Buprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2

1. To characterize the safety profile following long-term treatment with BUP/SAM

2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAM

FORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).

Of 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.

Long-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.

Funding Acknowledgements: Alkermes, Inc.

Anorexia nervosa is a serious mental disorder characterized by extreme food restriction and excessive demands for weight and appearance. Music therapy can help individuals relax both physically and mentally through methods such as music appreciation and music therapy. The University Union can provide various forms of health management services, offer rehabilitation support for anorexia, and enhance the positive psychology of faculty and staff.

150 faculty members aged between 25 and 50 in a certain university were selected, including 40 males and 110 females. According to the results of the Anorexia Self Test Scale, 20 people showed symptoms of anorexia nervosa. Among them, there are 18 people aged 25-29, 2 people aged 30-35, 3 males, and 17 females. Music therapy is used to treat patients, and psychological counseling from university unions is arranged twice a week. Six months later, the results of the Anorexia Self Test Scale were analyzed again using SPSS3.0 software.

After six months of treatment, 8 out of 20 patients recovered, 10 of them achieved significant improvement, and 2 of them achieved minor improvement. The P-value of the score data before and after treatment is less than 0.05, and the difference is statistically significant.

Through the application of music therapy and the health management services of university unions, more comprehensive and diverse measures can be provided to alleviate anorexia, promoting the psychological health and positive psychological development of faculty and staff.

Evidence is clear that the nation is experiencing an increasing number of incompetent to stand trial (IST) admissions to state hospitals. As a result, defendants in need of treatment can wait in jail for weeks for admission for restoration. This study was conducted to better understand this growing population and to inform hospital administration about the characteristics of IST admissions.

The study was conducted at the Department of State Hospitals (DSH) facility in Napa (DSH-Napa), a 1200-bed primarily forensic inpatient psychiatric facility located in northern California. The records of patients found IST and admitted to DSH-Napa for restoration of competence between the dates of 1/1/2009 and 12/31/2016 were eligible for inclusion in the study.

There were a total of 3158 unduplicated IST admissions available during the specified time period. Our data indicate that the number of admissions with more than 15 prior arrests increased significantly, from 17.7% in 2009 to 46.4% in 2016. In contrast, the percent of patients reporting prior inpatient psychiatric hospitalization evidenced a consistent decrease over time from over 76% in 2009 to less than 50% in 2016.

Our data add to the body of literature on the potential causes of the nationwide increase in competency referrals. The literature is clear that jails and prisons are now the primary provider of the nation’s mental health care. Our data suggest that another system has assumed this role: state hospitals and other providers charged with restoring individuals to competence.

No funding

The purpose of this case study is to review the clinical presentation and medical work of an adult male who experienced symptomatic hyperammonemia and first-degree atrio-ventricular block in the setting of valproic acid toxicity.

This case involves a 28-year-old African American male with a past psychiatric history of bipolar 1 disorder with psychotic features, antisocial personality disorder, PTSD, and ASD, who was psychiatrically hospitalized for mania and psychosis at a large midwestern university hospital. At the time of evaluation in the emergency department, the patient endorsed suicidal ideation, religious/persecutory delusions, and auditory hallucinations of demons. Zyprexa Zydis was started and titrated to 20 mg every 12 hours, which did not sufficiently improve symptoms. Depakote EC/DR 1000 mg every 12 hours was then added for treatment of mania. Approximately 1 week later, the patient was observed to be somnolent and complained of malaise, nausea, and vomiting.

Labs were collected which showed an elevated ammonia level of 336 umol/L and free valproic acid level of 13.3 mcg/ml. An EKG was performed which showed first-degree atrio-ventricular block with fusion complexes. The patient’s baseline EKG displayed sinus bradycardia with no evidence of atrio-ventricular block. The patient’s CMP was unremarkable except total bilirubin of 1.5 mg/dL and glucose of 104 mg/dL. His lactate was elevated at 1.95 mmol/L. The patient’s troponin and CRP were unremarkable. The patient was medically transferred for management of hyperammonemia and EKG changes. Depakote was discontinued and lactulose 20 g TID was initiated. Patient was placed on telemetry and the first-degree atrio-ventricular block resolved within 24 hours after discontinuation of Depakote. Daily ammonia level, chem 7, and magnesium were collected. Ammonia decreased to 79 and 59 umol/L on consecutive days. Sodium was mildly elevated at 144 on day 2 of medical admission. Poison control was contacted and L-carnitine 990 TID was started for suspected carnitine deficiency. The patient medically recovered after several days and was readmitted to the psychiatric hospital for further psychiatric management.

The patient’s presentation of hyperammonemia and first-degree atrio-ventricular block were likely due to valproic acid toxicity. We suspect that carnitine deficiency contributed to the patient’s valproic acid toxicity at lower-than-expected blood levels. Although antipsychotics can cause prolonged QTc interval, conduction disorders are not typical abnormalities. Caution should be taken when prescribing Depakote to individuals at higher risk of developing toxicity, including those with potential nutritional deficiencies as well as those with limited self-advocacy abilities secondary to psychiatric illness. Rapid identification of side effects, such as valproic acid toxicity, remain crucial for favorable patient outcomes.

No Funding

To describe the effect of supplemental psychotropic medications, specifically anxiolytics with sedative/hypnotics (ASH) combined with lamotrigine (LTG) on stabilization of symptoms in patients with bipolar I disorder.

Symptomatic patients participating in two LTG maintenance trials were classified post-hoc as those initiating LTG as monotherapy (n=313) or as adjunctive therapy (n=814) and further characterized by supplemental add-on therapies received during an open-label treatment phase. Patients were considered stabilized if they reached a stable dose of LTG monotherapy (100–200 mg/day) and had a Clinical Global Impressions-Severity scale score ≤3 for at least 4 weeks. Stabilization rates were compared across initial- and supplemental-treatment groups.

Patients who initiated and were maintained on LTG monotherapy were stabilized at a slightly higher rate compared with those taking LTG adjunctive therapy (55% vs 48%; P=.080). Stabilization rates were numerically higher for LTG monotherapy patients who later received only ASH as supplemental medication compared with LTG monotherapy throughout, but this difference was not significant (66% vs 55%; P=.271). Stabilization rates were significantly higher for monotherapy patients who later received ASH alone versus other psychotropic medications (66% vs 28%; P=.001). For patients initiating LTG as adjunctive therapy, adding ASH alone resulted in significantly higher stabilization rates than adding another psychotropic medication (62% vs 33%; P<.001).

LTG and adjunctive treatment with ASH may be useful in the treatment of acute mood symptoms in patients with bipolar I disorder.