Mean Young Mania Rating Scale Scores Research Articles

Network analysis of comorbid aggressive behavior and testosterone among bipolar disorder patients: a cross-sectional study

Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%–38.7%), level III aggression was 29.5% (95%CI = 26.3%–32.6%), and level VI aggression was 7.0% (95%CI = 5.4%–8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, “Increased motor activity-energy” emerged as the central symptom, with the highest centrality expected influence, followed by “Emotional Instability” and “Disruptive/aggression behavior”. Notably, “Emotional Instability” appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, “Speech rate and amount” exhibited the strongest positive correlation with testosterone levels, followed closely by “Disruptive/aggression behavior”. The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, “Increased motor activity-energy” stood out as the most influential symptom, and “Speech rate and amount” acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.

Psychopathological profile and sagittal alignment in low-back pain

IntroductionLow-back pain requires comprehensive care using a biopsychosocial model. The psychologic dimension plays an important role, but the link between sagittal alignment and a given psychopathological profile is little studied. The aim of this study was to analyze the psychopathological profiles and sagittal parameters of a population with low-back pain and to assess the link. Material and methods205 patients, with a mean age of 49.6 years (range, 18–70 years), presenting chronic common low-back pain without radicular involvement, were included prospectively. Mood scores comprised: the self-administered “Hospital Anxiety and Depression Scale” (HAD), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D) and Young Mania Rating Scale (YMRS). Radiological parameters, measured on lateral full-spine radiographs, included: L1-S1 lordosis, T1-T12 kyphosis, pelvic incidence, pelvic tilt, sacral slope, sagittal vertical axis (SVA), T1 slope, and Roussouly type. ResultsMean HAM-A score was 16.1; 54% of patients had scores ≥14, indicating anxiety disorder. Mean HAM-D score was 10.8; 55% of patients had scores ≥10, indicating depressive disorder. Mean YMRS score was 2.6; only 1 patient had a score ≥20, indicating manic disorder. The 112 patients with HAM-A score >14 showed mean 51.6° L1-S1 lordosis (p=0.356), 48.3° T1-T12 kyphosis (p=0.590), –4.3mm C7 SVA (p=0.900), and 29.3° T1 slope (p=0.451). In case of HAM-A <14, there were no significant differences. The 113 patients with HAM-D score >10 showed significant differences in T1-T12 kyphosis (mean 49.0°; p<0.05) and T1 slope (30.2°; p<0.05); mean L1-S1 lordosis was 50.5° (p=0.861) and C7 SVA 1.6mm (p=0.462). In case of HAM-D <10, T1-T12 kyphosis was 45.5° (p<0.05) and T1 slope 26.2° (p<0.05); mean lordosis was 50.9° (p=0.861) and mean C7 SVA –7.1mm (p=0.259). Multivariate analysis found no significant link between Roussouly type and psychiatric scores: HAD (p=0.715), HAM-A (p=0.652), and HAM-D (p=0.902). ConclusionMore than 50% of patients with common low-back pain presented a mood disorder. Depressive disorder was associated with greater T1-T12 kyphosis and T1 slope. There was no relationship between psychiatric scores and overall sagittal alignment. Level of evidenceII.

Effect of long acting injectable antipsychotics on course and hospitalizations in bipolar disorder – a naturalistic mirror image study

Purpose To determining whether the addition of a long-acting injectable antipsychotic (LAI-AP) has a positive effect on prognosis in bipolar disorder. Materials and methods Medical records of patients with bipolar disorder who were using LAI-AP at least for one year in the community mental health center (CMHC) until March 2020 were investigated. Comparisons were made between the period of one year before and after the initiation of LAI-AP. Hospital admission was the primary outcome. Residual symptom severity and functionality were evaluated with Personal and Social Performance Scale (PSP), Young Mania Rating Scale (YMRS), and Beck Depression Inventory (BDI). Results There were 197 patients with bipolar disorder who were attending to the CMHC and 17 of them were under maintenance treatment with LAI-AP for at least one year. The LAI-APs used were aripiprazole (n = 8), paliperidone (n = 5) and risperidone (n = 4). Duration of illness was 13.5 ± 8.02 years and duration of LAI-AP treatment was 24.8 ± 22.74 months (median: 18). During the one-year period after the LAI-AP initiation, there were fewer days spent in hospital (2.5 ± 5.68 vs. 15.5 ± 20.59 days, p = .026) and the number of hospitalizations was lower than the year before the LAI-AP use (0.1 ± 0.39 vs. 0.9 ± 1.24 hospitalizations, p = .013). During the recovery period with LAI antipsychotics, there were mild residual symptoms presented with mean PSP (70.2), YMRS (1.7) and BDI (7.6) scores. Conclusion LAI-AP use may have positive effect on course for selected patients with a long history of bipolar disorder.

