Bipolar disorder frequently has an early onset, with an estimated 1.8% prevalence of bipolar I disorder in children and adolescents. Childhood onset of bipolar disorder is typically associated with a chronic, severe, and disabling course of illness. Relatively few prospective studies are available that evaluate the long-term efficacy of atypical antipsychotics in achieving and sustaining response or remission in pediatric patients with bipolar depression. Lurasidone has been approved by the FDA as monotherapy for bipolar depression in pediatric patients ages 10–17 years. The aim of the current post-hoc analysis was to evaluate the long-term efficacy of lurasidone in achieving response or remission in children and adolescents with bipolar depression followed over a two-year period.

Patients 10–17 years with bipolar I depression who completed a 6-week double-blind (DB) study of lurasidone vs. placebo were eligible to enroll in a two-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20–80 mg/d) or switched from placebo to lurasidone. Efficacy measures included the Children’s Depression Rating Scale, Revised (CDRS-R) and the Clinical Global Impression, Bipolar Depression Severity scale (CGI-BP-S). Functioning was evaluated utilizing the Clinician-rated Children’s Global Assessment Scale (CGAS) score, with a score >70 indicating no clinically meaningful functional impairment. Responder criteria were met if a patient achieved criteria = 50% reduction from DB baseline in the CDRS-R total score: remission criteria were met if a patient achieved a CDRS-R Total Score =28 and a YMRS total score =8 and CGI-BP-S depression score =3, and a patient was considered to have met recovery criteria if they achieved remission with a CGAS score >70. In addition, a more stringent outcome, sustained remission, was also analyzed, which required a patient to meet remission criteria for =24 consecutive weeks.

A total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) patients completed one year of treatment and 168 (54.9%) patients completed two years of treatment. Responder rates at OL baseline, one year, and two years were: 51.0%, 88.4% and 91.1%, respectively; remission rates were 24.3%, 61.3%, and 75.6%, respectively; and recovery rates were 17.7%, 53.8%, and 73.8%. On a Pearson correlation analysis, there was a strong inverse relationship (r = −0.71) between CDRS-R total score, and global functioning as measured by the CGAS. Sustained remission was achieved by 37.2% of patients at one year and 57% of patients after two years.

In children and adolescents with bipolar depression, up to 2 years of treatment with lurasidone was associated with continued improvement in depressive symptoms, resulting in progressively higher rates of response, remission, recovery, and the more rigorously calculated outcome of sustained remission.

Sunovion Pharmaceuticals Inc.

The current study sought to examine the relationship between documented social media use and suicidality and self-injurious behaviors in adolescents at the time of psychiatric hospitalization.

We retrospectively identified adolescents (aged 12-17 years) hospitalized on an inpatient psychiatric unit during 1 year. Abstracted information included documented social media use, demographic variables, documented self-injurious behaviors, the Patient Health Questionnaire-9, and the Suicide Status Form-II. Logistic regression was implemented to examine the effect of social media use on the risk of self-injurious behaviors and suicidality.

Fifty-six adolescents who used social media were identified and matched with 56 non-social media users. Those with reported social media use had significantly greater odds of self-injurious behaviors at admission (odds ratio, 2.55; 95% confidence intervals, 1.17-5.71; P = .02) vs youth without reported social media use. Adolescents with reported social media use also had greater odds of increased suicidal ideation and suicide risk than those with no reported use, but these relationships were not statistically significant.

Social media use in adolescents with a psychiatric admission may be associated with the risk of self-injurious behaviors and could be a marker of impulsivity. Further work should guide the assessment of social media use as part of a routine adolescent psychiatric history.

Work-related stress presents a significant impact on work performance and physical health. It has been associated with the onset of a multitude of symptoms. The main aim of this investigation is to better understand the impact of post-traumatic stress symptomatology, using a specific self-assessment questionnaire, in subjects experiencing occupational stress with the rationale to address the variegated symptoms expressed by this particular population in a post-traumatic dimensional perspective.

Authors collected socio-demographic, occupational, and clinical data. They utilized Trauma and Loss Spectrum Self Report (TALS-SR), a questionnaire investigating post-traumatic stress symptoms. The population size was 345 subjects who presented at the Occupational Health Department of a university hospital over a 3 years period (2016–2018).

