Daily electronic monitoring of subjective and objective measures of illness activity in bipolar disorder using smartphones– the MONARCA II trial protocol: a randomized controlled single-blind parallel-group trial Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial. Voice analysis as an objective state marker in bipolar disorder The Bipolar Interactive Psychoeducation (BIPED) study: trial design and protocol 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 Anxiety disorder comobidity in Bipolar I Disorder: relationship to depression severity and treatment outcome. Beating Bipolar: exploratory trial of a novel Internet-based psychoeducational treatment for bipolar disorder. Using Smartphones to Monitor Bipolar Disorder Symptoms: A Pilot Study Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. A prospective study of the trajectories of clinical insight, affective symptoms, and cognitive ability in bipolar disorder. An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. Randomized trial of a population-based care program for people with bipolar disorder. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM). Interpersonal and social rhythm therapy for adolescents with bipolar disorder: treatment development and results from an open trial Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the Stanley Foundation bipolar treatment outcome network. Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study. A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Prodromal symptoms and signs of bipolar relapse: A report based on prospectively collected data Divalproex in the treatment of bipolar depression: a placebo-controlled study. Different profile of substance abuse in relation to predominant polarity in bipolar disorder: The Vitoria long-term follow-up study. Adolescents with or at ultra-high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker.
Background Patients with bipolar disorder often show decreased adherence with mood stabilizers and frequently interventions on prodromal depressive and manic symptoms are delayed . Recently , the MONARCA I r and omized controlled trial investigated the effect of electronic self-monitoring using smartphones on depressive and manic symptoms . The findings suggested that patients using the MONARCA system had more sustained depressive symptoms than patients using a smartphone for normal communicative purpose s , but had fewer manic symptoms during the trial . It is likely that the ability of these self-monitored measures to detect prodromal symptoms of depression and mania may be insufficient compared to automatically generated objective data on measures of illness activity such as phone usage , social activity , physical activity , and mobility . The Monsenso system , for smartphones integrating subjective and objective measures of illness activity was developed and will be tested in the present trial . Methods The MONARCA II trial uses a r and omized controlled single-blind parallel-group design . Patients with bipolar disorder according to ICD-10 who previously have been treated at the Copenhagen Clinic for Affective Disorder , Denmark are included and r and omized to either daily use of the Monsenso system including an feedback loop between patients and clinicians ( the intervention group ) or to the use of a smartphone for normal communicative purpose s ( the control group ) for a 9-month trial period . The trial was started in September 2014 and recruitment is ongoing . The outcomes are : differences in depressive and manic symptoms ; rate of depressive and manic episodes ( primary ) ; automatically generated objective data on measures of illness activity ; number of days hospitalized ; psychosocial functioning ( secondary ) ; perceived stress ; quality of life ; self-rated depressive symptoms ; self-rated manic symptoms ; recovery ; empowerment and adherence to medication ( tertiary ) between the intervention group and the control group during the trial . Ethical permission has been obtained . Positive , neutral and negative findings will be published . Discussion If the system is effective in reducing depressive and /or manic symptoms ( and other symptoms of bipolar disorder ) and the rate of episodes , there will be basis for extending the use to the treatment of bipolar disorder in general and in larger scale . Trial registration Clinical Trials.gov NCT02221336 . Registered 26th of September 2014 BACKGROUND The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence . Nevertheless , the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a r and omized controlled trial ( RCT ) . The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder . METHOD A total of 78 patients with bipolar disorder according to ICD-10 criteria , aged 18 - 60 years , and with 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and Young Mania Rating Scale ( YMRS ) scores ≤17 were r and omized to the use of a smartphone for daily self-monitoring including a clinical feedback loop ( the intervention group ) or to the use of a smartphone for normal communicative purpose s ( the control group ) for 6 months . The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS , respectively , between the intervention and control groups . RESULTS Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones  on depressive as well as manic symptoms . There was a tendency towards more sustained depressive symptoms in the intervention group ( B = 2.02 , 95 % confidence interval -0.13 to 4.17 , p = 0.066 ) . Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group . CONCLUSIONS These results highlight that electronic self-monitoring , although intuitive and appealing , needs critical consideration and further clarification before it is implemented as a clinical tool Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder . The present study aim ed at investigating ( 1 ) voice features collected during phone calls as objective markers of affective states in bipolar disorder and ( 2 ) if combining voice features with automatically generated objective smartphone data on behavioral activities ( for example , number of text messages and phone calls per day ) and  electronic self-monitored data ( mood ) on illness activity would increase the accuracy as a marker of affective states . Using smartphones , voice features , automatically generated objective smartphone data on behavioral activities  and  electronic self-monitored data  were collected from 28 out patients with bipolar disorder in naturalistic setting s on a daily basis during a period of 12 weeks . Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale 17-item and the Young Mania Rating Scale , respectively , by a research er blinded to smartphone data . Data were analyzed using r and om forest algorithms . Affective states were classified using voice features extracted during everyday life phone calls . Voice features were found to be more accurate , sensitive and specific in the classification of manic or mixed states with an area under the curve (AUC)=0.89 compared with an AUC=0.78 for the classification of depressive states . Combining voice features with automatically generated objective smartphone data on behavioral activities  and electronic self-monitored data  increased the accuracy , sensitivity and specificity of classification of affective states slightly . Voice features collected in naturalistic setting s using smartphones may be used as objective state markers in patients with bipolar disorder Background Bipolar disorders affect between 3–5 % of the population and are associated with considerable lifelong impairment . Since much of the morbidity associated with bipolar disorder is caused by recurrent depressive symptoms , which are often only poorly responsive to antidepressants , there is a need to develop alternative , non-pharmacological interventions . Psychoeducational interventions have emerged as promising long-term therapeutic options for bipolar disorder . Methods / design The study is an exploratory , individually r and omised controlled trial . The intervention known as ' Beating Bipolar ' is a psychoeducational programme which is delivered via a novel web-based system . We will recruit 100 patients with a diagnosis of DSM-IV bipolar disorder ( including type I and type II ) currently in clinical remission . The primary outcome is quality of life . This will be compared for those patients who have participated in the psychoeducational programme with those who received treatment as usual . Quality of life will be assessed immediately following the intervention as well as 10 months after r and omisation . Secondary outcomes include current depressive and manic symptoms , number of episodes of depression and mania/hypomania experienced during the follow-up period , global functioning , functional impairment and insight . An assessment of costs and a process evaluation will also be conducted which will explore the feasibility and acceptability of the intervention as well as potential barriers to effectiveness . Discussion Bipolar disorder is common , under-recognised and often poorly managed . It is a chronic , life-long , relapsing condition which has an enormous impact on the individual and the economy . This trial will be the first to explore the effectiveness of a novel web-based psychoeducational intervention for patients with bipolar disorder which has potential to be easily rolled out to patients .Trial registration Current Controlled Trials IS RCT 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 The present study investigated the greater symptom severity and poorer treatment response found in patients with bipolar illness and anxiety comorbidity , and examined depression as a potential mediator of this relationship . The sample consisted of 92 patients in an acute episode of Bipolar I Disorder with a current or past history of an anxiety disorder . Diagnoses were based on structured clinical interview , and participants were assessed at pre-treatment and then r and omly assigned to pharmacotherapy alone or pharmacotherapy plus family intervention . Patients were assessed on a monthly basis by blind assessors over 28 months . Compared to patients without anxiety comorbidity , individuals with bipolar disorder and an anxiety disorder possessed greater current symptom severity , even after controlling for depression severity . Logistic regression analysis identified that being female