Clinician-Administered Rating Scale For Mania Research Articles

A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

Increased sleep duration precedes the improvement of other symptom domains during the treatment of acute mania: a retrospective chart review.

BackgroundUnderstanding trajectories of symptom changes may help gauge treatment response and better identify therapeutic targets in treatment of acute mania. We examined how symptoms of sleep disturbance, mania, and psychosis resolved in a naturalistic treatment setting, hypothesizing that improvement in sleep would precede improvement in manic and psychotic symptoms.MethodsCharts of 100 patients with admitting diagnoses of bipolar mixed or manic episode were retrospectively reviewed. Medications and demographic variables were recorded, and the Clinician-Administered Rating Scale for Mania (CARS-M) mania and psychosis ratings and sleep hours were determined for 8 observation points. Times to minimum symptom level in each domain were compared via Wilcoxon signed-rank tests. Symptom correlations and trajectories and medication effects were explored using repeated measures ANOVA and regression models.ResultsManic and psychotic symptom resolution was linear over the time of hospitalization. In contrast, sleep showed a slow initial response, followed by rapid increase to peak, preceding peak improvement in mania and psychosis (p < 0.001). Rate of sleep restoration was a predictor of rate but not of magnitude of treatment response for symptoms mania and psychosis. Patterns of medication use did not affect symptom trajectories.ConclusionsIn acute mania, improvement in sleep with treatment is dissociable from resolution in symptoms of mania and psychosis, but there appears to be no therapeutic advantage to patient oversedation. Sleep improves first and may be both a predictor of the rate of treatment response and a useful therapeutic target.

Evaluating response to mood stabilizers in patients with mixed depression: A study of agreement between three different mania rating scales and a depression rating scale

BackgroundThe aim of the present study was to evaluate agreement between three pairs formed by one of three mania scales (Young Mania Rating Scale [YMRS], Bech-Rafaelsen Mania Scale [BRMS], or the Clinician-Administered Rating Scale for Mania [CARS-M]) and a single depression scale (21-item Hamilton Depression Rating Scale [21-HAM-D]) for evaluation of response to mood stabilizers in patients with mixed bipolar disorder. MethodsBetween 2010 and 2014, 68 consecutive bipolar type I and II outpatients with mixed depression as per DSM-IV-TR and Cincinnati criteria were included in this 8-week open-label trial to randomly receive carbamazepine, lithium carbonate, or valproic acid as monotherapy. ResultsPatterns of response (defined as a reduction of at least 50% in one of the mania scales and on the 21-HAM-D) were strikingly similar: 21-HAM-D+YMRS=22.1%, 21-HAM-D+BRMS=20.6%, and 21-HAM-D+CARS-M=23.5% (p<0.368). Assessment of agreement revealed very high kappa coefficients: 21-HAM-D+YMRS vs. 21-HAM-D+CARS-M, kappa=0.87; 21-HAM-D+YMRS vs. 21-HAM-D+BRMS, kappa=0.78; 21-HAM-D+CARS-M vs. 21-HAM-D+BRMS, kappa=0.91 (p<0.001). LimitationsThe decision to combine a depression rating scale with any one mania rating scale to assess treatment response in patients with mixed depression is questionable. ConclusionsThe present study suggests that any one of the three tested mania rating scales (YMRS, BRMS, and CARS-M) can be combined with the 21-HAM-D to assess treatment response in patients with mixed bipolar disorder. This should give clinicians an added measure of confidence in using this strategy until valid, and specific instruments are developed for assessment of mixed states.

A four week randomised control trial of adjunctive medroxyprogesterone and tamoxifen in women with mania

Emerging research has suggested that hormone treatments such as selective oestrogen receptor modulators (SERMs) or progestins may be useful in the treatment of mania. The current pilot study compared the use of the SERM tamoxifen and the progestin medroxyprogesterone acetate (MPA), as an adjunct to mood stabiliser medications, for the treatment of mania symptoms in 51 women in a 28-day double blind, placebo controlled study. The primary outcome was the change between baseline and day 28 mania scores as measured by the Clinician Administered Rating Scale for Mania (CARS-M). Adjunctive MPA treatment provided greater and more rapid improvement in mania symptoms compared with adjunctive placebo and tamoxifen treatment. Adjunctive therapy with MPA may be a potentially useful new treatment for persistent mania, leading to a greater and more rapid resolution of symptoms compared with mood stabiliser treatment alone.

