Fluoxetine in acute treatment of children and adolescents with obsessive-compulsive disorder: a systematic review and meta-analysis.

Background: Obsessive-compulsive disorder (OCD) is a common psychiatric illness in children and adolescents. Previous evidence suggests that fluoxetine is effective in the treatment of OCD in children and adolescents. However, those studies had small sample sizes. As a result, a systematic review, which is a more powerful method to calculate the true effect size, can be applied to examine the efficacy, acceptability and tolerability of fluoxetine in the treatment of OCD in children and adolescents.Objectives: The aims of this study were to review the efficacy, acceptability and tolerability of fluoxetine in the treatment of OCD in children and adolescents.Study appraisal and synthesis methods: The titles and abstracts collected from electronic databases were evaluated. Then, the full-text versions of relevant studies were thoroughly assessed and extracted.Results: A total of 188 randomized patients in three RCTs of fluoxetine versus placebo and one RCT of fluoxetine versus citalopram were included in this review. Considering efficacious outcomes, the pooled mean change score of the CY-BOCS in the fluoxetine-treated group was significantly greater than that in the placebo-treated group. Additionally, the CGI-S in the fluoxetine-treated group and the pooled mean change score of the NIMH-OC were also significantly different from those in the placebo-treated group.Limitation: This review included studies with small sample sizes.Conclusions and implications of key findings: Fluoxetine is associated with a significantly greater reduction in OCD severity, as measured by the CY-BOCS, NIMH-OC and CGI-S, in children and adolescents. Additionally, it is well tolerated in children and adolescents. The acceptability is comparable to that of the placebo-treated group. Nonetheless, further large prospective trials should be conducted to confirm these outcomes.

Adaptive behavior in adolescents and adults with Down syndrome: Results from a 6-month longitudinal study.

Measures of adaptive behavior are important in the assessment and treatment of individuals with intellectual disabilities (ID). The purpose of the current study was to evaluate the stability of an established and a novel measure of adaptive behavior over time, and their suitability as outcome measures in clinical trials targeting individuals with Down syndrome (DS). This 6-month, longitudinal, noninterventional, multinational study included adolescents (12-17 years) and adults (18-30 years) with DS. Participants were from seven countries (11 different sites) with English, Spanish and French as their native language. The Vineland Adaptive Behavior Scales-II (VABS-II) and a newly developed Clinician Global Impression (CGI) scale were administered at baseline, 1 and 6 months. Adults had lower composite standard scores on all domains of the VABS-II compared with adolescents. The communication domain was a weakness relative to the socialization and daily living skills domains on the VABS-II and the CGI-Severity scale. These findings were stable over 6 months, as exhibited by high intraclass correlations (>0.75). These results provide valuable baseline data for use in trial design and endpoint selection for studies including individuals with DS. ClinicalTrials.gov identifier: NCT01580384.

Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone.

AIMS: A new, long-acting, subcutaneous (SC) formulation of risperidone (RBP-7000) has been developed for the treatment of schizophrenia to address issues of non-adherence associated with oral risperidone treatment. The objective of this work was to establish an exposure-response relationship between total active moiety (AM) plasma exposure (risperidone + 9-hydroxy-risperidone) and Positive and Negative Syndrome Scale (PANSS) or Clinical Global Impression severity (CGI-S) scores using data from a registration trial. METHODS: This was a Phase 3 randomized, double-blind, placebo-controlled, multicenter study in 354 patients to evaluate the efficacy, safety and tolerability of RBP-7000 (90 mg and 120 mg). Non-linear mixed effects modelling was used to develop an integrated population pharmacokinetic/pharmacodynamic (PK/PD) model that included a joint PK model for risperidone and 9-hydroxy-risperidone with placebo and drug-effect models to establish the relation between total AM exposure and PANSS or CGI-S scores. RESULTS: CYP2D6 poor and intermediate metabolizers had lower formation rates of 9-hydroxy-risperidone (94% and 76% lower, respectively) compared to the extensive CYP2D6 metabolizers. The maximum placebo-corrected relative decrease in PANSS score from baseline following RBP-7000 treatment was 5.4%, half of which could be achieved at plasma concentrations of 4.6 ng ml-1 of the total AM. A proportional odds model for the CGI-S score related the total AM plasma concentration to the probability of improving/worsening scores over time. CONCLUSIONS: Exposure-response analysis was established between total AM concentrations and PANSS and CGI-S scores, with good precision in parameter estimates. CYP2D6 phenotype on risperidone metabolism was the only identified covariate.

