Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability.

We evaluated spontaneous reports of terms such as “alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse” in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA.

We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for “drug abuse.” In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method.

The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.

The Montgomery-Åsberg Depression Rating Scale (MADRS) is commonly used for the assessment of depressive symptom changes in patients with major depressive disorder (MDD) or bipolar depression. Categories of depression severity that correspond to ranges of MADRS total score have been previously reported in patients with MDD, but it appears that MADRS severity ranges have not been reported for patients with bipolar I disorder. The objective of this study was to evaluate MADRS total score ranges that correspond with different grades of depression severity in patients with bipolar I depression.

Data were pooled from 3 randomized, double-blind, placebo-controlled, 6- or 8-week trials of cariprazine in patients with bipolar I depression. MADRS severity ranges were evaluated using an anchor-based approach with the clinician-rated, 7-category Clinical Global Impression-Severity (CGI-S) scale. CGI-S has previously been used to determine severity thresholds in MDD. Correlations between MADRS total score and CGI-S score were assessed in the pooled dataset at week 6; placebo and active treatment arms were pooled together. Youden index from receiver operating characteristic (ROC) curves was used to determine the optimal threshold for MADRS total score corresponding to each CGI-S severity level.

The pooled dataset included 1523 patients with bipolar depression. Mean CGI-S scores were highly correlated with mean MADRS total scores at week 6 (r=.87; P<.0001), with MADRS total scores increasing with CGI-S severity. Using the ROC curves, MADRS total score ranges corresponding to each CGI-S severity category were estimated as follows: score of 0-6 for “normal, not at all ill”, 7-12 for “borderline mentally ill”, 13-18 for “mildly ill”, 19-23 for “moderately ill”, 24-36 for “markedly ill”, 37-39 for “severely ill”, and 40 or greater for “extremely ill”. Area under the curve (AUC) values for these cutoffs ranged from 0.930 to 0.997, representing outstanding sensitivity and specificity.

Utilizing data from 3 recent clinical trials of subjects with bipolar depression, we were able to identify MADRS severity thresholds. These empirical findings may help clinicians to understand and contextualize MADRS results from bipolar clinical research and apply to their patients in practice.

AbbVie Inc.

Deutetrabenazine is FDA approved for tardive dyskinesia (TD) based on two 12-week, placebo-controlled studies evaluating safety and efficacy in patients with baseline Abnormal Involuntary Movement Scale (AIMS) score ≥6. Deutetrabenazine reduced overall AIMS scores compared with placebo in ARM-TD (–3.0 vs –1.6, P=0.019) and AIM-TD (24 mg/day, –3.2 vs –1.4, P=0.003; 36 mg/day, –3.3 vs –1.4, P=0.001). This analysis assessed Minimal Clinically Important Difference (MCID) in AIMS score in patients with TD treated with deutetrabenazine.

MCID is the smallest change from baseline in AIMS score that is meaningful for patients. MCID analyses were performed based on Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors described by Hauser et al., where MCID is the difference between patients treated with deutetrabenazine who were minimally improved and patients treated with placebo who were unchanged. Additional MCID definitions were explored: difference between patients who demonstrated treatment improvement versus those who did not (Method 2); difference between patients who demonstrated treatment success versus those who did not (Method 3).

295 patients were analyzed. Based on PGIC, the suggested MCID was –2.8. Results were similar for Method 2 (75% of patients had treatment improvement; MCID = –2.8) and Method 3 (38% of patients had treatment success; MCID = –2.6). Based on CGIC, the suggested MCID was –2.6. Results were similar for Method 2 (76% of patients had treatment improvement; MCID = –2.8) and Method 3 (41% of patients had treatment success; MCID = –3.0). Therefore, the suggested MCID for deutetrabenazine is –3.

The MCID for change in AIMS score based on PGIC and CGIC for deutetrabenazine was –3 regardless of the analytical method. Findings suggest an AIMS score reduction of ~3 is associated with clinically meaningful improvement in TD symptoms.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

This review discusses the potential negative consequences of untreated insomnia in correctional settings.

A literature review was conducted on the association between insomnia and negative health outcomes, the best practices for treating insomnia with and without medications, and common practices that prohibit the treatment of insomnia in correctional settings.

Untreated insomnia was associated with increased psychiatric distress, increased risk for suicide, and increased all-cause mortality. Common practices in many correctional institutions impose restrictions on treating insomnia. These practices lead to an increased likelihood for negative health outcomes, including suicide and an increase in all-cause death.

Practices that prohibit the treatment of sleep in correctional settings increase the risk of death by suicide and other adverse health outcomes. The practices are often put in place due to pressure from the security staff who have trouble controlling the black-market trade of prescribed medications and other contraband within jails and prisons. Healthcare professionals in the correctional setting must advocate for the importance of treating sleep problems in jails and prisons and work with security staff on ways to overcome the problems of pill diversion and the trade of contraband in order to provide quality healthcare to this protected population.

