Baseline Young Mania Rating Scale Research Articles

0642 Effect of Iloperidone on Sleep Symptoms in Bipolar Patients with Manic and Mixed Episodes: A Randomized, Placebo Controlled Study

Abstract Introduction Iloperidone, a dopamine D2 receptor and serotonin 5HT2A receptor antagonist, was evaluated for the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a phase 3 clinical trial. A core symptom of bipolar I disorder is disturbance in sleep. During manic episodes this commonly presents as reduced need for sleep with studies finding that 69%–99% of bipolar individuals report a lessened need for sleep or difficulties in falling and/or staying asleep. Here we present a post hoc analysis evaluating iloperidone effects on the sleep component of the Young Mania Rating Scale (YMRS) in patients with bipolar I disorder which addresses both sleep and the reduced need for sleep in that component. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of iloperidone in patients with acute manic or mixed episodes associated with bipolar I disorder. Patients received four weeks of double-blind treatment. The primary analysis demonstrating an overall improvement from baseline YMRS score in iloperidone assigned patients versus placebo assigned patients (p = 0.000008) at the end of the study (week 4). A YMRS item level analysis evaluated changes on YMRS single items including the sleep component in the intent-to-treat population (N = 392) using a mixed-effects model for repeated measures approach. Results The least squares mean difference (LSMD) in change from baseline to day 28 was statistically significant on the YMRS sleep component in favor of iloperidone versus placebo (iloperidone = -1.26, placebo = -0.95; p = 0.008). Conclusion In addition to improving overall mania symptoms as reported by the YMRS, improvements were also seen in iloperidone treated patients in the sleep component which at baseline included assessments of both decreased sleep and decreased need or denial of the need for sleep. Support (if any) This work was supported by Vanda Pharmaceuticals Inc.

Comparison of effectiveness between Haloperidol and Quetiapine in acute manic episode.

This study was conducted to compare the response rate of Quetiapine and Haloperidol in patients with acute manic episodes. A total of 120 patients with acute episode of mania with baseline Young Mania Rating Scale (YMRS) of more than 20 were included and randomly allocated to either Quetiapine (Group A) or Haloperidol (Group B). Each patient was assessed at baseline. YMRS was administered at the start and at follow-up visit after six weeks. Comparison of response rate (>50% reduction in YMRS) was not statistically significant between the two groups (70% vs. 71.7%; p=0.410) after six weeks in acute manic episode. Quetiapine and Haloperidol emerged as equally effective pharmacological strategies for the treatment of bipolar mania. Quetiapine may be used as an alternative to conventional antipsychotics; Haloperidol can be used as replacement of Quetiapine as well, as it is of low cost.

A Randomized, Double-Blind Placebo-Controlled Trial on Effectiveness and Safety of Celecoxib Adjunctive Therapy in Adolescents with Acute Bipolar Mania.

Recent studies have focused on the role of inflammatory cascades as one of the possible etiologic factors of bipolar disorder. We hypothesize that celecoxib, through its anti-inflammatory properties, may have a therapeutic role in acute bipolar mania. Forty-two adolescent inpatients with the diagnosis of acute bipolar mania participated in a parallel, randomized, double-blind controlled trial, and 40 patients underwent an 8-week treatment with either celecoxib (100 mg twice daily) or placebo as an adjunctive treatment to lithium and risperidone. Patients were evaluated using Young Mania Rating Scale (YMRS) at baseline and weeks 2, 4, and 8. The primary outcome measure was to assess the efficacy of celecoxib compared with placebo in improving mania symptoms. General linear model repeated measures showed significant effect for time × treatment interaction on YMRS scores [F (2.54, 96.56) = 3.21, p = 0.03]. Significantly greater improvement was observed in YMRS scores in the celecoxib group compared with the placebo group from baseline YMRS score at week 8 (p = 0.04). Although a 35% greater response to treatment (considering a Clinical Global Impressions-Improvement score of ≤2, very much/much improved) was observed in the celecoxib group compared with the placebo group, the difference did not reach the statistical significance level (p = 0.09). No serious adverse event was reported. Celecoxib may be an effective adjuvant therapy in treatment of manic episodes (without psychotic features) of adolescents with bipolar mood disorder. The mood-stabilizing role of this drug might be mediated through its action on inflammatory cascades.