and having higher current depression but not manic severity predicted comorbid anxiety . Comorbid anxiety was associated with poorer treatment response in the sample regardless of treatment type , particularly in subsequent depressive symptoms . Multiple regression analyses indicated that current depression but not manic severity partially mediated the relationship between comorbid anxiety and treatment outcome . Results from the current study investigating comorbid anxiety disorders are consistent with past research limited to anxiety symptoms . Depression only partially accounted for the link between comorbid anxiety and greater symptom severity and poorer treatment response , and examination of other factors is warranted . Because of the clinical relevance of comorbid anxiety in severe affective disorders , treatments design ed to specifically address both concerns are needed OBJECTIVES Psychoeducational approaches are promising interventions for the long-term management of bipolar disorder . In consultation with professionals , patients , and their families we have developed a novel web-based psychoeducational intervention for bipolar disorder called Beating Bipolar . We undertook a preliminary exploratory r and omized trial to examine efficacy , feasibility and acceptability . METHODS This was an exploratory r and omized controlled trial of Beating Bipolar ( current controlled trials registration number : IS RCT N81375447 ) . The control arm was treatment-as-usual and the a priori primary outcome measure was quality of life [ measured by the brief World Health Organization Quality of Life ( WHOQOL-BREF ) scale ] . Secondary outcomes included psychosocial functioning , insight , depressive and manic symptoms and relapse , and use of healthcare re sources . Fifty participants were r and omized to either the Beating Bipolar intervention plus treatment-as-usual or just treatment-as-usual .  The intervention was delivered over a four-month period and outcomes were assessed six months later . RESULTS There was no significant difference between the intervention and control groups on the primary outcome measure ( total WHOQOL-BREF score ) but there was a modest improvement within the psychological subsection of the WHOQOL-BREF for the intervention group relative to the control group . There were no significant differences between the groups on any of the secondary outcome measures . CONCLUSIONS Beating Bipolar is potentially a safe and engaging intervention which can be delivered remotely to large numbers of patients with bipolar disorder at relatively low cost . It may have a modest effect on psychological quality of life . Further work is required to establish the impact of this intervention on insight , knowledge , treatment adherence , self-efficacy and self-management skills Background Relapse prevention in bipolar disorder can be improved by monitoring symptoms in patients ' daily life .  Smartphone apps are easy-to-use , low-cost tools that can be used to assess this information . To date , few studies have examined the usefulness of smartphone data for monitoring symptoms in bipolar disorder . Objective We present results from a pilot test of a smartphone-based monitoring system , Social Information Monitoring for Patients with Bipolar Affective Disorder ( SIMBA ) , that tracked daily mood , physical activity , and social communication in 13 patients . The objective of this study was to investigate whether smartphone measurements predicted clinical symptoms levels and clinical symptom change . The hypotheses that smartphone measurements are ( 1 ) negatively related to clinical depressive symptoms and ( 2 ) positively related to clinical manic symptoms were tested . Methods Clinical rating scales were administered to assess clinical depressive and manic symptoms . Patients used a smartphone with the monitoring app for up to 12 months . R and om-coefficient multilevel models were computed to analyze the relationship between smartphone data and externally rated manic and depressive symptoms . Overall clinical symptom levels and clinical symptom changes were predicted by separating between-patient and within-patient effects . Using established clinical thresholds from the literature , marginal effect plots displayed clinical relevance of smartphone data . Results Overall symptom levels and change in clinical symptoms were related to smartphone measures . Higher overall levels of clinical depressive symptoms were predicted by lower self-reported mood measured by the smartphone ( beta=-.56 , P<.001 ) . An increase in clinical depressive symptoms was predicted by a decline in social communication ( ie , outgoing text messages : beta=-.28 , P<.001 ) and a decline in physical activity as measured by the smartphone ( ie , cell tower movements : beta=-.11 , P=.03 ) . Higher overall levels of clinical manic symptoms were predicted by lower physical activity on the smartphone ( ie , distance travelled : beta=-.37 , P<.001 ) , and higher social communication ( beta=.48 , P=.03 ) . An increase in clinical manic symptoms was predicted by a decrease in physical activity on the smartphone ( beta=-.17 , P<.001 ) . Conclusions Clinical symptoms were related to some objective and subjective smartphone measurements , but not all smartphone measures predicted the occurrence of bipolar symptoms above clinical thresholds . Thus , smartphones have the potential to monitor bipolar disorder symptoms in patients ’ daily life . Further validation of monitoring tools in a larger sample is needed . Conclusions are limited by the low prevalence of manic and depressive symptoms in the study sample . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 05663421 ; http://www.controlled-trials.com/IS RCT N05663421 ( Archived by WebCite at http://www.webcitation.org/6d9wsibJB BACKGROUND More than half of all individuals with bipolar disorder have a substance abuse problem at some point in their lifetime . Patients with comorbid substance abuse disorders often are excluded from clinical trials . Thus , treatments targeting this high-risk clinical population are lacking . OBJECTIVE To evaluate the efficacy of divalproex sodium ( hereafter referred to as valproate ) in decreasing alcohol use and stabilizing mood symptoms in acutely ill patients with bipolar disorder and alcoholism . DESIGN A 24-week , double-blind , placebo-controlled , r and omized parallel-group trial . SETTING A university hospital serving as a primary catchment-area hospital and tertiary-care facility . PARTICIPANTS Fifty-nine subjects with diagnoses of bipolar I disorder and alcohol dependence . Intervention All study subjects received treatment as usual , including lithium carbonate and psychosocial interventions , and were r and omized to receive valproate or placebo . MAIN OUTCOME MEASURES Primary alcohol use outcomes included changes in alcohol use as indicated by changes in proportion of heavy drinking days and number of drinks per heavy drinking day . Other alcohol use outcomes included proportion of any drinking days , number of drinks per drinking day , and relapse to sustained heavy drinking . Mood outcomes included changes in depressive and manic symptoms . We used the mixed model to analyze longitudinal data . The first model used time of assessment , bipolar subtype ( mixed , manic , or depressed ) , and treatment group ( placebo or valproate ) as covariates . The second nested model included the additional covariate of medication adherence . RESULTS The valproate group had a significantly lower proportion of heavy drinking days ( P = .02 ) and a trend toward fewer drinks per heavy drinking day ( P = .055 ) than the placebo group . When medication adherence was added as covariate , the valproate group had significantly fewer drinks per heavy drinking day ( P = .02 ) and fewer drinks per drinking day ( P = .02 ) . Higher  valproate serum concentration significantly correlated with improved alcohol use outcomes . Manic and depressive symptoms improved equally in both groups . Level of gamma-glutamyl transpeptidase was significantly higher in the placebo group compared with the valproate group . CONCLUSIONS Valproate therapy decreases heavy drinking in patients with comorbid bipolar disorder and alcohol dependence . The results of this study indicate the potential clinical utility of the anticonvulsant mood stabilizer , valproate , in bipolar disorder with co-occurring alcohol dependence BACKGROUND Clinical insight in bipolar disorder is associated with treatment adherence and psychosocial outcome . The short-term dynamics of clinical insight in relationship to symptoms and cognitive abilities are unknown . METHODS In a prospect i ve observational study , a total of 106 out patients with bipolar disorder I or II were assessed at baseline , 6 weeks , 12 weeks , and 26 weeks . Participants were administered a comprehensive neuropsychological battery , clinical ratings of manic and depressive symptom severity , and self-reported clinical insight . Lagged correlations and linear mixed-effects models were used to determine the temporal associations between symptoms and insight , as well as the moderating influence of global cognitive abilities . RESULTS At baseline , insight was modestly correlated with severity of manic symptoms , but not with depressive symptoms or cognitive abilities . Insight and depressive symptoms fluctuated to approximately the same extent over time . Both lagged correlations and mixed effects models with lagged effects indicated that the severity of manic symptoms predicted worse insight at later assessment s , whereas the converse was not significant . There were no direct or moderating influences of global cognitive abilities . LIMITATIONS Our sample size was modest , and included relatively psychiatrically stable out patients , followed for a six month period . Our results may not generalize to acutely symptomatic patients followed over a longer period . CONCLUSIONS Clinical insight varies substantially over time within patients with bipolar disorder . Impaired insight in bipolar disorder is more likely to follow than to precede manic symptoms Background Atypical antipsychotics are widely used in the treatment of bipolar disorders .  Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia , major depressive disorder and , more recently , acute mania . At the moment , however , no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders . The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with st and ard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing st and ard therapies .  