Sheehan Disability Scale Scores Research Articles

Associations between readmission and patient-reported measures in acute psychiatric inpatients: a multicenter prospective longitudinal study.

This study examined whether patient-reported measures (PRMs) addressing quality of life, personal agency, functional impairment, and treatment satisfaction at hospital discharge were associated with future readmission during a 12-month follow-up period. The study also examined whether readmission influenced changes in the same measures. A multicenter prospective cohort study was conducted at 21 psychiatric hospitals in Japan. Participants completed the EuroQol-five-dimensions-five-level (EQ-5D), the Five-item Subjective Personal Agency Scale, and the Sheehan Disability Scale (SDS) at the time of index admission (T1), discharge from index admission (T2), and 6months (T3) and 12months (T4) after discharge. Inpatient treatment satisfaction was assessed at T2. Readmission and variables potentially associated with hospitalization and PRMs were evaluated using mixed-effects logistic regression models and mixed models for repeated measures. A total of 491 participants were followed for 12months (attrition rate: 19.4%), and 480 were included in the EQ-5D analysis. The most common diagnoses were schizophrenia (59%), depression (14%), and bipolar disorder (13%). No patient-reported measures were significantly associated with readmission over the follow-up period. Interaction of readmission and time did not significantly affect changes in EQ-5D. Readmission did significantly influence SDS score changes between T2 and T3 (B = 1.78, 95% CI = 0.30-3.25, p = 0.018) and between T3 and T4 (B = 1.43, 95% CI = 0.14-2.72, p = 0.029).The same influence of readmission on SDS score changes was not observed in the model which adjusted for all potential covariates. Readmission was potentially associated with changes in self-reported functional impairment. Findings highlight the potential role of intensive post-discharge services in preventing readmission, rather than relying on time-of-discharge PRMs in order to predict readmission risk. This study was registered in UMIN Clinical Trials Registry (UMIN000034220).

The Interplay Between Problematic Internet Use, Anxiety, Depression and Functional Impairment in Front-Line Healthcare Workers During the COVID-19 Pandemic.

We aimed to assess the interplay between functional impairment and anxiety, depression, and problematic Internet use levels in front-line healthcare workers who work in inpatient clinics of coronavirus disease-2019 (COVID-19) during the COVID-19 pandemic. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Internet Addiction Test (IAT), and Sheehan Disability Scale (SDS) were administered to assess the depression, anxiety, problematic Internet use, and functional impairment levels of the participants. Two hundred thirteen participants were enrolled in the present study. Medical doctors showed significantly higher scores of IAT than the nurses and other medical staff (Kruskal-Wallis=6.519, p=0.038). Levels of SDS total are significantly correlated with scores of IAT (r=0.257, p<0.001), BDI (r=0.383, p<0.001), and BAI (r=0.308, p<0.001). All subdomain scores of SDS (social, family, work) and total scores of SDS were significantly and positively correlated with BAI, BDI, and IAT scores (p<0.05). In the separation mediation analysis, problematic Internet use partially mediated the relationship between anxiety-depression and global functional impairment. Health politicians should produce policies to develop strategies for coping with consequences of anxiety and depression in healthcare professionals during any health crisis. In addition, we should raise healthcare professionals' awareness that problematic Internet use is not suitable for dealing with anxiety and depression and may even lead to increase of functional loss.

Association between sleep state misperception and bedtime behavior in patients with chronic insomnia

Previous studies on sleep state misperception have objectively evaluated sleep status in special environments using polysomnography. There is a paucity of data from studies that evaluated habitual sleep status in home environments. The present study aimed to investigate sleep state misperception in the home environment of patients with chronic insomnia using a lumbar-worn actigraphy to identify sleep habits associated with sleep state misperception severity. Thirty-one patients and 42 healthy volunteers were included in the insomnia and non-insomnia group, respectively. Participants recorded subjective assessments in sleep diaries, objective assessments with an actigraphy worn for 14 days, and self-assessments using questionnaires. Both groups had similar objective sleep ratings; however, insomnia group had significantly worse subjective ratings (total sleep time, wake after sleep onset, and sleep onset latency). A significant correlation was found between subjective and objective total sleep time scores in non-insomnia group but not in insomnia group. Insomnia group had earlier bedtimes, significantly longer bedtimes, and impaired daytime functioning (Sheehan Disability Scale score); additionally, they underestimated their total sleep time, particularly with earlier bedtimes and longer laying durations. Monitoring the sleep status and habits of individuals in home environments could be instrumental in identifying key points for targeted interventions on sleep hygiene and cognitive behavioral therapy for insomnia.

