***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence . METHOD Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use . Patients were started on open-label divalproex . After stabilization on divalproex sodium , weekly assessment s were undertaken for 8weeks . Subjects also attended dual recovery counseling . RESULTS The results revealed significant improvement on % cocaine abstinent days , dollars spent on cocaine , ASI 's drug use severity index , % alcohol abstinent days , drinks per drinking day , marijuana use and cigarettes smoking . They also had significant improvement on manic , depressive , and sleep symptoms and on functioning . There were no reported adverse events or increases in liver function tests . CONCLUSION The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence . Double-blind , placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted BACKGROUND Substance abuse frequently complicates the course of bipolar illness , promotes mixed states , and contributes to poor outcome in mania . Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse . This study compared remission patterns for mixed or pure manic episodes among bipolar in patients with or without substance abuse histories . METHOD Hospital records were retrospectively review ed for 204 DSM-III-R bipolar I in patients . Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode . Time until remission was analyzed by Kaplan-Meier survival analysis . Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse . RESULTS Past substance abuse was evident in 34 % of the bipolar sample and comprised most often alcoholism ( 82 % ) , followed by cocaine ( 30 % ) , marijuana ( 29 % ) , sedative-hypnotic or amphetamine ( 21 % ) , and opiate ( 13 % ) abuse . Substance abuse was more common among men ( p < .05 ) and those with mixed rather than pure mania ( p < .05 ) . Remission during hospitalization was less likely among patients with prior substance abuse ( p < .05 ) , especially alcohol or marijuana abuse , and among mixed manic patients with past substance abuse ( p < .05 ) . Bipolar patients with substance abuse histories who received divalproex or carbamazepine  remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer ( p < .05 ) . CONCLUSION These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes , but may show a better response to anticonvulsant mood stabilizers than lithium 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 Substance abuse is extremely common in patients with bipolar disorders , although minimal data are available on the treatment of this important clinical population . Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action , acting as a dopamine-2 receptor partial agonist , thereby increasing dopamine release in some parts of the brain and decreasing dopa-mine release in other brain regions . Dopamine release is implicated in substance use , and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse . To our knowledge , dopa-mine receptor partial agonists have not been investigated for treatment of substance abuse in humans . METHOD Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripipra-zole using an overlap and taper method . At baseline , diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria . Psychiatric symptoms , side effects , and substance use and craving were assessed over 12 weeks . Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , and Brief Psychiatric Rating Scale ( BPRS ) . Substance craving was assessed with visual analogue scales , and side effects were monitored using the Abnormal Involuntary Movement Scale , Simpson-Angus Scale , Barnes Akathisia Scale , and patient report .  Study enrollment was from April 2003 to February 2004 . RESULTS Significant baseline-to-exit improvement in HAM-D ( p = .002 ) , YMRS ( p = .021 ) , and BPRS ( p = .000 ) scores were observed without a significant change in antipsychotic-induced side effect scales . In 17 participants with current alcohol dependence , significant reductions in dollars spent on alcohol ( p = .042 ) and alcohol craving ( p = .003 ) were found . In 9 participants with cocaine-related disorders , significant reductions in cocaine craving ( p = .014 ) , but not use , were found . CONCLUSION A change to aripiprazole was associated with symptomatic improvement . Limitations of the study include a small sample size , high attrition , and an open-label design . Controlled trials in dual-diagnosis patients are needed to confirm these findings BACKGROUND Bipolar disorder is associated with the highest substance abuse rates of any psychiatric illness . Therefore , treatments that stabilize mood and decrease drug use or cravings are of great interest . Open-label lamotrigine was examined in 30 out patients with DSM-IV bipolar disorder and cocaine dependence .  Lamotrigine was either added to existing medication regimens or used as monotherapy . METHOD Lamotrigine was started at a dose of 25 mg/day ( 12.5 mg/day in those taking valproic acid ) and titrated to a maximum dose of 300 mg/day . Subjects received a baseline evaluation including a structured clinical interview and weekly assessment s for 12 weeks with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , Brief Psychiatric Rating Scale ( BPRS ) , and Cocaine Craving Question naire ( CCQ ) . At each appointment , a urine sample was obtained , and participants reported drug use during the previous week . The subjects consisted of 13 men and 17 women with cocaine dependence and bipolar I disorder ( N = 22 ) , bipolar II disorder ( N = 7 ) , or bipolar disorder not otherwise specified ( N = 1 ) , with a mean + /- SD age of 35.4 + /- 7.2 years . Data were analyzed using the last observation carried forward on all subjects who completed