Bipolar Symptoms Research Articles

P.2.079 Open-label study of risperidone in children with bipolar disorder

There are no randomized, placebo-controlled data for quetiapine in outpatients with bipolar spectrum disorder (ambulatory BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania).An 8-week, randomized, double-blind, placebo-controlled trial of quetiapine in ambulatory BSD with hypomanic/mild manic symptoms, defined operationally as a score of ≥ 3 but < 5 on the mania subscale of the Clinical Global Impressions Scale Modified for Bipolar Illness (CGI-BP) at baseline and one prior study visit, at least 3 days but no more than 2 weeks apart. The primary outcome measure was the rate of change in the Young Mania Rating Scale score (YMRS).During the 8-week study period, patients receiving quetiapine (average daily dose = 232 mg) had a marginally greater rate of reduction in mean total YMRS score than patients receiving placebo (p = 0.06). Additionally, CGI-BP mania (p = 0.01) and the CGI-BP overall (p < 0.001) scores were significantly reduced and the CGI-depression score (p = 0.08) was marginally reduced in the quetiapine group. Six (32%) quetiapine patients and 8 (40%) placebo patients did not complete the trial.Small sample size and high attrition (36%).Quetiapine was marginally more effective than placebo in reducing hypomanic/mild manic symptoms in ambulatory BSD as assessed by the YMRS. It was more effective than placebo in reducing manic symptoms and global bipolar symptoms as assessed by the CGI-BP. The drug's discontinuation rate was similar to placebo's. Controlled trials of quetiapine and other compounds with mood stabilizing properties in larger groups of ambulatory BSD patients with hypomanic/mild manic symptoms appear warranted.

Adjunctive quetiapine in bipolar patients partially responsive to lithium or valproate

Despite therapeutic treatment with lithium or valproate, patients with bipolar I disorder often require adjunctive therapy to treat persistent symptoms. In order to evaluate the effects of quetiapine for bipolar symptoms inadequately responsive to mood stabilizers, a retrospective chart review was undertaken at the Veterans Affairs (VA) Long Beach Mood Disorders Clinic for all bipolar I outpatients who had been prescribed adjunctive quetiapine during an 18-month study period. Among 75 lithium- or valproate-treated patients receiving quetiapine, 16 were identified in whom therapeutic treatment with lithium (≥0.8 meq/l) or valproate (≥75 μg/ml) could be verified during the 2-month period prior to quetiapine initiation. Chart notes were utilized by the principal investigator to assign Clinical Global Impression Bipolar ratings (CGI-BP) before and after 30–120 days of quetiapine treatment (mean=173±157 mg). Nine of 16 lithium- or valproate-stabilized bipolar patients (56%) were judged much or very much improved in CGI-BP overall ratings following adjunctive quetiapine. In addition, for the entire sample, quetiapine augmentation resulted in significant improvements in clinician-rated bipolar severity scores (CGI-BP) for mania, depression, and overall bipolar illness. The majority of quetiapine-related symptomatic improvement was due to diminished insomnia, agitation, irritability, and mood disturbance. Side effects were mild and transitory including sedation and dizziness. Low-dose quetiapine may be a useful and well-tolerated adjunct for some bipolar patients with incomplete response to lithium or valproate.

Bipolar disorder in children and adolescents: diagnosis and treatment

An improved understanding of bipolar disorder should help clinicians in the accurate diagnosis and treatment of children and adolescents with bipolar disorder. Clinicians should use preliminary evidence and sound clinical judgment when working with patients who have, or may be at risk of, bipolar disorder. Purpose of review This article reviews current literature on the diagnosis and treatment of bipolar disorder in children and adolescents. Controversies relating to diagnosis, common comorbid psychiatric disorders, and the safety and efficacy of pharmocotherapy are summarized. Recent findings The presentation of bipolar disorder in children and adolescents has been described by some as ‘atypical’ in that (1) the predominant mood is often one of irritability, (2) the irritability may be severe, persistent, and violent, (3) the pattern of cycling may be ultradian, (4) comorbid psychiatric disorders and family history of bipolar disorder are common, and (5) poor treatment response and recurrence are common. However, given the prevalence of mixed mania in adult bipolar disorder and the similarities between childhood- and adolescent-onset bipolar disorder and mixed mania, some claim that the child and adolescent variant may not be atypical after all. Adding to the confusion are the diverse manifestations of bipolar symptoms at different developmental stages. Lithium, valproate, and carbamazepine are the medications most commonly used to treat children and adolescents with bipolar disorder. However, current practice parameters are based on preliminary evidence and/or studies using adult patients. There is a need for randomized, double-blind, controlled trials to determine medication safety and efficacy in children and adolescents with bipolar disorder.

