Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia.

This was a multicenter, open-label, flexible-dose study of cariprazine 3–9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3–9 mg/d) and 4 weeks of safety follow-up.

A total of 586 patients received open-label cariprazine treatment, ~39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable.

Long-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.

Compulsivity refers to a tendency toward repetitive habitual behaviors. Multiple disorders have compulsive symptoms at their core, including substance use disorders, gambling disorder, and obsessive-compulsive disorder. The aim of this study was to validate a scale for the objective, transdiagnostic measurement of compulsivity.

The 15-item Cambridge–Chicago Compulsivity Trait Scale (CHI-T) was developed for the rapid but comprehensive measurement of compulsivity. Adults aged 18–29y were recruited using media advertisements, and completed the CHI-T in addition to demographic, clinical, and cognitive assessment. The validity and psychometric properties of the scale were quantified.

A total of 112 participants completed the study. The scale yielded a normal distribution with very few outliers. It had excellent psychometric properties, with high internal consistency (Cronbach’s alpha=0.8), and excellent convergent validity against gold-standard assessments of compulsive symptoms (each p<0.001 for gambling disorder, obsessive-compulsive, and substance use disorder symptoms). Total scores on the scale correlated significantly with less risk-adjustment on the decision-making task (rigid response style), and divergent validity was confirmed against other cognitive domains (response inhibition and executive planning). The above significant findings withstood Bonferroni correction. Factor analysis suggested the existence of two latent factors: one related mainly to reward-seeking and the need for perfection, and the other relating to anxiolytic/soothing features of compulsivity.

The CHI-T, a scale designed to measure transdiagnostic compulsivity, appears to show excellent psychometric properties in a normative population and merits further investigation in the context of clinical patient populations, including in treatment trials.

Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH).

Categorical efficacy and tolerability data were extracted from the clinical trial databases of the double-blind placebo-controlled studies of pimavanserin in persons with PDP. NNT and NNH values were calculated with their respective 95% confidence intervals. The likelihood to be helped or harmed (LHH) was then calculated contrasting therapeutic response versus discontinuation because of an adverse event.

NNT values for pimavanserin 34 mg/d versus placebo for several definitions of clinical response are <10, and as robust as 4. NNH values for tolerability outcomes for pimavanserin 34 mg/d (as well as for doses that range from 8.5 to 51 mg/d) are >10, and/or are not statistically significant, and/or show an advantage for pimavanserin over placebo (such as for postural hypotension). In terms of LHH, pimavanserin 34 mg/d is about five times more likely to result in clinical response (as measured by a ≥3 point decrease from baseline on the Scale for the Assessment of Positive Symptoms adapted for Parkinson’s disease) versus discontinuation due to an adverse event.

Using the metrics of NNT, NNH, and LHH, pimavanserin 34 mg/d for the treatment of PDP appears to have a compelling benefit/risk profile.

Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.

Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.

Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.

AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

We aimed to determine whether individuals with obsessive-compulsive disorder (OCD) and demographically matched healthy individuals can be clustered into distinct clinical subtypes based on dimensional measures of their self-reported compulsivity (OBQ–44 and IUS–12) and impulsivity (UPPS–P).

Participants (n=217) were 103 patients with a clinical diagnosis of OCD; 79 individuals from the community who were “OCD-likely” according to self-report (Obsessive-Compulsive Inventory–Revised scores equal or greater than 21); and 35 healthy controls. All data were collected between 2013 and 2015 using self-report measures that assessed different aspects of compulsivity and impulsivity. Principal component analysis revealed two components broadly representing an individual's level of compulsivity and impulsivity. Unsupervised clustering grouped participants into four subgroups, each representing one part of an orthogonal compulsive-impulsive phenotype.

Clustering converged to yield four subgroups: one group low on both compulsivity and impulsivity, comprised mostly of healthy controls and demonstrating the lowest OCD symptom severity; two groups showing roughly equal clinical severity, but with opposing drivers (i.e., high compulsivity and low impulsivity, and vice versa); and a final group high on both compulsivity and impulsivity and recording the highest clinical severity. Notably, the largest cluster of individuals with OCD was characterized by high impulsivity and low compulsivity. Our results suggest that both impulsivity and compulsivity mediate obsessive-compulsive symptomatology.