The role of loss and danger events in symptom exacerbation in bipolar disorder

Research concerned with the association between stressful life events [SLEs] and bipolar disorder [BD] is inconsistent. Drawing on the unipolar depression literature, specific classifications of events (in particular, humiliation and loss events) seem to be especially important, while for anxiety disorders loss and danger events have been found to be pertinent. However, little or nothing is known about the relationship between such events and BD. The aim of the present investigation is to examine the association between danger and loss events and symptom exacerbation in BD. A total of 96 BD participants were interviewed using the Life Events and Difficulties Schedule [LEDS] at two time points: baseline and 4 month follow-up. Self-report and observer-rated symptom measures were administered at both interviews. The Beck Depression Inventory-Second Edition and the Montgomery Asberg Depression Rating Scale were used to measure depressive symptoms. The Self-Report Mania Inventory and Clinician-Administered Rating Scale for Mania were used to rate manic symptoms. Independent severe events, independent loss events and independent danger events were found to be significantly associated with worsening of depressive symptoms over an 8-month period. No significant associations were observed for manic symptoms. Specific relationships with different types of SLEs may explain previous discrepant findings concerning the relationship between SLEs and BD.

Temperament and character dimensions in bipolar I disorder: A comparison to healthy controls

Research on phenotypic markers of vulnerability to bipolar disorder has focused on the identification of personality traits uniquely associated with the illness. To expand knowledge in this area, we compared Cloninger’s seven temperament and character dimensions in 85 euthymic/subsyndromal bipolar I inpatients and outpatients and 85 age and sex matched community controls. We also examined associations between Cloninger’s personality traits and mood state in the patient group. Bipolar subjects were administered the Structured Clinical Interview for DSM-IV (SCID), Hamilton Rating Scale for Depression, and Clinician-Administered Rating Scale for Mania. Controls received the SCID, a family psychiatric history questionnaire, and urine toxicology screen to confirm healthy status. Both groups competed the 240-item Temperament and Character Inventory (TCI). A multivariate analysis of covariance, accounting for demographic factors, was conducted to compare the groups on the TCI. Bipolar I patients scored higher on harm avoidance, lower on self-directedness, and higher on self-transcendence compared to controls. Harm avoidance and self-directedness were correlated with residual depressive symptoms positively and negatively, respectively; persistence was correlated with residual manic symptoms; and selftranscendence was correlated with residual psychotic symptoms in patients. The results indicate that bipolar I subjects do possess personality traits that are significantly different from non-ill individuals. However, only a prospective, longitudinal study may determine whether these traits mark a vulnerability to the disorder, or represent the scarring effect of affective episodes and chronic subsyndromal symptoms.

Neurocognitive test performance predicts functional recovery from acute exacerbation leading to hospitalization in bipolar disorder

Bipolar disorder (BPD) is associated with significant functional morbidity at a rate which is particularly elevated among patients discharged from hospital. The aim of this study was to examine the degree to which neurocognitive test performance, measured following hospitalization for an acute affective episode, is predictive of functional recovery 1 year later. Seventy-eight Zucker Hillside Hospital patients aged 18-59 years and having Structured Clinical Interview for DSM-IV diagnosis of bipolar I disorder (BPD I), bipolar II disorder (BPD II) or BPD not otherwise specified (NOS) confirmed through a rigorous diagnosis consensus procedure, underwent a comprehensive neurocognitive test battery after initial stabilization (baseline) and were followed for at least 12 months (follow-up). Hamilton Depression Rating Scale (HAM-D) and Clinician-Administered Rating Scale for Mania (CARS-M) ratings were made at baseline and follow-up. At follow-up, functionality was assessed using the Multidimensional Scale for Independent Functioning (MSIF). Logistic regression was used to examine the predictive value of each of six validated neurocognitive domains for determining functionality (MSIF) at follow-up. Baseline and follow-up HAM-D and CARS-M were entered as covariates as was number of days between baseline and follow-up. Attention and Ideational Fluency were significantly predictive of functional recovery 12 months later. Residual mania but not depression was associated with 12-month MSIF rating. Lithium and benzodiazepine treatment at the time of neurocognitive testing did not affect the results. This is the first study examining the predictive value of neurocognitive deficits, independent of residual mania or depression, for long-term functional recovery following hospitalization. Selective neurocognitive deficits are predictive of long-term functional recovery and, as such, should be candidate targets in treatment and rehabilitation programs.

