Case series of aripiprazole monotherapy in bipolar disorder with delayed sleep-wake phase syndrome.

Fatty acids and bipolar disorder

Recently, two large, 3-week, randomised, double-blind, placebo-controlled trials using nearly identical protocols demonstrated that monotherapy with carbamazepine extended-release capsules (CBZ-ERC) was effective for the treatment of acute mania in patients with bipolar I disorder. By pooling data from these two trials, a more highly powered analysis of the efficacy and safety of CBZ-ERC in bipolar I disorder could be conducted. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Clinical Global Impression (CGI)-Severity (CGI-S) scale, the CGI-Improvement (CGI-I) scale and the Hamilton Depression Rating Scale (HDRS). A sub-analysis of the data based on manic versus mixed presentation was performed, as well as sub-analyses by age, sex and ethnicity. Of the 443 randomised patients in the pooled population, 240 completed the studies. Forty-two percent of CBZ-ERC-treated patients did not complete the studies, compared with 50% of placebo-treated patients (p=0.087). Ten percent of patients given CBZ-ERC withdrew because of lack of efficacy, compared with 22% of patients given placebo (p<0.001). At endpoint, CBZ-ERC compared with placebo was associated with significant improvements in mean YMRS total scores in patients experiencing both manic (p<0.0001) and mixed (p<0.01) episodes, using last-observation-carried-forward analyses. CGI-I and CGI-S scores also showed significant improvements from baseline for both manic and mixed patients at endpoint. In patients with mixed episodes, at endpoint there was a mean improvement in HDRS total score of 4.8 points with CBZ-ERC, compared with 2.3 points with placebo (p<0.05). Ninety percent of patients given CBZ-ERC experienced an adverse event, compared with 64% of those patients given placebo. Discontinuation because of adverse events occurred in 10.8% of patients taking CBZ-ERC, compared with 5.5% of patients taking placebo. These results confirm previous findings that CBZ-ERC is effective in the treatment of bipolar I disorder patients with either acute manic or mixed episodes. These data suggest that further randomised controlled studies are warranted to delineate the effect of CBZ-ERC on depressive symptoms in patients with bipolar disorder.

The purpose of this study was to investigate the preliminary effectiveness and safety of lamotrigine for the treatment of depressive episodes in adolescents. This was a 12 week retrospective chart review of lamotrigine treatment among 37 adolescents (mean age 16.3±1.3 years) with depressive episodes (15 with bipolar disorder and 22 with major depressive disorder). Illness severity at the 4th, 8th, and 12th weeks were retrospectively scored using Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). The mean dose of lamotrigine was 65.4±37.5 mg/day (range 12.5-181.7 mg/day) for a mean duration of 199.9±217.4 days (range 14-879 days). The CGI-S scores were significantly decreased over 12 weeks (F=39.611, p<0.001, partial η2=0.531). Seventeen subjects (45.9%) showed a treatment response at 12 week follow up (defined by a CGI-I score ≤2). There were no differences in treatment effectiveness between the bipolar and unipolar groups. Overall, lamotrigine was well tolerated. The most common adverse event was skin rash (n=5, 13.5%), which resolved spontaneously after drug discontinuation. Our results provide preliminary evidence of the effectiveness and safety of lamotrigine in adolescents with bipolar and depressive disorders. Large, prospective, placebo-controlled studies are needed to confirm these findings.

BackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I), versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with schizophrenia are reported here.MethodsPatients with schizophrenia were randomized to receive Ari 2MRTU 960 every 56±2 days or AOM 400 every 28±2 days. Safety and tolerability assessments included adverse event (AE) reporting, Visual Analogue Scale [VAS] scores (scale range: 0–100) for patient-reported injection site pain, and extrapyramidal symptom (EPS) monitoring. Efficacy was evaluated at Week 32 using mean (standard deviation [SD]) Clinical Global Impression – Improvement (CGI-I) score, and mean (SD) change from baseline in Clinical Global Impression – Severity (CGI-S) score, Subjective Well-being under Neuroleptic Treatment – Short Form [SWN-S] Total score, and Positive and Negative Syndrome Scale (PANSS) Total score.ResultsStudy completion rate was 79.3% (73/92 patients) in the Ari 2MRTU 960 group and 67.7% (63/93 patients) in the AOM 400 group. Demographics and disease characteristics were well balanced between groups at baseline (mean [SD] PANSS Total score: Ari 2MRTU 960, 62.0 [13.5]; AOM 400, 61.8 [13.5]; mean (SD) CGI-S score: Ari 2MRTU 960, 3.3 [0.9]; AOM 400, 3.1 [0.9]). Treatment-emergent AE (TEAE) incidence was 66.3% with Ari 2MRTU 960 and 63.4% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 21.7%; AOM 400, 18.3%) and injection site pain (Ari 2MRTU 960, 15.2%; AOM 400, 9.7%). Mean (SD) VAS score for pain after last injection was 1.5 (4.58) with Ari 2MRTU 960 and 1.3 (2.79) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was similar between groups (Ari 2MRTU 960, 3.5 [1.0]; AOM 400, 3.6 [0.9]). Minimal change from baseline was seen at Week 32 in CGI-S score and SWN-S Total score. There was no clinically meaningful difference between the groups for PANSS Total score (difference of least squares mean change from baseline [95% confidence interval]: -0.9 [-3.5, 1.8]; p=0.5154).ConclusionsIn patients with schizophrenia, administration of Ari 2MRTU 960, as compared with AOM 400, was generally well tolerated, and clinical stability was maintained during the study.FundingOtsuka Pharmaceutical Development &amp; Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).

Identifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia. Adults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition. Of 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, ZPANSS = -2.21, p = 0.028; ZCGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02). A lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China. EudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.

Bipolar disorder is a common condition diagnosed by the occurrence of pathological mood elevation but most often dominated by dysphoria states. Over the past 10 years, understanding of bipolar disorder and the number of evidence-based treatments have increased dramatically. This article offers strategies for improving diagnostic confidence and simple benchmarks that facilitate integrating principles of evidence-based medicine into the management of patients with bipolar disorder. Simple systematic assessment techniques such as focusing the evaluation to assess the most extreme episode of mood elevation and longitudinal factors such as age of onset and course of illness can avoid errors of omission and raise diagnostic confidence. An iterative measurement-based treatment model that aims to bring patients and their supports into the collaborative care process for progressively better outcomes is recommended.

Ask the Expert: Treatment Strategy for Co-occurring Bipolar Disorder and Alcohol Abuse

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Context:The efficacy of yoga as an intervention for in-patients with psychosis is as yet unknown; although, previous studies have shown efficacy in stabilized out-patients with schizophrenia.Aim:This study aimed to compare the effect of add-on yoga therapy or physical exercise along with standard pharmacotherapy in the treatment of in-patients with psychosis.Settings and Design:This study was performed in an in-patient setting using a randomized controlled single blind design.Materials and Methods:A total of 88 consenting in-patients with psychosis were randomized into yoga therapy group (n=44) and physical exercise group (n=44). Sixty patients completed the study period of 1½ months. Patients who completed in the yoga group (n=35) and in the exercise group (n=25) were similar on the demographic profile, illness parameters and psychopathology scores at baseline.Results:The two treatment groups were not different on the clinical syndrome scores at the end of 2 weeks. At the end of 6 weeks, patients in the yoga group however had lower mean scores on Clinical Global Impression Severity (CGIS), Positive and Negative Syndrome Scale (total and general psychopathology subscale) and Hamilton Depression Rating Scale (HDRS) (P<0.05). Repeated measure analysis of variance detected an advantage for yoga over exercise in reducing the clinical CGIS and HDRS scores.Conclusion:Adding yoga intervention to standard pharmacological treatment is feasible and may be beneficial even in the early and acute stage of psychosis.

Lithium during pregnancy.

Study results supported that immuno-inflammatory pathways in the brain and environment contribute to the etiopathogenesis of bipolar disorder (BD), a chronic affective disease. Our study aimed to assess the relationship between BD risk and interleukin 2 (IL2) and interleukin 2 receptor subunit alpha (IL2RA) variants in a Turkish population. Genomic DNA from 86 diagnosed BD patients and 100 healthy blood donors was extracted. IL2RA rs2104286, IL2 rs2069762, and IL2 rs2069763 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. It was compared to the relationship between the genotype distributions of these variants and clinical characteristics. Results were evaluated statistically. A statistically significant difference in the genotype distribution of the IL2RA rs2104286 variant was found between patients and controls. There was no GG genotype in the patient group. The IL2RA rs2104286 AA genotype was more common in the patient group than the controls, and the AG genotype was higher in the controls compared to the patients (p = 0.001, p = 0.001, respectively). The IL2 rs2069762 and IL2 rs2069763 genotype distributions did not differ between the patient and control groups (p > 0.05). We found that the clinical global impression severity (CGI-S) score was higher in those with IL2 rs2069762 TG and GG genotypes. In this study, we showed for the first time that the genotype distribution of IL2RA rs2104286 and IL2 rs2069762 is associated with BD susceptibility and CGI-S score in a Turkish population.