Association between severity of symptoms and minimum mental health treatment duration in humanitarian contexts: a retrospective observational study.

Background: Understanding and optimising mental health and psychosocial support (MHPSS) interventions in humanitarian crises is crucial, particularly for the most prevalent mental health conditions in conflict settings: anxiety, depression, and post-traumatic stress disorder. However, research on what is the most appropriate length of psychological intervention is lacking in this setting. We aimed to establish which factors are most closely related to improvement and to determine the required number of consultations needed to achieve this improvement. Methods: We retrospectively analysed records from 9028 patients allocated to treatment for anxiety, depression, and post-traumatic symptoms from the MHPSS programme in Borno State, Nigeria, from January 2018 to December 2019. Patient characteristics, severity (Clinical Global Impression of Severity Scale, CGI-S scale), and clinical improvement were assessed by an attending counsellor (CGI-I scale) and by the patient (Mental Health Global State, MHGS scale). Improvement was defined as scores 1, 2, and 3 in the Clinical Global Impression of Improvement (CGI-I) scale, and as a decrease of at least 4 points in the MHGS scale. We investigated the associations between the category of symptoms, the severity of illness, and improvement of symptoms using multivariable logistic regression. We used Kaplan-Meier (KM) curves to assess the number of consultations (i.e., time of treatment) needed to achieve improvement of symptoms, by symptom category and symptom severity. Findings: The patients included were referred to treatment for anxiety (n = 3462), depression (n = 3970), or post-traumatic symptoms (n = 1596). Median age was 31 years (range 16-103), and 84.3% were female. Patients categorised as severe were less likely to present improvement according to the CGI-I scale (OR 0.11, 95% CI 0.05-0.25), while none of the other categories of symptoms showed significant results. Overall, three or more consultations were associated with improvement in both scales (OR 3.55, 95% CI 1.47-8.57 for CGI-I; and OR 3.04, 95% CI 2.36-3.90 for MHGS). KM curves for the category of symptoms showed that around 90% of patients with anxiety, depression, or post-traumatic symptoms, as well as those with mild or moderate severity, presented improvement after three consultations, compared with six consultations for those with severe symptoms. Interpretation: Classification by severity among patients with anxiety, depression, or post-traumatic symptoms could predict the probability of improvement, whereas classification by symptoms could not. Our study highlights the importance of classifying patient severity in MHPSS programmes to plan and implement the appropriate duration of care. A major limitation was the number of patients lost to follow up after the first consultation and excluded from the logistic regression and KM analysis. Funding: The study was funded and staffed entirely by Médicos Sin Fronteras (Médecins Sans Frontières), Spain.

Ketamine Infusion in a Resistant Obsessive-Compulsive Disorder Patient in Bangladesh with Severe Suicidal Ideation: A Case Report.

Treatment of resistant obsessive-compulsive disorder (OCD) typically results in insufficient symptom alleviation, and even long-term medication often fails to have the intended effect. Ketamine is a potent non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. Studies have shown that low-dose ketamine infusion results in a considerable reduction in obsessive-compulsive symptoms and a rapid resolution of suicidal ideation. This is a case report on the effect of intravenous ketamine infusion on a patient with resistant OCD and severe suicidal ideation. Intravenous (IV) ketamine was given once a week over consecutive three weeks with necessary precautions. Psychometric tools such as the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impressions Scale (CGI-S), the Beck Scale for Suicidal Ideations (BSSI), and Depression Anxiety and Stress Scale 21 (DASS-21) were applied before and after infusions. Obsessive-compulsive symptoms and suicidal severity started to decrease rapidly after the first infusion. However, after a transient improvement, these symptoms again began to increase after a stressful incident on the second day of the first infusion. All the symptoms measured by validated rating scales showed continued improvement after the following two infusions. The improvement was sustained until discharge (one week after the last infusion) and subsequent follow-up in the sixth and 12th weeks. The role of ketamine in reducing suicidal thoughts and behavior is already established. Very few studies emphasized its effectiveness in improving severe/resistant obsessive-compulsive symptoms. This pioneering work may offer scope for similar research in the relevant field.

