title: Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the Stanley Foundation bipolar treatment outcome network. Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders. Mindfulness-based Cognitive Therapy (MBCT) in bipolar disorder: Preliminary evaluation of immediate effects on between-episode functioning Response of patients with panic disorder and symptoms of hypomania to cognitive behavior therapy for panic. The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey. Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry. Anxiety as a correlate of response to the acute treatment of bipolar I disorder. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Suicidal ideation and suicide attempts in panic disorder and attacks. Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder. Benzodiazepine use and abuse among patients with severe mental illness and co-occurring substance use disorders. Clinical significance of lifetime panic spectrum symptoms in the treatment of patients with bipolar I disorder. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Panic attacks in the community. Social morbidity and health care utilization. Early stages in the development of bipolar disorder. Do comorbid anxiety disorders moderate the effects of psychotherapy for bipolar disorder? Results from STEP-BD. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.
abstract: OBJECTIVE The authors evaluated the efficacy and safety of lurasidone in the treatment of patients with major depressive episodes associated with bipolar I disorder . METHOD Patients were r and omly assigned to receive double-blind treatment with lurasidone ( 20 - 60 mg/day [ N=166 ] or 80 - 120 mg/day [ N=169 ] ) or placebo ( N=170 ) for 6 weeks . Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness ( CGI-BP ) , respectively . RESULTS Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20 - 60 mg/day group ( -15.4 ; effect size=0.51 ) and the 80 - 120 mg/day group ( -15.4 ; effect size=0.51 ) compared with placebo ( -10.7 ) . Similarly , lurasidone treatment result ed in significantly greater endpoint reduction in CGI-BP depression severity scores for both the 20 - 60 mg/day group ( -1.8 ; effect size=0.61 ) and the 80 - 120 mg/day group ( -1.7 ; effect size=0.50 ) compared with placebo ( -1.1 ) . Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms and in patient-reported measures of quality of life and functional impairment . Discontinuation rates due to adverse events were similar in the 20 - 60 mg/day ( 6.6 % ) , 80 - 120 mg/day ( 5.9 % ) , and placebo ( 6.5 % ) groups . The most frequent adverse events associated with lurasidone were nausea , headache , akathisia , and somnolence . Minimal changes in weight , lipids , and measures of glycemic control were observed with lurasidone . CONCLUSION Monotherapy with lurasidone in the dosage range of 20 - 120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression . Lurasidone was well tolerated , with few changes in weight or metabolic parameters 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 BACKGROUND The impact of anxiety disorders has not been well delineated in prospect i ve studies of bipolar disorder . AIMS To examine the association between anxiety and course of bipolar disorder , as defined by mood episodes , quality of life and role functioning . METHOD A thous and thous and out- patients with bipolar disorder were followed prospect ively for 1 year . RESULTS A current comorbid anxiety disorder ( present in 31.9 % of participants ) was associated with fewer days well , a lower likelihood of timely recovery from depression , risk of earlier relapse , lower quality of life and diminished role function over I year of prospect i ve study . The negative impact was greater with multiple anxiety disorders . CONCLUSIONS Anxiety disorders , including those present during relative euthymia , predicted a poorer bipolar course . The detrimental effects of anxiety were not simply a feature of mood state . Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course Background Bipolar disorder is highly recurrent and rates of comorbidity are high . Studies have pointed to anxiety comorbidity as one factor associated with risk of suicide attempts and poor overall outcome . This study aim ed to explore the feasibility and potential benefits of a new psychological treatment ( Mindfulness-based Cognitive Therapy : MBCT ) for people with bipolar disorder focusing on between-episode anxiety and depressive symptoms . Methods The study used data from a pilot r and omized trial of MBCT for people with bipolar disorder in remission , focusing on between-episode anxiety and depressive symptoms . Immediate effects of MBCT versus waitlist on levels of anxiety and depression were compared between unipolar and bipolar participants . Results The results suggest that MBCT led to improved immediate outcomes in terms of anxiety which were specific to the bipolar group . Both bipolar and unipolar participants allocated