Cariprazine for the treatment of bipolar mania with mixed features: A post hoc pooled analysis of 3 trials

Background: When bipolar I disorder (BP-I) mania is accompanied by subsyndromal depressive symptoms, a more complicated illness presentation results. To qualify for the mixed features specifier during mania, the DSM-5 requires ≥3 “non-overlapping” depressive symptoms (DS); notwithstanding, concerns of this definition's ecological validity and implications for timely diagnosis remain.Methods: Herein, patients were pooled from three similarly-designed pivotal trials of cariprazine compared to placebo for BP-I mania (NCT00488618/NCT01058096/NCT01058668) in post hoc analyses of mixed features using three criteria: ≥3 DS (DSM-5), ≥2 DS, and Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥10. Efficacy of cariprazine compared to placebo was assessed (Week 3) by Young Mania Rating Scale (YMRS) and MADRS scores and rates of mania response and remission.Results: In pooled patients (N = 1037), cariprazine significantly improved mean YMRS scores compared to placebo for each criterion; LSMDs were ≥3 DS = -3.79 (P = .0248), ≥2 DS = -2.91 (P = .0207), and ≥10 MADRS = -5.49 (P < .0001). More cariprazine- than placebo-treated patients met YMRS response and remission criteria, reaching significance for response in ≥2 DS (34% versus 47%; number-needed-to-treat [NNT] = 8, P = .0483) and ≥10 MADRS(31% versus 57%, NNT = 4, P < .0001) and for remission in ≥2 DS (27% versus 39%, NNT = 9, P = .0462), ≥10 MADRS (23% versus 44%, NNT = 5, P < .0001). Depressive symptoms were improved compared to placebo, reaching statistical significance in the MADRS ≥10 subgroup (LSMD = -1.59, P = .0082).Limitations: Post hoc analysis, MADRS < 18 entry criterion may have prevented assessment of MADRS changes.Conclusions: Cariprazine significantly reduced manic and depressive symptoms in patients with mixed features with differential efficacy across the subgroups analyzed herein.

Virtual Patients in Psychiatry: A Study of Mania And Schizophrenia.

This study using computer graphics based Virtual Patients of Mania and Schizophrenia is the first of its kind in Psychiatry in India. In Psychiatry, Virtual patients instead of live patients offer many advantages in cases of violence, suicide, complex phenomenology and where typical cases are few. 104 medical students of Maharajah's Institute of Medical Sciences, Nellimarla, India volunteered to rate the 3min 20 sec animation graphics video portraying Ravi as Mania and George as Schizophrenia using Young Mania Rating Scale (YMRS) and Positive and Negative Symptoms of Schizophrenia (PANSS). 53 students of Fifth Semester in two batches of 28 and 25 were compared with 51 students of Eighth Semester on their scoring patterns. All batches had mean YMRS and PANSS scores above cutoff indicating positive diagnosis but those with at least 5 hour theory exposure prior had significantly higher scores on PANSS and YMRS. The major differences in scoring were on Negative symptoms and YMRS. In conclusion, computer generated 3 d graphic virtual patients are quite effective as teaching tools in psychiatry.

Haloperidol, risperidone and quetiapine in the treatment of acute severe manic episode in bipolar disorder: The experience at the mood disorder unit in Milan