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study.

Objective: Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6-12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD. Methods: This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6-12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions-Severity (CGI-S) scale assessments were used to evaluate ADHD severity. Results: Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase. Conclusions: In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. ClinicalTrials.gov identifier: NCT03460652.

Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited. Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD). Results: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001). Conclusion: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.

Severity, symptomatology, and treatment duration for mental health disorders: a retrospective analysis from a conflict-affected region of northern Nigeria.

BACKGROUND: Mental Health and psychosocial support (MHPSS) programs are essential during humanitarian crises and in conflict settings, like Nigeria's Borno State. However, research on how types of traumatic stress and symptom severity affect clinical improvement is lacking in these contexts, as is consensus over how long these patients must engage in mental health care to see results. METHODS: Records from 11,709 patients from the MHPSS program in Pulka and Gwoza local government areas in Borno State, Nigeria from 2018 and 2019 were retrospectively analyzed. Patient information, symptoms, stress type, severity (CGI-S scale), and clinical improvement (CGI-I and MHGS scales) were assessed by the patient and counselor. Associations between variables were investigated using logistic regression models. RESULTS: Clinical improvement increased with consultation frequency (OR: 2.5, p < 0.001 for CGI-I; OR: 2, p < 0.001 for MHGS), with patients who received three to six counseling sessions were most likely to improve, according to severity. Survivors of sexual violence, torture, and other conflict/violence-related stressors were nearly 20 times as likely to have posttraumatic stress disorder (PTSD) (OR: 19.7, p < 0.001), and depression (OR: 19.3, p < 0.001) symptomatology. Children exposed to conflict-related violence were also almost 40 times as likely to have PTSD (OR: 38.2, p = 0.002). Most patients presented an improvement in outcome at discharge, per both counselors (92%, CGI-I) and self-rating scores (73%, MHGS). CONCLUSION: We demonstrate a threshold at which patients were most likely to improve (3 sessions for mild or moderate patients; 6 sessions for severe). In addition, we identify the specific types of stress and symptom severity that affected the number of sessions needed to achieve successful outcomes, and highlight that some stress types (especially torture or having a relative killed) were specifically linked to PTSD and depression. Therefore, we emphasize the importance of classifying patient stress type and severity to identify the appropriate duration of care needed.

Unique Trans-fatty Acid Profile in Children With Attention Deficit Hyperactivity Disorder.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common developmental disorder in children. Studies suggest an association between fatty acids composition and ADHD pathogenesis. We aimed to investigate whether children diagnosed with ADHD present unique fatty acid profiles in red blood cells (RBC), as compared to children without ADHD. Method: We examined 60 children aged 6-14 years, out of which 32 were diagnosed with ADHD, and 28 were not. Blood was collected from all children to quantify an array of 26 fatty acids from RBC membranes. Fatty acid methyl esters were generated by acid transesterification and analyzed by gas chromatography. Results: We found that children with ADHD presented unique fatty acid profiles on RBC membranes with significantly higher levels of most of the trans-fatty acids (Total trans-fatty acids 0.64 ± 0.21 vs. 0.49 ± 0.18 p = 0.003) and lower levels of docosahexaenoic acid (DHA), as compared to controls (4.06 ± 0.79 vs. 4.68 ± 1.37 p = 0.040). Additionally, total trans-fatty acids were higher in children with extremely severe clinical ADHD condition score, as compared to milder ADHD scores and to control children (0.72 ± 0.18, 0.64 ± 0.20, 0.61 ± 0.22, 0.49 ± 0.18, p = 0.010, accordingly). Conclusion: Children with ADHD have higher levels of trans-fatty acids in RBCs, compared to children without ADHD. This study points to a possible link between trans-fatty acids and ADHD. Understanding these findings and the clinical meaning will potentially contribute to a more targeted dietary intervention.

N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials.

