Binge-eating disorder (BED) is associated with obesity (BMI ≥30) in approximately 40-45% of patients. Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and an elimination half-life of 47-77 hours, permitting once-daily dosing. In a recent placebo-controlled, flexible-dose study, dasotraline demonstrated significant efficacy in patients with BED. We now report an analysis from this study of the effect of dasotraline on body weight.

Patients with moderate-to-severe BED, based on DSM-5 criteria, were randomized to 12 weeks of double-blind flexible-dose treatment with dasotraline (4-8 mg/d) vs. placebo. The primary efficacy outcome was number of binge-eating days/week. Mean change in body weight at Week 12 (assessed as a safety outcome) was analyzed by baseline body mass index (BMI, kg/m2) category. Inferential statistics were not performed.

The safety population consisted of 317 patients (female, 84%; mean age, 38.2 years; mean weight, 97.3 kg). At baseline, the proportions of patients in each BMI category were as follows: normal (<25 kg/m2: 5.7%), overweight (25 to <30 kg/m2: 18.3%), obesity class I (30 to <35 kg/m2: 24.9%), class II (35 to <40 kg/m2: 29.3%), and class III (≥40 kg/m2: 21.8%). For the overall patient sample, treatment with dasotraline significantly reduced the number of binge-eating days per week vs. placebo (-3.74 vs. -2.75; P<0.0001; effect size = 0.74). Mean changes at Week 12 in weight (kg) for completers treated with dasotraline vs. placebo, by baseline BMI category, were as follows: normal weight (-4.6 vs. -0.2), overweight (-5.8 vs. +1.3), and combined obesity classes I-III (-6.2 vs. +0.3). Among obese patients (Class I-III, combined) treated with dasotraline, weight reduction (≥5%) was observed in 45.3% of patients (vs. 4.1% on placebo); and weight reduction ≥10% in approximately 13.7% of patients (vs. none on placebo). Weight-related adverse events, for dasotraline vs. placebo, consisted of decreased appetite (19.7% vs. 6.9%), decreased weight (12.1% vs. 0%), and increased weight (0.6% vs. 1.3%).

Among patients completing 12 weeks of treatment with dasotraline, weight reduction ≥5% was observed in 45% of obese patients with a BMI ≥30. The most frequent weight-related adverse event was decreased appetite, reported in approximately one in five patients treated with dasotraline.

Clinicaltrials.gov number: NCT02564588

Supported by funding from Sunovion Pharmaceuticals Inc.

Hyperammonaemia (HA) is observed in decompensated liver disease. The picture of hyperammonemic encephalopathy in non-cirrhotic patients was reported mostly associated with valproic acid. There are few reports of hyperammonemia in people living with human immunodeficiency virus (PLHIV) and they are associated with other comorbidities and few with antiretrovirals (HAART), but not as adverse drug reactions associated with psychotropic drugs associated with the virus.

Report of cases of PLHIV in HARRT with hyperammonemia, its clinical impact and ammonium levels.

We report 67 PLHIV in treatment with HAART, negative viral loads, psychopharmacological treatment with valproic acid (n=45) or carbamazepine (n=22). Exclusion criteria were = HCV, HBV and alcohol consumption disorder (current or recent history) and decompensated liver pathology. We apply scales to evaluate side effects (UKU), subjective adherence (DAI), daily life activities (Barthel Index), liver severity (Child-Pugh Classification) and degrees of hepatic encephalopathy (West Haven Scale). The ethical-legal requirements were met. Results: 26.86% presented hyperammonemia, among which 38.88% was symptomatic. The clinical presentation was heterogeneous with a higher prevalence of gastrointestinal and cognitive alterations; the most severe cases presented alterations of the sensorium and 1 case of convulsions. We recorded a greater symptomatic severity with carbamazepine (average ammonia =104.4 pmol/L), but a higher prevalence of non-symptomatic hyperammonemia with valproic acid (62.3 pmol/L). The time of onset of symptoms was lower with carbamazepine, but the time until its decrease was higher with valproic acid.

