Neurobehavioral research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is multifaceted with different experimental tasks measuring different subprocesses, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD.

We investigated inhibition with the stop signal task (SST) and interference with the Eriksen Flanker task, and related performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate–glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel.

We found slower processing of complex stimuli in the Flanker task in GD (P < .001, η2p = 0.78), and no group differences in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = 0.92, P = .001). Larger positive correlations were found for those with GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, P = .004), as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, P = .03), indicating general Glx-related error processing deficits. Both groups expressed equivalent positive correlations between posterror slowing and Glx/Cr in the right dlPFC (GD: r = 0.74, P = .02; non-GD: r = .71, P = .01).

Inhibition and interference impairments are reflected in dACC baseline metabolite levels and error processing deficits in GD.

Increasing research is stressing the importance of identifying autistic traits (ATs) in clinical and general populations. University students may be a group at higher risk for the presence of ATs. Recently, specific attention has been paid to camouflaging strategies used by subjects in the autism spectrum in order to cope with the social environment. The aim of this work was to evaluate the prevalence of ATs and camouflaging behaviors in a population of University students.

Subjects were requested to anonymously fill out through an online form the Adult Autism Subthreshold Spectrum and the Camouflaging AT Questionnaire.

ATs were more represented among males and among students of specific fields of study. Camouflaging behaviors were significantly more frequent among subjects with more severe autism spectrum symptoms, without differences depending from sex.

Our study confirms the strong association between ATs and camouflaging behaviors and the relationship between ATs, sex, and specific fields of study.

Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.

This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).

Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.

IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.

To investigate the association between cognitive impairment and hospitalizations, quality of life and satisfaction with life among patients with schizophrenia.

A point-in-time survey was conducted between July and October 2019 via the Adelphi Schizophrenia Disease Specific Programme across the United States of America. Patients were stratified as mild or severe based on the level of cognitive impairment reported by their psychiatrist (normal, mild = mild; moderate, severe, very severe = severe). Multiple regression analysis was used to model the association between cognitive impairment and outcomes, adjusting for baseline characteristics.

Data were provided by 124 psychiatrists for 651 mildly and 484 severely impaired patients with schizophrenia; PSCs were completed by 349 mildly and 206 severely impaired patients. Severe cognitive impairment was associated with increased odds of hospitalization due to schizophrenia relapse since diagnosis (2.10 odds ratio [OR], P = .004) and within 12 months (1.95 OR, P < .001) compared to mild impairment. Moreover, patients with severe cognitive impairment had poorer quality of life according to the EuroQoL 5-dimension (EQ-5D) Health Index (−0.085 coefficient, P < .001) and EQ-5D Visual Analogue Scale (−6.24 coefficient, P = .041) compared to patients with mild cognitive impairment. Severe cognitive impairment was also associated with lower overall life satisfaction according to the Quality-of-Life Enjoyment and Satisfaction Questionnaire (−8.13 coefficient, P = .006) compared to mild cognitive impairment.

Schizophrenia patients with severe cognitive impairment had more hospitalizations due to relapse than patients with mild cognitive impairment. Additionally, patients with severe cognitive impairment had significantly lower quality of life and overall satisfaction with life compared to patients with mild cognitive impairment.

Sunovion Pharmaceuticals

Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates.

Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale.

Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed.

Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.

The extent to which obsessive–compulsive and related disorders (OCRDs) are impulsive, compulsive, or both requires further investigation. We investigated the existence of different clusters in an online nonclinical sample and in which groups DSM-5 OCRDs and other related psychopathological symptoms are best placed.

Seven hundred and seventy-four adult participants completed online questionnaires including the Cambridge–Chicago Compulsivity Trait Scale (CHI-T), the Barratt Impulsiveness Scale (BIS-15), and a series of DSM-5 OCRDs symptom severity and other psychopathological measures. We used K-means cluster analysis using CHI-T and BIS responses to test three and four factor solutions. Next, we investigated whether different OCRDs symptoms predicted cluster membership using a multinomial regression model.

The best solution identified one “healthy” and three “clinical” clusters (ie, one predominantly “compulsive” group, one predominantly “impulsive” group, and one “mixed”—“compulsive and impulsive group”). A multinomial regression model found obsessive–compulsive, body dysmorphic, and schizotypal symptoms to be associated with the “mixed” and the “compulsive” clusters, and hoarding and emotional symptoms to be related, on a trend level, to the “impulsive” cluster. Additional analysis showed cognitive-perceptual schizotypal symptoms to be associated with the “mixed” but not the “compulsive” group.