Patient- and Family-Rated Scale for Bipolar Disorder Symptoms: Internal State Scale

The monitoring of patients, by themselves and their caregivers, is very important in the prophylaxis of bipolar disorder. This study aimed to develop a Chinese-language version of an instrument for assessment of manic and depressive symptoms by patients and their families. Fifty-eight inpatients and outpatients with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) diagnosis of bipolar disorder were recruited. All subjects underwent clinical psychopathologic assessment by experienced psychiatrists using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). At the same time, each patient and key family members filled out the Chinese-language version of the Internal State Scale (ISS) for monitoring mental symptoms. Patients were examined a second time if they had entered remission or a new episode of the opposite polarity. The ISS was divided into two subscales, of well-being/activation and of irritability. Patients' well-being/activation and irritability subscales were significantly correlated with YMRS scores and the well-being/activation subscale was also significantly correlated with the HDRS score. Family members' irritability subscales were significantly correlated with HDRS scores only. The reliability and constructive validity of the ISS was good in both patients with bipolar disorder and their families.

The structure of affective symptoms in a sample of young adults.

Symptoms of bipolar disorders include depression and mania. The term "bipolar" implies states that are opposite to each other. Construing scales that define mania and depression as opposite ends of one dimension cannot account for the existence of mixed symptoms. One self-report instrument, the Internal State Scale (ISS), combines both dimensions in one measure. However, the ISS only assesses internal subjective states and does not tap other typical and more objective symptoms of (hypo-) mania. To explore the factorial structure of affective symptoms in a general population sample, we extended the Center for Epidemiologic Studies-Depression Scale (CES-D), adding items to assess manic symptoms as described in DSM-IV. The scale was completed by 2,059 young adults. The results for the original CES-D are comparable to prior studies. Factor-analysis for the extended CES-D revealed two factors in women and men: most manic symptoms loaded high on a factor "euphoria-activation," whereas the other factor included all typical dysphoric-depressive symptoms, but also included the "manic symptoms" of distractibility and irritability. Our results support a two-factor model of bipolar symptoms in the general population with irritability being more closely associated with dysphoria than euphoria. The implications and limitations of the present results are discussed.

Borderline personality disorder in patients with bipolar disorder and response to lamotrigine

Background: Recent reports suggesting lamotrigine as an effective treatment in bipolar disorder, and perhaps borderline personality disorder, a common comorbid personality disorder in bipolar patients, led us to retrospectively examine patients from two bipolar studies to investigate this pattern of comorbidity, and to determine whether lamotrigine effected the dimensions of borderline personality. Methods: Fifteen months following entry into either study, we retrospectively assessed DSM-IV dimensions of borderline personality disorder pre- and post-treatment with lamotrigine in 35 bipolar patients. Results: Forty percent met criteria for borderline personality disorder; this subgroup had a more frequent history of substance abuse and childhood symptoms of attention deficit hyperactivity disorder (ADHD). Dimensions of borderline personality improved significantly with treatment in both patient groups, and corresponded with response of bipolar symptoms. Six (43%) comorbid bipolar patients endorsed three or fewer criteria of borderline personality during treatment with lamotrigine. There was a trend for comorbid bipolar patients to require a second psychoactive medication in addition to lamotrigine during extended treatment. Limitations: Criteria for borderline personality and improvement were assessed retrospectively in an open manner. Conclusions: Dimensions of borderline personality disorder may respond to lamotrigine in comorbid bipolar patients; controlled studies appear warranted. Bipolar studies should assess and specify the number of patients with personality disorders in the trial.

