Numerous studies shown that structural hippocampal alterations are present in subjects at high risk of developing psychosis or schizophrenia. These findings indicate that in a subset of patients undergoing first-psychosis episode (FPE), hippocampal volume alterations are accompanied by associated cognitive and neuropsychological deficits. The combination of psychological deficits and neuroanatomical alterations, in turn, appears to increase treatment complexity and worsen clinical outcomes.

We aim to determine whether cognitive and neuropsychological functioning deficits precede or follow hippocampal alterations during early onset psychosis.

This cross-sectional study describes 3 case-studies of adolescent subjects, ages 16–17, admitted at the child and adolescent inpatient psychiatric unit in lieu of first psychotic episode. We conducted detailed structured clinical psychiatric interviews, anatomical-structural magnetic resonance imaging (MRI), sleep-deprived electroencephalogram (EEG) recordings, laboratory testing, and a comprehensive battery of psychological testing to better understand their clinical pictures.

Psychological testing in each patient demonstrated the presence of low to borderline intellectual functioning coupled with neuropsychological deficits in different psychiatric domains. Interestingly, these changes coincided with structural MRI alterations in the hippocampal area.

Our case report adds to the armamentarium of literature signifying that radiologically detectable alterations of the hippocampus may occur either concomitantly or closely following the development of early cognitive deficits in patients with FPE.

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.

To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.

In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).

343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.

These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA

Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel

Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.

A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.

There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).

The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.

1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.

At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.

Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.

Funding Acknowledgements: This study was supported by Assurex Health, Inc.

Social anxiety disorder is a mental illness that often occurs in adolescents or early adulthood. When engaging in social interactions, students may feel shy, embarrassed, and uneasy, and thus unwilling to socialize in public. All leads to a gradual decline in their social functions. Many factors including growth environment, genetic factors, levels of neurotransmitters and hormones, as well as certain psychological shocks contribute to social anxiety disorders. In order to explore more treatment and intervention methods for social anxiety disorder, the impact mechanism and effectiveness of digital reading promotion activities in university libraries on college students’ social anxiety disorder were analyzed.

120 college students with social anxiety disorder in a certain university were randomly divided into an experimental group and a control group. The experimental group participated in digital reading promotion activities in the university library. Before and after treatment, the patients were evaluated using Symptom Checklist 90 (SCL-90), Liebowitz Social Anxiety Scale (LSAS), and Hamilton Anxiety Scale (HAMA).

After participating in reading promotion activities, the scores of the Hamilton Anxiety Scale, Social Anxiety Scale, and Symptom Checklist in the experimental group were lower than those before participation (P<0.05), and the difference was statistically significant.

Digital reading promotion activities have a positive impact on social anxiety disorders among college students. Small-scale reading activities can encourage students to go out and socialize, help students establish confidence, help them change their irrational cognition, and overcome psychological fears.

2016 Tianjin education planning project (No. vesp3003).

Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.

A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.

These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.

Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel

Antidepressants are commonly prescribed for mood disorders. Epidemiological studies suggest antidepressant use may be associated with cataracts and glaucoma. We aim to investigate the association between antidepressants and cataracts and glaucoma.

Data was collected from the United States Food and Drug Administration Adverse Event Reporting System. Reporting odds ratio (ROR) and Bayesian information components (IC025) were calculated for antidepressants (ie, selective serotonin reuptake inhibitors [SSRIs], selective norepinephrine reuptake inhibitors [SNRIs], serotonin-norepinephrine-dopamine reuptake inhibitors, serotonin modulators and stimulators, serotonin antagonists and reuptake inhibitors [SARIs], norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, tricyclic antidepressants [TCAs], tetracyclic antidepressants [TeCAs], and monoamine oxidase inhibitors [MAOIs]). The reference agent was acetaminophen.

TeCAs and MAOIs were significantly associated with a decreased risk of cataracts (ROR = 0.11-0.65 and 0.16-0.69, respectively). TCAs, brexanolone, esketamine, and opipramol reported an increased cataract risk (ROR = 1.31-12.81). For glaucoma, SSRIs, SNRIs, SARIs, TCAs, MAOIs, and other investigated antidepressants reported significant RORs ranging from 1.034 to 21.17. There was a nonsignificant association of angle closure glaucoma (ACG) and open angle glaucoma (OAG) with the investigated antidepressants.

For adverse event cases, multiple suspected product names are listed, and as cases are not routinely verified, there may be a possibility of duplicate reports and causality cannot be established.

Most of the investigated antidepressants were associated with a lower risk of cataract reporting. TCAs, brexanolone, esketamine, and opipramol were associated with greater odds of cataract. For most antidepressants, there was an insignificant increase in reports of ACG and OAG.

Opioid use disorder (OUD) is a serious public health threat. Pharmacotherapy, commonly known as medications for opioid use disorder (MOUD), is established as the cornerstone of OUD treatment. MOUDs reduce likelihood of relapse, promote recovery, and save lives. However, many clinicians are still reluctant to use these medications, in part due to inadequate training and experience. In light of the ongoing opioid overdose epidemic, it has become ever more important for clinicians to confidently and thoughtfully deploy these medications to help patients struggling with OUD. To aid busy clinicians, we have put together a review of the extant literature on three FDA-approved pharmacotherapy options—methadone, buprenorphine, and extended-release naltrexone—with a heavy focus on practical clinical application. We discuss how to effectively engage patients with OUD and initiate them on MOUDs—especially when their primary misused drug is fentanyl. We also review novel strategies, such as buprenorphine microinduction, as well as suggested best practice to effectively transition between MOUDs. Finally, we synthesize our review and recommendations in an algorithmic flowchart to provide visually compelling information.