Our findings suggest that obsessive–compulsive disorder; body dysmorphic disorder and schizotypal symptoms can be mapped across the “compulsive” and “mixed” clusters of the compulsive–impulsive spectrum. Although there was a trend toward hoarding being associated with the “impulsive” group, trichotillomania, and skin picking disorder symptoms did not clearly fit to the demarcated clusters.

Schizophrenia is associated with health, social, and financial burdens for patients, caregivers, and society. Major systemic changes, reforms, and technological advances have happened in the USA since the prior estimate of the societal cost of schizophrenia, $155.7B in 2013. This study analyzes the most recent data and literature to update this estimate.

Direct and indirect costs associated with schizophrenia in the US in 2019 were estimated using a prevalence-based approach (ICD-10 codes: F20, F25). Direct healthcare costs were assessed retrospectively using a matched cohort design in the IBM Watson Health MarketScan Commercial, Medicare, and Medicaid databases from October 1, 2015, through December 31, 2019. Patients were matched to controls on demographics, insurance type, and index year. Direct nonhealthcare costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life years lost. Cost offsets were applied to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD.

The estimated excess economic burden of schizophrenia in the US in 2019 was $330.6B, including $62.3B in direct healthcare costs (19%), $19.7B in direct nonhealthcare costs (5%), and $251.9B in excess indirect costs (76%). The largest drivers of indirect costs were caregiving ($112.3B), premature mortality ($77.9B), and unemployment ($54.2B).

The estimated societal burden of schizophrenia in the USA in 2019 was $330.6B, which represented a 93.5% increase from 2013 to 2019, after accounting for inflation. This study underscores the increasing and apparent burden of schizophrenia not only on the patient, but also on caregivers and society.

Sunovion Pharmaceuticals

Highlighting the relationship between obsessive–compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new “tic-related” specifier for OCD, ie, obsessive–compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics.

A sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response.

The remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement.

Although remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

To provide evidence to the link between serotonin (5-HT), energy metabolism, and the human obese phenotype, the present study investigated the binding and function of the platelet 5-HT transporter (SERT), in relation to circulating insulin, leptin, and glycolipid metabolic parameters.

Seventy-four drug-free subjects were recruited on the basis of divergent body mass index (BMIs) (16.5-54.8 Kg/m2). All subjects were tested for their blood glycolipid profile together with platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th, 2019.

The [3H]-Par Bmax (fmol/mg proteins) was progressively reduced with increasing BMIs (P < .001), without changes in affinity. Moreover, Bmax was negatively correlated with BMI, waist/hip circumferences (W/HC), triglycerides (TD), glucose, insulin, and leptin, while positively with high-density lipoprotein (HDL) cholesterol (P < .01). The reduction of 5-HT uptake rate (Vmax, pmol/min/109 platelets) among BMI groups was not statistically significant, but Vmax negatively correlated with leptin and uptake affinity values (P < .05). Besides, [3H]-Par affinity values positively correlated with glycemia and TD, while [3H]-5-HT reuptake affinity with glycemia only (P < .05). Finally, these correlations were specific of obese subjects, while, from multiple linear-regression analysis conducted on all subjects, insulin (P = .006) resulting negatively related to Bmax independently from BMI.

Present findings suggest the presence of a possible alteration of insulin/5-HT/leptin axis in obesity, differentially impinging the density, function, and/or affinity of the platelet SERT, as a result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets, and adipose tissue. Furthermore, they support the foremost cooperation of peptides and 5-HT in maintaining energy homeostasis.

Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).

Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).

Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.

The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.

Functional cognitive disorders (FCD) are an important differential diagnosis of neurodegenerative disease. The utility of suggested diagnostic features has not been prospectively explored in “real world” clinical populations. This study aimed to identify positive clinical markers of FCD.

Adults with cognitive complaints but not dementia were recruited from memory, neurology, and neuropsychiatry clinics. Participants underwent structured interview, Mini International Neuropsychiatric Interview, Montreal Cognitive Assessment, Luria 3-step, interlocking fingers, digit span and Medical Symptom Validity Test, Patient Health Questionnaire 15, Hospital Anxiety and Depression Scale, Multifactorial Memory Questionnaire, and Pittsburgh Sleep Quality Inventory. Potential diagnostic variables were tested against expert consensus diagnosis using logistic regression.

FCD were identified in 31/49 participants. Participants with FCD were younger, spoke for longer when prompted “Tell me about the problems you’ve been having,” and had more anxiety and depression symptoms and psychiatric diagnoses than those without FCD. There were no significant differences in sex, education, or cognitive scores. Younger age and longer spoken response predicted FCD diagnosis in a model which explained 74% of diagnostic variability and had an area under the curve (AUC) of 94%.