Subsyndromal depression is associated with functional impairment in patients with bipolar disorder.

The purpose of this study was to assess whether a relationship exists between mild depressive symptoms and overall functioning in subjects with bipolar disorder. Twenty-five male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined using the Structured Clinical Interview for DSM-III-R, were evaluated for degree of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis V). GAF scores were significantly negatively correlated with HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a HAM-D score high enough to be considered clinically depressed. The results of this study support a relationship between subsyndromal depressive symptoms and functional impairment in bipolar subjects, despite their not meeting threshold criteria for a major depressive episode. These findings raise the possibility that in some patients with bipolar disorder subsyndromal depressive symptoms might contribute to ongoing functional impairment.

Prodromes, coping strategies and course of illness in bipolar affective disorder--a naturalistic study.

Psychosocial interventions for bipolar patients often include teaching patients to recognize prodromal symptoms and tackle them early. This prospective study set out to investigate which bipolar prodromal symptoms were reported frequently and reliably over a period of 18 months. Furthermore, we have also investigated which types of coping strategies were related to good outcome. Forty bipolar patients were interviewed for their bipolar prodromal symptoms and their coping strategies at recruitment and 18 months later. Patients were also assessed as to whether they had experienced relapses. Bipolar patients were able to report bipolar prodromal symptoms reliably. Mania prodromal symptoms tended to be behavioural symptoms. A quarter of patients reported difficulties in detecting depression prodromes, which tended to be more diverse and consisted of a mix of behavioural, cognitive and somatic symptoms. Significantly fewer patients who reported the use of behavioural coping strategies to curb excessive behaviour during the mania prodromal stage experienced a manic episode. Similarly, significantly fewer patients who reported the use of behavioural coping strategies experienced depression relapses. How well patients coped with mania prodromes predicted bipolar episodes significantly when the mood levels at baseline were controlled. Ratings of how well subjects coped with mania prodromal symptoms also predicted manic symptoms significantly at T2 when manic symptom at T1 was controlled. Our study suggests that bipolar patients are able to report prodromal symptoms reliably. It is advisable to teach patients to monitor their moods systematically and to promote good coping strategies.

PMH19: RISK OF HOSPITALIZATION FOR PATIENTS WITH BIPOLAR DISORDER

OBJECTIVES: Health care utilization for patients with bipolar disorder has received limited attention. This study utilizes medical and prescription claims data from the 1998 to mid-2000 MarketScan Databases to examine the risks of hospitalization, a major cost driver in treating bipolar patients. Hospitalizations are associated with a relapse of bipolar symptoms (often due to treatment ineffectiveness or discontinuation). METHODS: Bipolar patients are identified using diagnosis codes and prescription drug claims. An ‘intent-to-treat’ framework for classifying drug cohorts by initial bipolar prescription is used. Prescription claims are studied over a minimum of a six-month time period to analyze drug use patterns (e.g., switching and augmenting treatment). Descriptive profiles of the bipolar patients are presented. Cox proportional hazard models are used to examine the relationships among observable patient characteristics, drug choice, drug use patterns, and hospitalizations. This method accounts for the potential bias in parameter estimates due to data censoring. RESULTS: Among patients with at least 6-months of follow-up data (n = 6,536), the mean age is 43 years old and 63.3% are female. The majority of patients are initially observed on antimanic medications, with lesser percentages on other common pharmacological therapies (typical and atypical antipsychotics, and antiepileptics). During the 6-month follow-up, 14.5% of patients have at least one hospitalization and 7.2% have at least one bipolar-related hospitalization. During a 12-month follow-up, 23.3% have at least one hospitalization of any type and 11.5% have at least one bipolar-related hospitalization. The unadjusted risk of hospitalization increases over time, at a decreasing rate. CONCLUSION: The high incidence of hospitalization demonstrates the need for effective treatment options. This study also illustrates the importance of accounting for censored data to obtain unbiased estimates of factors associated with the risk of hospitalization.

Can personality traits predict increases in manic and depressive symptoms?