the baseline evaluation and at least 1 postbaseline assessment . RESULTS Significant improvement was observed in HAM-D , YMRS , and BPRS scores ( p < or = .02 ) . Cravings also significantly decreased as measured by the CCQ ( p < .001 ) . Dollar amount spent on drugs decreased nonsignificantly . Lamotrigine was well tolerated , with no subjects discontinuing due to side effects . CONCLUSION Lamotrigine treatment was well tolerated in this sample and associated with statistically significant improvement in mood and drug cravings but not drug use . The findings suggest that larger controlled trials of lamotrigine are needed in this population OBJECTIVE Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness . Therefore , treatments that stabilize mood and decrease drug use or cravings are of great interest . Atypical antipsychotics are in widespread use in patients with bipolar disorder . However , minimal data are available on their use in bipolar patients with comorbid substance abuse . METHODS Open-label , add-on , quetiapine therapy was examined for 12 weeks in 17 out patients with bipolar disorder and cocaine dependence . Subjects were evaluated with a structured clinical interview ; Hamilton Depression Rating ( HDRS ) , Young Mania Rating ( YMRS ) , Brief Psychiatric Rating ( BPRS ) scales ; and Cocaine Craving Question naire ( CCQ ) . Urine sample s and self-reported drug use were also obtained . Data were analyzed using a last observation carried forward method on all subjects given medication at baseline . RESULTS Significant improvement from baseline to exit was observed in HDRS , YMRS , BPRS and CCQ scores ( p < or = 0.05 ) . Dollars spent on cocaine and days/week of cocaine use decreased non-significantly , and urine drug screens did not change significantly from baseline to exit . Quetiapine was well tolerated , with no subjects to our knowledge discontinuing because of side-effects . CONCLUSIONS The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings . The findings are promising and suggest larger controlled trials of quetiapine are needed in this population Despite the availability of efficacious treatments for bipolar disorder , their effectiveness in general clinical practice is greatly attenuated , result ing in what has been called an ' efficacy-effectiveness gap ' . In design ing VA Cooperative Studies Program ( CSP ) Study # 430 to address this gap , nine principles for conducting an effectiveness ( in contrast to an efficacy ) study were identified . These principles are presented and discussed , with specific aspects of CSP # 430 serving as illustrations of how they can be implemented in an actual study . CSP # 430 hypothesizes that an integrated , clinic-based treatment delivery system that emphasizes ( 1 ) algorithm-driven somatotherapy , ( 2 ) st and ardized patient education , and ( 3 ) easy access to a single primary mental health care provider to maximize continuity-of-care , will address the efficacy-effectiveness gap and improve disease , functional , and economic outcome . It is an 11-site , r and omized controlled clinical trial of this multi-modal , clinic-based intervention versus usual VA care running from 1997 to 2003 . The trial has enrolled 191 subjects in each arm , using minimal exclusion criteria to maximize the external validity of the study . Subjects are followed for 3 years . The intervention is highly specified in a series of operations manuals for each of the three components . Several continuous quality improvement ( CQI ) interventions , process measures , and  statistical techniques  deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study . CSP # 430 is design ed to have impact well beyond the VA , since it evaluates a basic health care operational principle : that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs . If results are positive , this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today OBJECTIVE Although bipolar disorder and substance use disorder frequently co-occur , there is little information on the effectiveness of behavioral treatment for this population . Integrated group therapy , which addresses the two disorders simultaneously , was compared with group drug counseling , which focuses on substance use . The authors hypothesized that patients receiving integrated group therapy  would have fewer days of substance use and fewer weeks ill with bipolar disorder . METHOD A r and omized controlled trial compared 20 weeks of integrated group therapy or group drug counseling with 3 months of posttreatment follow-up . Sixty-two patients with bipolar disorder and current substance dependence , treated with mood stabilizers for > or=2 weeks , were r and omly assigned to integrated group therapy ( N=31 ) or group drug counseling ( N=31 ) . The primary outcome measure was the number of days of substance use . The primary mood outcome was the number of weeks ill with 
    Output:
    
Recent research on the causal relationship between the two disorders suggests that a subgroup of bipolar patients may develop a relatively milder form of affective illness that is expressed only after extended exposure to alcohol abuse .
Three open label medication trials provide limited evidence that quetiapine , aripiprazole , and lamotrigine may be effective in treating affective and substance use symptoms in bipolar patients with cocaine dependence and that aripiprazole may also be helpful in patients with alcohol use disorders .
The two placebo controlled trials to date suggest that valproate given as an adjunct to lithium in bipolar patients with co-occurring alcohol dependence improves both mood and alcohol use symptoms and that lithium treatment in bipolar adolescents improves mood and SUD symptoms .