The Association Between Moderate Alcohol Use and Illness Severity in Bipolar Disorder

To examine the association of alcohol consumption with symptoms, illness course, and health care utilization among non-alcoholic patients with bipolar disorder. Subjects were 148 patients with bipolar I or II disorder enrolled in a longitudinal study of cognitive-behavioral therapy versus psychoeducation. Subjects were 18 to 60 years old, in full or partial remission, and non-heavy drinkers with no history of substance use disorders. At least 4 weeks of consistent naturalistic treatment with mood stabilizer was required for enrollment. Measures included the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression, the Clinician-Administered Rating Scale for Mania, and the Khavari Alcohol Test. Data were gathered from July 2002 to December 2004. Mean weekly alcoholic beverage consumption was minimal among both men (3.8 standard drinks, SD = 8.9) and women (1.2 standard drinks, SD = 1.9). Nonetheless, total alcohol consumption among men was associated with lifetime manic episodes (F = 10.2, df = 1, p = .003) and emergency department visits (F = 4.3, df = 1, p = .046). Spirits consumption among men was strongly associated with lifetime manic episodes (F = 81.8, df = 1, p < .001) and emergency department visits (F = 14.0, df = 1, p < .001). Among women, the frequency of alcohol consumption was associated with lifetime episodes of depression (F = 15.5, df = 1, p < .001) and hypomania (F = 4.8, df = 1, p < .03). Wine consumption among women was associated with lifetime hypomanic episodes (F = 13.6, df = 1, p < .001) and current manic symptoms (F = 4.0, df = 1, p < .05). Despite low volumes of consumption, alcohol was associated with measures of illness severity in bipolar disorder among both men and women. The adverse effects of alcohol on bipolar disorder may occur over a range of consumption, rather than being confined to heavy drinkers.

The Mood Spectrum Self-Report: validation and adaptation into Spanish

This study explores the psychometric properties of the Spanish adaptation of the Mood Spectrum Self-Report (MOODS-SR), an instrument designed to assess a broad range of manifestations of mood psychopathology. A total of 71 Spanish subjects participated: 49 outpatients who met criteria for a mood disorder or generalized anxiety disorder, and 22 normal controls. The instrument proved to have good internal consistency and test-retest reliability. Significant positive correlations were found between the depressive subdomains of the questionnaire and the Beck Depression Inventory, as well as between the manic-hypomanic subdomains and the Clinician-Administered Rating Scale for Mania. Clinical subjects displayed higher mean scores than normal subjects in all domains, and patients with bipolar disorder displayed higher scores than patients with unipolar disorder in the Manic component, particularly in the Energy and the Cognition subdomains. Differences between patients with generalized anxiety and mood disorders were small. The former, however, did not differ from normal controls in several subdomains, whereas patients with mood disorders did.

Quality of life for patients with bipolar disorder: relationship with clinical and demographic variables

The aim of this study was to assess the quality of life in bipolar disorder patients, and to analyze a set of clinical variables and sociodemographic data that could act as quality-of-life predictors. The study sample included 50 euthymic outpatients attending a specific bipolar patient unit. Patients were assessed with the Clinician-Administered Rating Scale for Mania, and the Hamilton Scale for Depression. To evaluate quality of life, all patients received the Spanish version of the SF-36 Health Survey. At the same time, sociodemographic and clinical data were obtained. The scores were compared with those of a control group representative of the general population. The group of bipolar patients obtained statistically significantly lower scores on all the subscales when compared with the control population. No statistically significant differences appeared when comparing the SF-36 scores with the demographic variables. Bipolar patients experience lower functioning and well-being even in the stable phase of the disorder. Due to the great impact of bipolar disorder on many areas, it would be of interest to know the clinical predictors related to patient quality of life, as this would contribute to the design of different clinical interventions.

Development and application of the mania rating guide (MRG).

In this article we present the development and application of the Mania Rating Guide (MRG), a semi-structured interview. This guide was created in order to assist the filling of three mania Scales: Mania Rating Scale, Bech-Rafaelsen Mania Scale and Clinician-Administered Rating Scale for Mania. The MRG consists of twenty-one Psychopathological Dimensions, that correspond to the Items of the original Scales, and are structured in Questions. The guide was applied to fifteen manic patients admitted in the Psychiatric Unit of the Clinical Hospital of Porto Alegre. A psychiatrist interviewed them using the MRG, and the interviews were videotaped. Afterwards, three independent raters scored the Mania scales based on the films. The impression of the raters was that the MRG allows not only to easily score all the Items of the Scales but also to cover the wide spectrum of the symptomatological presentation of a manic syndrome.

