Randomized, placebo-controlled trial of quetiapine XR and divalproex ER monotherapies in the treatment of the anxious bipolar patient. A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder—the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes): a randomised controlled single-blind trial Family-focused treatment for adolescents with bipolar disorder.
BACKGROUND Anxiety disorders complicate the treatment of bipolar disorder but are seldom the focus of bipolar treatment studies . METHODS The anxiolytic effect of quetiapine XR 50 - 300 mg/day compared to divalproex ER ( 500 - 3000 mg/day ) was tested in an 8-week , double-blind , placebo-controlled , r and omized clinical trial in 149 patients with bipolar disorder and a co-occurring panic disorder or GAD . The primary efficacy measure was the Clinician Global Improvement-21 Anxiety Scale ( CGI-21 ) . Secondary measures included the Hamilton Anxiety Scale ( HAM-A ) and Sheehan Panic Disorder Scale ( SPS ) . RESULTS Repeated measures last-observation-carried-forward ( LOCF ) analyses of variance demonstrated significant treatment-by-time interaction effects on 3 of the 4 anxiety measures .  Quetiapine XR at a mean endpoint dose of 186 mg/day produced rapid sustained improvements relative to baseline , divalproex ER and placebo on anxiety . Mean baseline-to-endpoint improvement was significantly greater for quetiapine XR compared to divalproex ER and placebo on the HAM-A and SPS . Both active medications were well tolerated , but weight gain was higher on quetiapine XR . LIMITATIONS The study was limited to 8 weeks and to patients with bipolar disorder and comorbid panic disorder or GAD . The results may not be applicable to quetiapine XR as an add-on treatment to mood stabilizers or to bipolar disorder comorbid with other anxiety disorders . CONCLUSIONS Quetiapine XR in a dose range of 50 - 300 mg/day appears to reduce anxiety in bipolar patients with comorbid panic disorder or GAD treated for 8 weeks . The efficacy of other second-generation antipsychotics and mood stabilizers in patients with bipolar disorder and a co-occurring anxiety disorder should be investigated in double-blind , placebo-controlled studies Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder . Although it is a dopamine partial agonist , it also has substantial binding affinity for the serotonin 5HT2A receptor . Several double-blind r and omized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia , and 15–30 mg/day for manic or mixed states associated with bipolar I disorder . Relatively few comparative trials with other second-generation antipsychotics have been published for schizophrenia , with none available for bipolar disorder . The evidence so far suggests that in terms of efficacy for schizophrenia , aripiprazole is superior to placebo and haloperidol ( long term ) , similar to perphenazine and risperidone , and inferior to olanzapine .  Its tolerability profile in patients with schizophrenia appears superior to haloperidol , perphenazine , risperidone , and olanzapine .  Efficacy in treating manic or mixed states was established in placebo-controlled trials . Among some patients with bipolar disorder  , akathisia and gastrointestinal ( GI ) complaints can emerge at the start of treatment ; however , the GI symptoms were time-limited in many instances . Appropriate dosing may also be important in individualizing therapy to improve tolerability , with lower starting doses becoming more important when adding to , or switching from , another antipsychotic . Aripiprazole appears to have a low propensity for weight gain , a favorable metabolic profile , and no association with hyperprolactinemia Introduction Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms . It has never been tested in a r and omised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder . We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder . Methods We developed the MONARCA application for And roid-based Smartphones , allowing patients suffering from bipolar disorder to do daily self-monitoring — including an interactive feedback loop between patients and clinicians through a web-based interface . The effect of the application was tested in a parallel-group , single-blind r and omised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18–60 years who were given the use of a Smartphone with the MONARCA application ( intervention group ) or to the use of a cell phone without the application ( placebo group ) during a 6-month study period . The study was carried out from September 2011 . The outcomes were changes in affective symptoms ( primary ) , social functioning , perceived stress , self-rated depressive and manic symptoms , quality of life , adherence to medication , stress and cognitive functioning ( secondary and tertiary ) . Analysis Recruitment is ongoing . Ethics Ethical permission has been obtained . Dissemination Positive , neutral and negative findings of the study will be published . Registration details The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark ( H-2 - 2011 - 056 ) and The Danish Data Protection Agency ( 2013 - 41 - 1710 ) . The trial is registered at Clinical Trials.gov as NCT01446406 BACKGROUND Research has begun to eluci date the optimal pharmacological treatments for pediatric-onset bipolar patients , but few studies have examined the role of psychosocial interventions as adjuncts to pharmacotherapy in maintenance treatment . This article describes an adjunctive family-focused psychoeducational treatment for bipolar adolescents ( FFT-A ) . The adult version of FFT has been shown to be effective in forestalling relapses in two r and omized clinical trials involving bipolar adults . METHODS FFT-A is administered to adolescents who have had an exacerbation of manic , depressed , or mixed symptoms within the last 3 months . It is given in 21 outpatient sessions of psychoeducation , communication enhancement training , and problem solving skills training . We describe modifications to the adult FFT model to address the developmental issues and unique clinical presentations of pediatric-onset patients . RESULTS An open treatment trial involving 20 bipolar adolescents ( 11 boys , 9 girls ; mean age 14.8+/-1.6 ) found that the combination of FFT-A and mood stabilizing medications was associated with improvements in depression symptoms , mania symptoms , and behavior problems over 1 year . LIMITATIONS These early results are based on a small-scale open trial . CONCLUSIONS Results from an ongoing r and omized controlled trial will clarify whether combining FFT-A with pharmacotherapy improves the 2-year course of adolescent bipolar disorder . If the results are positive , then a structured manual-based psychosocial approach will be available for clinicians who treat adolescent bipolar patients in the community
Placebo response in bipolar disorder trials is more likely to occur in patients who are mildly ill , bipolar II , mixed-episode , first-episode , rapid cycling , atypical , non-psychotic , substance abusers and medically ill .
The use of concomitant medication such as benzodiazepines , a high frequency of visits , a high number of treatment groups and sites , fixed-dose design s , and the concomitant use of psychotherapy are likely to increase placebo response .
There are a number of clinical and method ological variables that are associated with placebo response
Background :  Placebo response is high in bipolar disorder trials .
This is a challenge for research ers and an enigma for clinicians .
This article will attempt to aid in the comprehension of the ethical questions and method ologies related to the use of placebo in bipolar disorder .
Results : Placebo has a very important role in the study of bipolar disorders .
From a method ological point of view , and given the limitations of non-inferiority design s , the use of placebo is necessary to evaluate the sensitivity of the study and ensure that the drug under investigation is really effective .