IntroductionPatients affected by severe manic episode, often with delusional symptoms, are commonly treated with a combination of mood stabilizers, antipsychotics and other sedatives. The choice of a specific drug, dose and term is still debated.ObjectivesA naturalistic study on a sample of 84 inpatients affected by acute severe mania treated with a combination therapy.AimsTo compare efficacy and tolerability of haloperidol/risperidone/quetiapine in association with lithium and/or valproate.MethodsEighty-four bipolar inpatients affected by a manic episode according to DSM-5 criteria. Drugs administered according to our best practice. Clinical course weekly monitored with Young Mania Rating Scale (YMRS) for 4weeks. Extrapiramidal side effects (EPSE) monitored with Saint Hans Rating Scale (SHRS).ResultsTwenty-five men (29.76%) and 59 women (70.24%); mean age 43.37 ± 13.58 years. Mean YMRS score T0 40.27 ± 9.04. Forty-one patients (48.81%) treated with haloperidol (3.4 mg/die); 16 (19.05%) with risperidone (4.3 mg/die); 27 (32.14%) with quetiapine (438 mg/die). The 3 groups showed no difference regarding clinical characteristics and YMRS basal scores. Chi2 analysis confirmed an higher response rate (50% of reduction of YMRS final score compared to T0) with haloperidol (χ2 = 14.88; P = 0.00). The repeated-measures model analysis showed a significant decrease (P &lt; 0.05) in YMRS scores in haloperidol vs. risperidone vs. quetiapine patients for all time points from second week. No statistical difference for EPSE was found.ConslusionsWe suggest that haloperidol could be advisable in the treatment of severe mania, with rapid efficacy, even with low doses. Occurrence of EPSE was not considerable during the acute treatment. Studies with a larger sample size, randomization, fixed doses, double blind design are needed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A multinational study to pilot the modified Hypomania Checklist (mHCL) in the assessment of mixed depression

BackgroundMixed depression is a common, dimensional phenomenon that is increasingly recognized in unipolar and bipolar disorders. We piloted a modified version of the Hypomania Checklist (mHCL-32) to assess the prevalence and clinical correlates of concurrent manic (hypo) symptoms in depressed patients. MethodsThe mHCL-32, Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAMD-24) were utilized in the assessment of unipolar (UP=61) and bipolar (BP=44) patients with an index major depressive episode confirmed by the Structured Clinical Interview for DSM-IV (SCID). Differential mHLC-32 item endorsement was compared between UP and BP. Correlation analyses assessed the association of symptom dimensions measured by mHCL-32, YMRS and HAMD-24. ResultsThere was no significant difference between mood groups in the mean mHCL-32 and YMRS scores. Individual mHLC-32 items of increased libido, quarrels, and caffeine intake were endorsed more in BP vs. UP patients. The mHCL-32 active-elevated subscale score was positively correlated with the YMRS in BP patients and negatively correlated with HAMD-24 in UP patients. Conversely, the mHCL-32 irritable-risk taking subscale score was positively correlated with HAMD-24 in BP and with YMRS in UP patients. LimitationsSmall sample size and cross-sectional design. ConclusionModifying the HCL to screen for (hypo) manic symptoms in major depression may have utility in identifying mixed symptoms in both bipolar vs. unipolar depression. Further research is encouraged to quantify mixed symptoms with standardized assessments.

A double‐blind, placebo‐controlled study of adjunctive calcitonin nasal spray in acute refractory mania

Calcitonin, a neuropeptide, has been shown in preliminary double-blind trials to reduce agitation in patients with acute mania. Given that it has effects similar to those of lithium and anticonvulsants on modulation of second-messenger signaling pathways and stabilization of neuronal membranes, this study examined the efficacy of calcitonin nasal spray in treating acute manic symptoms in patients with treatment-resistant mania using a double-blind, placebo-controlled design. A total of 46 hospitalized patients experiencing either a manic or a mixed episode, who were refractory to treatment with adequate doses of either a mood stabilizer or an antipsychotic, or a mood stabilizer/antipsychotic combination, and had a score of ≥16 on the Young Mania Rating Scale (YMRS), were randomized to receive adjunctive nasal calcitonin 200 IU (n = 24) or saline (n = 22) spray for three weeks. The primary efficacy measure was the change in YMRS scores using the last observation carried forward (LOCF) method. The clinical and demographic characteristics were similar between the groups. Patients had a mean YMRS score of 26 in the placebo group and a mean score of 25 in the calcitonin group. There were no significant differences in YMRS scores or percentage responders at three weeks between patients who received calcitonin and those who received placebo. There were also no significant differences in change scores on any other scales. Few patients experienced any adverse events. This study does not support the use of nasal calcitonin in the treatment of treatment-resistant mania.

