Bipolar Symptoms Research Articles

Bipolar I and II disorder residual symptoms: Oxcarbazepine and carbamazepine as add-on treatment to lithium in a double-blind, randomized trial

Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC ( n = 26) or CBZ ( n = 26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint ( p < 0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 ( p < 0.05) and from baseline to week 8 ( p < 0.001), except YMRS ( p < 0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings.

Family-Focused Treatment for Adolescents With Bipolar Disorder

Family interventions have been found to hasten episode recovery and delay recurrences among adults with bipolar disorder. To examine the benefits of family-focused treatment for adolescents (FFT-A) and pharmacotherapy in the 2-year course of adolescent bipolar disorder. Two-site outpatient randomized controlled trial with 2-year follow-up. A referred sample of 58 adolescents (mean [SD] age, 14.5 [1.6] years) with bipolar I (n = 38), II (n = 6), or not otherwise specified disorder (n = 14) with a mood episode in the prior 3 months. Patients were randomly assigned to FFT-A and protocol pharmacotherapy (n = 30) or enhanced care (EC) and protocol pharmacotherapy (n = 28). The FFT-A consisted of 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training. The EC consisted of 3 family sessions focused on relapse prevention. Independent "blind" evaluators assessed patients every 3 to 6 months for 2 years. Outcomes included time to recovery from the index episode, time to recurrence, weeks in episode or remission, and mood symptom severity scores. Analyses were by intent to treat. Rates of 2-year study completion did not differ across the FFT-A (60.0%) and EC conditions (64.3%). Although there were no group differences in rates of recovery from the index episode, patients in FFT-A recovered from their baseline depressive symptoms faster than patients in EC (hazard ratio, 1.85; 95% confidence interval, 1.04-3.29; P = .04). The groups did not differ in time to recurrence of depression or mania, but patients in FFT-A spent fewer weeks in depressive episodes and had a more favorable trajectory of depression symptoms for 2 years. Family-focused therapy is effective in combination with pharmacotherapy in stabilizing bipolar depressive symptoms among adolescents. To establish full recovery, FFT-A may need to be supplemented with systematic care interventions effective for mania symptoms.

Identifying hypomanic features in major depressive disorder using the hypomania checklist (HCL-32)

Background Recent studies have challenged the traditional unipolar/bipolar divide with increasing support for a more dimensional view of affective disorders. We here examine the occurrence of hypomanic symptoms in individuals with a history of major depression selected to exclude indicators of underlying bipolarity. Methods The presence of hypomanic symptoms was assessed by the Hypomania Checklist (HCL-32) self-report questionnaire in a sample of almost 600 patients meeting DSM-IV criteria for Bipolar I disorder (BPI N = 260) or Major Recurrent Depressive disorder (MDDR N = 322). Subjects were recruited and assessed using consistent, robust methodology. Results We found that a score of 20 or more on the HCL-32 yielded the best combination of sensitivity (68%) and specificity (83%) to distinguish between BPI and MDDR. Within our highly selected and well defined MDDR sample (for which exclusion criteria included personal or family histories of bipolar or psychotic illness), 17% of MDDR subjects scored over the threshold of 20 on the HCL-32. Conclusions The HCL-32 identified a substantial number of patients meeting DSM-IV criteria for recurrent major depression (even when selected to exclude personal and family histories of bipolar illness) who reported bipolar symptoms at a level similar to that reported by patients meeting diagnostic criteria for bipolar disorder. This demonstrates the limitations of using DSM-IV criteria to distinguish those with and without bipolar features of illness.

Service delivery in older patients with bipolar disorder: a review and development of a medical care model