A detailed description of cognitive failure is a sensitive and specific positive feature of FCD, demonstrating internal inconsistency between experienced and observed function. Cognitive and performance validity tests appear less helpful in FCD diagnosis. People with FCD are not “worried well” but often perform poorly on tests, and have more anxiety, depression, and physical symptoms than people with other cognitive disorders. Identifying diagnostic profiles is an important step toward parity of esteem for FCDs, as differential diagnoses of neurodegenerative disease and an independent target for clinical trials.

Extrapyramidal symptoms (EPS) affect 15% to 30% of patients with schizophrenia treated with antipsychotics and have been associated with poor patient outcomes.

To examine the incidence and economic burden of EPS in patients with schizophrenia initiating treatment with atypical antipsychotics (AAPs).

Patients with schizophrenia newly initiating AAPs with no prior EPS were identified in the MarketScan Commercial and Medicare Supplemental database from January 1, 2012 to December 31, 2018. Incidence of EPS (new diagnosis or medication) was assessed in the year following AAP initiation. Patients were classified as developing (EPS cohort) or not developing (non-EPS cohort) EPS. All-cause and schizophrenia-related healthcare resource use and costs were compared between cohorts over the year following the first EPS claim (EPS) or randomly assigned index date (non-EPS). Multivariate models were developed for total healthcare costs and inpatient admissions.

A total of 3558 patients qualified for the study; 22.1% developed EPS in the year following AAP initiation (incidence: 26.9 cases/100-person-years). Multivariate analyses demonstrated that EPS patients had a 34% higher odds of all-cause (OR:1.3361, 95% CI:1.0770-1.6575, P < .01) and 84% increased odds of schizophrenia-related (OR:1.8436, 95% CI:1.0434-2.4219, P < .0001) inpatient admissions, as well as significantly higher all-cause (EPS: $26,632 vs non-EPS: $21,273, P < .001) and schizophrenia-related (EPS: $9018 vs non-EPS: $4475, P < .0001) total costs compared to the non-EPS cohort.

Approximately 20% of patients developed EPS in the year following AAP initiation. The significant increases in healthcare resource utilization and costs in the EPS cohorts highlight the need for treatments that effectively target schizophrenia symptoms while reducing the risk of EPS.

Sunovion Pharmaceuticals

Individuals with internet gaming disorder (IGD) are generally characterized by impaired executive control, persistent game-craving, and excessive reward-seeking behaviors. However, the causal interactions within the frontostriatal circuits underlying these problematic behaviors remain unclear. Here, spectral dynamic causal modeling (spDCM) was implemented to explore this issue.

Resting-state functional magnetic resonance imaging data from 317 online game players (148 IGD subjects and 169 recreational game users (RGUs)) were collected. Using independent component analysis, we determined six region of interests within frontostriatal circuits for further spDCM analysis, and further statistical analyses based on the parametric empirical Bayes framework were performed.

Compared with RGUs, IGD subjects showed inhibitory effective connectivity from the right orbitofrontal cortex (OFC) to the right caudate and from the right dorsolateral prefrontal cortex to the left OFC; at the same time, excitatory effective connectivity was observed from the thalamus to the left OFC. Correlation analyses results showed that the directional connection from the right OFC to the right caudate was negatively associated with addiction severity.

These results suggest that the disrupted causal interactions between specific regions might contribute to dysfunctions within frontostriatal circuits in IGD, and the pathway from the right OFC to the right caudate could serve as a target for brain modulation in future IGD interventions.

Many people present to health services with concern about cognitive symptoms. In a significant proportion those symptoms are not the result of pathologically defined brain disease. In some they are part of a functional cognitive disorder (FCD). We assessed the frequency of cognitive lapses in a non-clinical sample in order to consider the utility of frequency of cognitive lapses in diagnosing cognitive disorders.

Healthy adults, who had never sought help for cognitive symptoms, completed a questionnaire, distributed via social media, about self-evaluation of cognitive function, frequency of cognitive lapses, and use of memory aids, including Schmitdke and Metternich’s functional memory disorder (FMD) inventory.

One hundred and twenty-four adults, aged 18–59 (median 23), most with further or higher education, responded. Thirty-one (25%) reported “fair” or “poor” memory. Forty-eight (39%) reported memory worse than 5 years ago, and 30 (24%) reported memory worse than others the same age. Participants endorsed a mean 13/18 specific cognitive lapses at least monthly. One hundred and eleven (89%) scored ≥4, the suggested cutoff for the FMD inventory.

