Correlates of suicidal ideation in dysphoric mania

BACKGROUND: Previous investigations have reported that suicidal ideation and behavior are more prevalent during mixed than pure mania. Uncertainties exist about whether suicidality in mania arises from multiple concurrent depressive symptoms, or rather, as a categorical phenomenon, reflecting dysphoria without necessarily a full major depression. To elucidate the relationship between suicidal ideation and dysphoric mania, we analyzed clinical and demographic features associated with suicidal versus nonsuicidal dysphoric manic inpatients. METHODS: Records were reviewed for 100 DSM-III-R bipolar I manic inpatients at the Payne Whitney Clinic of New York Hospital from 1991-1995. All had > or = 2 concomitant depressive symptoms (other than suicidality). Affective and psychotic symptoms, past suicide attempts, prior illness, and related clinical/demographic variables were assessed by a standardized protocol. RESULTS: Suicidal ideation was significantly more common among dysphoric manics who were caucasian, took antidepressant medications in the week prior to admission, had histories of alcohol abuse/dependence, and made past suicide attempts. Suicidal ideation was evident for nearly half of dysphoric manic patients with < or = 3 depressive symptoms who did not meet DSM criteria for a mixed state. No individual manic or depressive symptoms other than dysphoric mood were more common among suicidal than nonsuicidal patients. LIMITATIONS: Findings from this retrospective study require confirmation using a prospective assessment. Treatments were naturalistic and may have differentially influenced hospital course and illness characteristics. Factors related to suicide attempts (rare in this cohort) or completions (not a focus of this study) may differ from those related only to suicidal ideation. CONCLUSIONS: Caucasian dysphoric manic patients with past suicide attempts and substance abuse may have a significantly elevated risk for suicidality, even when full major depression does not accompany mania. Suicidality is a clinically important consideration in a majority of dysphoric manic patients.     

The feasibility of self-assessment of dysphoric mania in the French national EPIMAN study

BACKGROUND: There is presently considerable uncertainty on how to best assess mixed mania. The present contribution explores the feasibility of discriminating manic and dysphoric manic states on the basis of self-rating in the acute phase of the illness. METHODS: In the French four-site national EPIMAN study of 104 patients devoted to the clinical evaluation and subclassification of mania, we used the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self-assessment format. The study was conducted on consecutive patients hospitalized for an acute DSM-IV mania. The severity of mania was measured by the Beigel-Murphy scale (MSRS) assessed by psychiatrists. When mania abated, temperaments according to Akiskal and Mallya were administered in their French version. RESULTS: Principal component analysis revealed a general factor explaining 33% of the variance and, after rotation, seven factors defining different dimensions of the phenomenology of mania. The factorial scores, as well as the dimensional scores of the Carrol-Klein model significantly distinguished pure versus dysphoric mania made on clinical grounds. Gender seemed to influence two factors: high 'anxious-depressive' score in females (which is in line with female overrepresentation in mixed mania), vs. high score in males on the 'gregariousness' factor (which represents social disinhibition of the hyperthymic temperament known to be more prevalent in men). LIMITATION: Cross-sectional correlational study in need of longitudinal validation. CONCLUSIONS: EPIMAN data deriving from a national clinical population showed the feasiblity and face validity of self-assessment in acute mania, in particular its dysphoric subtype. Temperament in women seemed to contribute to the genesis of mixed (dysphoric) mania in accordance with Akiskal's hypothesis of opposition of temperament and polarity of bipolar episodes in mixed states. Self-assessment was capable of capturing accurately the subthreshold depressive symptomatology of mixed mania, which can be missed in hetero-evaluation by hasty clinical interview.     

Placebo-controlled trials do not find association of olanzapine with exacerbation of bipolar mania

BACKGROUND: Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania. METHODS: Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF). RESULTS: The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064). CONCLUSION: Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect. LIMITATIONS: Post-hoc analysis of pooled data from two different studies.     

Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN)

Background: This research derives from the French national multisite collaborative study on the clinical epidemiology of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along a “spectrum of mixity” extending into mixed mania with subthreshold depressive manifestations; to demonstrate the feasibility of obtaining clinically meaningful data on this entity on a national level; and to characterize the contribution of temperamental attributes and gender in its origin. Methods: EPIMAN involves training 23 French psychiatrists in four different sites, representing four regions of France; to rigorously apply a common protocol deriving from the criteria of DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll, modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya criteria; obtaining data on comorbidity, and family history (according to Winokur's approach as incorporated into the FH-RDC); and prospective follow-up for at least 12 months. The present report concerns the clinical and temperamental features of 104 manic patients during the acute hospital phase. Results: Dysphoric mania (DM defined conservatively with fullblown depressive admixtures of five or more symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence of ≥2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts had the best positive predictive values for mixed mania. In comparison to pure mania (0–1 depressive symptoms), DM was characterized by female over-representation; lower frequency of such typical manic symptomatology as elation, grandiosity, and excessive involvement; higher prevalence of associated psychotic features; higher rate of mixed states in first episodes; and complex temperamental dysregulation along primarily depressive, but also cyclothymic, and irritable dimensions; such irritability was particularly apparent in mixed mania at the lowest threshold of depressive admixtures of two symptoms only. Limitation: In a study involving hospitalized affectively unstable psychotic patients, it was difficult to assure that psychiatrists making the clinical diagnoses would be blind to the temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. Conclusions: Mixed mania, defined cross-sectionally by the simultaneous presence of at least two depressive symptoms, represents a prevalent and clinically distinct form of mania. Subthreshold depressive admixtures with mania actually appear to represent the more common expression of dysphoric mania. Moreover, an irritable dimension appears to be relevant to the definition of the expression of mixed mania with the lowest threshold of depressive symptoms. Neither an extreme, nor an endstage of mania, “mixity” is best conceptualized as intrusion of mania into its “opposite” temperament – especially that defined by lifelong depressive traits – and favored by female gender. These data suggest that reversal from a temperament to an episode of “opposite” polarity represents a fundamental aspect of the dysregulation that characterizes bipolar disorder. In both men and women with hyperthymic temperament, there appears “protection” against depressive symptom formation during a manic episode which, accordingly, remains relatively “pure”. Because men have higher rates of this temperament, pure mania is overrepresented in men; on the other hand, the depressive temperament in manic women seems to be a clinical marker for the well-known female tendency for depression, hence the higher prevalence of mixed mania in women.     

Economic,clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial

INTRODUCTION: The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania. METHODS: Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed. RESULTS: During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension. CONCLUSION: From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.     

Therapeutic factors in dysphoric disorders

The working group on the treatment of dysphoric disorders focused on ways to integrate variables and qualities that optimize treatment effects for this clinical population. The variables examined represent three aspects or domains of the treatment context that effect positive change. These included aspects of the patient and therapist (participant factors), those relating to the development and role of the therapeutic relationship (relationship factors), and those that defined the application of formal interventions that are implemented by the therapist (techniques factors). The treatment literature on dysphoric populations was reviewed and a variety of relationships was identified, which then were translated into principles that are thought to enhance treatment effects. The principles representing the three domains of this review are then collected, in this article, into a set of cohesive suggestions for treating patients whose problems are characterized by major or minor depression, alone or as a comorbid condition.     

Post-abortion mania

We describe case histories of three women with post-abortion mania, including two women who underwent a change in diagnosis from bipolar II to bipolar I disorder and another woman who had no prior history of psychiatric disturbance. It is argued that the study of post-abortion mania should provide an opportunity to better understand the aetiology of puerperal mania.     

Emotion regulation in women with premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.     

Principal components of mania

OBJECTIVE: An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS: One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS: Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS: Patients of the sample were all medicated inpatients. CONCLUSIONS: Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.     

Treatment of mixed mania

Mixed mania (i.e., a manic syndrome accompanied by depressive symptoms) and its response to long-term preventive drug treatment was studied as part of a larger NIMH collaborative study. Following recovery from a manic episode, patients received either lithium, imipramine, or the combination of lithium and imipramine for a 2-year period. It was found that patients who had recovered from a mixed manic state were at significantly higher risk for recurrences than patients who had recovered from a pure (non-mixed) manic state. Lithium and the combination of lithium and imipramine were highly effective preventive treatments for the pure manic group and poor treatments for the mixed group. Imipramine was ineffective for both the pure and mixed groups. The need for identifying mixed mania in therapeutic trials and in evaluating alternative treatments for lithium with this subgroup is discussed.     

The diagnosis of mania

Manic illnesses are often misdiagnosed, particularly in adolescence when they are commonly and wrongly regarded as schizophrenic. Recent American studies suggest that the presence of Schneiderian and other schizophrenic symptoms has no influence on the duration or the response to treatment of manic illnesses, or on the morbidity of first-degree relatives, and that the concept of schizoaffective disorder, manic type is therefore redundant. Other evidence suggests that, although delusions of reference or persecution have no effect on outcome, the presence of auditory hallucinations or passivity phenomena is associated with a considerably worse outcome over the next few years.