Oxcarbazepine versus Divalproex Sodium for the Continuing Treatment of Mania

Oxcarbazepine, an antiepileptic and a derivative of carbamazepine, has been shown to have clinical utility as an antimanic agent. This study sought to assess the efficacy and tolerability of oxcarbazepine compared with divalproex sodium in the treatment of patients with mania. 57 patients from a large clinical practice who had recently begun treatment with divalproex sodium were randomly assigned to one of two treatment groups. In this open-label, single (rater)-blind study, group 1 remained on treatment with divalproex sodium and group 2 was switched to oxcarbazepine. Both treatment groups were followed for 10 weeks after the switch. Pharmacotherapeutic efficacy was compared using the Clinician Administered Rating Scale for Mania (CARS-M). Weight and adverse events were monitored throughout the study. 83% of patients using oxcarbazepine showed a decrease in mania as assessed using the CARS-M, and 70% showed a net decrease in weight over the 10-week course of the study. For the divalproex sodium group, 53% showed a decrease in mania, as assessed by CARS-M, and 37% lost weight. Oxcarbazepine showed comparable efficacy to divalproex sodium, yet appeared to do so with an equal or more benign side-effect profile, particularly with regard to weight. These results suggest that oxcarbazepine, which has been used in Europe for the treatment of mood disorders for some time (albeit used off-label for this purpose) may show promise for use in the US as an agent for maintenance of non-acute mania.

Measuring mania and critical appraisal of rating scales.

In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects. To critically assess rating scales used in measuring mania. A systematic search of the literature, retrieval of reports of clinical trials of drugs used in mania and the rating scales and a critical and systematic appraisal of their quality. Eight symptom-rating scales were identified. The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response. Two more recently developed scales are the Manchester Nurse Rating Scale for Mania (MNRS-M) and the Clinician-Administered Rating Scale for Mania (CARS-M). The latter appears well validated but its in-use reliability needs to be explored further. The translation of observed changes in instrumental ratings into clinically meaningful change has to be established further. In particular, the relative weighting to be attached to the individual items needs further study. The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required.

The Altman Self-Rating Mania Scale

We report on the development, reliability, and validity of the Altman Self-Rating Mania Scale (ASRM). The ASRM was completed during medication washout and after treatment by 22 schizophrenic, 13 schizoaffective, 36 depressed, and 34 manic patients. The Clinician-Administered Rating Scale for Mania (CARS-M) and Mania Rating Scale (MRS) were completed at the same time to measure concurrent validity. Test-retest reliability was assessed separately on 20 depressed and 10 manic patients who completed the ASRM twice during washout. Principal components analysis of ASRM items revealed three factors: mania, psychotic symptoms, and irritability. Baseline mania subscale scores were significantly higher for manic patients compared to all other diagnostic groups. Manic patients had significantly decreased posttreatment scores for all three subscales. ASRM mania subscale scores were significantly correlated with MRS total scores (r = .718) and CARS-M mania subscale scores (r = .766). Test-retest reliability for the ASRM was significant for all three subscales. Significant differences in severity levels were found for some symptoms between patient ratings on the ASRM and clinician ratings on the CARS-M. Mania subscale scores of greater than 5 on the ASRM resulted in values of 85.5% for sensitivity and 87.3% for specificity. Advantages of the ASRM over other self-rating mania scales are discussed.

The clinician-administered rating scale for mania (CARS-M): Development, reliability, and validity

There are currently seven rating scales available to assess manic symptomatology. All, however, have some limitations that could restrict their clinical and research utility. To resolve these deficiencies the Clinician-Administered Rating Scale for Mania (CARS-M) was developed and normed on 96 patients with mixed diagnoses during baseline and following treatment. Interrater reliability was established across multiple raters viewing 14 videotaped interviews and comparing agreement among individual items and total scores. Test-retest reliability was assessed on 36 patients twice during baseline. The mean intraclass correlation coefficient among five raters across items for each of the 14 patients was 0.81, and for total scores 0.93. Principal components analysis of items revealed two factors: mania, and psychosis. Test-retest reliability was significant for both factors (range = 0.78 to 0.95). Internal validity, comparing each item with its respective total factor score, revealed significant correlations for all items. Correlation of CARS-M total scores with mania rating scale (MRS) total scores was 0.94. Results indicate the CARS-M is both a reliable and valid measure of the severity of manic symptomotology, which incorporates a number of methodological improvements leading to greater precision and clinical utility.