Graduate students, as highly intelligent individuals, are more likely to experience mania during their studies than the general population. They are affected by learning pressure, environmental factors, and other factors and manifested as high spirits and irritability. Art therapy, as a relatively effective treatment method, is often used for psychological intervention and treatment. Therefore, this study innovatively constructs music courses from the perspective of ideological and political education to alleviate graduate students’ mania.

Fifty graduate students with mania from a certain university were selected as the research subjects and randomly divided into Group A and Group B. Group A used traditional treatment methods, while Group B added innovative music courses to the traditional treatment methods for combined treatment. After the experiment, the data were processed and analyzed using SPSS 20.0.

After the combination of results and intervention treatment, the overall compliance rate of student patients reached 98%, significantly higher than 60% in Group A; In the quality of life score, the social function score of Group B was 65.95 ± 4.20, the mental health score was 64.54 ± 4.89, and the psychological function score was 67.39 ± 5.14, all of which were higher than those of Group A.

From the perspective of ideological and political education in the curriculum, the innovative construction of music courses has an effective alleviating effect on graduate students’ mania.

Guangxi academic degree and postgraduate education reform project (No. JGY2021162).

Bipolar I disorder frequently has an early onset, with an estimated prevalence rate of 1.8% in pediatric populations. Early onset is associated with a high degree of chronicity; however, limited data are available on the long-term efficacy of drug therapies in pediatric populations. The aim of the current study was to evaluate the long-term safety and efficacy of lurasidone in children and adolescents with bipolar depression.

Patients 10-17 years with bipolar I depression were randomized to 6 weeks of double-blind (DB) treatment with lurasidone or placebo. Patients who completed the study were eligible to enroll in a 2-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20-80 mg/d; LUR-LUR) or switched from placebo to lurasidone (PBO-LUR). The primary efficacy measure was the Children’s Depression Rating Scale, Revised (CDRS-R); response was defined as ≥50% reduction from DB baseline in the CDRS-R total score.

A total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. Mean CDRS-R total score at DB baseline was 59.4 in patients treated with lurasidone, and 58.7 in patients treated with placebo; and mean CDRS-R total score at OL baseline (after 6 weeks of DB treatment) was 36.6 in the LUR-LUR group and 41.9 in the PBO-LUR group. For the total sample of patients in the OL study, mean change (from OL baseline) in the CDRS-R score was -13.4 at week 52 and -16.4 at week 104; and responder rates were 51.0% at OL baseline (64.5% for LUR-LUR; 36.9% for PBO-LUR), 88.4% at week 52, and 91.1% at week 104. During OL treatment with lurasidone, 31 patients (10.1%) discontinued due to an adverse event. The most commonly reported events were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of 3.76 kg based on CDC normative data), and +6.75 kg at week 104 (vs. CDC expected weight gain of 6.67 kg).

Two years of treatment with lurasidone in children and adolescents with bipolar depression was generally well-tolerated, with relatively low rates of study discontinuation. Lurasidone treatment was associated with few effects on weight, metabolic parameters, and prolactin. Patients also continued to experience improvement in depressive symptoms during long-term treatment with lurasidone.

Clinicaltrials.gov identifier: NCT01914393

Supported by funding from Sunovion Pharmaceuticals Inc.

Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).

Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.

Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.

These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.

Myriad Neuroscience/Assurex Health

The psychological problems of college students are the focus of social concern and hot discussions. Influenced by the epidemic, college students’ study, life and employment have been affected to a certain extent. Schools should strengthen mental health education to improve college students’ ability to resist pressure and help students improve their ability to adapt to society. Positive psychology can help students improve their mental health by guiding their mental activities and tapping their own strengths. In the process of using positive psychological knowledge to intervene with college students, self-help incentive training and personality cultivation can help students understand their own mental health problems. Therefore, in the psychological health education of colleges and universities, we can consider taking these two methods to carry out psychological intervention on college students, so as to improve the students’ ability to withstand pressure.

In the experiment, 360 college students who meet the requirements were randomly selected in colleges and universities through a questionnaire survey as the research objects of mental health problems. There are 187 boys and 173 girls, with an average age of (20 ± 2) years. The 360 college students were randomly divided into the intervention group and the control group, 180 in each. The intervention group used positive psychological thinking for psychological intervention, while the control group did not take any psychological intervention measures. The Perceived Stress Scale (PSS) was selected as the test scale of college students’ compressive capacity, and SPSS23.0 was used to analyze the score results.

The score of the PSS scale is shown in Table 1. It can be seen from the table that after the intervention group received the psychological intervention, their problem-solving and rationalization abilities were significantly improved (P < 0.05), and their withdrawal emotions were significantly reduced (P < 0.05).Table 1.

PSS score

The results show that after the intervention of positive psychology, the psychological pressure resistance of college students has been significantly improved, which helps to improve the level of mental health of college students, so as to better solve many psychological problems caused by the epidemic.