Data analysis revealed 33.9% of subjects who met post-traumatic stress disorder (PTSD) criteria. Gender distribution of this set was (36.4% female, 31% male). A family history or personal history of mental disorders were related to higher scores in almost all TALS-SR domains and were related, respectively, to higher scores of criterion B “intrusion symptoms” (P = .014), criterion D “negative alterations in cognitions and mood” (P = .023), and criterion E “arousal” (P = .033) of PTSD. Differences in TALS-SR scores also emerged based on age and gender.

PTSD symptoms manifest at a significant level in those who experience work-related stress. Personal background of individuals, both in terms of family and personal history for mental disorders, seems to increase their vulnerability to develop post-traumatic stress symptoms. This study suggests the importance of evaluating occupational stress from a post-traumatic stress perspective also at an early stage.

Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.

Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines—including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)—were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.

Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.

Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.

SEP-363856 is a novel psychotropic agent without dopamine D2 receptor occupancy. Although its mechanism of action has not been fully elucidated, preclinical data suggest that agonism at trace amine receptor 1 (TAAR1) and the serotonin 5-H1A receptor contributes to its efficacy. In a double-blind (DB), placebo-controlled study, SEP−363856 demonstrated significant efficacy in the treatment of an exacerbation of schizophrenia (Koblan et al, NEJM 2020; 82:1497–1506). We present results of a 6-month extension study whose aim was to evaluate the safety and effectiveness of longer-term treatment with SEP−363856.

Patients with an acute exacerbation of schizophrenia who completed a 4-week, DB, placebo-controlled, flexible-dose (50 or 75 mg) study of SEP−363856 were given the option to enroll in an extension study in which they were treated, open-label (OL), with flexible doses (25/50/75 mg/d) of SEP−363856 for 26-weeks. The primary outcomes were safety measures; effectiveness outcomes were secondary and included the PANSS total score and the Brief Negative Symptom Scale (BNSS) total score.

A total of 193 patients completed the 4-week DB study, and 156 (80.8%) were dosed in the OL extension study and received at least one dose of SEP−363856 (safety population). Study completer rate was 66.9%; reasons for discontinuation consisted of adverse event (11.5%), withdrawal of consent (10.2%), lack of efficacy (5.1%), and other (6.4%). 15 patients experienced an SAE: schizophrenia (n=11); acute psychosis (N=1); uterine hemorrhage and suicidal ideation (N=1 each); there were no deaths in the study. Individual AEs with an incidence =2% were schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), anxiety (5.1%), somnolence (4.5%), nasopharyngitis (4.5%), nausea (3.8%), irritability (3.2%), influenza (3.2%), weight decreased (3.2%), and prolactin increased (2.6%). On movement scales, minimal mean change from OL-baseline to Week 26 occurred on the Barnes total score (−0.1), AIMS total score (0.0) and SAS score (−0.1). Mean month 6 change from DB baseline in weight was −0.3 kg. No clinically meaningful median changes were observed at week 26 in metabolic laboratory parameters (total and LDL cholesterol, triglycerides, hemoglobin A1c) or in prolactin levels. During 6 months of OL treatment, one patient had an increase in QTcF =60 msec; no patients had a QTcF interval =480 msec. Treatment with SEP−363856 was associated with significant improvement from OL baseline to week 26 in PANSS total score (−22.6) and BNSS total score (−11.3).

Treatment with SEP−363856 was associated with continued improvement from open-label baseline in the PANSS total (−22.6) and BNSS total (−11.3) scores. The most frequently reported adverse events (= 5%) were schizophrenia, headache, insomnia and anxiety. SEP−363856 had minimal effects on weight, lipids, glycemic indices, prolactin, and was associated with minimal risk of extrapyramidal symptom.

Sunovion Pharmaceuticals Inc.

Relatively few studies have assessed the prevalence, correlates, and independent impact on quality of life (QoL) of trichotillomania (TTM) in large samples.