We observed a higher prevalence of hyperammonemia and associated symptomatology in PLHIV with HAART medicated with carbamazepine. The significant percentage of this adverse drug reaction suggests a biochemical, perhaps preventive, control.

Schizophrenia is a debilitating mental illness that affects patient’s function and quality of life. Estimates indicate a lifetime prevalence of 0.48%, causing up to 13.4 million years of life burdened by disability. 30% of these patients are deemed as having treatment-resident schizophrenia (TRS), a subset of which do not respond to clozapine, the medication designated for TRS. Those that do not respond to clozapine are deemed to have clozapine-resistant schizophrenia (CRS), requiring further augmentation or multiple antipsychotics.

Clozapine only has limited formulations available (oral [PO] and dissolving [ODT]) and has a substantial side effect burden. Most serious among these side effects includes agranulocytosis, which in some cases can cause severe infections such as septicemia. Regular blood draws monitoring for this are vital to prevent this dangerous consequence, but place further burden on patients, requiring weekly to monthly lab work and visits. Other common and burdensome side effects include tachycardia, hypotension, sialorrhea, weight gain, and metabolic syndrome, to name a few. However, treatment for TRS is still needed, and further alternatives must be explored.

Among studies done on clozapine, few compare second-generation antipsychotics head-to-head, and those that do find similar improvement in overall symptom burden among multiple antipsychotics, especially olanzapine and paliperidone (in particular, paliperidone palmitate). Due in part to the improved receptor profile of these medications (especially 5-HT2A, 6, and 7) compared to clozapine, they can have similar or superior effect in patients with TRS without substantial patient side effect and functional burden. Paliperidone palmitate formulations are developing that can be spaced further and further apart, allowing for minimal impact on patient’s livelihood, while demonstrating similar overall effect with improved side effect profile. However, onset of action is slow, and an effective adjunct strategy may be to initially administer olanzapine for the first 6 months until peak effect is expected from paliperidone palmitate, at which point monotherapy with paliperidone is preferred.

Alternative therapies for patients with TRS may be more functional with fewer side effects, and this work indicates a particularly effective strategy may be to pursue paliperidone palmitate monotherapy long-term while utilizing the unique combination of paliperidone and olanzapine in the short-term (first 6 months) while awaiting peak efficacy.

No Funding

To examine socioeconomic disparities in use of electroconvulsive therapy (ECT) among homeless or unstably housed (HUH) veterans with mental illness.

National data from medical records in years 2000 to 2019 on 4 to 6 million veterans with mental illness, including 140 000 to 370 000 homeless veterans served annually from the U.S. Department of Veterans Affairs (VA) healthcare system, were analyzed to examine ECT utilization and changes in utilization over time.

ECT utilization was higher among HUH veterans (58–104 per 1000) than domiciled veterans with mental illness (9–15 per 1000) across years with a trend toward increasing use of ECT use among HUH veterans over time. Among HUH and domiciled veterans who received ECT, veterans received an average of 5 to 9 sessions of ECT. There were great regional differences in rates of ECT utilization among HUH and domiciled veterans with the highest overall rates of ECT use at VA facilities in the Northeast and Northwest regions of the country.

ECT is commonly and safely used in HUH veterans in a comprehensive healthcare system, but geographic and local factors may impede access to ECT for veterans who may benefit from this treatment. Efforts should be made to reduce barriers to ECT in the HUH population.

The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression.

Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision).

The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group.

This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged antipsychotic use. RE KINECT, a real-world screening study of antipsychotic-treated outpatients, included patients with movements that were clinician-confirmed as possible TD (Cohort 2) and patients with no involuntary movements (Cohort 1). Baseline data from the patient rated EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and Sheehan Disability Scale (SDS) were analyzed to evaluate health related quality of life (Cohort 2 vs. Cohort 1) and the effects of possible TD on quality of life (Cohort 2).