A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents

Treatment studies for the management of pediatric bipolar disorder are limited. This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders. An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]). Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children's Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32.8 ± 6.1) were enrolled in the study and 11 (73 %) completed the 8-week trial. The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects. Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18.7 ± 13.9, p < 0.001) at endpoint. Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms. Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4.1 ± 5.5 lb) were substantial. Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth. Future placebo-controlled studies are warranted to confirm these findings.

Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study

Allopurinol promotes the salvage of purines, possibly increasing endogenous adenosine levels. Recent studies suggest that adenosine has neuroprotective and inhibitory effects. Two previous inpatient trials demonstrated that allopurinol has anti-manic activity. Our objective was to test allopurinol as an adjunct to standard medications in bipolar disorder manic outpatients. In this double-blind, placebo-controlled trial, 27 subjects who met DSM-IV criteria for bipolar disorder and scored ≥ 14 on the Young Mania Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo for six weeks. The primary efficacy measure was the YMRS. The primary safety measure was the Treatment Emergent Symptom Scale. The effect of allopurinol augmentation in decreasing mean YMRS scores was modest, with an overall effect size of -0.25 (Cohen's d). Allopurinol-treated individuals who abstained from caffeine (n = 4) had a greater decrease in YMRS scores (-15.3 ± 1.8) than subjects using caffeine (n = 5) (-9.6 ± 3.4, p = 0.219), with an effect size of -0.86. In this small outpatient pilot study, allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms. Subjects with restricted caffeine use showed a greater effect size compared to caffeine users. This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol's anti-manic effect in previous studies.

An open-label trial of divalproex sodium extended release for pediatric bipolar spectrum disorder in children age 6 - 12 years

Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.

A Prospective Open‐Label Trial of Lamotrigine Monotherapy in Children and Adolescents with Bipolar Disorder

To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. This was a 12-week, open-label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Thirty-nine children with bipolar disorder (YMRS at entry: 31.6 +/- 5.5) were enrolled in the study and 22 (56%) completed the 12-week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 +/- 128.3 in subjects <12 years of age (N = 22) and 219.1 +/- 172.2 mg/day in children 12-17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (-14.9 +/- 9.7, P < 0.001) at endpoint. Lamotrigine treatment also resulted in significant improvement in the severity of depressive, attention-deficit/hyperactivity disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 +/- 18.0 kg vs. 47.2 +/- 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Open-label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo-controlled, double-blind studies are warranted to confirm these findings.

A Prospective Open-Label Trial of Extended-Release Carbamazepine Monotherapy in Children with Bipolar Disorder

The aim of this study was to evaluate the safety and efficacy of extended release carbamazepine (CBZ-ER) monotherapy in the treatment of pediatric bipolar disorder (BD). This was an 8-week, open-label, prospective trial of CBZ-ER monotherapy (788 +/- 252 mg/day) to assess the effectiveness and tolerability of this compound in treating pediatric bipolar spectrum disorders. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale, Children's Depression Rating Scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Of the 27 participating children with BD, 16 (59.%) completed the study. CBZ-ER treatment was associated with statistically significant, but modest, levels of improvement in mean YMRS scores (-10.1 +/- 10.2, p < 0.001) with end-point mean YMRS score (21.8 +/- 12.2) suggesting a lack of complete resolution of mania. CBZ-ER treatment also resulted in significant improvement in the severity of depressive, attention-deficit/hyperactivity disorder, and psychotic symptoms. With the exception of 2 participants who discontinued due to skin rash, CBZ-ER was well tolerated with marginal increase in body weight (0.8 +/- 2.5 kg, p = 0.04) and was not associated with any abnormal changes in laboratory parameters. Open-label CBZ-ER treatment was beneficial for the treatment of BD in children. Future controlled trials are warranted.

Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study.

The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400-800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode.

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.

P01-188 A double-blind, placebo-controlled trial of divalproex and olanzapine in bipolar I disorder, mixed episode