A Real-life Study of Brexpiprazole as an Adjunctive Treatment for Major Depressive Disorder in Asian Patients in Singapore (BADA).

: To investigate the effectiveness and safety of brexpiprazole as an adjunctive treatment to antidepressant therapy (ADT) in Asian adults with major depressive disorder (MDD) and inadequate response in a real-life clinical setting in Singapore. : This was a prospective, observational 3-month study of patients with MDD who had brexpiprazole added to their existing ADT. The study was conducted at two sites in Singapore between September 2020 and October 2021. The co-primary endpoints were Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S). Other endpoints included Clinical Global Impression-Improvement (CGI-I), Sheehan Disability Scale (SDS), Generalized Anxiety Disorder 7-item scale (GAD-7), and safety. : Twenty patients were enrolled and 16 completed the study. There were improvements in PHQ-9, CGI-S, SDS, and GAD-7 scores from baseline at Week 12, with a mean difference of -4.8, -1.3, -8.5, and -6.2, respectively. The CGI-I score improved from baseline with a mean score of 2.3 at Week 12. One third achieved response and 25% achieved remission based on PHQ-9 scores at Week 12. Similar results were obtained using CGI-S scores (38% for both). The incidences of adverse events (AEs) and treatment-related AEs were 55% (11/20) and 50% (10/20), respectively. There were no deaths or severe AEs. Two patients withdrew brexpiprazole during the study. : The observed effects and safety of adjunctive brexpiprazole in Asian adults with MDD in the real-world setting in Singapore were consistent with those from clinical trials.

Equipercentile linking of the Sheehan Disability Scale and the World Health Organization Assessment Schedule 2.0 scales in people with mental disorders

BackgroundThe Sheehan Disability Scale (SDS) and the World Health Organization Disability Assessment Scale (WHODAS 2.0) have been widely used to measure functional impairment and disability. To ensure that the scores from these two scales are practically exchangeable across diseases, therapies, and care programmes, the current study aimed to examine the linkage of the WHODAS 2.0 with the SDS and develop a simple and reliable conversion table for the two scales in people with mental disorders. MethodsA total of 798 patients (mean age = 36.1, SD = 12.7) were recruited from outpatient clinics of the Institute of Mental Health, and the Community Wellness Clinic in Singapore. Using a single-group design, an equipercentile equating method with log-linear smoothing was used to establish a conversion table from the SDS to the WHODAS 2.0 and vice versa. ResultsThe conversion table showed that the scores were consistent for the entire range of scores when the scores were converted either from the SDS to the WHODAS 2.0 or from the WHODAS 2.0 to the SDS. The agreement between the WHODAS 2.0's raw and converted scores and SDS's raw and converted scores were interpreted as good with intraclass correlation coefficient of 0.711 and 0.725, respectively. ConclusionThis study presents a simple and reliable method for converting the SDS scores to the WHODAS 2.0 scores and vice versa, enabling interchangeable use of data across these two disability measures.

Dysfunction of circulating endothelial progenitor cells in major depressive disorder.

Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD. We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays. The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups. The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

Validation of the 12-item World Health Organization Disability Assessment Schedule 2.0 in individuals with schizophrenia, depression, anxiety, and diabetes in Singapore.

There is limited evidence on the reliability and validity of the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in an Asian patient population with mental and physical disorders. The current study aimed to examine the psychometric properties of the WHODAS 2.0 among patients with schizophrenia, depression, anxiety, and diabetes. A total of 1076 patients (M = 40.9 years, SD = 14.7) were recruited from the outpatient clinics of a tertiary psychiatric hospital and a primary care clinic. Internal consistency and test-retest reliability, structural validity, convergent validity, agreement, and floor and ceiling effects were examined. Our confirmatory factor analysis (CFA) showed that the 1-factor model fits our data. Multigroup CFA demonstrated metric and scalar invariance, indicating the scores can be compared across the four conditions. The WHODAS 2.0 scale had excellent reliability in the overall sample and good to excellent reliability across conditions. The test-retest reliability and agreement between self-administered and interviewer-administered modes were good. The WHODAS 2.0 scores had moderate to strong correlations with the Social and Occupational Functioning Scale and the Sheehan Disability Scale scores in the overall sample and across four conditions. Findings suggest that the WHODAS 2.0 is a valid tool to measure functioning and disability in those with schizophrenia, anxiety, depression, and diabetes in an Asian patient population.