Medical comorbidities, especially cardiovascular disease (CVD), occur disproportionately in older patients with bipolar disorder. We describe the development, implementation, and feasibility/tolerability results of a manual-based medical care model (BCM) designed to improve medical outcomes in older patients with bipolar disorder. The BCM consisted of (i) self-management sessions focused on bipolar disorder symptom control, healthy habits, and provider engagement, (ii) telephone care management to coordinate care and reinforce self-management goals, and (iii) guideline dissemination focused on medical issues in bipolar disorder. Older patients with bipolar disorder and a CVD-related risk factor (n = 58) were consented, enrolled, and randomized to receive BCM or usual care. Baseline assessment (mean age = 55, 9% female, 9% African American) revealed a vulnerable population: 21% were substance users, 31% relied on public transportation, and 22% reported problems accessing medical care. Evaluation of BCM feasibility revealed high overall patient satisfaction with the intervention, high fidelity (e.g., majority of self-management sessions and follow-up contacts completed), and good tolerability (dropout rate <5%). Use of telephone contacts may have mitigated barriers to medical care (e.g., transportation). The BCM is a feasible model for older, medically ill patients with bipolar disorder, and could be an alternative to more costly treatment models that involve co-location and/or additional hiring of medical providers in mental health clinics. Future research directions pertinent to the development of the BCM and other medical care models for older patients with bipolar disorder include assessment of their long-term effects on physical health and their cost-effectiveness across different treatment settings.

Distinctions of bipolar disorder symptoms in adolescence

Bipolar disorder in adolescents is a serious mental illness with problematic diagnosis that adversely affects social, academic, emotional, and family functioning. The objective of this study was to analyze features of premorbid and clinical symptoms, comorbidity, and course of bipolar disorder in adolescence. Data for analysis were collected from all case histories (N=6) of 14-18-year-old patients, hospitalized with diagnosis of bipolar disorder in the Unit of Children's and Adolescents' Psychiatry, Department of Psychiatry, Hospital of Kaunas University of Medicine, during the period from 2000 to 2005. Analysis of bipolar disorder course showed that five patients previously had been diagnosed with an episode of depression. The most frequent symptoms typical to bipolar disorder were disobedience and impulsive behavior, rapid changes of mood. The most common premorbid features were frequent changes of mood, being active in communication, hyperactive behavior. Adolescence-onset bipolar disorder was frequently comorbid with emotionally instable personality disorder, borderline type. Findings of the study confirm the notion that oppositional or impulsive behavior, rapid changes of mood without any reason, dysphoric mood and euphoric mood episodes with increased energy were cardinal symptoms of bipolar disorder with mania in adolescents. Most frequent premorbid features of these patients were quite similar to attention-deficit/hyperactivity disorder making differential diagnosis problematic.

Improving Medical and Psychiatric Outcomes Among Individuals With Bipolar Disorder: A Randomized Controlled Trial

Improving Medical and Psychiatric Outcomes Among Individuals With Bipolar Disorder: A Randomized Controlled Trial

Improving Medical and Psychiatric Outcomes Among Individuals With Bipolar Disorder: A Randomized Controlled Trial

Comorbid medical conditions, notably cardiovascular disease, occur disproportionately among persons with bipolar disorder; yet the quality and outcomes of medical care for these individuals are suboptimal. This pilot study examined a bipolar disorder medical care model (BCM) and determined whether, compared with usual care, individuals randomly assigned to receive BCM care had improved medical and psychiatric outcomes. Persons with bipolar disorder and cardiovascular disease-related risk factors were recruited from a large Department of Veterans Affairs mental health facility and randomly assigned to receive BCM or usual care. BCM care consisted of four self-management sessions on bipolar disorder symptom control strategies, education and behavioral change related to cardiovascular disease risk factors, and promotion of provider engagement. Primary outcomes were physical and mental health-related quality of life; secondary outcomes included functioning and bipolar symptoms. Fifty-eight persons participated. Twenty-seven received BCM care, and 31 received usual care. The mean+/-SD age was 55+/-8 years, 9% were female, 90% were white, and 10% were African American. Repeated-measures analysis was used, and significant differences were observed between the two groups in change in scores from baseline to six months for the 12-Item Short-Form Health Survey (SF-12) subscale for physical health (t=2.01, df=173, p=.04), indicating that the usual care group experienced a decline in physical health over the study period. Change in SF-12 scores also indicated that compared with the usual care group, the BCM group showed improvements in mental health-related quality of life over the six-month study period; however, this finding was not significant. Compared with usual care, BCM care may have slowed the decline in physical health-related quality of life. Further studies are needed to determine whether BCM care leads to long-term positive changes in physical and mental health-related quality of life and reduced risk of cardiovascular disease among persons with bipolar disorder.