Aims:This unique study of treatment of the mixed state of bipolar I disorder using simultaneous depression and mania response criteria compared divalproex monotherapy versus olanzapine augmentation in a 6-week, randomized, double-blind trial.Methods:Patients (age 18-60 years) with 14-28 days of divalproex monotherapy (blood levels of 75-125 μg/mL) were randomized to augmentation with olanzapine 5-20 mg/day or placebo. Data collected included: Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression for Bipolar Illness (CGI-BP), hospitalizations, concomitant medications, and adverse events (AEs). Primary co-objectives were comparisons of baseline to endpoint changes in HDRS and YMRS. Secondary objectives included comparisons of times to onset (25% reduction) and response (50% reduction) in both HDRS and YMRS, change in CGI-BP, hospitalizations, and safety.Results:Patients were 59% female, 51% Caucasian, 33% African American, and 14% Hispanic with mean standard deviation (SD) HDRS and YMRS scores of 22.2 (4.5) and 20.9 (4.4). Mean standard error (SE) score changes for the olanzapine (n=100) or placebo (n=101) arms, respectively, were: HDRS, -9.37 (.55) and -7.69 (.54), p=.022; YMRS, -10.15 (.44) and -7.68 (.44), p&lt; .001; and CGI-BP, -1.34 (.11) and -1.06 (.11), p=.056. Times-to-onset (median 7 vs 14 days) and response (median 25 vs 49 days) were significantly shorter for olanzapine augmentation. One olanzapine patient required hospitalization (p=1.0). Treatment-emergent AEs were consistent with previously-published rates.Conclusion:Six-week olanzapine treatment augmentation was associated with greater and earlier reduction of manic and depressive symptoms in mixed episode patients on divalproex treatment.

Double‐blind randomized controlled study comparing short‐term efficacy of bifrontal and bitemporal electroconvulsive therapy in acute mania

Bifrontal electrode placement is as efficacious as bitemporal placement during electroconvulsive therapy (ECT) in depression but is associated with fewer cognitive adverse effects. There are no studies comparing these techniques in acute mania. This study compared the short-term efficacy and adverse effects of bifrontal and bitemporal ECT in the treatment of acute mania. Thirty-six DSM-IV mania inpatients referred for ECT were recruited for study. They were randomized to receive bifrontal (BFECT; n = 17) or bitemporal (BTECT; n = 19) ECT. None of the subjects were on mood stabilizers during the course of ECT. Severity of mania was measured on the Young Mania Rating Scale (YMRS) before beginning ECT and then on Days 3, 7, 11, 14, and 21 of treatment. Cognitive functions were assessed eight hours after the fifth ECT session using the Mini-Mental Status Examination (MMSE), Paired Associate Learning Test, Complex Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail Making Test, Part A. The subjects in the two groups were comparable on sociodemographic and clinical variables, including severity of mania at baseline. They were also similar in ECT parameters, including seizure threshold and seizure duration. Mean YMRS scores showed faster decline in the BFECT than in the BTECT group. Kaplan-Meier survival analysis showed that a greater proportion of subjects in the BFECT group responded (50% reduction in YMRS score) significantly earlier than in the BTECT group. There were no significant differences between the groups in performance on cognitive function tests. In this pilot study, mania patients treated with BFECT responded faster than those treated with BTECT, with comparable cognitive adverse effects. Since ECT is usually prescribed for rapid control of symptoms, BFECT may be preferred over BTECT in the treatment of acute mania.

Brain oscillatory responses in patients with bipolar disorder manic episode before and after valproate treatment

Background GABA/Glutamatergic dysfunction and neural circuits which regulate cognitive processing are involved in the underlying pathology of bipolar disorder. Event related oscillatory neuroelectrical activity reflects integrative brain functioning, different frequency bands representing different cognitive functions. Methods Event Related Potentials to visual odd-ball paradigm in ten manic/hypomanic medication free, DSM-IV bipolar patients were measured before and after six weeks of valproate monotherapy in comparison to ten sex and age matched healthy controls. Different frequency band responses were obtained by digital filtration of ERPs. Young mania rating scale (YMRS) was used to assess clinical response. Repeated measures ANOVA, Wilcoxon and Mann Whitney U tests were used for statistical analysis. Results Patients showed significantly higher baseline occipital beta (18–30 Hz) ( p: 0.014) response than healthy controls. They were devoid of the occipito-frontal alpha (8–13 Hz) dominance presented by the control group. Occipital beta response reduced significantly ( p: 0.009) and became similar to controls after treatment. Post-treatment alpha responses were significantly lower than baseline in anterior temporal ( p: 0.038) and occipital ( p: 0.027) locations. Healthy controls displayed a significantly increased frontal alpha response at the second assessment but the patients did not. Mean YMRS score reduced significantly compared to baseline at the end of six weeks ( p: 0.004). Conclusions Alpha response is the universal operator in the brain. Increased occipital beta response in mania may be compensatory to the dysfunctional alpha operation. Its reduction after valproate may be through modulation of glutamatergic and GABAergic mechanisms and indicate medication’s corrective effect on the underlying pathogenesis.

Venlafaxine versus lithium monotherapy of rapid and non-rapid cycling patients with bipolar II major depressive episode: A randomized, parallel group, open-label trial

BackgroundThere is a paucity of controlled clinical data on the best initial therapy for treating patients with bipolar type II (BP II) major depressive episode (MDE). In this analysis, we examined the safety and antidepressant efficacy of short-term venlafaxine versus lithium monotherapy in rapid and non-rapid cycling patients with BP II MDE. We hypothesized that lithium would have superior efficacy to venlafaxine, with fewer syndromal and sub-syndromal hypomanic and mixed mood conversions in the rapid cycling BP II MDE patients. MethodsPatients were randomized to monotherapy with either venlafaxine 37.5–375 mg daily or lithium 300–2100 mg daily for 12 weeks. The primary outcome measure was the 28-item Hamilton Depression Rating (HAM-D 28), with embedded ‘typical’ HAM-D 17 and ‘atypical’ HAM-D 17-R symptom scores. Secondary outcomes included the Young Mania Rating Scale (YMRS), clinical global impressions severity (CGI/S) and change (CGI/C) ratings, the proportion of responders (with ≥50% reduction in baseline HAM-D score) and remitters (with a final HAM-D score ≤8), and the proportion of patients with syndromal and sub-syndromal mood conversions. ResultsForty-three patients received venlafaxine (12 rapid cycling) and 40 patients received lithium (15 rapid cycling): 48 (57.8%) were women and 69 (82.1%) were Caucasian. Thirty-three patients (39.8%) prematurely discontinued therapy: 11 for lack of efficacy, 13 for adverse events, 2 for non-compliance, and 7 who were lost to follow up. Venlafaxine produced a greater reduction in HAM-D 28 (p=0.001) and HAM-D 17 (p=0.002) scores (versus lithium) that was independent of cycling status (0.358). Venlafaxine also resulted in a higher rate of responders (p=0.021) and remitters (p=0.001) in rapid cycling patients. There was no significant difference in baseline mean YMRS scores, or mean YMRS change scores over time, between rapid and non-rapid cycling patients. Venlafaxine did not result in a higher proportion of mood conversions (versus lithium) in either the rapid or non-rapid cycling patients. LimitationsThis was a secondary analysis of rapid versus non-rapid cycling BP II MDE patients. The study was originally powered to detect differences in efficacy between treatment conditions, and was not specifically powered to detect differences in efficacy or mood conversion episodes between rapid and non-rapid cycling groups. We used a conservative life-time definition of rapid cycling (i.e., an average ≥4 affective episodes per year). We did not employ a patient-recorded daily chrono-record to identify ultra-short mood conversions. The study used a randomized, parallel group, open-label design. ConclusionThese observations from this exploratory analysis suggest that venlafaxine monotherapy may be more effective than lithium monotherapy, with a similar mood conversion rate, in rapid and non-rapid cycling patients with BP II MDE. These data support prior observations that venlafaxine monotherapy may be effective initial treatment for BP II MDE.

Comparison of Short-Term Venlafaxine Versus Lithium Monotherapy for Bipolar II Major Depressive Episode

Practice guidelines for the initial treatment of bipolar II (BP II) major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial AD monotherapy would be superior to MS monotherapy for BP II MDE with a low hypomanic switch rate. Bipolar II MDE patients were randomized to a 12-week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium carbonate monotherapy (n = 40). The primary outcome measure was the 28-item Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures included the Young Mania Rating Scale (YMRS), clinical global impressions severity and change ratings, and the proportion of patients classified as responder (with > or = 50% reduction in baseline HAM-D score) or as remitter (final HAM-D score, < or = 8). Thirty-four venlafaxine-treated patients (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005). Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18) (P = 0.017) between treatment conditions. There was a greater proportion of venlafaxine-treated (vs lithium-treated) patients classified either as treatment responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS scores over time in the venlafaxine (vs lithium) treatment condition, and no significant increase in mean YMRS scores at any study visit compared with baseline for either treatment. Results from this study suggest that AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE with a low hypomanic switch rate.