Εfficacy and safety of vortioxetine (Lu AA21004) in the treatment of adult patients with major depressive disorder: A systematic review and a meta‑analysis of randomized controlled trials.

Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of MDD, while it can effectively prevent the recurrence of MDD during the maintenance period. Currently, the results of systematic reviews on vortioxetine are insufficient since several efficacy measures, such as the 24-Items Hamilton Rating Scale for Depression (HADRS-24) total score and other safety factors have not been evaluated. Therefore, the present study aimed to evaluate the efficacy and safety of different doses of vortioxetine on the treatment of adult patients with MDD via assessing more efficacy and safety indicators. The clinical, double-blind, parallel and randomized controlled trials (RCTs) on the effect of vortioxetine on MDD were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and clinical trial registration websites from database inception to November 2022. A total of two investigators independently screened the included references and independently evaluated their quality. The meta-analysis was performed using Revman 5.0 software. The present systematic review was registered in PROSPERO (registration no. CRD42018106343). In the present study 11 RCTs were included, with a total of 4,908 adult patients with MDD. More specifically, 1,158 patients were included in the 5-mg vortioxetine group, 736 in the 10-mg group, 298 in the 15-mg group, 864 in the 20-mg group and 1,852 in the placebo group. All 11 studies were randomized, double-blinded and parallel control trials, and all publications were evaluated as high quality. The meta-analysis results showed that patients in the 5-, 10- and 20-mg vortioxetine groups exhibited significantly higher Montgomery-Asberg Depression Rating Scale (MADRS) response (≥50%) and remission (≤10%) rates compared with the placebo group (P<0.05). The pooled analysis also revealed a statistically significant change in the total score of HADRS-24, MADRS, Sheehan Disability Scale (SDS), Clinical Global Impression Scale-Improvement (CGI-I) and HADRS-24 response rate in the 10- and 20-mg vortioxetine groups compared with the placebo group (P<0.05). However, no statistically significant changes in the total score of HADRS-24, MADRS, SDS, CGI-I and HADRS-24 response rate were obtained in the 5-mg group compared with the placebo group (P>0.05). Furthermore, the most common adverse events were nausea, hyperhidrosis, insomnia and vomiting, the incidence of which was increased with higher doses of vortioxetine. Overall, the results suggested that vortioxetine administration at doses of 5-20 mg was significantly effective and safe compared with placebo in the treatment of MDD. However, 5 mg vortioxetine displayed no difference in the HADRS-24, MADRS, SDS and CGI-I total scores, and HADRS-24 response rate. Furthermore, patient treatment with increasing vortioxetine doses was associated with good tolerance and high safety. Nevertheless, more multi-center, high-quality and long-term RCTs are still needed to support the aforementioned findings.

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was −23.7 (−26.94, −20.44) for MDMA-AT versus −14.8 (−18.28, −11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was −3.3 (−4.03, −2.60) for MDMA-AT versus −2.1 (−2.89, −1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437.

Single-Dose Psilocybin Treatment for Major Depressive Disorder

Psilocybin shows promise as a treatment for major depressive disorder (MDD). To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. ClinicalTrials.gov Identifier: NCT03866174.

Agomelatine in the treatment of anhedonia, somatic symptoms, and sexual dysfunction in major depressive disorder.