A number of recent studies have questioned whether, despite modern treatment, the natural course of bipolar illness today still involves multiple relapses and impaired psychosocial functioning. This prospective follow-up study examined longitudinal outcome in a large group of inpatients with affective disorders. Fifty-one bipolar manic patients and 49 unipolar depressed patients were interviewed three times: 1) during hospitalization, 2) approximately 2 years after discharge, and 3) approximately 4.5 years after discharge. Subjects were treated under routine conditions and assessed for global adjustment, rehospitalization, and work and social functioning. Only 41% of the bipolar group had a good overall outcome by the time of the 4.5-year follow-up. The bipolar patients had more severe work impairment than the unipolar group. More than one-half of the bipolar patients were rehospitalized at least once during the 4.5-year follow-up period. Outcome for both diagnostic groups improved significantly over time. Many contemporary bipolar patients demonstrate gradual improvement in the first several years after hospitalization. However, a subgroup approaching 60% still experience poor posthospital adjustment in one or more areas of functioning.

Long-Term Follow-Up Study of Patients With Refractory Obsessive-Compulsive Disorder

Resilience is the capacity to bounce back from adversity. Severe mental illnesses are associated with poor and heterogeneous functional outcomes. Symptom remission is inadequate to achieve patient-oriented outcome, and positive psychopathology constructs like resilience have emerged as possible mediators. An exploration of resilience and its association with functional outcomes can drive therapeutic endeavors. To assess and compare the influence of resilience on disability among patients diagnosed and treated for bipolar disorder and schizophrenia in a tertiary care facility. Study design - Hospital-based, cross-sectional, comparative design; study population - patients of bipolar disorder and schizophrenia with 2-5 years illness and Clinical Global Impression - Severity (CGI-S) <4; sampling procedure - consecutive sampling; sample size - 30 patients each; scales used - Connor-Davidson Resilience Scale (CD-RISC), Indian Disability Evaluation and Assessment Scale (IDEAS), and CGI-S; patients were evaluated with IDEAS, and 15 persons with and without a significant disability were recruited in each group of schizophrenia and bipolar disorder. The mean CD-RISC 25 score for persons with schizophrenia was 73.60 ± 13.87, whereas that for persons with bipolar disorder was 78.10 ± 15.26. For schizophrenia, only CDRISC-25 scores are statistically significant (t = -2.582, P = 0.018) for predicting IDEAS global disability. For bipolar disorder, CDRISC-25 scores (t = -2.977, P = 0.008) and CGI-severity scores (t = 3.135, P = 0.005) are statistically significant for predicting IDEAS global disability. When disability is factored in, resilience is comparable in persons with schizophrenia and bipolar disorder. Resilience independently predicts disability in both groups. However, the type of disorder does not significantly affect the relationship between resilience and disability. Irrespective of diagnosis, higher resilience is associated with lower disability.

Background Bipolar disorder (BD) requires long-term management to prevent relapse of depressive episodes. The use of pramipexole, a dopamine agonist, in combination with mood stabilizers has been explored for its potential to prevent antidepressant relapse. Objective This case series aims to evaluate the efficacy and safety of pramipexole in combination with mood stabilizers in preventing antidepressant relapse in patients with bipolar disorder. Methods Two patients with bipolar disorder who were at high risk of relapse after discontinuation of antidepressants were treated with pramipexole in combination with mood stabilizers. Clinical assessments were conducted using the Mood Disorder Questionnaire (MDQ), Clinical Global Impression-Severity (CGI-S), Hamilton Depression Rating Scale (HDRS), and Global Assessment of Functioning (GAF) before and after the addition of pramipexole. Results The combination therapy of pramipexole and mood stabilizers effectively prevented relapse in both patients. MDQ scores decreased, CGI-S scores improved, HDRS scores reduced, and GAF scores increased, with no significant adverse effects reported over a follow-up period of 12 months. Conclusion Pramipexole in combination with mood stabilizers appears to be an effective and safe strategy for preventing antidepressant relapse in patients with bipolar disorder. These findings suggest that this combination therapy could be considered for patients at high risk of relapse after antidepressant discontinuation.