Efficacy of Sodium Valproate and Olanzapine in treating bipolar affective disorder 'mania' at a tertiary care hospital in Nepal: A comparative study

Background and Objectives: Bipolar affective disorder, mania is the mood of an abnormally elevated arousal energy level or a state of heightened overall activation with enhanced affective expression together with lability of affect. The objective of the study was to compare the efficacy of sodium valproate and olanzapine in bipolar affective disorder, mania patients at a tertiary care hospital in NepalMaterial and Methods: A randomized observational prospective open label study was conducted for one and half year at College of Medical Sciences-Teaching Hospital (CMS-TH), Bharatpur, Nepal in the Psychiatry Department. Sixty patients diagnosed with bipolar affective disorder, mania were enrolled. 30 patients received sodium valproate and 30 patients received olanzapine. Patients were monitored and evaluated on baseline (day 0), day 7 and day 30 and compared to the baseline for the severity of illness using the 11-item Young Mania Rating Scale (YMRS).Results: The mean baseline YMRS score for all cases on sodium valproate (n=30) on day 0 was 38.87 ± 3.73, while it was reduced to 13.90 ± 1.95 (p < 0.001) on day 30. Similarly, the mean baseline YMRS score for all cases on olanzapine (n=30) on day 0was 40.83 ± 6.50, while it was reduced to 14.47 ± 2.83 (p < 0.001) on day 30.The mean decrease in YMRS score by sodium valproate was 64.24% and by olanzapine was 64.56%.Conclusion: Treatment with sodium valproate and olanzapine significantly improves the mean mania ratings score and there is no statistically significant difference in efficacy of both the drugs in patients diagnosed with bipolar affective disorder, mania.Janaki Medical College Journal of Medical Sciences (2016) Vol. 4(1): 27-35

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking. This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (-0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.

Electroconvulsive therapy in 197 patients with a severe, drug-resistant bipolar mixed state: treatment outcome and predictors of response.

We prospectively evaluated the short-term outcome and the predictors of response to electroconvulsive therapy (ECT) in a large sample of patients with a bipolar mixed state. From January 2006 to May 2011, we performed an analysis using data obtained from 197 of 203 consecutive patients with a bipolar mixed state, according to DSM-IV-TR diagnostic criteria, who were treated with ECT at the Department of Psychiatry of the University of Pisa. All patients were evaluated prior to and after the ECT course using the Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scale. The CGI subscale "global improvement" and final HDRS-17 and YMRS total scores were used to identify nonresponder, responder, and remitter groups. At the end of the ECT course, 55 patients (27.9%) were considered nonresponders, 82 responders (41.6%), and 60 remitters (30.5%). As expected, at the end of the ECT trial, the CGI-Severity scale (CGI-S; P < .0001), HDRS-17 (P < .0001), and BPRS (P < .0001) scores were significantly lower in remitters than in responders and nonresponders. Using backward stepwise logistic regression, the length of current episode, lifetime comorbidity of obsessive-compulsive disorder, and baseline YMRS total mean score were statistically significant predictors of nonresponse versus remission (P < .0001). Less than 30% of the patients included in the study were nonresponders to ECT. Long-lasting mixed episode with excitatory symptoms and lifetime comorbidity of obsessive-compulsive disorder significantly predicted a lack of complete remission.

Asenapine in Clinical Practice: Responders Vs Non-responders

Introduction Asenapine is a second-generation antipsychotic approved in Europe for the treatment of manic or mixed episodes. Objective To describe the clinical features of Asenapine responders and non-responders. Methods A naturalistic, observational study is ongoing in patients treated with Asenapine. We have already recruited 37 manic patients with a lifetime diagnosis of Bipolar I (BDI) or Schizoaffective Disorder referring to our Psychiatric Ward. Patients are assessed with the Young Mania Rating Scale (YMRS) at baseline (T0), and after 1 (T1) and 4 weeks (T2) of treatment. According to YMRS scores, patients are classified as responders and non-responders. Results The preliminary results highlight a significant improvement of the YMRS score from T0 to T2 in most patients. Asenapine seems particularly effective in patients with less severe manic symptoms, and responders are more likely to have lower baseline YMRS score. No correlation has currently emerged between responder status and diagnosis. Non-responders in our sample are females sharing some clinical features: early onset BDI diagnosis, several previous treatments (antipsychotics, mood stabilizers), initial cognitive impairment confirmed with the Mini Mental State Examination, Alzheimer Disease Assessment Scale and neuroimaging. Conclusions Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes and poorer response to pharmacological treatment, which may prove effective in reducing agitation but not mania ratings. Diagnosis (BDI or schizoaffective disorder) does not seem to have a significant impact on Asenapine efficacy. The further recruitment and assessment of patients is expected to support the results described above.