Current research in child and adolescent bipolar disorder

Although recently more research has considered children with bipolar disorder than in the past, much controversy still surrounds the validity of the diagnosis. Furthermore, questions remain as to whether or not childhood expressions of bipolarity are continuous with adult manifestations of the illness. In order to advance current knowledge of bipolar disorders in children, researchers have begun to conduct phenomenological, longitudinal, treatment, and neuroimaging studies in youths who exhibit symptoms of bipolar illness, as well as offspring of parents with bipolar disorders. Regardless of the differences between research groups regarding how bipolar disorder in children is defined, it is agreed that pediatric bipolarity is a serious and pernicious illness. With early intervention during the period of time in which youths are exhibiting subsyndromal symptoms of pediatric bipolarity, it appears that the progression of the illness to the more malignant manifestation of the disorder may be avoided. This paper will review what is currently known and what still is left to learn about clinically salient topics that pertain to bipolar disorder in children and adolescents.

Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort

Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. One thousand ninety manic patients included in the French National Study EPIMAN-II Mille were submitted to a cluster analysis on the basis of multiple variables related to the history of bipolar illness and symptoms of the current episode. Four clusters were identified: "classic mania" (29.3% of patients) with less severe mania; "psychotic mania" (22.7%) with psychotic symptoms, more severe mania, younger age and social impairment; "depressive mania" (30.4%) characterized by female gender, suicide attempts, high number of previous episodes and residual symptoms; and "dual mania" (17.6%) characterized by male gender, substance use, earlier onset and poor compliance. Patients groups also differed in manic symptoms, marital status, stressors preceding illness onset, prior diagnoses, first episode polarity and temperamental characteristics. Cross-sectional assessment of patients. In comparing our findings with those of four prior cluster analytic studies, we integrate clinical characteristics of mania subtypes found in this very large representative French sample in contemporary practice, we suggest how such convergence of data may help improve earlier recognition, differential response to different treatments, and prevention of these subtypes. We finally suggest that such subtyping might provide clues to phenotype delineation suitable for pharmacogenetic investigations.

Overview of Patient Care Issues and Treatment in Bipolar II Disorder

Recent studies have reported lifetime prevalence estimates of 1.0% for bipolar I disorder, 1.1% for bipolar II disorder, and 2.4% to 4.7% for subthreshold bipolar disorder, illustrating the need for consensus definitions of bipolar spectrum disorders. These definitions will aid researchers in studying viable treatments options, as well as help clinicians in the differential diagnosis of patients. Broader definitions of bipolar spectrum disorders would also allow clinicians to more accurately diagnose patients, rather than placing them in the catchall category of bipolar disorder not otherwise specified. Bipolar symptoms that are currently labeled as subthreshold symptoms are becoming increasingly recognized as having relevant clinical implications. Despite diagnostic controversy, screening for the presence of mania in patients who present with depressive symptoms is a critical step in the appropriate treatment of bipolar spectrum disorders. Identifying the early onset of bipolar symptoms as manifested in prodromal disorders such as childhood major depressive disorder and attention-deficit/hyperactivity disorder is also important for possible early intervention and improved outcomes.

Comparative Clinical Responses to Risperidone and Divalproex in Patients with Pediatric Bipolar Disorder

To compare clinical responses of patients with pediatric bipolar disorder being treated with risperidone versus divalproex. Medical records of outpatients younger than 18 years of age were reviewed to gather data on those who received risperidone or divalproex monotherapy for the treatment of bipolar disorder. Effectiveness was assessed using the Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales assigned by the treating clinician at visits during the initial 3 months of treatment with risperidone or divalproex. Change in CGI-S score over time was the primary outcome variable. The number of patients with a CGI-I score of < or = 2 at endpoint who did not discontinue the index medication because of adverse events was also compared. A total of 28 patients aged 5-14 years who were being treated for bipolar disorder were identified (risperidone n = 16; divalproex n = 12). Regression analysis of change in CGI-S scores revealed greater reductions in bipolar symptoms (p = 0.022) and a faster reduction in CGI-S scores (p = 0.016) in patients receiving risperidone than divalproex. A significantly shorter time to achieving a CGI-I score of < or = 2 was observed with risperidone than divalproex (26.8 +/- 20.7 days vs. 33.8 +/- 11.3 days; p = 0.048). However, the proportion of patients with a CGI-I score < or = 2 at endpoint was not significantly different (risperidone 69% versus divalproex 42%, p = 0.250). Three patients discontinued risperidone and 2 discontinued divalproex. Of these, none of the patients treated with risperidone and only 1 patient treated with divalproex discontinued treatment because of a documented adverse event. Risperidone was associated with significantly more weight gain then divalproex at 3 months (risperidone 2.46 +/- 1.16 kg versus divalproex 0.43 +/- 0.77 kg, p = 0.034). Patients receiving risperidone experienced a faster decrease in the severity of their bipolar symptoms, as measured by faster decreases in CGI-S scores, than did those who received divalproex. However, risperidone was also associated with significantly greater weight gain.