Assessments included EQ-5D-5L utility score (0=equivalent to death to 1=perfect health); SDS total score (0=no impact to 30=highest impact); patient- and clinician-rated severity of possible TD in 4 body regions (0=none, 1=some, and 2=a lot; summary score, 0 to 8); and patient-rated impact of possible TD in 7 daily activities (0=none, 1=some, and 2=a lot; summary score, 0 to 14). Populations included Cohort 1 (N=450); full Cohort 2 (N=204); and limited Cohort 2 (N=111, patients who self-reported “some” or “a lot” of TD severity in ≥1 body region). Mean differences between Cohort 2 and Cohort 1 in EQ-5D-5L utility and SDS total scores were analyzed using a generalized linear regression model that was adjusted for potentially confounding factors (e.g., age, sex, psychiatric diagnosis). Associations between TD summary scores (severity, impact) and quality of life (EQ-5D-5L utility, SDS total) were analyzed using a regression model.

The mean score difference between full Cohort 2 (N=204) and Cohort 1 (N=450) was significant for EQ-5D-5L utility (-0.037; P<0.05 [adjusted analysis]) but not SDS total (0.267; P>0.05). However, when limited to Cohort 2 patients who self-reported “a lot” of TD severity (n=53) or impact (n=33), both EQ 5D 5L utility and SDS total scores were significantly worse than in Cohort 1 (P<0.05). Regression coefficients indicated significant associations between patient-rated impact and EQ 5D-5L utility in the full Cohort 2 (-0.021, P<0.001) and limited Cohort 2 (-0.024, P<0.001). A significant association was also found with patient rated severity in limited Cohort 2 (P<0.05), but not with clinician-rated severity. Similar results were found for SDS total score.

RE-KINECT patients were consistent in evaluating the severity and impact of TD, whether based on subjective assessments or standardized patient-reported instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD. Patient self-assessments (focused on symptom impact) can be clinically relevant; incorporating such measures into everyday practice may provide a more comprehensive approach to TD assessment and management.

Supported by Neurocrine Biosciences, Inc.

Othello syndrome, also known as morbid jealousy, pathological jealousy, and conjugal paranoia, is a rare delusional disorder related to partner’s infidelity. There are no large scale or comprehensive studies on delusional jealousy, and only few case reports and cases series leave delusional disorder jealous type (DDJT) largely unknown. Herein, we report a case of DDJT, its possible etiology and describe its characteristics, comorbidities, and interventions.

A 65-year-old married, retired, and disabled Caucasian male with a history of closed traumatic brain injury and chronic pain presented for outpatient care accompanied by his wife with a chief complaint of paranoid delusions. The patient was a car racer when he sustained over 25% total body surface area burns after his motor vehicle crashed at the speed of almost 160 mph. The patient was in a coma for more than nine weeks, coded three times, and was resuscitated each time. Per imaging, the patient suffered subarachnoid hemorrhage to the right outer parietal and left front parietal lobes. The patient developed chronic pain from the extensive burns and has been on opioids for many years until he gradually tapered himself off about six years ago. For the last couple of years, the patient has experienced cognitive decline associated with disorientation and memory deficit. The patient has been perseverative on his wife’s trip two years ago during which the patient believed that she had an affair with one of their mutual acquaintances. The patient denied visual or auditory hallucinations and continued to express his love and affection toward his wife. Although his wife has continually provided reassurance, and multiple family members confirmed her faithfulness, the patient had minimal insight into his delusion and expressed disappointment in loss of sexual intimacy between him and his wife. The patient has been prescribed duloxetine 60mg and trazodone 150mg, and his mood, anxiety, and sleep have been stable. The patient has also started taking pimozide 1mg nightly since beginning of this year with good response.

The DSM estimates the prevalence of DDJT to be less than 1%. At least a third of cases show neurological basis involving frontal lobe dysfunction associated with strokes, Parkinson’s disease, brain trauma and tumors, neurodegenerative disorder, encephalitis, multiple sclerosis, and even normal pressure hydrocephalus. Association with alcohol, amphetamine, cocaine, and dopamine therapy (pergolide, ropinirole, levodopa, amantadine, and pramipexole) were reported. Finally, DDJT is known to be a risk factor of violent crimes including homicide. Treatment with pimozide shows the strongest evidence, and most patients show improvement with any antipsychotic medication along with CBT. Continued research and further clinical trials are warranted for DDJT considering patients’ positive response to interventions, and because DDJT can become a dangerous condition in forensic situations.