No Funding

While physical activity has been shown to promote positive mental health and aid in treatment, the association between involvement in other activities and depressive symptoms among adolescents remains unclear. We sought to fill a gap in the literature by examining relationships between involvement in sports, art, and leadership activities during high school and depressive symptoms among adolescents. Hypothesis: We hypothesized that all types of involvement would be associated with lower levels of depressive symptoms.

We performed a secondary data analysis using the 2016 Minnesota Student Survey, a population-based survey of students in grades 9 and 11 (N=81,885). Descriptive sample statistics (e.g., frequencies) and chi-square tests, stratified by sex, were used to examine relationships between depressive symptoms and involvement in different extracurricular activities among males and females. Analyses were performed using SPSS.

For males and females, involvement in sports was associated with lower levels of depression, compared to non-involvement. Compared to males who did not participate in arts (16.6%), those who did were significantly more likely to report depressive symptoms (21.2%). In addition, females involved in leadership activities were significantly less likely to report depressive symptoms (21.9%) than those who were not involved in these activities (28.7%). Consistent with previous research, females were more likely to report depressive symptoms than males. Females also were more likely to participate in arts and leadership activities.

For males and females, sports participation, and for females, involvement in leadership activities, may represent protective factors against depressive symptoms during adolescence. However, clinicians might consider inquiring about depressive symptoms among adolescent males involved in art-related activities.

The goal of this study was to determine physician performance in diagnosis and management of postpartum depression (PPD) and to provide needed education in the consequence free environment of a virtual patient simulation (VPS).

∙ A continuing medical education activity was delivered via an online VPS learning platform that offers a lifelike clinical care experience with complete freedom of choice in clinical decision-making and expert personalized feedback to address learner’s practice gaps

∙ Physicians including psychiatrists, primary care physicians (PCPs), and obstetricians/gynecologists (ob/gyns) were presented with two cases of PPD designed to model the experience of actual practice by including use of electronic health records

∙ Following virtual interactions with patients, physicians were asked to make decisions regarding assessments, diagnoses, and pharmacologic therapies. The clinical decisions were analyzed using a sophisticated decision engine, and clinical guidance (CG) based on current evidence-based recommendations was provided in response to learners’ clinical decisions

∙ Impact of the education was measured by comparing participant decisions pre- and post-CG using a 2-tailed, paired t-test; P <.05 was considered statistically significant

∙ The activity launched on Medscape Education on April 26, 2018, and data were collected through to June 17,2018.

∙ From pre- to post-CG in the simulation, physicians were more likely to make evidence-based clinical decisions related to:

∙ Ordering appropriate baseline tests including tools/scales to screen for PPD: in case 1, psychiatrists (n=624) improved from 34% to 42% on average (P<.05); PCPs (n=197) improved from 38% to 48% on average (P<.05); and, ob/gyns (n=216) improved from 30% to 38% on average (P<.05)

∙ Diagnosing moderate-to-severe PPD: in case 2, psychiatrists (n=531) improved from 46% to 62% (P<.05); PCPs (n=154) improved from 43% to 55% (P<.05); and, ob/gyns (n=137) improved from 55% to 73% (P<.05)

∙ Ordering appropriate treatments for moderate-to-severe PPD such as selective serotonin-reuptake inhibitors: in case 2, psychiatrists (n=531) improved from 47% CG to 75% (P<.05); PCPs (n=154) improved from 55% to 74% (P<.05); and, ob/gyns (n=137) improved from 51% to 78% (P<.05)

∙ Interestingly, a small percentage of physicians (average of 5%) chose investigational agents for PPD which were in clinical trials pre-CG, and this increased to an average of 9% post-CG

Physicians who participated in VPS-based education significantly improved their clinical decision-making in PPD, particularly in selection of validated screening tools/scales, diagnosis, and pharmacologic treatments based on severity. Given that VPS immerses physicians in an authentic, practical learning experience matching the scope of clinical practice, this type of intervention can be used to determine clinical practice gaps and translate knowledge into practice.

Funding Acknowledgements: The educational activity and outcomes measurement were funded through an independent educational grant from Sage Therapeutics, Inc.

No funding

With the improvement of people’s living standards, more and more people are paying attention to their mental health, and many people choose to travel to alleviate the impact of anxiety.

This study selected 20 patients with different levels of anxiety, including mild anxiety, moderate anxiety, and severe anxiety, and divided them equally into an experimental group and a control group. The experimental group was treated with a combination of long and short acting drugs and green ecotourism, while the control group was only treated with a combination of long and short acting drugs. After six months of treatment, follow-up visits will be conducted to investigate the patient’s anxiety relief.

The survey showed that a total of 9 patients with severe anxiety in the experimental group had symptoms relieved, with 4 patients transitioning from severe anxiety to moderate anxiety, and 5 patients transitioning from severe anxiety to mild anxiety Among them, 4 experienced mild anxiety, while the rest were cured. 6 patients with mild anxiety were cured. In the control group, 6 patients with severe anxiety had symptoms relieved, all of whom turned to moderate anxiety. Among patients with moderate anxiety, 4 experienced relief in symptoms, with 3 transitioning from moderate anxiety to mild anxiety and 1 being cured. Four patients with mild anxiety have been cured.

The experimental results indicate that the combination of green ecological tourism industry construction and drug use in the context of rural revitalization has a good therapeutic effect on alleviating anxiety symptoms in anxiety patients

The Henan Provincial Department of Science and Technology (2022 Key R&D and Promotion Special Project), No. 222400410137.