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At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing. [ABSTRACT FROM AUTHOR]

The article discusses a study on the prevalence of complex multi-drug prescriptions among participants in the U.S. National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Complex polypharmacy regimens are found to be prescribed to a substantial proportion of individuals with bipolar disorder. It states that antidepressant use is linked with multiple depressive episodes. Receiver operating characteristic (ROC) approach for creating clinical profiles are said to beneficial.

Carbamazepine began to be studied in a systematic fashion in the 1970s and became more widely used in the treatment of bipolar disorder in the 1980s. Interest in carbamazepine has been renewed by (i) the recent US FDA approval of a long-acting preparation for the treatment of acute mania; (ii) studies suggesting some efficacy in bipolar depression; and (iii) evidence of prophylactic efficacy in some difficult-to-treat subtypes of bipolar illness. A series of double-blind controlled studies of the drug were conducted at the US National Institute of Mental Health from the mid-1970s to the mid-1990s. This review summarises our experience in the context of the current literature on the clinical efficacy, adverse effects and pharmacokinetic interactions of carbamazepine.Carbamazepine has an important and still evolving place in the treatment of acute mania and long-term prophylaxis. It may be useful in individuals with symptoms that are not responsive to other treatments and in some subtypes of bipolar disorder that are not typically responsive to a more traditional agent such as lithium. These subtypes might include those patients with bipolar II disorder, dysphoric mania, substance abuse co-morbidity, mood incongruent delusions, and a negative family history of bipolar illness in first-degree relatives. In addition, carbamazepine may be useful in patients who do not adequately tolerate other interventions as a result of adverse effects, such as weight gain, tremor, diabetes insipidus or polycystic ovarian syndrome.We review our clinical and research experience with carbamazepine alone and in combination with lithium, valproic acid and other agents in complex combination treatment of bipolar illness. More precise clinical and biological predictors and correlates of individual clinical responsiveness to carbamazepine and other mood stabilisers are eagerly awaited. [ABSTRACT FROM AUTHOR]

Objective: This study compared demographic and phenomenological variables between bipolar patients with and without rapid cycling as a function of bipolar I versus bipolar II status. Method: The authors examined demographic, historical, and symptomatic features of patients with and without rapid cycling in a cross-sectional study of the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. Results: Rapid-cycling bipolar disorder occurred in 20% of the study group. Rapid cycling patients were more likely to be women, although the effect was somewhat more pronounced among bipolar I patients than bipolar II patients. In addition, rapid-cycling bipolar patients experienced onset of their illness at a younger age, were more often depressed at study entry, and had poorer global functioning in the year before study entry than nonrapid-cycling patients, Rapid-cycling patients also experienced a significantly greater number of depressive and hypomanic/manic episodes in the prior year. A lifetime history of psychosis did not distinguish between rapid and nonrapidcycling patients, although bipolar I patients were more likely to have experienced psychosis than bipolar II patients, Conclusions: Patients with rapid-cycling bipolar disorder demonstrate a greater severity of illness than nonrapid-cycling patients on a number of clinical measures. This study highlights the need to refine treatments for rapid cycling to reduce the overall morbidity and mortality of patients with this illness course modifier. [ABSTRACT FROM AUTHOR]

Calabrese JR, Keck PE Jr, Bowden CL, Ketter TA, Sachs G, Findling RL, Sajatovic M. A US perspective of the CANMAT bipolar guidelines.Bipolar Disord 2005: 7 (Suppl. 3): 70–72.© Blackwell Munksgaard, 2005 [ABSTRACT FROM AUTHOR]

Focuses on the symptomatology of mania, an altered mental state in the U.S. Association of facial emotion with mania behavior; Emergence of psychotic symptoms and grandiosity; Discussion on the clinical behaviors of patients with mania symptoms.

Background: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial.Methods: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS.Results: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics.Limitations: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders.Conclusions: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable. [ABSTRACT FROM AUTHOR]

Aims: Antidepressant use is controversial in bipolar disorder (BD) due to questionable efficacy/psychiatric tolerability. We assessed demographic/clinical characteristics of baseline antidepressant use in BD patients.Methods: Prevalence and correlates of baseline antidepressant use in 503 BD I and BD II outpatients referred to the Stanford Bipolar Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation.Results: Antidepressant use was 39.0%, overall, and was higher in BD II versus BD I (46.9% versus 30.5%, p = 0.0002). Both BD I and BD II antidepressant compared to non-antidepressant users had higher rates of complex pharmacotherapy (≥ 4 mood stabilizers, antipsychotics, and/or antidepressants) and use of other psychotropics. Antidepressant use in BD II versus BD I was higher during euthymia (44.0% vs. 28.0%) and subsyndromal symptoms (56.1% vs. 28.6%), but not depression or mood elevation.Limitations: American tertiary BD clinic referral sample receiving open naturalistic treatment.Conclusions: In our sample, antidepressant use was higher in BD II versus BD I patients, and was associated with markers of heightened illness severity in both BD I and BD II patients. Additional research is warranted to investigate these complex relationships. [ABSTRACT FROM AUTHOR]

Background: Prevalence and relative severity of bipolar II disorder (BDII) vs. bipolar I disorder (BDI) are controversial.Methods: Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation.Results: BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) disorders, first-degree relative with mood disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0±8.6 vs. 18.9±8.1 years), longer illness duration (19.0±13.0 vs. 16.1±13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1±1.4 vs. 3.7±1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%).Limitations: American tertiary bipolar disorder clinic referral sample, cross-sectional design.Conclusions: Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII. [ABSTRACT FROM AUTHOR]

Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management.

The American Psychiatric Association guidelines for treating bipolar disorder recommend combination therapies to treat patients experiencing severe acute manic or mixed episodes and breakthrough manic or mixed episodes during maintenance therapy. Combination therapies approved by the U.S. Food and Drug Administration for the treatment of acute manic states include the use of second-generation antipsychotics, such as olanzapine, risperidone, quetiapine, and aripiprazole in combination with lithium or divalproex; for the treatment of acute bipolar depression, the olanzapine plus fluoxetine combination; and for maintenance treatment, quetiapine combined with lithium or valproate. When combining medications for the management of patients with bipolar disorders, physicians face a potentially complex treatment strategy. Available agents have different mechanisms of action, routes of metabolism and excretion, therapeutic effects, and side effects. Combining treatments can be advantageous owing to therapeutic synergy; however, the liability is an increased possibility of adverse effects. The decision to use a combination therapy should be made on the basis of the efficacy, tolerability, and safety of each medication and their specific combination for individual patients., (Copyright 2008 Physicians Postgraduate Press, Inc.)