Are Bipolar Mood Symptoms Affected by the Phase of the Menstrual Cycle?

Evidence suggests gender differences may exist in bipolar disorder, and a review of the literature shows that more women than men may experience rapid-cycling bipolar disorder. The issues contributing to these gender differences are unknown; a number of case reports have indicated the possibility of mood changes secondary to hormonal influences during the menstrual cycle. We sought to examine the relationship between bipolar disorder and menstrual cycle-related mood changes. To our knowledge, this is one of the largest samples in the literature addressing this issue. Outpatient women with bipolar disorder I, bipolar disorder II, and not otherwise specified (NOS), between the ages of 18 and 45, were evaluated. The National Institute of Mental Health Life Chart Method-p (NIMH-LCM-p) was used for daily mood ratings of depression and mania. Repeated measures of ANOVA and t tests were conducted separately for depressive and for manic symptom scores. One hundred nineteen women met the age criterion, and only 41 women met the rest of the inclusion criteria. In this sample of 41 women, there was no significant relationship between phases of the menstrual cycle (early and late follicular and early and late luteal phases) and changes in depression or mania. In an exploratory examination, 8 of 41 women showed a numerically higher mean depression score in the luteal phase than in the follicular phase; 5 of 41 women showed a numerically higher mean mania score in the luteal phase than in the follicular phase of the menstrual cycle. Different phases of the menstrual cycle were unrelated to depression and mania in a heterogeneous group of women with bipolar disorder. Prospective studies are needed to identify a vulnerable subpopulation in a homogeneous clinical sample.

Do current beliefs predict hypomanic symptoms beyond personality style? Factor analysis of the hypomanic attitudes and positive predictions inventory (HAPPI) and its association with hypomanic symptoms in a student population

A self-report scale called the Hypomanic Attitudes and Positive Predictions Inventory (HAPPI) has been developed to assess cognitions that distinguish between bipolar disorder and nonclinical controls (Mansell, 2006; Mansell & Jones, 2006). We recruited 191 undergraduate students to assess the associations between the HAPPI and self-reported past (MDQ; Hirschfeld et al., 2000) and present (ISS; Bauer et al., 1991) bipolar symptoms, and to explore the factor structure of the scale. The HAPPI correlated with past and present symptoms independently of the BIS/BAS subscales (Carver & White, 1994) and the HPS (Eckblad & Chapman, 1986). Five factors of the HAPPI were identified: success activation and triumph over fear, activating response style, reduced social regulation, loss of control when activated, and catastrophic beliefs about internal states. The HAPPI factors showed specific relationships with current bipolar symptoms that largely fitted with predictions based on the model. Further work is required to establish whether they have a causal role.

Bipolar disorders across the lifespan

Bipolar disorders across the lifespan

Bipolar Symptoms, Depression Cluster in Epilepsy Patients

Bipolar Symptoms, Depression Cluster in Epilepsy Patients

Should Bipolar Medication Be Halted During Pregnancy?

Should Bipolar Medication Be Halted During Pregnancy?