Predictors of Remission in 208 Drug-Resistant Depressive Patients Treated With Electroconvulsive Therapy

This study aimed to explore predictors of remission to electroconvulsive therapy (ECT) in a sample of depressive patients resistant to pharmacological treatments. Two hundred eight patients, 31 of whom had major depressive disorder, 101 had bipolar disorder II (BP II), and 76 had bipolar disorder I (BP I), diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were treated with bilateral ECT on a twice-a-week schedule. All patients included were undergoing a depressive episode, excluding patients with mixed and manic episodes. Patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale, and the Clinical Global Impression-Improvement (CGI-I). At the end of the ECT course, 56 patients (26.9%) were considered nonresponders, and 80 patients (38.4%) were considered responders (HAM-D score of at least 50% and CGI-I subscale rating of 2, "much improved") and 72 remitters (34.6%) (HAM-D scores ≤8 and a CGI-I subscale rating of 1). On backward stepwise logistic regression length of current episode, Bipolar Disorder and baseline YMRS total mean scores were statistically significant predictors of nonresponders versus remitters. Among the YMRS items at basal evaluation 8 (thought content), 10 (appearance), and 11 (insight), the mean scores were significantly lower in the remitters than in the responders and nonresponders. Major depressive disorder, short duration of the current episode, absence of psychotic symptoms, preserved insight, and adequate personal care are associated with complete remission in our sample of drug-resistant depressive patients treated with ECT.

Early improvement with lithium in classic mania and its association with later response

Despite lithium's clinical efficacy in treating mania in bipolar disorder (BD), studies evaluating early improvement and subsequent treatment response are sparse. This study investigated whether early improvement (within one week) to lithium monotherapy predicted later response and remission in individuals with BD mania. BD-I patients (n=46) experiencing a manic episode received lithium monotherapy for four weeks (initial dose: 600mg/d, adjusted to therapeutic levels); individuals experiencing a mixed episode, rapid cyclers, previous non-responders to lithium, and those with current drug abuse/dependence were excluded. Symptoms were rated using the Young Mania Rating Scale (YMRS) at baseline and at Days 7, 14, 21, and 28. Thirty-three percent of the total sample responded to lithium within the first week of treatment, defined as a ≥50% decrease from baseline YMRS scores; 63% responded by study endpoint. In addition, 39% of the total sample showed early improvement (at least 20% decrease in YMRS scores) after one week of treatment. In this group, 79% responded to lithium by study endpoint. Among those showing less than 20% improvement at Week 1, only 23% responded to lithium by study endpoint. History of episodes sequence was not assessed. Early improvement in response to lithium monotherapy in subjects with BD mania predicted later response and remission. Most patients who did not show early improvement in response to lithium during the first week of treatment showed no response after one month. The findings provide a valuable clinical tool for early identification of those patients most likely to benefit from lithium in clinical practice.

Age-grouped differences in bipolar mania

ObjectiveThis review of published studies compares scores on individual items of mania rating scales that systematically recorded symptom severity in persons diagnosed with bipolar disorder to identify age-grouped differences. MethodsAn extensive literature search identified item scores from mania rating scales, with a particular emphasis on baseline Young Mania Rating Scale (YMRS) item scores in published double-blind, placebo-controlled studies of bipolar I manic disorder. These baseline YMRS item scores were assessed as a proportion of the total YMRS score and compared by age group. Additional YMRS item/total scores in subjects with bipolar spectrum disorders were added to expand the analysis. ResultsPreadolescents with bipolar disorder had significantly higher YMRS item scores than adolescents on aggression, irritability, and motor activity. Young Mania Rating Scale baseline item scores relative to the YMRS total score revealed that adolescents diagnosed with bipolar I mania scored comparatively higher than did adults on YMRS aggression and irritability items, whereas adults with bipolar I manic disorder scored comparatively higher on the grandiosity and sexual interest items. Age-grouped findings from subjects diagnosed with bipolar I, II, and Not Otherwise Specified (NOS) disorders yielded similar age-grouped results. ConclusionIn age-grouped YMRS item assessments of bipolar mania, anger dyscontrol was most prominent for youth, whereas disordered thought content was paramount for adults.

