To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD).

Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models.

In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (−12.8 [0.46] vs −10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044).

In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS.

ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management.

A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores.

Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P-scores (0.8186), followed by beta-blockers and NaSSA.

Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement.

Orthorexia nervosa (ON) is characterized by the pursuit of extreme dietary purity due to an exaggerated focus on food quality that could ultimately lead to a new kind of eating disorder. Even though researchers have tried to reach a univocal description of ON, to this date, there is no consensus on its diagnostic criteria, making it considerably more difficult to develop a valid questionnaire for assessing the symptoms of ON and to assess its actual prevalence. The aim of this review was to evaluate and gather scientific evidence about the prevalence of ON in both clinical and non-clinical adult populations, using the main validated scale for ON evaluation.

Electronic databases (PubMed, Scopus, and Web of Science) were reviewed to identify studies in accordance with PRISMA guidelines; at the end of the selection process, 62 studies were included.

Prevalence rates of ON vary greatly due to the differences in psychometric qualities of the tools used and the socio-cultural norms of the countries, with the lowest being obtained with the Dusseldorf orthorexic scale (DOS) (2.6% up to 36.7% in cancer survivor women) and the BOS-T (12.8% up to 34.7%), the greatest variability concerning the two thresholds of the ORTO-15 (14.6% with the >35 threshold and up to 86% with the >40 threshold) and the higher score being reported with the ORTO-11 in post-partum women (87.7%).

Additional research is necessary to support the development of a thorough, sensitive, and valid questionnaire for assessing the symptoms of ON.

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used for treating obsessive-compulsive disorder (OCD). Although several meta-analyses have explored its effectiveness and safety, there is no umbrella review specifically focused on rTMS for OCD. This umbrella review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and analyzed relevant meta-analyses on rTMS for OCD.

Twenty-three articles were identified from PubMed, and after screening, 12 meta-analyses were included in the review. The studies analyzed in the meta-analyses ranged from 10 to 27, with total participants ranging from 282 to 791. The most commonly studied regions were the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and orbito-frontal cortex (OFC).

The majority of the meta-analyses consistently supported the effectiveness of rTMS in reducing OCD symptoms when applied to the DLPFC and SMA. Encouraging results were also observed when targeting the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) through deep transcranial magnetic stimulation (dTMS). However, there was a high level of heterogeneity in the findings of nine out of 12 meta-analyses.

In conclusion, existing evidence suggests that rTMS targeting the DLPFC and SMA consistently reduces OCD symptoms, but targeting the mPFC and ACC through dTMS shows variable results. However, the high heterogeneity in the study findings indicates a need for further research and standardization in the field.

Postpartum depression (PPD), now referred to as perinatal depression, is a prevalent and debilitating mood disorder that reduces health-related quality of life (HRQoL) and psychosocial functioning. Esketamine, which is efficacious in adults with treatment-resistant depression and individuals with depression and suicidality, is also analgesic in pain management during childbirth labour. Herein, we investigate the efficacy of prophylactic esketamine in reducing the incidence of PPD.

We performed a systematic review (i.e., PubMed, Scopus, and Ovid databases; inception to January 22, 2024) of randomized controlled trials that investigated the use of esketamine for PPD. We delimited our search to studies that prespecified the prevention of PPD with esketamine as the primary outcome. A meta-analysis was performed on PPD incidence rates using a random effects model.

Our analysis consisted of seven studies that met our eligibility criteria. We found that esketamine was significantly associated with a decreased incidence of PPD diagnosis within one week of childbirth (OR = 0.30, 95% CI = [0.15, 0.60], p = 0.0047). We also observed that esketamine was significantly associated with a decreased incidence of PPD diagnosis between 4 to 6 weeks post-delivery (OR = 0.33, 95% CI = [0.18, 0.59], p = 0.0034).

Our results indicate that esketamine may have preventive antidepressant effects during the postpartum period. The aforementioned points have both mechanistic and clinically meaningful implications for the treatment of PPD.

How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown.

We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models.

Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment (p < 0.001). By week 8, the response for benzodiazepines and SSRIs (p = 0.103) and SNRIs (p = 0.911) did not differ nor did SSRIs and SNRIs differ (p = 0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference − 12.42, CrI: −25.05 to −0.78, p = 0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4 weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders.

Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

Recent literature has suggested that individuals with autism spectrum disorder (ASD) or autistic traits (ATs) would be more likely to encounter traumatic events in their lifetime and to develop post-traumatic stress disorder (PTSD). However, the nature of this relationship has not yet been fully elucidated. The aims of this study were to evaluate the relationship between AT and PTSD and to investigate which specific autistic dimension was more associated with trauma and stress-related symptoms.

A total of 68 subjects with ASD and 64 healthy controls (HCs) were assessed with the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Trauma and Loss Spectrum (TALS) questionnaires. Statistical analyses included Mann–Whitney U test, chi-square test, calculation of Spearman’s coefficients, and logistic regression analysis.

Patients with significant AT reported a 30% rate of PTSD and higher TALS total and domain scores than HCs, among whom no PTSD was found instead. Significant positive correlations were reported between AdAS Spectrum and TALS-SR scores in the whole sample. AdAS Spectrum total scores were statistically predictive of the presence of PTSD. High scores at AdAS Spectrum Hyper-Hyporeactivity to sensory input and Restrictive interest and rumination domains were identified as positive predictors of a probable PTSD.

Compared to HCs, subjects with significant AT are more likely to present symptoms of PTSD. In particular, AT related to ruminative thinking, narrow interests, and sensorial reactivity would seem to predict the presence of post-traumatic stress symptomatology.

The relationship between psychosis and violence is often construed focusing on a narrow panel of factors; however, recent evidence suggests violence might be linked to a complex interplay of biopsychosocial factors among forensic psychiatric patients with psychosis (FPPP). This review describes violence incidents in FPPP, the factors associated with violence, and relevant implications.

This review was conducted following the preferred reporting items for systematic reviews and meta-analyses guideline. Databases, including CINAHL, EMBASE, Medline/PubMed, PsycINFO, and Web of Science, were searched for eligible studies that examined violence among adult FPPP. Screening of reports and data extraction were completed by at least two independent reviewers.

Across the 29 included studies, violence was consistently related to prior contact with psychiatric services, active psychotic symptoms, impulsivity, adverse experiences, and low social support. However, FPPP who reported violence varied in most other biopsychosocial domains, suggesting the underlying combinatorial effects of multiple risk factors for violence rather than individual factors. Variability in violence was addressed by stratifying FPPP into subgroups using composite/aggregate of identifiable factors (including gender, onset/course of illness, system-related, and other biopsychosocial factors) to identify FPPP with similar risk profiles.

There are multiple explanatory pathways to violence in FPPP. Recent studies identify subgroups with underlying similarities or risk profiles for violence. There is a need for future prospective studies to replicate the clinical utility of stratifying FPPP into subgroups and integrate emerging evidence using recent advancements in technology and data mining to improve risk assessment, prediction, and management.

To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF.

Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF.

Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF.

Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.

Healthcare workers (HCWs) were considered a population at risk for developing psychiatric symptoms during the COVID-19 pandemic, such as anxiety, depression, and post-traumatic stress disorder (PTSD). Peritraumatic distress is associated with post-traumatic psychopathological symptoms; however, little is known about how it may affect functioning. The study aimed at evaluating the level of peritraumatic distress in a sample of HCWs during the first wave of the COVID-19 pandemic and at examining the relationship between peritraumatic distress, mental health symptoms, and functioning impairment.

A sample of 554 frontline HCWs were consecutively enrolled in major university hospitals and community services in Italy. The PDI, IES-R, PHQ-9, and GAD-7 were used to assess peritraumatic distress, symptoms of PTSD, depression, and anxiety, respectively, and the WSAS to investigate functioning impairment. PDI scores were higher among females, community services, physicians, and nurses. Furthermore, the PDI correlated significantly with the GAD-7, PHQ-9, IES-R, and WSAS.

In a mediation analysis, the direct effect of PDI on WSAS and the indirect effects through the PHQ-9 and IES-R were statistically significant (P < .001).

Peritraumatic distress reported by HCWs was associated with symptoms of PTSD, depression, and anxiety, but the association with reduced functioning may be only partially mediated through symptoms of depression and PTSD.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.

About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.

The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG.

Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria.

We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis.

Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.

Trichotillomania and skin picking disorder have been characterized as body-focused repetitive behavior (BFRB) disorders (i.e., repetitive self-grooming behaviors that involve biting, pulling, picking, or scraping one’s own hair, skin, lips, cheeks, or nails). Trichotillomania and skin picking disorder have also historically been classified, by some, as types of compulsive self-injury as they involve repetitive hair pulling and skin picking, respectively. The question of the relationship of these disorders to more conventional forms of self-injury such as cutting or self-burning remains incompletely investigated. The objective of this study was to examine the relationship of these two disorders with non-suicidal self-injury (NSSI).

Adults with trichotillomania (n = 93) and skin picking (n = 105) or both (n = 82) were recruited from the general population using advertisements and online support groups and completed an online survey. Participants completed self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed a mental health history questionnaire.

Of the 280 adults with BFRB disorders, 141 (50.1%) reported a history of self-injury independent of hair pulling and skin picking. Participants with a history of self-injury reported significantly worse pulling and picking symptoms (p < .001) and were significantly more likely to have co-occurring alcohol problems (p < .001), borderline personality disorder (p < .001), buying disorder (p < .001), gambling disorder (p < .001), compulsive sex behavior (p < 001), and binge eating disorder (p = .041).

NSSI appears common in trichotillomania and skin picking disorder and may be part of a larger constellation of behaviors associated with impulse control or reward-related dysfunction.