This study evaluated the treatment outcomes of agomelatine on anhedonic state, anxiety/somatic symptoms, and sexual function in Chinese patients with major depressive disorder (MDD). In total, 93 adult patients with MDD were enrolled, and 68 of them were included in a prospective, open-label, multicenter clinical study. All patients received agomelatine monotherapy during a 9-week treatment phase. The effectiveness of the treatment was reflected by the improvement of anhedonia and somatic symptoms based on the 17-item Hamilton Depression Rating Scale (HAMD-17). In addition, the Arizona Sexual Dysfunction Scale (ASEX), Sheehan Disability Scale (SDS), and Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) were administered to all participants at baseline and at the 3-, 6-, and 9-week follow-ups. After 9 weeks of treatment with agomelatine, the response and remission rates were 73.5% and 39.7%, respectively. Somatic symptoms significantly improved at week 9 (p < 0.001), and significant effects were also observed on the HAMD anhedonia items (p < 0.001). The patients exhibited lower levels of disease severity (the SDS score dropped from 15.52 ± 4.7 to 7.09 ± 5.62 at week 9; the ASEX score dropped from 21.89 ± 4.06 to 16.19 ± 4.79, p < 0.001) and higher levels of QOL (the Q-LES-Q-SF score dropped from 41.02 ± 5.99 to 50.49 ± 8.57, p < 0.001) during the follow-up. Furthermore, treatment with agomelatine improved depressive symptoms without causing serious adverse events. These analyses indicate that agomelatine is a treatment option for improving anhedonic status, anxiety/somatic symptoms, and sexual dysfunction in MDD patients.

Exposure-response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder.

In the 10-week, phase 2 CLARITY study of patients with major depressive disorder, adjunctive therapy to antidepressants with pimavanserin 34mg once daily statistically significantly improved the Hamilton Depression Rating Scale (HAMD-17) total score (primary endpoint) and Sheehan Disability Scale (SDS) score (secondary endpoint) versus placebo. This analysis characterized the exposure-response (E-R) relationships of pimavanserin in this CLARITY patient population. Exposure measures were estimated for each patient based on population-pharmacokinetic empirical Bayesian estimates. E-R models were developed to describe exposure-efficacy (HAMD-17, SDS, and Clinical Global Impression-Improvement [CGI-I] scale) and exposure-safetyrelationships (Karolinska Sleepiness Scale [KSS], Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI], and adverse events [AEs] of headache, sedation, and somnolence) relationships. For the primary efficacy endpoint (HAMD-17 scores), a sigmoid maximum-effect model described the time course of response, and a linear function of pimavanserin exposure was statistically significant. HAMD-17 scores decreased steadily over time following placebo and pimavanserin treatment; separation from placebo increased as peak pimavanserin plasma concentration (Cmax ) increased. At median pimavanserin Cmax (34-mg dose), the reduction from baseline in HAMD-17 scores was -11.1 and -13.5 at weeks 5 and 10, respectively. Relative to placebo, the model predicted comparable reductions in HAMD-17 scores at weeks 5 and 10. Similar improvements in favor of pimavanserin were detected with SDS, CGI-I, MGH-SFI, and KSS scores. No E-R relationship was found for AEs. E-R modeling predicted a relationship between higher pimavanserin exposure and improvement in HAMD-17 score and improvement across multiple secondary efficacy endpoints.

Sex differences in residual somatic symptoms in patients with first-episode depression after acute-phase treatment

BackgroundResidual somatic symptoms (RSS) are common in depressed patients, predicting treatment effectiveness. However, sex differences in RSS have received little systematic study. This study was conducted to compare sex differences of RSS in patients with first-episode depression (FED).MethodsNine hundred eighty-two patients with FED were selected and treated for 8 to 12 weeks. We evaluated the subjects' socio-demographic characteristics and residual depressive symptoms. Using the Patient Health Questionnaire-15 (PHQ-15) scale to assess residual somatic symptoms, the Sheehan Disability Scale (SDS) for the assessment of patients' function, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) for quality of life.ResultsThe incidence of RSS with FED was 46.4%. For patients with residual symptoms, the age and age of onset in females were higher than males, but males had more years of education than females. The degree of "stomach pain" in females was more severe than in males, while "trouble sleeping" in males was more severe than that in females. Multiple regression analysis showed that the total Q-LES-Q-SF score was an independent influencing factor of RSS in both males and females, while the total SDS score only affected female RSS.ConclusionsThe prevalence of RSS in FED after acute-phase treatment is high. The symptom of "stomachache" is more pronounced in females, while "trouble sleeping" is more severe in males. Quality of life plays an essential role in RSS in both genders. Thus, sex needs to be considered when assessing the relationship between RSS and therapeutic effect in depression.

Disability during Early Pregnancy: Using the Sheehan Disability Scale during the First Trimester in Japan.