Correlates of Treatment Response in Depressed Older Adults With Bipolar Disorder

To identify baseline clinical factors associated with acute treatment response in depressed older adults with bipolar disorder (BD) receiving lamotrigine. Secondary analysis of a multisite, 12-week, open-label, uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was measured with total serum cholesterol and the Cumulative Illness Rating Scale-Geriatric (CIRS-G) item #13 (endocrine/metabolic burden). Neurocognitive (executive) function was evaluated using the Trail Making Test. Greater reduction in MADRS from baseline was associated with higher baseline cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12 weeks, improvement in the MADRS from baseline was no longer significantly related to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of MADRS scores corroborated these findings with a significant finding of time-by-baseline cholesterol level interaction. In a subset of participants, better baseline executive function was related to greater improvement in the MADRS at 9 weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS scores were related to greater likelihood of dropout. Lamotrigine appears to work best in depressed elderly patients with BD who have high cardiometabolic risk and low level of mania. Agents like lamotrigine that act primarily on neuroprogressive pathways involving oxidative stress, neurotrophins, and inflammation may be particularly effective in individuals with BD who have significant cardiometabolic burden because of their effects on shared vulnerability factors in BD and medical illness.

Asenapine as Adjunctive Treatment for Acute Mania Associated With Bipolar Disorder

In a 12-week randomized, placebo-controlled study evaluating the efficacy and safety of adjunctive asenapine, bipolar I disorder patients experiencing manic or mixed episodes despite pretreatment with lithium or valproate monotherapy were treated with flexible-dose, twice-daily asenapine 5 or 10 mg (n = 158) or placebo (n = 166). The primary efficacy end point was change from baseline Young Mania Rating Scale (YMRS) total score at week 3. Secondary outcomes included YMRS response and remission and Clinical Global Impression for Bipolar Disorder and Montgomery-Asberg Depression Rating Scale score changes. Patients completing the core study were eligible for a 40-week double-blind extension assessing safety and tolerability. Adjunctive asenapine significantly improved mania versus placebo at week 3 (primary end point) and weeks 2 to 12. The YMRS response rates were similar at week 3 but significantly better with asenapine at week 12. The YMRS remission rates and changes from baseline on Clinical Global Impression for Bipolar Disorder for mania and overall illness were significantly better with asenapine at weeks 3 and 12. No other statistically significant differences on secondary outcomes were observed. Only a small number of patients entered the extension, making firm statistical conclusions on efficacy difficult. Treatment-emergent adverse events reported by 5% or more of asenapine patients and at twice the incidence of placebo were sedation, somnolence, depression/depressive symptoms, oral hypoesthesia, and increased weight in the 12-week core study. Adjunctive asenapine to lithium or valproate was more effective than mood stabilizer monotherapy in the core study and was well tolerated for up to 52 weeks.

Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression

This study aimed to ascertain predictors of nonresponse to electroconvulsive therapy (ECT) in a large sample of major depressive patients resistant to pharmacologic treatment. A total of 208 depressive patients (31 with major depression [UP], 101 with bipolar disorder II [BP II], and 76 with bipolar disorder I [BP I] according to DSM-IV criteria) were included in the study and treated with bilateral ECT on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Improvement (CGI). Responders were defined as those patients with a reduction of at least 50% in HAM-D-17 score and a rating of 2 ("much improved") or 1 ("very much improved") in the CGI-Improvement subscale. At the end of the ECT course, 152 patients (64%) were classified as responders and 56 patients (36%) were classified as nonresponders. On backward stepwise logistic regression, bipolar subtype (odds ratio [OR]=17.85; 95% confidence level [CL]=1.786-178.407), higher mean baseline YMRS scores (OR=1.094; 95% CL=1.025-1.166), lower mean baseline HAM-D-17 scores (OR=0.928; 95% CL=0.860-1.002), and length of current episode (OR=1.047; 95% CL=1.009-1.086) were identified as statistically significant predictors of nonresponse. ECT was an effective treatment for approximately two-thirds of the patients with medication-resistant depression who were included in this study. ECT nonresponse was associated with bipolar subtype, presence of manic symptoms during depression, slightly less severe depressive symptomatology, and protracted duration of the episode.