Background: There has been limited research investigating personality traits as predictors of manic and depressive symptoms in bipolar individuals. The present study investigated the relation between personality traits and the course of bipolar disorder. The purpose of this study was to identify specific personality traits that predict the course of manic and depressive symptoms experienced by bipolar individuals. Methods: The sample consisted of 39 participants with bipolar I disorder assessed by the Structured Clinical Interview for DSM-IV. Personality was assessed using the NEO Five-Factor Inventory. The Modified Hamilton Rating Scale for Depression and the Bech–Rafaelsen Mania Rating Scale were used to assess symptom severity on a monthly basis. Results: Consistent with previous research on unipolar depression, high Neuroticism predicted increases in depressive symptoms across time while controlling for baseline symptoms. Additionally, high Conscientiousness, particularly the Achievement Striving facet, predicted increases in manic symptoms across time. Limitations: The current study was limited by the small number of participants, the reliance on a shortened version of a self-report personality measure, and the potential state-dependency of the personality measures. Conclusions: Specific personality traits may assist in predicting bipolar symptoms across time. Further studies are needed to tease apart the state-dependency of personality.

Effects of Antimanic Mood-Stabilizing Drugs on Fetuses, Neonates, and Nursing Infants

Pregnancy presents a special problem to the clinician treating bipolar disorders in women. Since the first episode of mania typically occurs before the age of 30, many women in their prime childbearing years may be exposed to potentially teratogenic mood-stabilizing agents. This exposure may also continue for the nursing infant during lactation. Pregnancy itself can exacerbate bipolar symptoms and also alter the pharmacokinetics of mood-stabilizing drugs. Risks to mother and fetus can be reduced with a number of simple strategies, including monotherapy with the lowest effective dose of a drug for the shortest period necessary, periconceptional use of multivitamins with folate, prescription of drugs with established safety records, and avoidance of exposure to antimanic agents during the first trimester of pregnancy. In this article, we review existing evidence on the risks to fetuses and nursing infants of mothers taking specific mood-stabilizing agents, and we present appropriate management guidelines designed to minimize these risks.

Responsiveness to Threat and Incentive in Bipolar Disorder: Relations of the BIS/BAS Scales With Symptoms.

Over the past 10 years, theorists have suggested that bipolar disorder symptoms result from increases and decreases in the activity of the Behavioral Activation or Facilitation System (BAS or BFS) and the Behavioral Inhibition System (BIS). These neurobehavioral systems are thought to determine the intensity of affective and behavioral responses to incentives and threats. This study examined cross-sectional and prospective associations of self-reported BIS and BAS with mania and depression in a sample of 59 individuals diagnosed with Bipolar I disorder. Depression was tied to BIS, pointing to the importance of sensitivity to threats in depression. However, links between BIS and depression appeared state-dependent. BAS subscales did not correlate with manic symptoms in a state-dependent manner; however, BAS (total scale and reward responsiveness subscale) predicted relative intensification of manic symptoms over time. Thus, evidence suggests that BAS sensitivity may constitute a vulnerability to mania among persons diagnosed with bipolar disorder. Discussion focuses on the integrative potential of the BIS/BAS constructs for linking psychosocial and biological research on bipolar disorder.

The epidemiology of DSM-III-R bipolar I disorder in a general population survey.

Data are presented on the general population epidemiology of DSM-III-R bipolar I disorder in the United States. Data come from the US National Comorbidity Survey (NCS), a general population survey of DSM-III-R disorders. A modified version of the Composite International Diagnostic Interview was used to make diagnoses. A small (N = 59) clinical reappraisal study showed that the only manic symptom profile that could validly be assessed with the CIDI is characterized by euphoria, grandiosity and the ability to maintain energy without sleep, which described approximately half of all clinically validated bipolar I cases in the NCS. Further analysis focused on this symptom profile, which involved N = 29 cases in the total sample. Lifetime prevalence was estimated to be 0.4% and 12-month prevalence only slightly lower. Caseness was negatively related to income, education and age, positively related to urbanicity, and elevated among the previously married, never married and non-whites. All cases reported at least one other NCS/DSM-III-R disorder and 59.3% reported that their episode of bipolar disorder (either mania or depression) occurred at a later age than at least one other NCS/DSM-III-R disorder. Although 93.2% of lifetime cases reported some lifetime treatment, only 44.7% of recent cases were in treatment. The type of bipolar disorder examined here is highly chronic, co-morbid and impairing. Increased efforts are required to attract current cases into appropriate treatment. Methodological research is needed to develop more accurate measures of other bipolar symptom profiles for use in general population epidemiological studies.