Delusions, such as belief in conspiracy theories (CT), exist on a continuum representing clinical and subclinical populations. Some individuals are more susceptible to CT belief. Social media has allowed conspiracy theories to spread relatively unchecked. We report a previously healthy male hospitalized for delusions and reckless behavior. We analyze potential risk factors affecting this patient.

A 54-year-old Caucasian male presents with worsening persecutory and grandiose delusions over the past 6 months. An active participant in conspiracy theory-related online forums, he believes he has sensitive information regarding the Federal Bureau of Investigation. He endorses delusions of surveillance and tracking by family members, citing these concerns prompted him to rely on public transportation and prepaid cell phones, and even trespassing on U.S. Navy property. On evaluation, the patient prompts the team to review his collection of classified evidence claiming government involvement in a global sex trafficking operation. When challenged, the patient becomes argumentative, citing social media sources. He shows no evidence of overt depression, mania, or post-traumatic stress. The patient’s level of functioning is reduced but not markedly impaired and he maintains employment. CBC, CMP, noncontrast head CT, CXR, and EKG are unremarkable. Cannabinoids are found on UTOX. He has a Positive and Negative Syndrome Scale score of 23/49 (positive), 10/49 (negative), and 31/112 (General Psychopathology), and Brown Assessment of Beliefs Scale score of 19/24.

Conspiracy theories (CT) are the result of an altered perception of reality. Belief in CT correlates with negative social, health, and civic outcomes, including increased tolerance to violent and antisocial behavior. Magical thinking, trait Machiavellianism, narcissistic traits, and primary psychopathy have been shown to be significant positive predictors of belief in CT. Individuals with maladaptive perception/attribution styles may also develop cognitive distortions. Finally, intuitive thinking, as opposed to analytical thinking, is associated with CT beliefs. Social or political crises may incite elevated emotional responses, causing increased popularity of CT during times of major social or political change. Identifying these traits may be useful for clinicians providing interventions for patients with CT ideation. This patient’s presentation with delusions and nonimpaired functioning may be explained by deficits in objective reasoning as a result of maladaptive cognitive and affective response mechanisms, rather than psychotic illness.

Conspiracy theories are generated as a consequence of social and political discontent and can result in a clinically significant impact on mental health and well-being. Patients with narcissistic traits and primary psychopathy are more likely to demonstrate impaired judgment related to CT.

No funding

Approved therapeutics for bipolar depression are associated with a range of undesirable side effects. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. The efficacy of LUMA in bipolar depression was previously established in two Phase 3 trials, as monotherapy (NCT03249376) and as adjunctive to lithium or valproate (NCT02600507).

A recent Phase 3 multi-center trial, Study 401 (NCT02600494) investigated the efficacy and safety of LUMA in bipolar depression and comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension (OLE) period. Here, we report the results of the OLE period, examining long-term safety.

Patients, aged 18–75 years, with a clinical diagnosis of bipolar I or II disorder who were experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and a Clinical Global Impression Scale-Bipolar Version, Severity [CGI-BP-S] score ≥4) were eligible for Study 401. Patients who completed the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to the initiation of the OLE. During the OLE, LUMA 42 mg was administered once-daily in the evening for 25 weeks.

The primary objective was safety and tolerability of LUMA as measured by incidences of adverse events (AEs) and changes in laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. The secondary objective was improvement/maintenance of symptoms of depression as measured MADRS and CGI-BP-S Total scores.

A total of 127 patients were enrolled in the OLE, with 74 (58.3%) completing the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Most patients who had normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Symptoms of depression improved as measured by the mean change from baseline to Day 175 in MADRS Total score (−8.9) and CGI-BP-S Total score (−2.3).

In patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.

Intra-Cellular Therapies, Inc.

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.