Study design and patient characteristics and outcome in acute mania clinical trials

The objective of this systematic review was to identify trial design and patient characteristics associated with symptom improvement in acute mania clinical trials. Drug trials in acute mania that used the Young Mania Rating Scale (YMRS) score as the primary endpoint were identified using a systematic search strategy. Details of the trial, patient population, and treatment assignment were recorded. Covariates associated with change in YMRS were analyzed using a multiple regression model. A total of 41 studies, comprising 89 treatment arms and 10,471 patients, were selected for this analysis. Three variables were statistically significantly associated with change in YMRS score: treatment assignment, baseline mania score, and study location. Compared with placebo, greater mean (95% confidence interval) reductions in YMRS score were noted for all three active treatment arms [-4.7 (-6.4 to -3.0) for mood stabilizers; -5.9 (-7.6 to -4.2) for antipsychotics; and -8.3 (-10.2 to -6.4) for combined mood stabilizer/antipsychotics; all comparisons p < 0.0001]. Greater changes in YMRS score were associated with higher baseline YMRS scores (p = 0.002) and with studies performed outside of the USA (p= 0.02). Year of study publication was not associated with YMRS score change. Study size, number of study sites, YMRS score required for study entry, inclusion of patients with mixed mania or treatment resistance, and enrollment of inpatients versus outpatients had no significant influence on change in YMRS score. These findings may assist in the design of future drug trials for acute mania.

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Objective: Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression. Method: A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania. Results: Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder. Conclusions: These data suggest that minimal manic symptoms at baseline co-existing with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression. (Reprinted with permission from American Journal of Psychiatry 2009; 166:164–172)

Comparison of Open-Label, 8-Week Trials of Olanzapine Monotherapy and Topiramate Augmentation of Olanzapine for the Treatment of Pediatric Bipolar Disorder

The aim of this study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents. Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23). Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg. Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.

Baseline Characteristics and Outcomes in Patients With First Episode or Multiple Episodes of Acute Mania

Previous studies have reported differential responses to therapeutic interventions depending on the patient's history with bipolar disorder, which highlights the importance of understanding the longitudinal nature of the disorder. The goal of the present analyses was to describe and compare the baseline characteristics, response to treatment, and medication patterns in adult patients experiencing a first episode versus multiple episodes of mania. The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study was a 2-year prospective, observational study to evaluate outcomes in patients experiencing a DSM-IV- or ICD-10-diagnosed manic or mixed episode. The study was conducted from December 2002 to June 2004. Among 3,115 patients, 256 (8.2%) enrolled with a first manic or mixed episode. Relative to multiple-episode patients, first-episode patients were younger and had a lower body mass index (BMI), a higher incidence of past or current cannabis abuse, significantly higher baseline Young Mania Rating Scale total and Clinical Global Impressions-Bipolar Disorder (CGI-BP) mania scores, and lower CGI-BP depression and Hamilton Depression Rating Scale (5-item version) total scores. At the 12-week endpoint, rates of recovery and remission were greater for first-episode patients, and times to recovery and remission were shorter. Limitations of the study were that entry of patients into this study with an acute manic or mixed episode was determined by clinical interview but not confirmed with a structured diagnostic interview. That information on the course of illness prior to entry into the study was obtained retrospectively. First-episode patients presented with different baseline illness characteristics and achieved recovery and remission more rapidly than multiple-episode patients.

A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

ObjectivesTo compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study. MethodIn the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 μg/mL. Sixty-six patients enrolled in the extension study. ResultsIn the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER −8.8 [n = 74]; placebo −7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting. ConclusionsThe results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study.

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: A pilot study

Objective This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. Subjects and methods In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1000–2400 mg/day) or divalproex (750–2000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were ≤12 for remission and ≥15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. Results Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group ( p = 0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p < 0.01). Conclusion Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression. A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania. Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder. These data suggest that minimal manic symptoms at baseline coexisting with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression.