Clinical outcome in patients with bipolar I disorder, obsessive compulsive disorder or both

BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive (OCD) and other anxiety disorders, but the impact of such comorbidity on long-term outcome has not been evaluated systematically. METHODS: Extensive follow-up assessments were carried out at 4.3 years after index hospitalizations in a mixed BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20) alone. RESULTS: At follow-up, ratings of functional status were similar across groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9-times more frequent among comorbid than OCD patients. OCD symptoms averaged 150% more severe in OCD than comorbid subjects, and were not measured in BPD subjects. CONCLUSIONS: Despite potential sampling bias with previously hospitalized subjects, the findings suggest that comorbid BPD-OCD patients may be clinically more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not negatively impact the long-term clinical outcome.     

A Randomized,Double-Blind,Placebo-Controlled,Trial of Lamotrigine Therapy in Bipolar Disorder,Depressed or Mixed Phase and Cocaine Dependence

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1–10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.     

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

Introduction: Several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission.

Areas covered: This paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice.

Expert opinion: Aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic–maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.     

Comparison of mania patients suitable for treatment trials versus clinical treatment

It remains uncertain whether bipolar disorder (BPD) patients in randomized-controlled trials (RCTs) are sufficiently representative of clinically encountered patients as to guide clinical-therapeutic practice. We complied inclusion/exclusion criteria by frequency from reports of 21 RCTs for mania, and applied them in a pilot study of patients hospitalized for DSM-IV BPD manic/mixed states to compare characteristics and clinical responses of patients who did versus did not meet exclusion criteria. From 27 initially identified inclusion/exclusion criteria ranked by citation frequency, we derived six inclusion, and 10 non-redundant-exclusion factors. Of 67 consecutive patients meeting inclusion criteria, 15 (22.4%) potential "research subjects" met all 10 exclusion criteria. The remaining 52 "clinical patients" differed markedly on exclusion criteria, including more psychiatric co-morbidity, substance abuse, involuntary hospitalization, and suicide attempts or violence, but were otherwise similar. In both groups responses to clinically determined inpatient treatments were similar, including improvement in mania ratings. Based on applying reported inclusion/exclusion criteria for RCTs to a pilot sample of hospitalized-manic patients, those likely to be included in modern RCTs were similar to patients who would be excluded, most notably in short-term antimanic-treatment responses. The findings encourage further comparisons of subjects included/excluded from RCTs to test potential clinical generalizability of research findings. The pilot study is limited in numbers and exposure times with which to test for the minor differences between "research subjects" and "clinical patients."     

Efficacy and safety of fluoxetine monotherapy in bipolar depression: a systematic review

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries with up to 30% of the population affected. Since NAFLD is associated with an increased risk of cardiovascular (CV) disease, these patients should be stratified for CV risk factors, including atherogenic dyslipidemia, and managed accordingly. Lifestyle modifications represent an effective treatment for NAFLD, since most patients are overweight or obese. Also, promising, but not conclusive, results are available for current pharmacologic treatment. Drugs potentially effective against NAFLD include insulin sensitisers as well as fibrates and omega-3 polyunsaturated fatty acids, while there is reluctance to use statins in patients with suspected or established chronic liver disease. Several other therapeutic options are potentially available, and more data are expected from new peroxisome proliferator-activated receptor agonists and incretin-based therapies.     

Lithium,but not Valproate,Reduces Impulsive Choice in the Delay-Discounting Task in Mice

Both lithium and valproate are well-established treatments for bipolar disorder. Studies have also found that lithium is effective at reducing suicidal behaviors in patients with mood disorders. Impulsivity is a validated endophenotype of both bipolar disorder and suicidal behavior. We assessed effects of treatment with lithium or valproate on cognitive impulsivity in selectively bred mice previously shown to manifest relatively high levels of cognitive impulsivity. Mice were trained in the delay-discounting paradigm, a measure of cognitive impulsivity reflecting a behavioral bias towards immediacy, and then treated with lithium, valproate, or control chow. After 3 weeks of drug treatment, mice were tested at various delays to a large, delayed reward. Drug treatment continued during this time. Lithium reduced impulsivity, whereas valproate had no effect on choice behavior. Both drugs increased the number of choice trials and reinforcer intake, but effects on choice behavior did not depend on these motivational changes. To our knowledge, this is the first study demonstrating lithium''s effects to reduce cognitive impulsivity. Future studies may focus on the ability of putative pharmacotherapies for patients at risk for bipolar disorder or suicide to modify the impulsive choice dimension of this diseases.     

An update on the treatment of bipolar depression

Background: Although depression accounts for a large part of the burden associated with bipolar disorder, its drug treatment has been under-studied. Objective: To provide the best available evidence supporting the pharmacotherapy of bipolar depression. Methods: A systematic review was conducted, focusing on randomized, controlled trials (RCTs) and meta-analyses. Results/conclusions: Despite FDA approval of both the olanzapine–fluoxetine combination and quetiapine for the treatment of acute bipolar depression, independent RCTs (i.e., not trials conducted ‘under the umbrella’ of a drug company) have not found any drug to have antidepressant effects similar to those seen in unipolar depression. A practice-based suggestion, valuable for both short- and long-term treatment, might be to have a background of mood stabilizers and to add drugs, following one of several treatment options, trusting to find a drug with a degree of effectiveness by trial and error. The list of drugs that could be used would include all the current antidepressants, the olanzapine–fluoxetine combination and probably quetiapine too. Special features and situations might also influence treatment options.     

抗抑郁药物在双相情感障碍治疗中的应用

抗抑郁药物在双相情感障碍中的应用备受关注。抗抑郁药物治疗双相抑郁急性期疗效较为肯定,但有转躁等问题;长期治疗的预防效果尚有待进一步研究。本文从循证医学角度,综述抗抑郁药物在双相情感障碍(主要是双相抑郁)急性期和维持期治疗中的疗效以及转躁情况,阐述双相情感障碍治疗中抗抑郁药物合理使用的重要性和必要性。     

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.     

Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders

A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels.     

拉莫三嗪与碳酸锂治疗双相抑郁的对照研究

目的:评价拉莫三嗪治疗双相抑郁的疗效和安全性.方法:采用开放,随机,活性药物平行对照设计.入选双相抑郁患者34例,随机分为拉莫三嗪组18例,碳酸锂组16例.分别口服拉莫三嗪50～200mg·d-1,碳酸锂750～1 500 mg·d-1,疗程8周,疗效观察指标包括基线以及治疗终点的17项汉密尔顿抑郁量表(HAMD17)、蒙哥马利抑郁量表(MADRS)、临床总体印象量表(CGI)评分.结果:治疗结束时,两组HAMD17总分与基线相比均明显降低,两组HAMD减分率差异有显著性,分别为24.8%和47.4%;以HAMD17减分率判断的有效率,两组间差异无显著性,分别为33.3%和50%.拉莫三嗪组治疗结束时体重无变化,有2例皮疹报告,其他不良事件两组发生频率相当.结论:拉莫三嗪治疗轻中度的双相抑郁部分有效.安全性较好.     

Evaluating aripiprazole as a potential bipolar disorder therapy for adults

Introduction: Second generation antipsychotics (SGAs) have emerged as new treatment options for bipolar disorders (BDs). Aripiprazole (ARI) is already an SGA approved therapy for the treatment of BD type-I, both as a monotherapy as well as an add-on therapy in acute mania and in long-term maintenance therapy.

Areas covered: The authors provide a systematic review that illustrates ARI’s pharmacological profile including its efficacy on various aspects of BD in adults. It also reviews its role in bipolar treatment algorithms and provides a focus on future research developments and further potential uses of the compound. Additional aspects such as safety and tolerability are also considered.

Expert opinion: Compared with haloperidol, ARI shows fewer extrapyramidal symptoms (EPS), but has a slightly lower efficacy in mania. It has a better metabolic parameter profile and fewer cardiovascular adverse events than other SGAs although the add-on treatment shows a higher risk of EPS. Presently, data doesn’t support its use as a first choice maintenance monotherapy but it may be useful as a combination therapy for BD patients with comorbidities such as drug abuse and obsessive-compulsive disorders. Studies on ARI in bipolar depression are disappointing. However, future studies on the drug, at a low dose combined with a stabilizer or antidepressant may prove interesting.