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 World Health Organization (WHO) has defined Post-COVID-19 Condition (PCC) as the onset of symptoms within three months after resolution of an acute SARS-CoV-2 infection, wherein symptoms persist for at least two months and cannot be explained by another medical/psychiatric condition. Persons living with PCC report debilitating symptoms including, but not limited to, depressive symptoms and motivational deficits. The aim of this post-hoc analysis was to evaluate the association between depressive symptoms and motivation in adults with PCC.

We conducted a post-hoc analysis of an 8-week, double-blind, randomized, placebo-controlled trial evaluating adults (18 years or older) in Canada with WHO-defined PCC and cognitive symptoms. This post-hoc analysis is comprised of baseline data that evaluates the association between depressive symptom severity measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) and motivational systems measured by the Behavioral Inhibition System/Behavioral Activation System Questionnaire (BIS/BAS).

There was a statistically significant association between depressive symptoms and BIS (β = -0.041 95% CI [-0.066, -0.016], p<0.05), BAS reward responsiveness (β = 0.043 95% CI [0.012, 0.074], p<0.05), sex (β = -0.137 95% CI [-0.266, -0.008], p<0.05), and confirmed COVID-19 infection (β = 0.196 95% CI [0.061, 0.332], p<0.05).

Depressive symptoms were associated with motivational deficits in persons living with PCC. Optimizing treatment for depressive symptoms may potentially improve aspects of motivational impairment amongst persons with PCC. All patients presenting with MDD and a history of COVID-19 infection should be assessed for the presence of PCC.

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.

This study examined children at the onset of tic disorder (tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the baseline shape and volume of subcortical nuclei, diagnosis, and tic symptom outcomes.

187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder/Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic metric mapping. Linear regression models correlated baseline structural shapes with follow-up TTS while accounting for covariates, with relationships mapped onto structure surfaces.

We found that the NT group had a larger right hippocampus compared to HC. Surface maps illustrate distinct patterns of inward deformation in the putamen and outward deformation in the thalamus for NT compared to controls. We also found patterns of outward deformation in almost all studied structures when comparing the TS group to controls. The NT group also showed consistent outward deformation compared to TS in the caudate, accumbens, putamen, and thalamus. Subsequent analyses including clinical symptoms revealed that a larger pallidum and thalamus at baseline correlated with less improvement of tic symptoms at follow-up.

These observations constitute some of the first prognostic biomarkers for tic disorders and suggest that these subregional shape and volume differences may be associated with the outcome of tic disorders.

Cognitive and psychiatric symptoms have been increasingly reported after severe acute respiratory syndrome coronavirus 2 infection, developing soon after infection and possibly persisting for several months. We aimed to study this syndrome and start implementing strategies for its assessment.

Consecutive patients, referred by the infectious disease specialist because of cognitive complaints after COVID-19, were neurologically evaluated. Neurological evaluation included a cognitive screening test (Montreal Cognitive Assessment, MoCA). Moreover, patients were invited to fill out a general symptom questionnaire and a self-administered multidimensional assessment of psychiatric symptoms, followed by a full psychiatric assessment if scores were above validated cutoffs.

Of 144 referred patients, 101 (mean age 55.2±13.1, 63.4% females) completed the cognitive screening and the self-administered psychiatric questionnaire. Acute infection severity was low for most patients and the most common persisting symptoms were fatigue (92%), sleep problems (69.5%), and headache (52.4%). MoCA outlined cognitive deficits in ≥1 cognitive domain in 34% of patients, mainly in memory and attention. About 60% of patients presented depressive, anxiety, or stress-related symptoms. Psychiatric scale scores significantly correlated with overall symptom burden and MoCA score. No significant correlation was found between MoCA scores and overall symptom burden.

We hypothesize that persistent cognitive complaints after COVID-19 might reflect a concomitant or reactive psychopathological condition, possibly coupled with an infection-related impact on cognitive functions. The application of a combined neurological and psychiatric assessment seems crucial to appraise the nature of post-COVID-19 condition.

