This study aimed to compare the efficacy of early augmentation with low-frequency rTMS (LF-rTMS) and continuous theta burst stimulation (cTBS) in improving psychopathology in OCD patients.

The study design was a parallel-group, double-blind, randomized clinical trial. The study recruited 46 OCD patients who were randomly allocated to receive either LF-rTMS or cTBS (23 patients in each group) following the computer-generated random table method. All participants were rated on YBOCS, HAM-A, and HAM-D at baseline and third week and sixth weeks. These patients received a total of 15 sessions of LF-rTMS or cTBS stimulation once daily for 5 consecutive days in a week for 3 consecutive weeks over the right dorso-lateral pre-frontal cortex (DLPFC) area.

There was a statistically significant improvement in the total YBOCS score for both the LF-rTMS group and the cTBS group at the end of the third and sixth week when compared with their baseline scores. However, there was no statistically significant difference between the 2 groups in terms of the improvement in the total YBOCS score, as well as the total scores for the HAM-A and HAM-D during the follow-up periods.

The study results suggest that both LF-rTMS and cTBS were equally effective in managing OCD patients as an early augmentation strategy.

To investigate whether anxiety reductions attributed to healing crystals reflect placebo responses driven by conditioning and belief-related biases rather than specific therapeutic effects.

In a randomized, controlled study, 138 adults were classified as believers or nonbelievers in crystal efficacy and assigned to rose quartz (experimental) or a visually matched placebo. Participants followed a standardized 14-day protocol. Anxiety was assessed pre- and post-intervention with the Beck Anxiety Inventory and the Spanish Kuwait University Anxiety Scale. Multilevel analyses of variance (ANOVA) and Bayesian models were used to evaluate main effects, interactions, and evidence for treatment specificity.

Anxiety reductions occurred only among believers, regardless of crystal assignment. No differences were detected between groups in primary outcomes, and improvements did not exceed the magnitudes typically associated with placebo responses. Bayesian estimates favored the null hypothesis for specific treatment effects. Preexisting belief strongly predicted perceived efficacy and symptom change, consistent with causal illusions plausibly shaped by conditioning mechanisms. Nonbelievers showed no reliable improvement.

Healing crystals did not demonstrate anxiolytic effects beyond those of the placebo. Symptom change was mediated by expectancy and conditioning, particularly in individuals inclined toward intuitive or magical thinking. Although nonspecific, context-dependent factors—such as elements of the therapeutic alliance—may amplify placebo responsiveness in clinical settings, these findings do not support attributing inherent therapeutic value to crystals. Future work should delineate how expectations, clinician-patient rapport, and related variables interact to shape placebo response and how such mechanisms might be ethically leveraged to enhance evidence-based care without promoting pseudoscientific practices.

DNA methylation plays a crucial role in gene regulation and has been implicated in various neuropsychiatric disorders, including alcohol use disorder (AUD). The rs27072 polymorphism within the SLC6A3 gene has been studied in addictive disorders; however, its role in epigenetic modifications remains unclear. This study investigates the methylation levels of CpG sites near rs27072 and their potential associations with AUD, personality traits, and environmental stressors.

One hundred twenty-four male participants (66 patients with AUD and 58 controls) were analyzed for DNA methylation at CpG islands proximal to the rs27072 locus. The personality traits and life stress events were assessed in all participants.

AUD patients had a lower methylation level than healthy controls (p = 0.003 for total average). However, the results changed to borderline significance after adjusting for clinical covariates in the analysis (p = 0.042), and the genotype at rs27072 did not modulate the methylation levels. There is high novelty seeking (p < 0.001), and more bad life events in patients with AUD than healthy controls (p < 0.001). Additionally, no significant correlations were found between methylation levels and personality traits or life stress scores (p > 0.05).

The methylation of the SLC6A3 gene may be marginally associated with AUD; however, the rs27072 genotype, personality, and life stress may not be directly linked to epigenetic modifications. Cross-sectional epigenetic studies may not establish causality; future studies with larger, more diverse cohorts and longitudinal designs are warranted to elucidate the complex interplay in AUD pathophysiology.

The origins and treatment-target-related mechanisms of schizophrenia remain to be fully understood. Pharmacological and non-pharmacological treatments require expansion and improvements to meet peoples’ needs and goals. Nevertheless, antipsychotics are a cornerstone when managing schizophrenia, being essential for reducing symptom severity, preventing relapse, improving long-term functional outcomes, and reducing premature mortality risk.

This narrative review synthesizes key evidence on the efficacy and risks associated with antipsychotic medications. The concept of effect sizes is introduced, allowing to compare antipsychotics across trials with different rating instruments and across different conditions.

The available evidence in schizophrenia and comparison with medications used for medical conditions counters the sometimes-voiced criticism that antipsychotics “do not work.” Instead, for a substantial group of people with schizophrenia, positive psychotic symptoms and global psychopathology improve witha small-medium effect size of about 0.4 versus placebo. These results are comparable to median effect sizes across commonly used medications for somatic disorders. When patients with initial response are continued on antipsychotics, the effect size increases to 0.9 for relapse prevention, translating into a number needed to treat (NNT) of about 3 to prevent one more relapse versus no treatment. This NNT is 10–20 times higher than that for the prevention of poor outcomes in some common medical conditions.

Despite general efficacy and effectiveness of antipsychotics for schizophrenia, further development is needed regarding preventive interventions and medications with mechanisms other than postsynaptic dopamine receptor blockade, with broader efficacy for positive, negative, cognitive, suicidality, and/or reward dysregulation symptomatology, and the identification of illness mechanism/biomarker-targeting treatments to enhance treatment personalization.