to MBCT showed reductions in residual depressive symptoms relative to those allocated to the waitlist condition . Limitations Analyses were based on a small sample , limiting power . Additionally the study recruited participants with suicidal ideation or behaviour so the findings can not immediately be generalized to individuals without these symptoms . Conclusions The study , although preliminary , suggests an immediate effect of MBCT on anxiety and depressive symptoms among bipolar participants with suicidal ideation or behaviour , and indicates that further research into the use of MBCT with bipolar patients may be warranted OBJECTIVES The purpose of this cohort study was to determine in patients with Panic Disorder ( PD ) : ( 1 ) . the prevalence of subsyndromal symptoms of hypomania , and ( 2 ) . whether subsyndromal hypomania symptoms affect the outcome of cognitive behavior therapy ( CBT ) for panic . METHODS Using the Diagnostic Interview Schedule , and DSM-III-R criteria we identified 18 individuals with a history of symptoms of hypomania among 56 patients with PD . Patients were treated in an open CBT group program . They were assessed before treatment and 6 and 12 months later . We used the  Brief Symptom Inventory ( BSI ) , the Perceived Stress Scale ( PSS ) , the Pearlin-Schooler Mastery Scale ( PMS ) , and the Social Adjustment Scale ( SAS )  at all assessment s. RESULTS The total group significantly improved on all measures . The Clinical ly Significant Change was 71.4 % and the Reliable Change Index 48.2 % . Between 6 and 12 months , there was a trend for the hypomania symptom subgroup ( PH ) to continue to improve on the BSI Depression Scale , the Perceived Stress Scale , the Pearlin-Schooler Mastery Scale , and the Social Adjustment Scale but to lose gains on the BSI Phobic Anxiety and Somatization subscales compared with the group without symptoms of hypomania ( PNH ) . CONCLUSIONS Thirty-two percent of patients with PD had symptoms of hypomania . With CBT for panic , patients with PD and symptoms of hypomania improve as much as those without hypomania symptoms . The presence or absence of symptoms of hypomania might help explain the inconsistent effects of depression and personality disorders on the treatment of PD In order to estimate the prevalence of affective disorders in Hungary a sample of the Hungarian adult population ( 18 - 64 years ) selected at r and om was interviewed using the Diagnostic Interview Schedule ( DIS ) which generated DSM-III-R diagnoses . The lifetime rate for Major Depressive Disorder ( MDD ) was 15.1 % , and for Bipolar Disorders ( BD ) 5.1 % . The female-to-male ratio was 2.7 for MDD and nearly equal for BD . The 1-year and 1-month period prevalence rates were 7.1 % and 2.6 % for MDD and 0.9 % and 0.5 % for manic episodes . A higher rate of divorced or separated persons was found among individuals with a lifetime diagnosis of MDD . Besides these , the lifetime diagnosis of BD coexisted with higher rates of the never-married state . The highest hazard rate for the development of BD or MDD was in the range 15 - 19 years but in MDD another peak was also found in the range 45 - 50 years . The first peak was characteristic of the recurrent , and the other one of the single form of MDD . Insomnia , loss of energy , decreased interest , concentration problems were the most common symptoms during the depressive episode , independent of polarity . Higher rates of lifetime diagnosis of dysthymia and all kinds of anxiety disorder were revealed among persons with MDD . BD was associated with GAD ( Generalized Anxiety Disorder ) , and panic disorder more often than chance OBJECTIVE To evaluate the prevalence of substance abuse dependence and /or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry . METHOD One hundred r and omly selected registrants in a voluntary case registry for bipolar disorder were interviewed , using the Structured Clinical Interview for DSM-IV Axis I Disorders , to vali date the diagnosis of this registry . Corroborative information was obtained from medical records , family members and the treating psychiatrist . Eighty-nine adults ( 18 - 65 years ) met criteria for bipolar disorder ( bipolar I = 71 , bipolar II = 18 ) and were included in this analysis . RESULTS Forty-one ( 57.8 % ) subjects with bipolar I disorder abused , or were dependent on one or more substances or alcohol , 28.2 % abused , or were dependent on , two substances or alcohol , and 11.3 % abused or were dependent on three or more substances or alcohol . Nearly 39 % of bipolar II subjects abused or were dependent on one or more substances , nearly 17 % were dependent on two or more substances or alcohol , and 11 % were dependent on three or more substances or alcohol . Alcohol was the most commonly abused drug among either bipolar I or II subjects . CONCLUSIONS Consistent with other epidemiologic and hospital population studies , this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and /or substance abuse dependence . Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects ; however , as the number of bipolar II subjects was rather small , this suggestion needs confirmation OBJECTIVE Given the adverse impact of anxiety on treatment outcome in unipolar depression and the paucity of data on the role of anxiety in bipolar disorder , the authors sought to determine the effect of anxiety on the acute treatment response of patients with bipolar I disorder . METHOD The authors examined the correlates of response to the acute treatment of 124 consecutively treated patients with bipolar I disorder . Measures of anxiety included history of panic attacks and a composite variable reflecting current or past anxiety symptoms . RESULTS History of panic attacks proved to be a significant correlate of nonremission . Anxiety , as assessed with the composite variable , was associated with longer time to remission , as was the treatment of depressive versus manic symptoms and mixed versus manic symptoms . Patients with anxiety as assessed with the composite variable and patients with a history of panic attacks reported more severe medication side effects . They also required a greater number of medications , either sequentially or in combination , in order to achieve remission . CONCLUSIONS The findings suggest that anxiety is a clinical ly meaningful correlate of poor outcome in the acute treatment of bipolar I disorder OBJECTIVE Few studies have been reported that support the efficacy of adjunctive therapy for patients with bipolar I depression who have had an insufficient response to monotherapy with mood-stabilizing agents . The authors investigated the efficacy of lurasidone , a novel antipsychotic agent , as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression . METHOD Patients were r and omly assigned to receive 6 weeks of double-blind adjunctive treatment with lurasidone  ( N=183 )  or placebo  ( N=165 ) , added to therapeutic levels of either lithium or valproate . Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness ( CGI-BP ) , respectively . RESULTS Lurasidone treatment significantly reduced mean MADRS total score at week 6 compared with the placebo group ( -17.1 versus -13.5 ; effect size=0.34 ) . Similarly , lurasidone treatment result ed in significantly greater endpoint reduction in CGI-BP depression severity scores compared with placebo ( -1.96 versus -1.51 ; effect size=0.36 ) as well as significantly greater improvement in anxiety symptoms and in patient-reported measures of quality of life and functional impairment . Discontinuation rates due to adverse events were 6.0 % and 7.9 % in the lurasidone and placebo groups , respectively . Adverse events most frequently reported for lurasidone were nausea , somnolence , tremor , akathisia , and insomnia . Minimal changes in weight , lipids , and measures of glycemic control were observed during treatment with lurasidone . CONCLUSIONS In patients with bipolar I depression , treatment with lurasidone adjunctive to lithium or valproate significantly improved depressive symptoms and was generally well tolerated OBJECTIVE The authors provide a detailed perspective on the correlates of comorbid anxiety in a large , well-characterized sample of bipolar disorder patients . METHOD Anxiety and its correlates were examined in a cross-sectional sample from 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 design ed to evaluate the longitudinal outcome of patients with bipolar disorder . RESULTS Lifetime comorbid anxiety disorders were common , occurring in over one-half of the sample , and were associated with younger age at onset , decreased likelihood of recovery , poorer role functioning and quality of life , less time euthymic , and greater likelihood of suicide attempts . Although substance abuse disorders were particularly prevalent among patients with anxiety disorders , comorbid anxiety appeared to exert an independent , deleterious effect on functioning , including history of suicide attempts ( odds ratio=2.45 , 95 % CI=1.4 - 4.2 ) . CONCLUSIONS An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated , highlighting the need for greater clinical attention to anxiety in this population , particularly for enhanced clinical monitoring of suicidality . In addition , it is important to determine whether effective treatment of anxiety symptoms can lessen bipolar disorder severity , improve response to treatment of manic or depressive symptoms , or reduce suicidality Panic disorder , which is found in about 1.5 percent of the population at some time in their lives , includes recurrent episodes of sudden , unpredictable , intense fear accompanied by symptoms such as palpitations , chest pain , and faintness . Panic attacks , which do not meet these diagnostic criteria fully , are two to three times more prevalent . Since panic symptoms can mimic those of other medical disorders , patients with these symptoms use medical services frequently . To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks , we studied a r and om sample of 18,011 adults drawn from five U.S. communities . Subjects who had panic disorder , as compared with other psychiatric disorders , had more suicidal ideation and suicide attempts , with an adjusted odds ratio for suicide attempts of 2.62 ( 95 percent confidence interval , 1.83 to 3.74 ) . The odds ratio was 17.99 ( 95 percent confidence interval , 12.18 to 26.58 ) when the group with panic disorder was compared with subjects who had no psychiatric disorder . Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts . These results could not be explained by the coexistence of major depression or of alcohol or drug abuse . We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts . Physicians working in general medical setting s and emergency departments should be alert to this problem BACKGROUND Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder . However , few studies have utilized public sector sample s , and only one has attempted to separate contributions of each type of comorbidity . METHODS 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports . RESULTS Comorbidity was common ( current : 57.3 % ; lifetime : 78.4 % ) , with multiple current comorbidities in 29.8 % . Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient sample s ( 33.8 % current , 72.3 % lifetime ) . Selected anxiety comorbidity rates exceeded those in other inpatient sample s and appeared more chronic than episodic/recurrent ( 38.3 % current , 43.3 % lifetime ) . 49 % of PTSD was due to non-combat stressors . Major correlates of current substance comorbidity alone were younger age , worse marital status , and higher current employability . Correlates of current anxiety comorbidity alone were early age of onset , greater number of prior-year depressive episodes , higher rates of disability pension receipt , and lower self-reported mental and physical function . Combined comorbidity resembled anxiety comorbidity . LIMITATIONS This is a cross-sectional analysis of acutely hospitalized veterans . CONCLUSIONS Distinct patterns of substance and anxiety comorbidity are striking , and may be subserved by distinct neurobiologic mechanisms . The prevalence , chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted . Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built " from the patient out . OBJECTIVES Because use of benzodiazepines may exacerbate existing substance use disorders or become abused substances , prescription of benzodiazepines for patients with severe mental illness ( schizophrenia or bipolar disorder ) and co-occurring substance use disorders ( abuse or dependence ) is controversial . The authors examined benzodiazepine use and associated psychiatric , substance abuse , and institutional outcomes in a six-year longitudinal study of patients with co-occurring disorders . METHODS At baseline and yearly follow-up for six years , 203 patients with co-occurring severe mental illness and substance use disorder were prospect ively assessed for medication use , substance use , psychiatric symptoms , use of hospitalization , and quality of life . RESULTS Almost one-half of the patients ( 43 percent ) reported taking prescribed benzodiazepines at the time of at least one assessment . Patients taking prescribed benzodiazepines were more likely to have high scores on measures of overall symptoms and affective symptoms ( anxiety and depression ) and low ratings for general quality of life throughout the study . Benzodiazepine use was unrelated to remission of substance use disorder or hospitalization , but a greater proportion of patients who were prescribed benzodiazepines developed  benzodiazepine abuse , compared with those who were not prescribed benzodiazepines ( 15 percent compared with 6 percent ) . CONCLUSIONS Prescription benzodiazepine use was common among patients with co-occurring severe mental illness and a substance use disorder and was not associated with any of the measured outcomes other than increasing the likelihood of benzodiazepine abuse . Physicians should consider other treatments for anxiety in this population BACKGROUND Given the observed association between panic disorder and bipolar disorder and the potential negative influence of panic symptoms on the course of bipolar illness , we were interested in the effects of what we have defined as " panic spectrum " conditions on the clinical course and treatment outcome in patients with bipolar I ( BPI ) disorder . We hypothesized that lifetime panic spectrum features would be associated with higher levels of suicidal ideation and a poorer response to acute treatment of the index mood episode in this patient population . METHODS A sample of 66 patients with BPI disorder completed a self-report measure of lifetime panic-agoraphobic spectrum symptoms .  