Visual release hallucinations are perceptual disturbances that occur in individuals who have experienced vision loss. Almost 50 million people worldwide are believed to experience visual release hallucinations, yet they are profoundly underdiagnosed. Although first described within the Charles Bonnet syndrome, the paradigm underlying this syndrome precludes their consideration in many populations, such as those with underlying psychiatric illness or dementia. Consequently, visual release hallucinations have rarely been studied in patients presenting with psychosis. We conducted a scoping review to determine whether visual-release hallucinations occur in psychotic patients.

The PubMed research database was searched from inception through April 2023. Cases were collected reporting on psychotic patients experiencing suspected visual release hallucinations. Individual treatment courses and responses were extracted.

Thirteen cases compiled from 11 different studies were summarized to provide baseline characteristics and overall trends in treatment response. Most patients did not remit from pharmacological management alone. All patients who received reafferentation therapy remitted, though many were not candidates. Almost half of the patients did not achieve remission.

Visual release hallucinations can manifest in psychosis and may contribute to treatment-resistant psychosis among psychiatric populations. A shift in our understanding of visual release hallucinations may aid their recognition in psychotic patients by shifting the focus toward visual release features. Recognizing release features among patients with hallucinatory conditions may open new treatment avenues for managing patients with psychosis. A preliminary screening index for visual release features is provided to support this shift.

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.

Cognitive and psychiatric symptoms are frequently reported after SARS-CoV-2 infection, but their interplay has been only partially explored. We investigated frequency and severity of psychiatric symptoms in patients with persistent cognitive complaints after COVID-19.

We conducted a cross-sectional study. Neurologists assessed 101 patients reporting cognitive symptoms after COVID-19. Patients were invited to fill a screening battery with self-reported psychometric scales (Depression Anxiety Stress Scales-21, Impact of Event Scale-Revised, Insomnia Severity Index). Patients scoring above validated cut-offs in ≥1 scale were referred to psychiatrists who administered the Mini-International Neuropsychiatric Interview (M.I.N.I.), Hamilton Anxiety (HAM-A), and Hamilton Depression (HAM-D) rating scales and asked to complete the Personality Inventory for DSM-5-Brief Form (PID-5-BF).

Out of the 57 referred patients, 38 (64.4%) accepted to undergo the psychiatric examination. Among these, 18 (47.4%) were diagnosed with adjustment disorder (23.7%), anxiety disorder (10.5%), major depressive disorder (7.9%), and post-traumatic stress disorder (2.6%). Pharmacologic treatment before post-COVID condition (present in 12 patients, 31.6%) was associated with a score above cut-off on the HAM-A and HAM-D scales. A longer duration of untreated psychiatric illness after COVID-19 was associated with worse scores on the same scales. Patients with a higher PID-5-BF total score had a higher probability of receiving a psychiatric diagnosis.

Almost half of patients with post-COVID-19 conditions reporting cognitive symptoms were found to suffer from a psychiatric condition after psychiatric evaluation. The application of a psychiatric screening in a population suffering from long-term effects of COVID-19 can lead to early diagnosis and timely treatment.

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M.

Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12 months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests.

Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively.

Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor outcomes in Parkinson’s disease (PD) but may have adverse long-term effects on specific cognitive domains. The aim of this study was to investigate the association between total electrical energy (TEED) delivered by DBS and postoperative changes in verbal fluency.

Seventeen PD patients undergoing bilateral STN-DBS were assessed with the Alternate Verbal Fluency Battery (AVFB), which includes phonemic (PVF), semantic (SVF), and alternate verbal fluency (AVF) tests, before surgery (T0) and after 6 (T1) and 12 months (T2). Bilateral TEED and average TEEDM were recorded at T1 and T2. For each AVFB measurement, changes from T0 to T1 (Δ-01) and from T0 to T2 (Δ-02) were calculated.

At T1, PVF (p = 0.007) and SVF scores (p = 0.003) decreased significantly. TEED measures at T1 and T2 were unrelated to Δ-01 and Δ-02 scores, respectively. However, an inverse, marginally significant association was detected between the TEEDM and Δ-01 scores for the AVF (p = 0.041, against an αadjusted = 0.025).

In conclusion, the present reports provide preliminary evidence that TEED may not be responsible or only slightly responsible for the decline in VF performance after STN-DBS in PD.

In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.