Cognitive lapses described in FCDs are common in highly educated adults. The high frequency of lapses in this healthy population suggests self-reported frequency of lapses alone cannot discriminate FCDs from “normal” experiences. Further research is required to clarify the role of abnormal metacognition in FCD. Better understanding of the factors moderating subjective interpretation of cognitive failures will also aid development of better clinical risk-stratification methods in people concerned about future dementia.

Despite the prevalence of antidepressant-related sexual side effects, comparisons of treatments for these problematic side effects are lacking.

To address this, we performed a systematic review and Bayesian network meta-analysis to compare interventions for antidepressant-induced sexual dysfunction in adults. Using PubMed and clinicaltrials.gov, we identified published and unpublished prospective treatment trials from 1985 to September 2020 (primary outcome: the Arizona sexual experience scale [ASEX] score). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

We identified 57 citations (27 randomized controlled trials, 66 treatment arms, 27 open-label trials, and 3 crossover trials) that evaluated 33 interventions (3108 patients). In the systematic review, 44% (25/57) of trials reported successful interventions; this was more common in open-label (70%, 19/27) compared to placebo-controlled studies (22%, 6/27). In the meta-analysis of placebo-controlled studies that used the ASEX (N = 8), pycnogenol was superior to placebo (standardized mean difference: −1.8, 95% credible interval [CrI]: [−3.7 to 0.0]) and there was evidence that, at a 6% threshold, sildenafil improved sexual dysfunction (standardized mean difference: −1.2, 95% CrI [−2.5 to 0.1]). In the meta-analysis including single-arm studies (15 studies), treatment response was more common with sildenafil, tianeptine, maca, tiagabine, and mirtazapine compared to placebo, but these differences failed to reach statistical significance.

While heterogeneity across randomized controlled trials complicates identifying the single best intervention, multiple trials suggest that sildenafil ameliorates antidepressant-induced sexual dysfunction. More randomized controlled trials are needed to examine the putative efficacy of other interventions.

Cotard’s syndrome is a nihilistic delusion where the individual believes they are dead, partly dead, or replaced by an animal. The delusion that their body has been replaced by a purely inanimate azooic (but physical entity), such as a robot or a droid, has not hitherto been described.

Case study: This 60-year-old, right-handed, female, with a past history of schizophrenia presented with complaints of depression, irritability, and anger. When confronted with commitment papers signed by her father, she denied their truthfulness, insisting that he had been replaced by an imposter. This belief persisted unabated, despite treatment with 20 mg of haloperidol per day. Over time, she expressed the belief that she had been replaced by another person, whom she refused to identify. The following day she refused all food and water proclaiming that she had died and been replaced by a machine revealing, “I am not her. I am a robot.” Soon thereafter she developed tremulousness, stiffness, and rigidity. After haloperidol was decreased and benztropine started, these parkinsonism symptoms subsided, but her delusions persisted.

Abnormalities in physical examination: General: decreased blink frequency. Neurologic examination: Mental status examination: bradyphrenia, hypoverbal, blunted affect. Oriented ×2. Motor examination: bradykinetic, cogwheel rigidity in both upper extremities. Gait examination: slow shuffling gait, reduced bilateral arm swing. Cerebellar examination: resting tremor in both upper extremities at 3 cycles per second. Other: EEG: focal sharp transients in the left temporal region. MRI with and without contrast: normal. Toxicological, metabolic, endocrine screening: normal.

This illustrated sequential presentations of three delusions of misidentification. Upon presentation, she exhibited Capgras syndrome, the delusional belief that a familiar person has been replaced by a double. The nidus for this may have been the discovery that her father had signed her commitment papers. This was followed by the belief she was a double of herself, which is the syndrome of Reverse Subjective Doubles. Finally, she manifested Cotard’s syndrome in a previously undescribed manner, believing she had died and become a robot. Cotard’s and Capgras syndromes are known to present sequentially rather than concurrently, whereas the patient presented concurrently with all three syndromes. Drug-induced parkinsonism may have made the patient subjectively feel stiff, which she interpreted as being rigid like a robot. She was bradykinetic, did not eat or drink, and had rigidity, suggesting that these were somatic manifestations of her underlying delusion of being a robot or alternatively, may have been the somatic nidus for the delusion. Those who present with Cotard’s syndrome warrant evaluation for underlying medical conditions, serving as a substrate for this delusion.

No funding

Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia.

Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score.

About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104.

In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.