RATIONALE: It remains unclear whether using N-acetylcysteine as an adjunctive treatment has any benefit for bipolar depression and major depressive disorder. OBJECTIVES: A systematic review and random-effect meta-analysis of double-blind, randomized placebo-controlled trials was conducted to explore the clinical question. METHODS: Outcomes included improvement in depression scale scores (primary), Young Mania Rating Scale score, Hamilton Anxiety Rating Scale score, Clinical Global Impression-Severity Scale (CGI-S) score, Global Assessment of Functioning Scale score, Social and Occupational Functioning Assessment Scale score, Range of Impaired Functioning Tool score, Streamed Longitudinal Interval Clinical Evaluation for the Longitudinal Interview Follow-Up Evaluation score, quality of life scales scores, and the incidence of all-cause discontinuation and individual adverse events. RESULTS: Seven studies (n = 728, 8-24 weeks, mean age = 46.81, % female = 58.45%) were included. N-acetylcysteine did not improve depressive symptoms compared with placebo (N = 7, n = 579, standardized mean difference (SMD) = - 0.12, 95% confidence interval (95% CI) = - 0.38, 0.14, p = 0.38, I2 = 52.74%). The meta-regression analysis detected an association between effect size and publication year (coefficient = 0.06, 95% CI = 0.00, 0.11, p = 0.04, I2 = 27.56%). Although N-acetylcysteine was superior to placebo in CGI-S score (N = 6, n = 563, SMD = - 0.28, 95% CI = - 0.47, - 0.10, p < 0.01, I2 = 14.88%), there was no significant difference in the other efficacy outcomes between the treatment groups. Although N-acetylcysteine was associated with a higher incidence of gastrointestinal adverse events compared with placebo (N = 4, n = 537, risk ratio = 1.79, 95% CI = 1.37, 2.32, p < 0.01, I2 = 0.00%, number needed to treat to harm = 7), there was no significant difference in all-cause discontinuation and other safety outcomes between the treatments. CONCLUSIONS: Although N-acetylcysteine decreased CGI-S score, no specific improvements in symptoms were identified.

Results of Gamma Knife anterior capsulotomy for refractory obsessive-compulsive disorder: results in a series of 10 consecutive patients.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a severe psychiatric condition. The authors present their experience with Gamma Knife radiosurgery (GKRS) in the treatment of patients with OCD resistant to any medical therapy. METHODS: Patients with severe OCD resistant to all pharmacological and psychiatric treatments who were treated with anterior GKRS capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with structural and functional MRI before and after GKRS treatment. Strict study inclusion criteria were applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. Clinical global changes were assessed using the Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) scale, EQ-5D, Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI). OCD symptoms were determined by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: Ten patients with medically refractory OCD (5 women and 5 men) treated between 2006 and 2015 were included in this study. Median age at diagnosis was 22 years, median duration of illness at the time of radiosurgery was 14.5 years, and median age at treatment was 38.8 years. Before GKRS, the median Y-BOCS score was 34.5 with a median obsession score of 18 and compulsion score of 17. Seven (70%) of 10 patients achieved a full response at their last follow-up, 2 patients were nonresponders, and 1 patient was a partial responder. Evaluation of the Y-BOCS, BDI, STAI-Trait, STAI-State, GAF, and EQ-5D showed statistically significant improvement at the last follow-up after GKRS. Neurological examinations were normal in all patients at each visit. At last follow-up, none of the patients had experienced any significant adverse neuropsychological effects or personality changes. CONCLUSIONS: GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It reduces both obsessions and compulsions, improves quality of life, and diminishes depression and anxiety.

Evaluation of sleep profile in schizophrenia patients treated with extended-release paliperidone: an open-label prospective study in Southeast Asia.

OBJECTIVE: To evaluate the effect of 6 months of treatment with paliperidone extended-release (ER) tablets on the sleep profile of patients with schizophrenia. METHODS: A total of 984 patients meeting the The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia who switched their antipsychotic to paliperidone ER were recruited from 61 sites in five countries in Southeast Asia. We recorded patient demographics and assessed sleep quality and daytime drowsiness using visual analog scales. RESULTS: Approximately 70% of patients completed the 6-month study. After the use of paliperidone ER, patients reported significantly better sleep quality (76.44 vs 65.48; p<0.001) and less daytime drowsiness compared with their baseline value (23.18 vs 34.22; p<0.001). Factors predicting sleep profile improvement were completion of the study and higher baseline Positive and Negative Syndrome Scale scores. CONCLUSION: Paliperidone ER can help schizophrenia patients to improve sleep quality and reduce daytime drowsiness; this was seen especially in the patients who completed the 6-month treatment period and had higher baseline Positive and Negative Syndrome Scale scores.

Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

BACKGROUND: The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. RESEARCH DESIGN AND METHODS: These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. RESULTS: In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. CONCLUSION: PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

Safety and efficacy of paliperidone extended-release in Chinese patients with schizophrenia: a 24-week, open-label extension of a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The long-term safety, tolerability, and efficacy of paliperidone extended-release (ER) were evaluated in Chinese patients with schizophrenia. METHODS: Patients (aged ≥18 years) with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria) who had completed run-in (8-week), stabilization (6-week), and double-blind (DB) phases (variable) of a phase-3, placebo-controlled study entered this 24-week, open-label extension (OLE) study. These patients, who had either experienced a relapse or remained relapse-free through DB phase of the study, were treated with flexible-dose paliperidone-ER (3-12 mg/day) during the OLE phase. Major safety evaluations included treatment-emergent adverse events (TEAEs) and extrapyramidal symptoms. Efficacy endpoints included changes in Positive and Negative Syndrome Scale total score, Clinical Global Impression-Severity scale, and Personal and Social Performance scale from OLE baseline to OLE endpoint. RESULTS: Out of 106 patients who entered the OLE phase (placebo: 59, paliperidone-ER: 47), a total of 85 (80%) completed it. Thirty-five (33%) patients experienced at least one TEAE; most common were akathisia, somnolence, nasopharyngitis, and constipation (3.8% each). Serious TEAEs were noted in two patients (completed suicide; schizophrenia worsening). No TEAEs with an onset during the OLE phase led to discontinuation. Extrapyramidal symptoms related-TEAEs were reported in eight (7.5%) patients. Mean (standard deviation) changes in Positive and Negative Syndrome Scale total scores (-10.4 [13.2]), Clinical Global Impression-Severity scores (-0.6 [0.96]) and Personal and Social Performance scores (7.4 [13.2]) from OLE baseline to OLE endpoint showed patients who had been treated with placebo during the DB phase experienced more pronounced improvements. CONCLUSION: In this OLE study, flexibly dosed paliperidone-ER (3-12 mg/day) was tolerable and efficacious in Chinese patients with schizophrenia.

Repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorders: Double blind randomized clinical trial.

Repetitive transcranial magnetic stimulation (rTMS) has become widely used as a therapeutic tool in psychiatric research. The aim of this study was to evaluate the impact of different frequencies of rTMS over right dorsolateral prefrontal cortex (DLPFC) in OCD. Forty five patients with OCD participated in the study. Patients were evaluated using: Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity scale (CGI-S). They were randomly classified into three groups: 1st group received 1Hz rTMS; 2nd group received 10Hz rTMS; and 3rd group received sham stimulation all at 100% of the resting motor threshold for 10 sessions. They were followed up after the last treatment session and 3 months later. There was a significant "time"×"group" interaction for 1Hz versus Sham but not for 10Hz versus Sham. 1Hz versus 10Hz groups showed a significant interaction for Y-BOCS and HAM-A (P=0.001 and 0.0001 respectively). 1Hz rTMS has a greater clinical benefit than 10Hz or Sham. There was also a significantly larger percentage change in GCI-S in the 1Hz group versus either 10Hz or sham. We conclude that 1Hz-rTMS, targeting right DLPFC is a promising tool for treatment of OCD.

D-cycloserine augmentation in behavioral therapy for obsessive-compulsive disorder: a meta-analysis.

