Mood stabilization in the treatment of bipolar disorder: focus on quetiapine

The use of at least one mood-stabilizing agent is common clinical practice in the treatment of bipolar disorder, regardless of the treatment setting or disease phase. However, a consensus definition of 'mood stabilizer' remains to be established. A mood stabilizer has been operationally described as an agent that is useful in at least one phase of bipolar disorder while not worsening any other phase of the illness. More stringent definitions have been proposed, and it can be argued that a clinically effective mood stabilizer would have efficacy in a broad range of affective, psychotic, behavioral and cognitive domains in all phases of bipolar disorder and would be well tolerated across a range of doses for sustained periods. Clinically effective mood stabilizers should treat mania and depression, while preventing recurrence and improving quality of life. Effective treatment should not precipitate mania, depression, or rapid cycling, and should minimize the burden of treatment-emergent side effects. Data from clinical studies of quetiapine are reviewed in context with the literature discussing traditional and emerging mood stabilizers. Using a liberal definition, the evidence for quetiapine qualifies it as a bimodal mood stabilizer based on its demonstrated effectiveness in the treatment of bipolar mania and depression. Further data suggest that quetiapine has promise across all phases of bipolar disorder with the potential to meet even the most stringent definitions of a mood stabilizer.     

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。     

Psychosocial functioning of people with substance abuse and bipolar disorders

This study assessed whether a secondary diagnosis of a substance use disorder in hospitalized people with bipolar disorder was associated with poorer outcomes on self‐reported measures of mood (Profile of Mood States), subjective distress (Behavior and Symptom Identification Scale), and coping resources (Coping Resources Inventory), and with specific patient characteristics. Sixty‐two patients with bipolar disorder and a secondary diagnosis of a substance use disorder and 60 patients with only a bipolar disorder diagnosis participated. Patients with bipolar disorder and a secondary diagnosis of a substance use disorder perceived significantly more impairment on all three measures than did patients without the secondary diagnosis. Moreover, the background characteristics of a history of violence, past or current involvement with the criminal justice system, and not having an antipsychotic medication prescribed during hospitalization had the strongest association with having a secondary diagnosis of a substance use disorder among the characteristics examined. These findings suggest the existence of a subgroup of patients with substance abuse and bipolar disorders who have substantial psychosocial impairment and probably require more intense treatment.     

Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD

Relatively absent from previous studies of the pharmacotherapy for bipolar disorder is examination of the impact of comorbidity on treatment choices. This has occurred despite the presence of high levels of comorbid anxiety and substance use disorders, and the association of these disorders with severity and course markers of bipolar disorder. In this study, we examined comorbid disorders, identified by structured interviews, and the pharmacotherapy reported at study entry by the first 1000 patients entered into a large, multicenter study of bipolar disorder (Systematic Treatment Enhancement Program for Bipolar Disorder). Our study focused on the degree to which comorbid conditions are linked to the reported use of mood stabilizers deemed "minimally adequate" and the association between specific comorbidities and pharmacotherapy treatment, such as the use of anxiolytics in patients with anxiety disorders. Despite the presence of high levels of comorbidity, the presence of these disorders was only minimally associated with pharmacotherapy. Of the sample of bipolar outpatients, only 59% reported pharmacotherapy use meeting criteria for "minimally adequate" mood stabilizer, regardless of comorbid diagnoses, rapid cycling, or bipolar I or II status. Moreover, the cross-sectional use of "comorbidity-specific" pharmacotherapy for anxiety disorders, substance use disorders, and attention deficit disorder in this outpatient sample of patients with bipolar disorders was limited, suggesting that comorbid conditions in patients with bipolar disorder may be undertreated. Our findings highlight the need for greater clinical guidance and treatment options for patients with bipolar disorder and comorbidity.     

Psychosocial Functioning of People with Substance Abuse and Bipolar Disorders

This study assessed whether a secondary diagnosis of a substance use disorder in hospitalized people with bipolar disorder was associated with poorer outcomes on self-reported measures of mood (Profile of Mood States), subjective distress (Behavior and Symptom Identification Scale), and coping resources (Coping Resources Inventory), and with specific patient characteristics. Sixty-two patients with bipolar disorder and a secondary diagnosis of a substance use disorder and 60 patients with only a bipolar disorder diagnosis participated. Patients with bipolar disorder and a secondary diagnosis of a substance use disorder perceived significantly more impairment on all three measures than did patients without the secondary diagnosis. Moreover, the background characteristics of a history of violence, past or current involvement with the criminal justice system, and not having an antipsychotic medication prescribed during hospitalization had the strongest association with having a secondary diagnosis of a substance use disorder among the characteristics examined. These findings suggest the existence of a subgroup of patients with substance abuse and bipolar disorders who have substantial psychosocial impairment and probably require more intense treatment.     

丙戊酸盐治疗双相情感障碍的研究进展

作为心境稳定剂,丙戊酸盐治疗各型双相情感障碍均有一定的疗效。近年来对各型双相情感障碍患者进行的临床研究证实：丙戊酸盐能改善躁狂症状;联合镇静药物治疗可有效改善抑郁症状;联合抗抑郁药物预防抑郁发作的疗效优于锂盐。丙戊酸盐与其他心境稳定剂联合治疗快速循环型双相情感障碍患者时可能更有益,也更适用于非快速循环型双相情感障碍患者的长程治疗。     

Combination of aripiprazole with mood stabilizers for the treatment of bipolar disorder: from acute mania to long-term maintenance

Introduction: Bipolar disorder is characterized by a complex set of symptoms, including recurrent manic, depressive or mixed episodes. Acute and long-term treatment of patients with bipolar disorder is mandatory to prevent symptom relapse and episode recurrences. Outcomes with monotherapy are often unsatisfactory in clinical practice, hence combinations of mood stabilizers and antipsychotics are widely utilized in patients showing no or partial response to, as well as intolerance to, monotherapies. This may offer a therapeutic advantage, however, the possibility of an increased incidence of side effects should be considered.

Areas covered: This paper reviews the current treatment guidelines for the treatment of bipolar disorder and examines the rationale behind the use of aripiprazole in combination with mood stabilizers for acute and long-term treatment of bipolar disorder.

Expert opinion: The combination of aripiprazole and mood stabilizers seems to offer an effective and relatively well-tolerated option for the treatment of acute mania and for the maintenance treatment of patients with bipolar I disorder. The combination presents a lower risk of metabolic side effects compared with other combination therapies, but increases the risk of extrapyramidal side effects with long-term treatment. The aripiprazole–valproate combination seems to be particularly promising in the treatment of patients with comorbidities such as anxiety and drug abuse, obsessive-compulsive disorder and bipolar disorder, as well as in mixed depressive disorder. Controlled trials are necessary in order to confirm these observations and to provide a useful insight for improving the use of drug combinations in bipolar patients.     

The use of stimulants and atomoxetine in adults with comorbid ADHD and bipolar disorder

Introduction: Attention deficit/hyperactivity disorder (ADHD) persists into adulthood in about 50% of the affected children, with high rates of comorbidity with bipolar disorder (BD). Stimulants and atomoxetine (ATX) are effective treatments for ADHD, but their use in adults with comorbid BD (ADHD-BD) has not been extensively studied and may be problematic.

Areas covered: The aim of the paper is to summarize the available literature regarding the use of these medications in ADHD-BD adult patients. Results of randomized-controlled and open-label trials, case reports, and case series are reviewed. We also reviewed data relative to some specific issues of this comorbidity in adults, especially substance use disorder, malingering, and stimulants misuse.

Expert opinion: ADHD-BD may be associated with more severe symptoms, course, and worst outcome of both conditions. The frequent coexistence with alcohol and substance abuse may further complicate treatment management. Stimulants are the most effective medications for ADHD, but their use may be contraindicated in the presence of a comorbid drug abuse or in patients that simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse. ATX may be effective in the treatment of ADHD symptoms in BD patients, with a modestly increased risk of (hypo)manic switches and destabilization of the mood disorder when utilized in association with mood stabilizers. In the majority of the cases, a hierarchical approach is desirable, with mood stabilization preceding the treatment of ADHD symptoms. Although systematic trials on the use of stimulants and ATX in ADHD-BD comorbidity in adulthood are necessary, both treatments should be considered possible options to be carefully evaluated once the patient has been stabilized.     

Adjunctive topiramate in the maintenance treatment of bipolar disorders: an open-label study

SUMMARY

Objective: A considerable number of patients with bipolar disorder fail to respond completely to mood stabilizers. The anti-epileptic topiramate shares some pharmacological actions with carbamazepine and valproate. We therefore explored the efficacy and tolerability of topiramate in the prophylaxis of bipolar disorder.

Methods: Fifty-six patients receiving outpatient treatment for bipolar affective disorder who had been on mood stabilizers, and had relapsed at least once in the past 12?months, were treated with topiramate in an add-on design and were evaluated for 1?year. Patients were assessed biweekly for the first 3?months and every month thereafter.

Results: Fifty out of 56 patients completed the 1-year study, which indicated that adjunctive topiramate was associated with a significant reduction of new manic and depressive episodes compared to the past 12?months. The most common adverse effects were reduced appetite, fatigue and somnolence.

Conclusions: This was an open-label, uncontrolled study involving retrospective evaluation of episodes prior to the initiation of treatment, and the use of more than one mood stabilizer in a few patients. However, these preliminary observations of adjunctive topiramate as a maintenance treatment encourage further investigations, especially with controlled trials, for its long-term effect.     

Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge

Comorbidity in bipolar disorder is the rule rather than the exception more than 60% of bipolar patients have a comorbid diagnosis and is associated with a mixed affective or dysphoric state; high rates of suicidality; less favourable response to lithium and poorer overall outcome. There is convincing evidence that rates of substance use and anxiety disorders are higher among patients with bipolar disorder compared to their rates in the general population. The interaction between anxiety disorders and substance use goes both ways: patients with bipolar disorder have a higher rate of substance use and anxiety disorder, and vice versa. Bipolar disorder is also associated with borderline personality disorder and ADHD, and to a lesser extent with weight gain. As more than 40% of bipolar patients have anxiety disorder, it is indicated that while diagnosing bipolar patients, systematic enquiry about different anxiety disorders is called for. This also presents a therapeutic challenge, since agents that effectively treat anxiety disorders are associated with the risk of induced mania. Therefore, the treating psychiatrist needs to carefully evaluate the potential benefit of treating the anxiety against the potential cost of inducing a manic episode. A possible solution would be to use, when possible, a non-pharmacological intervention, such as a cognitivebehavioural approach. Alternately, it is suggested that the clinician attempts to ensure that the patient receives adequate treatment with mood stabilizers before slowly and carefully attempting the addition of anti-anxiety compounds with a relatively lower risk of mania induction (e.g. SSRIs compared to TCAs).     

Lamotrigine in mood disorders

SUMMARY

Lamotrigine is an anticonvulsant drug with good efficacy and safety in the treatment of epilepsy. There is now substantial evidence that lamotrigine is also useful in treating resistant depression, rapid cycling bipolar affective disorder, depressive episodes in bipolar affective disorder and in the maintenance phase or prophylaxis of bipolar affective disorder. There are possible roles in managing mood changes in borderline personality disorder, reducing chronic pain and treating schizoaffective disorder.

The general range of doses found effective in affective disorders is from 50 to 300?mg daily.

Clinical use seems to involve a titration of dose upwards over several weeks until the desired ! effect is obtained.

However, further definitive double-blind, randomised controlled trials against gold standard treatments are required.

Lamotrigine has a preferable side-effect profile compared to standard agents for bipolar affective disorder such as lithium or carbamazepine. Further research is certainly warranted and, given its tolerability, could point to lamotrigine as the treatment of choice for some affective disorders.     

Comparison of the Internal State Scale to Clinician-Administered Assessments in Patients with Bipolar Disorder and Alcohol Abuse or Dependence

Abstract

Objectives: Self-report measures require less clinician time to administer than clinician-rated assessments. The Internal State Scale (ISS) is a well-validated self-report measure that assesses symptoms of mania and depression in patients with bipolar disorder (BPD). However, the ISS has never been specifically evaluated in patients with BPD and comorbid substance misuse. Substances can induce mood symptoms complicating diagnosis and mood state assessment.

Methods: The ISS was compared with the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in 21 patients with BPD and alcohol abuse/dependence at baseline and for up to 16 weeks postbaseline. In addition, ISS-determined mood state was compared to mood state from a structured diagnostic interview.

Results: Significant baseline correlations were observed between the ISS depression subscale and HRSD, ISS activation subscale and YMRS, and ISS perceived conflict subscale and BPRS. Significant correlations of baseline to exit change scores were found between the ISS activation and YMRS, but not ISS depression and HRSD, or ISS perceived conflict and BPRS. All participants had a mixed mood state by structured diagnostic interview. The ISS diagnosed the manic/hypomanic portion of this mood state in 76% of participants but found depression in only 38%.

Conclusions: As in BPD patients without substance abuse, the ISS generally showed correlations with clinician-rated scales at baseline, with less strong correlations observed on change scores. The ISS diagnosis of mania or hypomania appeared to correspond more highly than depression with the findings from a structured diagnostic interview.     

Bipolar Disorder in a Population of Adolescents with Alcohol Use Disorders

ABSTRACT

Objectives: The objective of this paper is to present the prevalence of Bipolar Disorder (BPD) in a population of adolescents and young adults with alcohol use disorders (AUD) and to compare salient alcohol use, mood, and diagnostic variables between adolescents with BPD, those with Major Depressive Disorder (MDD), and those with AUD without a mood disorder.

Methods: The subjects were 452 adolescents and young adults, age 12.9 to 28.3 years, who met DSM-IV criteria for a lifetime history of either alcohol abuse or alcohol dependence. DSM-IV psychiatric and AUD diagnoses were obtained by semi-structure interviews (K-SADS and SCID) to discern the possible effect of comorbid BPD on alcohol and other drug variables, we compared adolescents or young adults who met DSM-IV criteria for concurrent BPD and AUD with adolescents with MDD plus AUD and those with AUD and no mood disorder. Following one-way ANOVA comparing across the 3 groups, we proceeded with post hoc analysis comparing the BPD+AUD group with either the MDD + AUD or AUD only group.

Results: 6.4% of the subjects met criteria for BPD. While there were no differences between groups on the alcohol consumption variables, subjects with BPD had a significantly earlier onset of an AUD diagnosis than either the MDD group or the AUD only group. The BPD + AUD group had a significantly greater percentage of subjects meeting criteria for alcohol dependence than the AUD only group.

Conclusions: Comorbid mood disorders, particularly Bipolar Disorder, may have an important effect on alcohol and substance use variables and diagnosis. More research is needed to determine the effect of treatments for mood disorder on both mood and substance use variables.     

Evaluating lurasidone as a treatment option for bipolar disorder

ABSTRACT

Introduction: Lurasidone has been approved in the United States as a monotherapy and adjunct for acute bipolar I depression, as well as an antipsychotic for patients with schizophrenia.

Areas covered: Herein, the authors review the pharmacodynamics and pharmacokinetics of lurasidone as well and the major randomized clinical trials. The authors also provide their expert opinion.

Expert opinion: Lurasidone has not been studied in patients with mania or bipolar psychosis. It has been studied, both as a monotherapy and adjunctive treatment to lithium or valproate, in acute depression and in prevention of recurrence of any mood episode in patients with bipolar disorder initially treated for bipolar depression or mania. It is approved in the United States for acute bipolar I depression. It has clinically meaningful treatment effect sizes for improvement in depression compared to placebo (0.51 monotherapy, 0.34 adjunct). The number needed to treat (NNT) for response with monotherapy was 5 (for both lower and higher dose groups), and for remission was 6 and 7 (for lower dose and higher dose groups, respectively); the NNT for adjunctive therapy was 7. It has not demonstrated efficacy in relapse prevention when added to a mood stabilizer but is safe in combination with other medications.     

拉莫三嗪治疗双相情感障碍的研究进展

拉莫三嗪作为心境稳定剂治疗双相情感障碍已经应用于临床。在2013年最新的CANMAT指南中新增了拉莫三嗪单药或联合其他药物的治疗方案,提示目前应用拉莫三嗪治疗双相情感障碍已受到广泛关注。本文综述了近几年拉莫三嗪在治疗双相情感障碍各亚型中的临床研究、安全性及应用前景,为双相障碍的治疗提供新观点及新思路。     

Switching antipsychotic medication to aripiprazole: position paper by a panel of Italian psychiatrists

Introduction: Patients with schizophrenia or bipolar disorder treated with antipsychotic medication can frequently experience lack of efficacy and persistent side-effects, so much so that switching from one antipsychotic to another with a different side-effect profile has become a recommended strategy for improving the tolerability and safety of long-term antipsychotic treatment. Aripiprazole is an atypical antipsychotic with proven efficacy in schizophrenia and bipolar I disorder, with a pharmacological profile distinct from other available antipsychotics and a side-effect profile that is different from other agents in the class; these characteristics make it a possible alternative in patients requiring a change in antipsychotic treatment due to lack of efficacy or persistent side-effects.

Areas covered: A panel of Italian experts in psychiatry met to discuss the appropriateness of current strategies for the switch to aripiprazole in patients with schizophrenia or bipolar disorder once a clinician has decided to adopt this choice and also to propose alternate strategies where required. The strategies for the switch to aripiprazole presented in this position paper consider various scenarios encountered in clinical practice, highlight the importance of tapering the prior antipsychotic based on its pharmacological characteristics and provide detailed guidance throughout the entire switching process. Literature searches were conducted using the PubMed database and the search strategy (aripiprazole and switching); additional references were added from the reference lists of the papers obtained and also from the authors’ knowledge of the topic.

Expert opinion: Few studies have addressed the indications for antipsychotic switching and the best practical strategies to achieve the desired goal in the clinical practice setting. Studies on antipsychotic switching should clarify why, when and how a switch should be done. The results should standardize the reasons for switching an antipsychotic, assess the optimal time to switch and evaluate the best ways to switch. Both clinical and pharmacological factors should be considered when a patient needs to switch antipsychotics, and specific guidelines for antipsychotic switching that address all these factors are needed.     

Characteristics of bipolar disorder patients given antidepressants

Evidence concerning efficacy of antidepressants in bipolar disorder remains inconsistent and inconclusive. As the appropriate clinical use for such patients remains unclear, we characterized outpatients with bipolar disorders who were or were not treated with antidepressants. Clinical data were collected systematically from consecutive outpatients in 11 participating Argentine mood‐disorder clinics in 2007–2008. Diagnoses met DSM‐IV criteria, supported by structured interviews based on the MINI‐500. Of 338 outpatients diagnosed with bipolar I (45.0%), II (29.3%), or not‐otherwise‐specified (NOS) (25.7%) disorder, 128 (37.9%) received antidepressants. Subjects given antidepressants or not did not differ significantly by presence or severity of current depression or being suicidal but were more likely to be women. Bipolar I disorder patients were three times less likely than types II or NOS to receive an antidepressant, with or without a mood‐stabilizer or antimanic agent. Despite inconclusive evidence for efficacy and safety of antidepressants in various phases of bipolar disorders, 37.9% of such patients were receiving an antidepressant in 11 Argentine outpatient clinics. Antidepressant treatment was least likely with type I disorder and was independent of current depression and not associated with more use of mood‐stabilizing or antimanic agents. Copyright © 2012 John Wiley & Sons, Ltd.     

Lithium augmentation of topiramate for bipolar disorder with comorbid binge eating disorder and obesity

OBJECTIVE: To evaluate the effectiveness of lithium augmentation of topiramate on mood symptoms, binge eating behavior, and body weight in obese bipolar patients with binge eating disorder (BED) seeking weight management. METHOD: We conducted a naturalistic study of 12 consecutive outpatients with bipolar disorders, BED, and obesity who received lithium augmentation for mood instability during the course of topiramate-based pharmacotherapy for obesity and BED. Lithium was added to topiramate (mean dose 514 mg i.d.) and titrated to a mean dose of 1009 mg i.d. (mean plasma concentration 0.7 mmol/L). Treatment response was assessed by comparing changes in clinical severity scales for mood and eating disorders, weekly binge eating frequency, and weight for the 2 months before and the first 2 months during lithium treatment. RESULTS: A statistically significant improvement in global severity of mood symptoms was observed after as compared to before lithium augmentation. Statistically insignificant reductions in weight and in binge frequency and severity were also observed after lithium addition. CONCLUSION: Optimal weight loss treatment in obese patients with comorbid bipolar and BEDs may require stabilization of mood. The combination of lithium and topiramate may have a role in the management of this difficult-to-treat population.     

Treatment of bipolar affective disorder in clinical practice

A case note survey of 100 outpatients with a clinical diagnosis of bipolar affective disorder in a UK inner city teaching hospital revealed monotherapy with a mood stabilizer in only 23% of patients, mostly lithium (15%). Overall, 51% of patients were prescribed lithium, 19% carbamazepine and 5% valproate with only 8% receiving a combination of two mood stabilizers. Treatment appeared to be inadequate in 13/51 of patients on lithium, 9/19 of those on carbamazepine and 1/5 of those on valproate. Antipsychotics were used as monotherapy in 20% of patients and combined with a mood stabilizer in 43% of patients. Only 6% of patients were on atypical antipsychotics. These findings suggest that the treatment for many patients does not match recommendations. Clearer evidence on the place of combination mood stabilizers and adjunctive antipsychotics, particularly atypicals is needed in the treatment of bipolar affective disorder.     

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.