Patients falling above and below a predefined clinical threshold for panic spectrum were compared for clinical characteristics , the presence of suicidal ideation during acute treatment , and acute treatment response . RESULTS Half of this outpatient sample reported panic spectrum features above the predefined threshold . These lifetime features were associated with more prior depressive episodes , higher levels of depressive symptoms , and greater suicidal ideation during the acute-treatment phase . Patients with BPI disorder who reported high lifetime panic-agoraphobic spectrum symptom scores took 27 weeks longer than those who reported low scores to remit with acute treatment ( 44 vs 17 weeks , respectively ) . CONCLUSIONS The presence of lifetime panic spectrum symptoms in this sample of patients with BPI disorder was associated with greater levels of depression , more suicidal ideation , and a marked ( 6-month ) delay in time to remission with acute treatment . Alternate treatment strategies are needed for patients with BPI disorder who endorse lifetime panic spectrum features CONTEXT Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treatment of bipolar I disorder . Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population . OBJECTIVE To compare 2 psychosocial interventions : interpersonal and social rhythm therapy ( IPSRT ) and an intensive clinical management ( ICM ) approach in the treatment of bipolar I disorder . DESIGN R and omized controlled trial involving 4 treatment strategies : acute and maintenance IPSRT ( IPSRT/IPSRT ) , acute and maintenance ICM ( ICM/ICM ) , acute IPSRT followed by maintenance ICM ( IPSRT/ICM ) , or acute ICM followed by maintenance IPSRT ( ICM/IPSRT ) . The preventive maintenance phase lasted 2 years . SETTING Research clinic in a university medical center . PARTICIPANTS One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient setting s , clinical referral , public presentations about bipolar disorder , and other public information activities . INTERVENTIONS Interpersonal and social rhythm therapy , an adaptation of Klerman and Weissman 's interpersonal psychotherapy to which a social rhythm regulation component has been added , and ICM . MAIN OUTCOME MEASURES Time to stabilization in the acute phase and time to recurrence in the maintenance phase . RESULTS We observed no difference between the treatment strategies in time to stabilization . After controlling for covariates of survival time , we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode ( P = .01 ) , irrespective of maintenance treatment assignment . Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment ( P<.001 ) . Ability to increase regularity of social rhythms during acute treatment was associated with reduced likelihood of recurrence during the maintenance phase ( P = .05 ) . CONCLUSION Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder , particularly with respect to prophylaxis of new episodes This article focuses on social morbidity and health care utilization in persons with panic attacks not meeting full diagnostic criteria for panic disorder . The findings are based on data from a r and om sample of over 18,000 adults drawn from five US communities . Panic attacks not meeting full criteria for panic disorder have a relatively high lifetime prevalence ( 3.6 % of the adult population ) . Persons with panic attacks had impairment in perceived physical and emotional health , and in occupational and financial functioning , increased use of health care facilities , emergency departments , and psychoactive drugs . Persons with panic attacks were intermediate in severity between those with panic disorder and those with other psychiatric disorders . The findings could not be explained by comorbidity with other psychiatric disorders . We conclude that panic attacks have clinical significance and are associated with substantial morbidity BACKGROUND Numerous studies have observed that offspring of bipolar parents manifest a broad spectrum of psychiatric disorders . We tested the hypothesis that in high risk offspring , bipolar disorder evolves in a predictable clinical sequence from non-specific ( non-mood ) to specific ( mood ) psychopathology . METHODS Offspring from well-characterized families with one bipolar parent ( high risk ) or two well parents ( controls ) were assessed annually or at anytime symptoms developed using KSADS-PL interviews for up to 15 years . DSM-IV diagnoses were made on blind consensus review using all available clinical material . We compared the age-adjusted risks of lifetime psychopathology between high risk and control subjects and assessed the conditional probability of developing a mood disorder given a history of non-mood disorders . In subjects meeting full DSM-IV criteria for bipolar disorder , we assessed the sequence of psychopathology against a clinical staging model . RESULTS High risk offspring manifest higher rates of anxiety and sleep disorders , as well as major mood and substance use disorders compared to controls . Antecedent anxiety increased the age-adjusted