FDA Evaluating New Drugs for Schizophrenia Treatment

Back to table of contents Previous article Next article Professional NewsFull AccessFDA Evaluating New Drugs for Schizophrenia TreatmentJun YanJun YanSearch for more papers by this authorPublished Online:4 Jan 2008https://doi.org/10.1176/pn.43.1.0004aSeveral new antipsychotics have been submitted to the Food and Drug Administration (FDA) for marketing review, making the therapeutic landscape for schizophrenia and bipolar disorder in the near future hard to predict.One of the most recent new drug applications (NDAs) was for asenpine sublingual tablet, developed by Organon. The drug binds with both dopamine D2 receptor and a host of serotonin 5-HT receptors subtypes, with a greater antagonism to all serotonin receptor subtypes except 5-HT1a and 5-HT1b, according to Steven Potkin, M.D., of the Department of Psychiatry and Human Behavior at the University of California, Irvine, and two researchers from Organon in their study published in the October 2007 Journal of Clinical Psychiatry.In this randomized, double-blind, controlled study, asenapine was compared with placebo and risperidone in 174 patients with acute schizophrenia for six weeks. The asenapine group saw a significantly greater reduction in mean Positive and Negative Syndrome Scale total, negative symptom, and positive symptom scores compared with placebo. Asenapine had a better profile than risperidone in terms of weight gain and prolactin levels, but the authors acknowledged that the 6 mg/day of risperidone given in this study was at the high end of usual dosage.In an earlier phase 3 study in 488 patients, asenapine produced a significantly greater reduction in bipolar manic symptoms compared with placebo after three weeks. The study results were presented at APA's 2007 annual meeting in San Diego in May.Asenapine has a somewhat curious history. Initially developed by Organon, it was licensed to Pfizer. In late 2006, however, Pfizer terminated the deal and gave the molecule back when an interim assessment of the phase 3 trials of asenapine became available. Schering-Plough acquired Organon last November, shortly before the announcement that the FDA had accepted the new drug application for a standard review.Regulatory success is, however, far from certain for novel antipsychotics. Another previously promising molecule, bifeprunox, was rejected by the FDA last August as “unapprovable” based on the submitted clinical data; the agency appeared to be lukewarm about the drug's efficacy compared with other available antipsychotics in treating acute schizophrenia, according to the announcement from Wyeth, the manufacturer. The company stated that it would continue with the development of bifeprunox.An NDA for paliperidone palmitate intramuscular injection, intended for once-monthly use, was filed with the FDA in October 2007 by its makers, Johnson and Johnson and Elan Pharmaceuticals. The oral extended-release tablet formulation of paliperidone has been approved for acute and maintenance treatment for schizophrenia. Paliperidone is an active metabolite of risperidone.A third new antipsychotic, iloperidone, is also waiting for the FDA to render a judgment on its NDA, which was filed by Vanda Pharmaceuticals last September and accepted by the agency in late November. The drug binds to a spectrum of dopamine and serotonin receptors and, according to the company,“ provides a favorable profile on adverse symptoms such as weight gain, extrapyramidal symptoms, akathisia, and prolactin elevation.”An abstract of “Efficacy and Tolerability of Asenapine in Acute Schizophrenia: A Placebo- and Risperidone-Controlled Trial” is posted at<www.psychiatrist.com/abstracts/200710/100704.htm>.▪ ISSUES NewArchived

Chronic N-methyl-d-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat

Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-d-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In unanesthetized rats, on day 21, [1-(14)C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25-34%) as well as the turnover of arachidonic acid within brain phospholipids (35-58%). These changes were absent at 3 h after a single NMDA injection. The changes, opposite to those after chronic administration of antimanic drugs to rats, suggest that excessive NMDA signaling via arachidonic acid may be a model of upregulated arachidonic acid turnover in brain phospholipids.

Prevention of bipolar disorder in at-risk children: theoretical assumptions and empirical foundations.

This article examines how bipolar symptoms emerge during development, and the potential role of psychosocial and pharmacological interventions in the prevention of the onset of the disorder. Early signs of bipolarity can be observed among children of bipolar parents and often take the form of subsyndromal presentations (e.g., mood lability, episodic elation or irritability, depression, inattention, and psychosocial impairment). However, many of these early presentations are diagnostically nonspecific. The few studies that have followed at-risk youth into adulthood find developmental discontinuities from childhood to adulthood. Biological markers (e.g., amygdalar volume) may ultimately increase our accuracy in identifying children who later develop bipolar I disorder, but few such markers have been identified. Stress, in the form of childhood adversity or highly conflictual families, is not a diagnostically specific causal agent but does place genetically and biologically vulnerable individuals at risk for a more pernicious course of illness. A preventative family-focused treatment for children with (a) at least one first-degree relative with bipolar disorder and (b) subsyndromal signs of bipolar disorder is described. This model attempts to address the multiple interactions of psychosocial and biological risk factors in the onset and course of bipolar disorder.

Med Check

Med Check