Methods The study enrolled fourteen bipolar I out patients , not responding to ongoing st and ard therapy .  Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before ( range 3–24 months ) and 5.2 ± 2.7 months after the introduction of amisulpride ( range 3–9 months ) . Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version ( CGI-BP ) score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization . Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride . The relative risk of relapse in the absence of amisulpride therapy was 3.1 ( χ2 = 4.2 , P < 0.05 ) . Similarly , the rates of manic/mixed and depressive relapse were decreased but only manic episodes reached statistical significance ( RR = 5.3 , χ2 = 5.2 , P < 0.02 ) . Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses . Large , r and omized , double-blind , placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to st and ard therapies for bipolar disorder OBJECTIVE Previous studies have found that family-focused treatment is an effective adjunct to pharmacotherapy in stabilizing symptoms in adult bipolar disorder . The authors examined whether pharmacotherapy and family-focused treatment for adolescents with bipolar disorder was more effective than pharmacotherapy and brief psychoeducation ( enhanced care ) in decreasing time to recovery from a mood episode , increasing time to recurrence , and reducing symptom severity over 2 years . METHOD A total of 145 adolescents ( mean age , 15.6 years ) with bipolar I or II disorder and a DSM-IV-TR manic , hypomanic , depressive , or mixed episode in the previous 3 months were r and omly assigned , with family members , either to pharmacotherapy and family-focused treatment , consisting of psychoeducation ( i.e. , recognition and early intervention with prodromal symptoms ) , communication enhancement training , and problem-solving skills training , delivered in 21 sessions over 9 months ; or to pharmacotherapy and three weekly sessions of enhanced care ( family psychoeducation ) . Independent evaluators assessed participants at baseline , every 3 months during year 1 , and every 6 months during year 2 , using weekly ratings of mood . RESULTS Twenty-two participants ( 15.2 % ) withdrew shortly after r and omization . Time to recovery or recurrence and proportion of weeks ill did not differ between the two treatment groups . Secondary analyses revealed that participants in family-focused treatment had less severe manic symptoms during year 2 than did those in enhanced care . CONCLUSIONS After an illness episode , intensive psychotherapy combined with best- practice pharmacotherapy does not appear to confer advantages over brief psychotherapy and pharmacotherapy in hastening recovery or delaying recurrence among adolescents with bipolar disorder BACKGROUND Despite the availability of efficacious medications and psychotherapies , care of bipolar disorder in everyday practice is often deficient . This trial evaluated the effectiveness of a multi-component care management program in a population -based sample of people with bipolar disorder . METHOD Four hundred and forty-one patients treated for bipolar disorder during the prior year were r and omly assigned to continued usual care or usual care plus a systematic care management program including : initial assessment and care planning , monthly telephone monitoring including brief symptom assessment and medication monitoring , feedback to and coordination with the mental health treatment team , and a structured group psychoeducational program -- all provided by a nurse care manager . Blinded quarterly assessment s generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation . RESULTS Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period ( Z= 2.44 , p=0.015 ) and approximately one-third less time in hypomanic or manic episode ( 2.59 weeks v. 1.69 weeks ) . Mean depression ratings across the entire follow-up period did not differ significantly between the two groups , but the intervention group showed a greater decline in depression ratings over time ( Z statistic for group-by-time interaction = 1.98 , p = 0.048 ) . CONCLUSIONS A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months . Preliminary results suggest a growing effect on depression over time , but longer follow-up will be needed BACKGROUND The risk of switching from mania to depression in bipolar disorder has been poorly studied . Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in " real world " patients . METHOD EMBLEM ( European Mania in Bipolar Longitudinal Evaluation of Medication ) is a 2-year , prospect i ve , observational study of patients with a manic/mixed episode . Symptom severity measures included Clinical Global Impression-Bipolar Disorder scale ( CGI-BP ) , Young Mania Rating Scale ( YMRS ) and 5-item Hamilton Depression Rating Scale . Switching was defined using CGI-BP mania and depression such that patients changed from manic and not depressed to depressed but not manic over two consecutive observations within the first 12 weeks of follow-up . Cox proportional hazards models identified baseline variables independently associated with switch to depression . RESULTS Of 2390 patients who participated in the maintenance phase ( i.e. up to 24 months ) , 120 ( 5.0 % ) switched to depression within the first 12 weeks . Factors associated with greater switching to depression include previous depressive episodes , substance abuse , greater CGI-BP overall severity and benzodiazepine use . Factors associated with lower switching rates were greater CGI-BP depression , lower YMRS severity and atypical antipsychotic use . LIMITATIONS The definition of switching biased against patients with mixed episodes being likely to switch . CONCLUSIONS Strictly defined , switch to depression from mania occurs in a small proportion of bipolar patients . Clinical history , illness severity , co-morbidities and treatment patterns are associated with switching to depression . Atypical antipsychotics may protect against switch to depression Background : In adolescents and adults , bipolar disorder ( BD ) is associated with significant morbidity , mortality , and impairment in psychosocial and occupational functioning . IPSRT is an empirically supported adjunctive psychotherapy for adults with bipolar disorder , which has been shown to help delay relapse , speed recovery from a bipolar depressive episode , and increase occupational and psychosocial functioning in adults with BD . This study is design ed to describe the adolescent‐specific developmental adaptations made to IPSRT ( i.e. , IPSRT‐A ) and to report the results from an open trial of IPSRT‐A with 12 adolescents with a bipolar spectrum disorder . Method : Interpersonal and Social Rhythm Therapy was adapted to be developmentally relevant to adolescents with bipolar disorder . Twelve adolescents ( mean age 16.5±1.3 years ) diagnosed with a bipolar spectrum disorder participated in 16–18 sessions of adjunctive IPSRT‐A over 20 weeks . Manic , depressive , and general symptoms and global functioning were measured at baseline , monthly during treatment , and at post‐treatment . Adolescent satisfaction with treatment was also measured . Results : Feasibility and acceptability  of IPSRT‐A were high ; 11/12 participants completed treatment , 97 % of sessions were attended , and adolescent‐rated satisfaction scores were high . IPSRT‐A participants experienced significant decreases in manic , depressive , and general psychiatric symptoms over the 20 weeks of treatment . Participants ' global functioning increased significantly as well . Effect sizes ranged from medium‐large to large . Conclusions : IPSRT‐A appears to be a promising adjunctive treatment for adolescents with bipolar disorder . A current r and omized controlled trial is underway to examine effects of adjunctive IPSRT‐A  on psychiatric symptoms and psychosocial functioning . Depression and Anxiety , 2010 . © 2010 Wiley‐Liss , OBJECTIVE The authors assessed gender differences in the proportion of clinical visits spent depressed , manic , or euthymic in patients with bipolar disorder . METHOD Data were analyzed from 711 patients with bipolar I or II disorder who were followed prospect ively over 7 years ( 13,191 visits ) . The main outcome measures were the presence of symptoms of depression or of hypomania or mania , measured by the Inventory of Depressive Symptomatology and the  Young Mania Rating Scale . Data were analyzed using three separate repeated- measures regressions with a logistic link function to model the probability that an individual was depressed , manic , or euthymic . The models controlled for bipolar I or bipolar II diagnosis , rapid cycling , age , time in the study , comorbid anxiety disorders , and comorbid substance use disorders . RESULTS In approximately half of visits , patients had depressive , manic , or hypomanic symptoms . The likelihood of having depressive symptoms was significantly greater for women than for men . This was accounted for by higher rates in women of rapid cycling and anxiety disorders , each of which was associated with increased rates of depression . All patient groups showed an increase in number of euthymic visits and a decrease in number of visits with depressive and manic symptoms with increased time in study . CONCLUSIONS Bipolar patients spend a substantial proportion of their time ill . Significant gender differences exist , with women spending a greater proportion of their visits in the depressive pole . This finding appears to be related to the corresponding differences in rates of rapid cycling and anxiety disorders OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders , and this comorbidity may be associated with a more severe course of illness , but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined . The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder . METHOD Subjects ( N=3,750 ) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) were followed prospect ively for up to 2 years . Prospect ively observed depressive episodes were identified for this analysis . Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic , hypomanic , or mixed episode . RESULTS During follow up , 2,154 subjects developed a new-onset major depressive episode ; of these , 457 subjects switched to a manic , hypomanic , or mixed episode prior to recovery . Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity . However , those with current or past substance use disorder were more likely to experience switch from depression directly to a manic , hypomanic , or mixed state . CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic , mixed , or hypomanic states . The mechanism conferring this increased risk merits further study CONTEXT Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder ( BP-I ) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder ( BP-II ) . OBJECTIVE To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II . DESIGN A naturalistic study with 20 years of prospect i ve , systematic follow-up . SETTING Inpatient and outpatient treatment facilities at 5 US academic centers . Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean ( SD ) of 15 ( 4.8 ) years in the National Institute of Mental Health Collaborative Depression Study . MAIN OUTCOME MEASURES The relationship , by r and om regression , between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews . RESULTS Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II , and they may even enhance functioning . Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and , in some cases , significantly more so . At each level of depressive symptom severity , BP-I and BP-II are equally impairing . When asymptomatic , patients with bipolar disorder have good psychosocial functioning , although it is not as good as that of well controls . CONCLUSIONS Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II . Important findings for clinical management are the following : ( 1 ) depressive episodes and symptoms , which dominate the course of BP-I and BP-II , are equal to or more disabling than corresponding levels of manic or hypomanic symptoms ; ( 2 ) subsyndromal depressive symptoms , but not subsyndromal manic or hypomanic symptoms , are associated with significant impairment ; and ( 3 ) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II BACKGROUND There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive . This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospect ively for an average of three years . METHOD Detailed life-charting data were obtained from 138 patients with bipolar disorder . Mood states were characterized as euthymic , subsyndromal , minor or major affective episodes based on rigorously defined criteria . The amount of time spent in these mood states during follow-up was examined . RESULTS Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic . The remainder of the time was spent in varying severity of mood states . However , the majority of time was spent with minor and subsyndromal symptoms , both manic and depressive . Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal , minor and manic symptoms . There was no difference in time spent with depressive symptoms between the two groups . CONCLUSIONS Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal . Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder Prospect ively collected data on 19 recently hospitalized patients with bipolar disorder were examined for prodromal changes preceding relapse . The 4-month periods before six manic and six depressive relapses were compared with each other and with a comparable period for seven patients who did not relapse . The  Brief Psychiatric Rating Scale  was used to assess symptoms . Significant elevations in unusual thought content were found 1 month before manic relapse . Depressive relapsers evidence d higher levels of conceptual disorganization throughout the prerelapse period . Nonrelapsers showed very stable symptom profiles BACKGROUND The treatment of bipolar disorder in the depressed phase is complicated by a tendency for conventional antidepressant drugs to worsen the course of the illness by precipitating a manic episode or increasing cycle frequency . Thus , the potential antidepressant efficacy of mood stabilizers , such as divalproex , which is an effective treatment for the manic phase of bipolar disorder , is of considerable interest . METHODS The clinical efficacy of divalproex ( valproate , Depakote ) was tested in an 8-week , double-blind , placebo-controlled , r and omized clinical trial in 25 out patients with bipolar I depression . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression , and secondary measures included the Hamilton Rating Scale for Anxiety , the Clinician Administered Rating Scale for Mania , and the Clinical Global Impression scale . RESULTS Using repeated measures ANOVA with last observation carried forward , divalproex was more effective than placebo in improving symptoms of depression ( p = 0.0002 ) and symptoms of anxiety ( p = 0.0001 ) than placebo . LIMITATIONS The sample size was small , and most patients were male . CONCLUSIONS These pilot results indicate that divalproex is effective in reducing the symptoms of depression and anxiety in bipolar I , depressed phase . These positive results support the need to perform a larger , multisite study of divalproex treatment for bipolar depression BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms , especially the course of comorbid alcohol/substance abuse . METHOD A naturalistic sample of bipolar I patients ( n=120 ) was followed prospect ively for up to 10years . At baseline , number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes , respectively . 