risk of mood disorder from 40 to 85 % ( hazard ratio of 2.6 ) . High risk subjects who developed a mood disorder had an increased risk of a substance use disorder ( hazard ratio of 2.4 ) , typically meeting diagnostic criteria during or after the first major mood episode . The evolution of psychopathology leading to bipolar disorder generally followed the proposed sequence , although not all subjects manifest all stages . LIMITATIONS Larger numbers of high risk offspring prospect ively assessed over the risk period would allow confirmation of these preliminary findings . CONCLUSIONS Clinical staging may be a useful approach to refine the early diagnosis and facilitate research into the evolution of bipolar disorder in those at familial risk OBJECTIVE At least 50 % of individuals with bipolar disorder have a lifetime anxiety disorder . Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration , greater illness severity , and poorer treatment response . The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome . METHOD In the Systematic Treatment Enhancement Program r and omized controlled trial of psychotherapy for bipolar depression , participants received up to 30 sessions of intensive psychotherapy ( family-focused therapy , interpersonal and social rhythm therapy , or cognitive-behavioral therapy ) or collaborative care , a three-session comparison treatment , plus pharmacotherapy . Using the number needed to treat , we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year . RESULTS A total of 269 patients ( 113 women ) with a comorbid lifetime anxiety disorder ( N=177 ) or without a comorbid lifetime anxiety disorder ( N=92 ) were included in the analysis . Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care ( 66 % compared with 49 % recovered over 1 year ; number needed to treat=5.88 , small to medium effect ) . For patients without a lifetime anxiety disorder , there was no difference between rates of recovery in psychotherapy compared with collaborative care ( 64 % compared with 62 % recovered ; number needed to treat=50 , small effect ) . Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care ( 84 % compared with 53 % recovered ; number needed to treat=3.22 , medium to large effect ) , whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments ( 54 % compared with 46 % recovered ; number needed to treat=12.5 , small effect ) . CONCLUSIONS Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression . These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status BACKGROUND Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers , relatively few controlled studies have examined treatment strategies for bipolar depression . OBJECTIVE To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression . DESIGN Double-blind , 8-week , r and omized controlled trial . SETTING Eighty-four sites ( inpatient and outpatient ) in 13 countries . Patients A total of 833 r and omized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score of at least 20 . Intervention Patients were r and omly assigned to receive placebo ( n = 377 ) ; olanzapine , 5 to 20 mg/d ( n = 370 ) ; or olanzapine-fluoxetine combination , 6 and 25 , 6 and 50 , or 12 and 50 mg/d ( n = 86 ) . MAIN OUTCOME MEASURE Changes in MADRS total scores using mixed-effects model repeated- measures analyses . RESULTS During all 8 study weeks , the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P<.001 for all ) . The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8 . At week 8 , MADRS total scores were lower than at baseline by 11.9 , 15.0 , and 18.5 points in the placebo , olanzapine , and olanzapine-fluoxetine groups , respectively . Remission criteria were met by 24.5 % ( 87/355 ) of the placebo group , 32.8 % ( 115/351 ) of the olanzapine group , and 48.8 % ( 40/82 ) of the olanzapine-fluoxetine group . Treatment-emergent mania ( Young Mania Rating Scale score < 15 at baseline and > or = 15 subsequently ) did not differ among groups ( placebo , 6.7 % [ 23/345 ] ; olanzapine , 5.7 % [ 19/335 ] ; and olanzapine-fluoxetine , 6.4 % [ 5/78 ] ) . Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea . CONCLUSIONS Olanzapine is more effective than placebo , and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of  bipolar I depression without increased risk of developing manic symptoms
target: Our results suggest a high rate of lifetime concurrent anxiety disorders in bipolar disorder .
  The diagnostic issues at the interface are particularly difficult because of the substantial symptom overlap .
background: BACKGROUND Bipolar affective disorder has a high rate of comorbidity with a multitude of psychiatric disorders and medical conditions .
  Among all the potential comorbidities , co-existing anxiety disorders st and out due to their high prevalence .
  AIMS To determine the lifetime prevalence of comorbid anxiety disorders in bipolar affective disorder under the care of psychiatric services through systematic review and meta- analysis .