Perinatal distress and bipolar affective disorder symptoms

Perinatal distress and bipolar affective disorder symptoms

Effect of Tricyclic Antidepressants on Switching to Mania and on the Onset of Bipolarity in Depressed 6− to 12-Year-Olds

The authors present data on the rates of onset of bipolar phenomena, at 2- to 3-year follow-up, in depressed 6- to 12-year olds. The subjects had participated in the nortriptyline drug study. There were high rates of onset of bipolarity and of switching to mania while patients were on tricyclic antidepressants (TCAs). Mania developed only in subjects who had received TCAs at some time in the past or were receiving them concurrent with the onset of mania. These findings were analyzed with respect to the influence of multiple covariates, including family history of manic disorders and pubertal status. The authors discuss the implications of these findings for the prescription of TCAs to children who present with major depressive disorder and have a family history of bipolarity or a history of bipolar symptoms. The relevance of these findings for the later development of rapid cycling is discussed and compared with predictors of rapid cycling in adults.

Schizoaffective mania reconsidered.

Schizoaffective mania refers to a heterogeneous group of disorders characterized by mixtures of schizophrenic and manic (or bipolar) symptoms. Of the proposed diagnostic criteria, the Research Diagnostic Criteria (RDC) most clearly distinguish relevant subgroups. Family, clinical, and treatment studies suggest that the RDC's mainly affective subtype of schizoaffective mania is a variant of psychotic bipolar disorder. Limited available data suggest that the mainly schizophrenic subtype has a poorer prognosis and includes cases more closely related to schizophrenia. Schizoaffective mania also overlaps with proposed categories such as reactive and cycloid psychosis. It is premature to assume that all schizoaffective manic disorder represents a bipolar variant. Further studies that differentiate patients according to subtype, drug response, and course are needed.

Mania following head trauma

The authors present psychiatric and neurologic data on 20 patients who developed mania after closed head trauma. An association was seen between severity of head trauma (based on length of posttraumatic amnesia), posttraumatic seizure disorder, and type of bipolar disorder. The manic episodes were characterized by irritable mood rather than euphoria and by assaultiveness. Psychosis occurred in only 15% of the sample, and 70% had no depressive episodes. Bipolar disorders were absent among 85 first-degree relatives. The authors suggest that posttraumatic seizures may be a predisposing factor in posttraumatic mania.

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Abstract Bipolar disorder is a prevalent psychiatric disorder with a high rate of misdiagnosis and evidence of degenerative progression. Research indicates that the interval between bipolar episodes decreases steadily until the patient settles into a relatively frequent course of mania and depression. Various imaging techniques have been used in the understanding of the brain pathology underlying bipolar disorder through identification of patterns consistent with disruption of the normal brain activity in bipolar patients. These techniques have demonstrated evidence of abnormalities in the structure and function of the prefrontal cortex. In addition, the cerebellar vermis, which serves as an error-detection function to modulate the iterative network, appears to shrink with recurrent episodes. Functional imaging demonstrates that the anterior limbic network is overactivated and overresponsive in patients with bipolar disorder. In many patients, those deficits are often compensated for by activation of other brain areas. Ultimately, when the compensation fails, expression of bipolar symptoms arise. Using magnetic resonance spectroscopy, simple models can be constructed based on the hypothesis that mitochondrial function may be impaired in bipolar disorder. There is also increasing evidence that psychotropic medications can affect specific brain regions that are thought to be involved in the pathogenesis of psychiatric disorders. Glutamate levels appear to be elevated in untreated patients with bipolar disorder, which may cause glutamatergic neurotoxicity and negative therapeutic implications. Further advances in brain imaging may contribute to the improvement of available therapies and the understanding which treatments will be most suitable for specific patients.