Background: Many pregnant women experience impairments in social, occupational, or other important functioning. Aim: This study aimed to confirm measurement and structural invariance of the Sheehan Disability Scale (SDS) and its validity during early pregnancy. Design: Longitudinal study with two observations. Methods: Questionnaires were distributed to pregnant women attending antenatal clinics at gestational weeks 10-13. Of 382 respondents, 129 responded to the SDS again 1 week later. Results: Confirmatory factor analysis shows good fit with the data: χ2/df = 0, comparative fit index (CFI) = 1.000, standardized root mean square residual (SRMR) = 0, and root mean square error of approximation (RMSEA) = 0.718. There is acceptable configural, measurement, and structural invariance of the factor structure between primiparas and multiparas as well as between two observation occasions. The Pregnancy-Unique Quantification of Emesis and Nausea, Patient Health Questionnaire-9, and Insomnia Severity Index subscales explain 47% of the variance in SDS scores. Conclusion: Perinatal health care professionals should pay more attention to the difficulties and disabilities that pregnant women face.

Study protocol for "MDMA-assisted therapy as a treatment for major depressive disorder: A proof of principle study".

Major depressive disorder (MDD) is a world-leading cause of disability. The available treatments are not effective in all patients, and there is a significant need for more effective treatment options. Here we present the protocol for an investigator-initiated and publicly funded trial of MDMA-assisted therapy (MDMA-AT) for MDD. This single-site, open-label study investigates the proof of principle and safety of MDMA-AT in participants with MDD and provides an initial impression of treatment effectiveness. A total of 12 participants [>18 years] with DSM-5 diagnosis of MDD will receive a flexible dose of MDMA in a therapeutic setting on two dosing days over a 4 week period preceded by three preparatory sessions. Each MDMA dosing session will be followed by three integration sessions. The primary outcome is change in MDD symptom severity, as measured by the mean change in MADRS scores from Baseline to 8 weeks after the second MDMA session. The secondary outcome is change in functional impairment, as evaluated by the mean change in Sheehan Disability Scale scores from Baseline to 8 weeks after the second MDMA session. Safety measures include vital signs, the incidence of Adverse Events and suicidality as measured by the Colombia-Suicide Severity Rating Scale. This proof of principle trial will inform the development of fully powered clinical trials, optimize the protocol for the administration of MDMA-AT in participants with MDD and explore uncertainties including barriers to recruitment, retention and acceptability of MDMA-AT as a treatment for MDD. EudraCT number 2021-000805-26.

A New Treatment Protocol of Combined High-Dose Levothyroxine and Repetitive Transcranial Magnetic Stimulation for the Treatment of Rapid-Cycling Bipolar Spectrum Disorders: A Cohort Evaluation of 55 Patients.

Background: Bipolar spectrum disorders (BSD) are highly disabling, with rapid cycling being treatment resistant. High-dose levothyroxine (HDT) has been reported to be effective. Diagnosis is associated with mutations in thyroid-activating enzymes and cerebral transporter protein carrier. Repetitive transcranial magnetic stimulation (rTMS) has neuroplastic effects. Methods: We report data on 55 severely symptomatic patients with rapid-cycling BSD treated with a combination protocol of HDT and rTMS. Of the patients, 31 patients (56.4%) were female and 40 (72.7%) had at least one additional diagnosis. Results: Patients were evaluated at three monthly intervals after acute treatment. Remission was measured using the Sheehan Disability Scale (SDS). The average number of medications prescribed was 1.8, with 32 patients (58.2%) needing only levothyroxine. The average dose of levothyroxine was 303.7 mcg (50 mcg–1000 mcg). A total of 53 patients were in remission (96.4%), with an average duration of 2.0 years. The SDS scores decreased significantly (Cohen’s d = 2.61 (95% C.I. 1.81 to 2.83, p < 0.001). One patient had reversible side effects. A total of 52 (94.3%) patients had Deiodinase 1 and 2 (DiO1/DiO2) or SLCO1C1 protein carrier gene mutations. Conclusion: The data support the safety and acceptability of combined HDT/rTMS. Patients achieved long remissions with substantial improvements in quality of life.