Individuals with OCD can be clustered into distinct subtypes based on measures of compulsivity and impulsivity, with the latter being found to be one of the more defining characteristics of the disorder. These dimensions may serve as viable and novel treatment targets.

Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients.

A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson’s chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable.

14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables.

Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.

Emotional crying is hypothesized to serve intra- and interpersonal functions. Intrapersonal functions are assumed to facilitate the capacity to recover from emotional distress, thus promoting well-being. Interpersonal functions are postulated to have a major impact on social functioning. We hypothesized that non-criers would have lower well-being and poorer social functioning than criers.

Study participants included 475 people who reportedly lost the capacity to cry and 179 “normal” control criers. Applied measures assessed crying, well-being, empathy, attachment, social support, and connection with others. Prevalence estimates of not crying by gender were obtained from a panel survey of 2,000 Dutch households.

In the main survey, tearless cases had less connection with others, less empathy, and experienced less social support, but were equal in terms of well-being. They also reported being less moved by emotional stimuli and had a more avoidant and less anxious attachment style. In multivariate analyses, being male, having an avoidant attachment style, and lacking empathy were independent predictors of tearlessness. Some 46.1% felt that not being able to cry affected them negatively; however, despite these findings, only 2.9% had sought any kind of professional help. Loss of the capacity to cry occurred in 8.6% of the men and 6.5% of the women in the large panel survey.

Despite reduced empathy, less connection with others, and a more avoidant/less anxious attachment type, well-being is maintained in tearless people. Additional clinical and therapeutic investigations of tearlessness may lead to clarification of bidirectional associations between psychiatric disorders (e.g., alexithymia, posttraumatic stress disorder, psychopathy) and tearlessness.

Transient fluctuation of smell concurrent with phantosmia has not been reported. Four such cases are presented.

Case 1: A 27-year-old left handed (pathological) female, 7 years prior to presentation, noted constant olfactory hallucinations of dried blood and rotten sour eggs, level 8/10 in intensity.

Results: Without phantosmia: Alcohol Sniff Test (AST): 14 (hyposmia). Brief Smell Identification Test (BSIT): 10 (normosmia). Retronasal Smell Index: 0 (abnormal).

With phantosmia: AST: 1 (anosmia). BSIT: 12 (normosmia). Retronasal Smell Index: 0 (abnormal). Normal 72-hour EEG and MRI.

Case 2: A 19 year old right-handed woman presented with a 4 month history of unpleasant, fruity, rotten phantosmia occurring three times a day, 6-7/10 in intensity.

Results: Without phantosmia: Pocket Smell Test (PST): 3 (normosmia). AST: 30 (normosmia). With phantosmia: AST: 13 (hyposmia). CT scan: normal. MRI: normal.

Case 3: A 40 year old right-handed female presented with ashtray/cigarette phantosmia , occurring 10 times a day, lasting seconds to all day, 10/10 in intensity. Her sense of smell is normal except when the phantosmia is present, during which time it decreases to 70% of normal.

Results: Without phantosmia: BSIT: 11 (normosmia). AST: 30 (normosmia). With phantosmia: AST: 11 (hyposmia). PST: 3 (normosmia). EEG: normal. MRI: few subcortical white matter hyperintensities on flair imaging.

Case 4: A 60 year old right handed male with type 1 diabetes mellitus presented with four months of phantosmia of sweet tobacco, level 8/10 in severity, involves both nostrils, lasting 10 seconds and occurring two times a day. Over time, the hallucinated odor changed to a soapy smell 2-3/10 in intensity.

Results: Without phantosmia: AST: 6 (hyposmia). BSIT: 8 (hyposmia). With phantosmia: AST: 1 (anosmia). PST: 2 (hyposmia). CT scan: normal.

Olfactory ability should be assessed in those with phantosmia, both during and in the absence of hallucinated odors, to detect transient olfactory deficits in order to direct treatment towards this condition.