Consecutive participants (N = 7639) were recruited from a cross-sectional web-based study. Sociodemographic data were collected and several validated self-reported mental health measures were completed (Minnesota Impulsive Disorders Interview, Hypomania checklist, Fagerström Test for Nicotine Dependence, Alcohol Use Disorders Identification Test, Early Trauma Inventory Self Report–Short Form, and the Symptom Checklist-90–Revised Inventory). Health-related QoL was assessed with the World Health Organization QoL abbreviated scale (WHOQOL-Bref). Multivariable models adjusted associations to potential confounders.

The sample was predominantly composed of young females (71.3%; mean age: 27.2 ± 7.9 years). The prevalence of probable TTM was 1.4% (95% confidence intervals [CI]: 1.2-1.7), and was more common among females. Participants with probable TTM had a greater likelihood of having co-occurring probable depression (adjusted odds ratio [ORadj] = 1.744; 95% CI: 1.187-2.560), tobacco (ORadj = 2.250; 95% CI: 1.191-4.250), and alcohol (ORadj = 1.751; 95% CI: 1.169-2.621) use disorders. Probable TTM was also independently associated with suicidal ideation (ORadj = 1.917; 95% CI: 1.224-3.003) and exposure to childhood sexual abuse (ORadj = 1.221; 95% CI: 1.098-1.358). In addition, a positive screen for TTM had more impaired physical and mental QoL.

TTM was associated with a positive screen for several psychiatric comorbidities as well as impaired physical and psychological QoL. Efforts towards the recognition and treatment of TTM across psycho-dermatology services are warranted.

The Leuven Affect and Pleasure Scale (LAPS) was developed as an outcome measure in major depressive disorder (MDD) tha treflects patient treatment expectations. The present report investigates whether the LAPS negative affect, the LAPS positive affect, and the LAPS hedonic tone have added value on top of the Hamilton Depression Rating Scale (HAMD) in explaining generic as well as patient-centered outcomes.

A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for MDD were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS, HAMD, Snaith–Hamilton Pleasure Scale (SHAPS), Positive and Negative Affect Scale (PANAS), and Sheehan Disability Scale were administered. The Clinical Global Impression of Improvement (CGI-I) and the Patient Global Impression of Improvement (PGI-I) were also administered at endpoint.

Changes in LAPS negative affect, LAPS positive affect, and LAPS hedonic tone explain 14% of the additional variance in CGI-I, 21% in PGI-I, 37% in cognitive functioning, 32% in overall functioning, 31% in “my life is meaningful,” and 45% in “I feel happy.” Compared to standard scales (PANAS and SHAPS), the LAPS negative affect, LAPS positive affect, and LAPS hedonic tone differentiate better between different levels of CGI-I or PGI-I.

The LAPS has added value (on top of the HAMD) in explaining changes in both generic outcomes (CGI-I/PGI-I) and patient-centered dimensions. The LAPS negative and positive affects and the LAPS hedonic tone differentiate CGI-I and PGI-I scores better than corresponding scales supposed to cover the same domains.

Clinicians who recognize functional neurological disorders (FND) may not share that diagnosis with patients. Poor communication delays treatment and contributes to substantial disability in FND. Diagnostic (ICD-10) coding, one form of medical communication, offers an insight into clinicians’ face-to-face communication. Therefore, quantifying the phenomenon of noncoding, and identifying beliefs and practice habits that reduce coding, may suggest routes to improve medical communication in FND.

We reviewed all pediatric neurology consultations in our hospital from 2017 to 2020, selecting those in which neurologists explicitly stated an FND-related diagnosis (N = 57). We identified the neurological symptoms and ICD-10 codes assigned for each consultation. In parallel, we reviewed all encounters that utilized FND-related codes to determine whether insurers paid for this care. Finally, we assessed beliefs and practices that influence FND-related coding through a nationwide survey of pediatric neurologists (N = 460).

After diagnosing FND, neurologists selected FND-related ICD-10 codes in only 22.8% of consultations. 96.2% of neurologists estimated that they would code for non-epileptic seizure when substantiated by electroencephalography; in practice, they coded for 36.7% of such consultations. For other FND manifestations, neurologists coded in only 13.3% of cases. When presented with FND and non-FND scenarios with equal levels of information, neurologists coded for FND 41% less often. The strongest predictor of noncoding was the outdated belief that FND is a diagnosis of exclusion. Coding for FND never resulted in insurance nonpayment.