Changes and Prediction of Social Functional Disability and Quality of Life in Patients with Major Depressive Disorder over the Course of 1-Year Medication

To investigate the changes in social function impairment and quality of life and their predictive factors in patients with major depressive disorder (MDD) over the course of 1-year drug treatment. A total of 54 MDD patients were enrolled for the study. The 17-item Hamilton Rating Scale for Depression (HAMD-17, hereafter referred to simply as HAMD), Sheehan Disability Scale (SDS), and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were used to evaluate depressive symptoms, social functioning, and quality of life, respectively, at baseline (0), as well as 1 month (1 m), 2 months (2 m), 3 months (3 m), 6 months (6 m), 9 months (9 m), and 12 months (12 m) after medication started. The symptoms and the recovery of social function at different time points was analyzed, and correlation analysis and regression analysis were done to explore the influencing factors of functional recovery. Among the 54 MDD patients, 27 completed the 12-month follow-up, and 2 patients relapsed at 12 m. The total baseline score of SDS (SDS 0) in MDD patients was higher than that in healthy controls ( t=12.161, P<0.001), and the baseline score of Q-LES-Q-SF (Q-LES-Q-SF 0) was lower than that in the controls ( t=12.260, P<0.001). Comparison of the HAMD score, SDS total score and the factor scores, and Q-LES-Q-SF total scores of the MDD patients at different time points showed significant differences, presenting an F value of 65.987, 28.944, 23.589, 27.070 and 28.668, respectively (all P<0.001). HAMD 0 was negatively correlated with age. The HAMD score was positively correlated with SDS score of the same time point and negatively correlated with Q-LES-Q-SF score of the same time point. At 3 m, the change in HAMD score (HAMD 3 m-0) was positively correlated with the change in SDS score (SDS 3 m-0) and negatively correlated with the change in Q-LES-Q-SF score (Q-LES-Q 3 m-0). At 12 m, the change in HAMD score (HAMD 12 m-0) was positively correlated with the change in SDS score (SDS 12 m-0) and negatively correlated with the change in Q-LES-Q-SF score (Q-LES-Q 12 m-0). Regression analysis revealed that SDS 0 and Q-LES-Q 0 could be used to predict SDS 3 m-0, R 2=0.391, while SDS 0 and full-time employment status could be used to predict SDS 12 m-0, R 2=0.640. Q-LES-Q 0 could be used to predict Q-LES-Q 3 m-0, R 2=0.294, while Q-LES-Q 0 and full-time employment status could be used to predict Q-LES-Q 12 m-0, R 2=0.591. Long-term regular medication can improve social dysfunction in patients with MDD and symptom relief is the basis for improvement of social function level and quality of life, while increasing employment saturability to some extent may help improve the long-term social function and quality of life.

Real-world effectiveness of vortioxetine in outpatients with major depressive disorder: functioning and dose effects

BackgroundFunctional recovery is an important treatment goal in major depressive disorder (MDD). This study assessed the real-world effectiveness of vortioxetine in patients with MDD, with particular focus on functioning; dose–response was also assessed.MethodsThis was a non-interventional, prospective, multicenter study conducted in Greece. Adult outpatients with MDD (n = 336) initiating vortioxetine (5–20 mg/day flexible dosing) as treatment for a current major depressive episode were followed for 3 months. Analyses were stratified according to vortioxetine dosage at 3 months: 5–10 mg/day versus 15–20 mg/day. Functioning was assessed using the Sheehan Disability Scale (SDS).ResultsMean ± standard error SDS total score decreased (improved) from 18.7 ± 0.3 at baseline to 12.9 ± 0.3 after 1 month of vortioxetine treatment and 7.8 ± 0.4 after 3 months (p < 0.001 vs. baseline for all comparisons). Functional recovery (SDS score ≤ 6) was achieved in 14.6% of patients after 1 month of treatment and 48.4% of patients after 3 months. Improvement from baseline in SDS total and domain scores at 3 months was more pronounced in patients receiving vortioxetine 15–20 mg/day than in those receiving vortioxetine 5–10 mg/day. The mean ± standard error change in SDS total score from baseline was 9.2 ± 0.8 in the 5–10 mg/day group and 12.1 ± 0.4 in the 15–20 mg/day group (p < 0.001). Limitations of this study include its non-interventional study design and lack of a control group or active comparator.ConclusionsStatistically significant and clinically relevant improvements in functioning were seen in patients with MDD treated with vortioxetine in a real-world setting. Higher doses of vortioxetine were associated with significantly greater improvements in functioning.