OBJECTIVE: To evaluate the overall effect of D-cycloserine (DCS) augmentation on exposure and response prevention (ERP) therapy for obsessive-compulsive disorder (OCD). METHODS: Clinical studies on the effect of DCS augmentation on ERP therapy for OCD compared to placebo were included for meta analysis. The primary outcome was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Meta-analyses were performed with a random-effect model or a fixed-effect model using the Cochrane Review Manager (RevMan, version 5.2) to calculate the odds ratio and the mean difference, with their corresponding 95% confidence intervals. RESULTS: A total of six studies was included in the current meta-analyses, and their data were extracted. Among them, four were for analyses of DCS and Y-BOCS at midtreatment, six for analysis at posttreatment, and four at 3-month follow-up. Besides, three of the six eligible studies were included in the meta-analysis of the DCS and Clinical Global Impression-Severity Scale at posttreatment, and three in the meta-analysis of DCS and proportions of treatment responders and of subjects attaining clinical remission status criteria at posttreatment. Our meta-analyses do not reveal a significant effect of DCS augmentation in ERP therapy for OCD patients, except when measured at midtreatment. Compared to the placebo group, DCS augmentation did show a trend toward significantly lower/decreased Y-BOCS; when measured at posttreatment and in the subpopulation of DCS taken before some of the ERP sessions, DCS augmentation showed a trend toward significantly lower/decreased Y-BOCS. CONCLUSION: Our result suggested that with the careful optimization of DCS-augmented ERP therapy by fine-tuning timing and dosing of DCS administration and number and frequency of ERP sessions, DCS may enhance the efficacy of ERP therapy in reducing the symptomatic severity of OCD patients, especially at early stage of the treatment; therefore, DCS augmentation could possibly reduce treatment cost, reduce treatment drop and refusal rate, and help to improve access to the limited number of experienced therapists.

A cross-sectional study on perception of stigma by Chinese schizophrenia patients.

OBJECTIVE: In this cross-sectional study, we sought to assess the extent of internalized stigma among inpatients and outpatients with schizophrenia in the People's Republic of China and to investigate whether education level correlated with the experience of stigma. METHODS: Schizophrenia patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity of Illness (CGI-S) scale and the Stigma Scale for Mental Illness (SSMI-C). Patients were categorized into high education and low education groups, according to their educational levels. RESULTS: One hundred thirty-three subjects were included in the study. Their mean course of illness was 4.32±6.14 years (range: 1 month to 15 years). Their mean BPRS score was 19.87±5.46, their mean PANSS score was 44.11±13.1, and their mean CGI-S score was 2.22±0.81. In addition, their mean SSMI-C score was 6.49±0.9. The mean SSMI-C score of patients who have received high school education or above was 7.15±0.98, which was markedly higher than that of patients who have received middle school education or below, which was 5.75±0.79 (P<0.05). Before the study most patients (92.5%, 123/133) took atypical drugs. CONCLUSION: Education level impacts on the perception of stigma by schizophrenia patients, and more psychoeducation should be undertaken to improve patients' knowledge about schizophrenia.

Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use.

The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine.

Relief of depression and pain improves daily functioning and quality of life in patients with major depressive disorder.

OBJECTIVE: The objective of this study was to investigate the effects of depression relief and pain relief on the improvement in daily functioning and quality of life (QOL) for depressed patients receiving a 6-week treatment of fluoxetine. METHOD: A total of 131 acutely ill inpatients with major depressive disorder (MDD) were enrolled to receive 20mg of fluoxetine daily for 6 weeks. Depression severity, pain severity, daily functioning, and health-related QOL were assessed at baseline and again at week 6. Depression severity, pain severity, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed by three primary domains of the SF-36, including social functioning, vitality, and general health perceptions. Pearson's correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. In model 1, depression relief alone improved daily functioning and QOL. In model 2, pain relief alone improved daily functioning and QOL. In model 3, depression relief, mediated by pain relief, improved daily functioning and QOL. In model 4, pain relief, mediated by depression relief, improved daily functioning and QOL. In model 5, both depression relief and pain relief improved daily functioning and QOL. RESULTS: One hundred and six patients completed all the measures at baseline and at week 6. Model 5 was the most fitted structural equation model (χ(2) = 8.62, df = 8, p = 0.376, GFI = 0.975, AGFI = 0.935, TLI = 0.992, CFI = 0.996, RMSEA = 0.027). CONCLUSION: Interventions which relieve depression and pain improve daily functioning and QOL among patients with MDD. The proposed model can provide quantitative estimates of improvement in treating patients with MDD.