Noncoding for FND is common. Most factors that amplify noncoding also hinder face-to-face communication. Research based on ICD-10 coding (eg, prevalence and cost) may underestimate the impact of FND by >fourfold.

The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.

Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.

The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.

The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.

Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.

In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively).

OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.

Sexual response in obsessive–compulsive disorder (OCD) research and practice is overlooked. According to the Dual Control Model, satisfactory sexual response is based upon a balance of sexual excitation and inhibition. The assessment of sexual response in OCD may have clinical implications, such as the integration of sex therapy in psychotherapeutic intervention. The present study was aimed at comparing sexual excitation and inhibition levels between OCD patients and matched control subjects, and investigating whether obsessive beliefs might predict sexual excitation/inhibition.

Seventy-two OCD patients (mean age ± standard deviation [SD]: 34.50 ± 10.39 years) and 72 matched control subjects (mean age ± SD: 34.25 ± 10.18) were included (62.50% men and 37.50% women in both groups). The Obsessive Compulsive Inventory-Revised (OCI-R), the Obsessive Beliefs Questionnaire-46 (OBQ-46), and the Sexual Inhibition/Sexual Excitation Scales (SIS/SES) were administered.

Patients with OCD showed significantly higher levels of sexual excitation, inhibition due to threat of performance failure, and inhibition due to threat of performance consequences than the controls. In addition, the patients with more severe symptoms showed lower excitation than those with less severe symptoms, and those with higher perfectionism had stronger inhibition due to threat of performance failure than those with lower perfectionism.

This is the first study exploring sexual response in OCD according to the Dual Control Model. Sexual response is an impaired quality of life outcome in OCD that should be assessed in routine clinical practice. These findings support the importance of addressing specific obsessive beliefs to improve sexuality in OCD patients.

The Leuven Affect and Pleasure Scale (LAPS) is a depression outcome measure aiming to better reflect patient treatment expectations. We investigated the evolution of the LAPS and some comparator scales during antidepressant treatment and compared scores of remitters with scores of healthy controls.

A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) major depressive disorder were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS as well as the Hamilton Depression Rating Scale (HAMD), the Snaith–Hamilton Pleasure Scale (SHAPS), the Positive and Negative Affect Scale (PANAS), and the Sheehan Disability Scale (SDS) were administered. Healthy controls consisted of 38 Italian adults and 111 Belgian students.

Correlations between baseline positive and negative affect were only moderate (R between −0.20 and −0.41). LAPS positive affect and hedonic tone showed higher correlations with LAPS cognitive functioning, overall functioning, meaningfulness of life, and happiness than HAMD scores or PANAS negative affect. HAMD remission was associated with normal levels of LAPS negative affect but with significantly lower levels of LAPS positive affect, hedonic tone, cognitive functioning, overall functioning, meaningfulness of life, and happiness. The scores on the latter subscales only reached healthy control scores when the HAMD approached a score of 0 or 1.

The standard definition of remission (HAMD cutoff of 7) is probably adequate for remitting negative mood, but not good enough for recovering positive mood, hedonic tone, functioning, or meaningfulness of life.

It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.

Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.

DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.

The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.

Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.

Patients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.

In this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.

Lumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.

Intra-Cellular Therapies, Inc.

The nature and significance of impulse-control difficulties in binge-eating disorder (BED) are uncertain. Most emerging research has focused on food-specific rather than general impulsivity. The current study examines the clinical presentation of patients with BED categorized with and without clinical levels of general impulsivity.

A total of 343 consecutive treatment-seeking patients with BED were categorized as having BED with general impulsivity (GI+; N = 73) or BED without general impulsivity (GI−: N = 270) based on structured diagnostic and clinical interviews. The groups were compared on demographic, developmental, and psychological features, and on rates of psychiatric and personality comorbidity.

Individuals with BED and general impulsivity (GI+) reported greater severity of eating-disorder psychopathology, greater depressive symptoms, and greater rates of comorbidity than those without general impulsivity (GI−).

A subtype of individuals with BED and general impulsivity may signal a more severe presentation of BED characterized by heightened and broader psychopathology. Future work should investigate whether these impulse-control difficulties relate to treatment outcomes.