25 patients were excluded from the analyses . Outcomes including episodes , hospitalisations and suicide attempts were recorded at bimonthly visits . Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients . RESULTS Of the 95 patients analyzed , 44 ( 46.3 % ) had predominantly manic episodes and 51 ( 53.7 % ) had predominantly depressive episodes . At baseline , the predominantly depressive group had more history of suicide attempts ( 45.1 % vs. 20.5 % ; p=0.021 ) and more family history of affective disorders ( 64.7 % vs. 38.6 % ; p=0.020 ) , but they had fewer previous hospitalisations than the manic group ( mean 0.38 vs. 0.50 ; p=0.025 ) . During the 10-year follow-up , the predominantly depressive group was associated with more episodes ( p=0.001 ) , more hospitalisations ( p=0.004 ) and more suicide attempts ( p=0.002 ) . At baseline , there were no differences between the manic and depressive groups in the frequency of alcohol abuse ( 43.2 % and 35.3 % , p=0.565 ) or other substance abuse ( 13.6 % and 9.8 % , p=0.794 ) . During the 10-year follow-up , the frequency of alcohol and other substance abuse decreased significantly in the manic group only , after controlling by age at onset and civil ( marital ) status . CONCLUSION Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients , with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse . These differences should be considered when design ing treatment approaches for bipolar patients with comorbid alcohol/substance abuse AIM Mood disorders are associated with low levels of the long-chain omega-3 ( LCn-3 ) fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker . METHOD Erythrocyte fatty acid composition was determined in healthy adolescents ( n = 28 , HC ) , asymptomatic adolescents with a biological parent with bipolar I disorder ( n = 30 ; ' high risk ' , HR ) , adolescents with a biological parent with bipolar I disorder and major depressive disorder , or depressive disorder not otherwise specified ( n = 36 ; ' ultra-high risk ' , UHR ) , and first-episode adolescent bipolar manic patients ( n = 35 , BP ) . RESULTS Group differences were observed for DHA ( P ≤ 0.0001 ) and EPA ( P = 0.03 ) . Compared with HC , erythrocyte EPA + DHA ( ' omega-3 index ' ) was significantly lower in BP ( -24 % , P ≤ 0.0001 ) and UHR ( -19 % , P = 0.0006 ) groups , and there was a trend in the HR group ( -11 % , P = 0.06 ) . Compared with HC ( 61 % ) , a greater percentage of HR ( 77 % , P = 0.02 ) , UHR ( 80 % , P = 0.005 ) and BP ( 97 % , P = 0.001 ) subjects exhibited EPA + DHA levels of ≤4.0 % . Among all subjects ( n = 130 ) , EPA + DHA was inversely correlated with manic ( r = -0.29 , P = 0.0008 ) and depressive ( r = -0.28 , P = 0.003 ) symptom severity . The AA/EPA + DHA ratio was significantly greater in BP ( + 22 % , P = 0.0002 ) and UHR ( + 16 % , P = 0.001 ) groups . CONCLUSIONS Low EPA + DHA levels coincide with the initial onset of mania , and increasing risk for developing bipolar disorder is associated with grade d erythrocyte EPA + DHA deficits . Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospect i ve studies
Taken together , the literature presented in this dissertation illustrates that 1 ) smartphone-based electronic self-monitoring of mood  seems to reflect clinical ly assessed depressive and manic symptoms and enables the long-term characterization of mood instability in bipolar disorder ; 2 ) preliminary results suggest that smartphone-based automatically generated data ( e.g. the number of text messages sent/day ; the number of incoming and outgoing calls/day ; the number of changes in cell tower IDs/day ; and voice features ) seem to reflect clinical ly assessed depressive and manic symptoms in bipolar disorder ; 3 ) smartphone-based electronic self-monitoring had no effects on the severity of depressive and manic symptoms in bipolar disorder , according to a r and omized controlled trial ; and 4 ) electronic  monitoring of psychomotor activity and heart rate variability seems to reflect illness activity in bipolar disorder and differentiate between patients with bipolar disorder and healthy control individuals .
These findings point toward the usefulness of  electronic monitoring  as a marker of illness in bipolar disorder .
Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and decreased adherence to psychopharmacological treatment .
The reliance on subjective information and clinical evaluations when diagnosing and assessing the severity of depressive and manic symptoms calls for less biased and more objective markers .
By using electronic devices , fine-grained data on complex psychopathological aspects of bipolar disorder can be evaluated unobtrusively over the long term .
Using electronic monitoring as a treatment intervention could provide innovative and novel interventions on-dem and with a potential global reach , filling the gap between availability and the need for treatment .