The Chinese version of the family accommodation scale for obsessive-compulsive disorder self-rated: reliability, validity, factor structure, and mediating effect.

BackgroundFamily accommodation (FA) in obsessive compulsive disorder (OCD) is a common phenomenon. Based on the cost of training interviewers and the time required to administer the scale, the Family Accommodation Scale for Obsessive-Compulsive Disorder Interviewer-Rated (FAS-IR) has been restricted to specific settings. A self-rated version of the family accommodation scale may solve these problems. The aim of this study was to examine the reliability, validity and factor structure of the Family Accommodation Scale Self-rated version (FAS-SR), and the relationship among FA, symptom severity and functional impairment.MethodsIn total, 171 patients with OCD and 145 paired relatives participated in this study. The Sheehan Disability Scale (SDS), Obsessive-Compulsive Inventory Revised (OCI-R), Zung Self-Rating Depression Scale (Zung-SDS), 12-item Family Assessment Devices (FAD-12), Clinical Global Impression of Severity Scale (CGI-S), Global Assessment of Functioning (GAF), and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used as tools for patients. The FAS-SR, FAS-IR, FAD-12, and the patients’ symptom severity of Y-BOCS compulsion were used as tools for relatives. The psychometric properties of the FAS-SR were evaluated using Cronbach’s alpha coefficient, test-retest reliability and validity. Mediation analysis was used to determine the relationship among FA, symptom severity and functional impairment.ResultsA total of 97.9% of relatives of OCD patients reported at least one kind of FA behavior, and 56.6% of participants engaged in FA every day in the past week. The FAS-SR includes a three-factor structure: (1) providing reassurance and participation; (2) facilitation; and (3) modification. The scale’s Cronbach’s alpha and test-retest coefficients were 0.875 and 0.970, respectively. The total FAS-SR score was significantly positively associated with the Y-BOCS, FAD-12, CGI-S, FAS-IR, and SDS scores, and negatively associated with the total GAF score. FA partially mediated the relationship between symptom severity and functional impairment.ConclusionThe FAS-SR was proven to have satisfactory psychometric properties, and can play an important role in the evaluation and early intervention of OCD. This result indicates the importance of assessing symptom severity in conjunction with FA when evaluating OCD patients’ functional impairment.

A machine-learning model to predict suicide risk in Japan based on national survey data.

ObjectiveSeveral prognostic models of suicide risk have been published; however, few have been implemented in Japan using longitudinal cohort data. The aim of this study was to identify suicide risk factors for suicidal ideation in the Japanese population and to develop a machine-learning model to predict suicide risk in Japan.Materials and MethodsData was obtained from Wave1 Time 1 (November 2016) and Time 2 (March 2017) of the National Survey for Stress and Health in Japan, were incorporated into a suicide risk prediction machine-learning model, trained using 65 items related to trauma and stress. The study included 3,090 and 2,163 survey respondents >18 years old at Time 1 and Time 2, respectively. The mean (standard deviation, SD) age was 44.9 (10.9) years at Time 1 and 46.0 (10.7) years at Time 2. We analyzed the participants with increased suicide risk at Time 2 survey. Model performance, including the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, were also analyzed.ResultsThe model showed a good performance (AUC = 0.830, 95% confidence interval = 0.795–0.866). Overall, the model achieved an accuracy of 78.8%, sensitivity of 75.4%, specificity of 80.4%, positive predictive value of 63.4%, and negative predictive value of 87.9%. The most important risk factor for suicide risk was the participants' Suicidal Ideation Attributes Scale score, followed by the Sheehan Disability Scale score, Patient Health Questionnaire-9 scores, Cross-Cutting Symptom Measure (CCSM-suicidal ideation domain, Dissociation Experience Scale score, history of self-harm, Generalized Anxiety Disorder-7 score, Post-Traumatic Stress Disorder check list-5 score, CCSM-dissociation domain, and Impact of Event Scale-Revised scores at Time 1.ConclusionsThis prognostic study suggests the ability to identify patients at a high risk of suicide using an online survey method. In addition to confirming several well-known risk factors of suicide, new risk measures related to trauma and trauma-related experiences were also identified, which may help guide future clinical assessments and early intervention approaches.