Maintenance Phase Of Bipolar Disorder Research Articles

Carbamazepina no tratamento do transtorno bipolar: uma revisão sistemática

ABSTRACT Objective: Expand knowledge on the role and efficacy of carbamazepine (CBZ) in bipolar disorder (BD), based on original studies. Methods: The authors performed a systematic review of the scientific literature on the efficacy of CBZ in BD, using the PubMed/MEDLINE, Web of Science (ISI), and SciELO databases. The search terms were: (“carbamazepine”) AND (“bipolar” OR “mania” OR “manic”). There was no restriction on the year of publication. Results: A total of 27 articles were selected. Among the selected articles, 14 evaluated the use of CBZ in the manic phase of BD, two in the depressive phase of BD, and 11 in the maintenance phase of BD. In the studies on the manic phase of BD, CBZ proved superior to placebo (PLA). As for the depressive phase of BD, there were two studies, both with small samples. In the maintenance phase, CBZ was inferior to lithium, and no studies compared CBZ to PLA. Conclusion: The results of the clinical studies suggest that CBZ is effective for the treatment of the manic phase. Regarding the treatment of acute depression and maintenance of BD, the results of the studies indicate that there is not enough data demonstrating the effectiveness of CBZ.

Evidence-based Pharmacological Treatment in the Maintenance Phase of the Type I Bipolar Disorder: Anticonvulsants or Antipsychotics?

IntroductionType I bipolar disorder (BDI) is characterized by a chronic evolution, with recurrent mood episodes that severely disrupt the overall functionality and quality of patients’ life. An adequate maintenance treatment is necessary to prevent relapses and to improve the functional prognosis of these patients.ObjectivesTo find data regarding the most evidence-based therapeutic strategies in the maintenance phase of BDI.MethodsA literature review was performed through the main electronic databases (PubMed, CINAHL, SCOPUS, EMBASE) using the search paradigm “type I bipolar disorder” AND “mood stabilizers” AND “antipsychotics” AND “anticonvulsants”. All papers published between January 2000 and August 2021 were included.ResultsThe main recommendation is to continue in the maintenance phase the same medication that has proven its efficacy and tolerability in the acute phase. In BDI the most evidence-supported pharmacological approaches for the maintenance phase were lithium, valproate, lamotrigine, and carbamazepine as anticonvulsants/mood stabilizers, as well as olanzapine, quetiapine, and aripiprazole as antipsychotics. Lithium and valproate have been associated with positive influence over neuroplasticity, while antipsychotics have considerably higher metabolic adverse events. Monotherapy is recommended, but drugs associations are frequently met in clinical practice. There are no consistent data about the superiority of one class over the other, but lithium has a proven effect of decreasing the suicide rate in this population.ConclusionsBoth anticonvulsants and antipsychotics are used in the maintenance phase of the BDI, without significant differences in the efficacy rates. However, benefits and risks should be weighted for each class and each individual agent recommended.DisclosureNo significant relationships.

Overview of lithium's use: a nationwide survey

BackgroundLithium is considered the gold standard treatment for bipolar disorder (BD). Current clinical guidelines and scientific evidence support its use as a first-line treatment in BD. However, over the last two decades, there has been a downward tendency in lithium's use in several developed countries. Based on a nationwide survey, this study's objective is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD.MethodsData were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of lithium's use (indication, dosage, monitoring, and information for patients).Results212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6–0.8 mmol/L), and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients on lithium treatment.ConclusionsFrom the results of the present study, it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease with a typical onset in adolescence, the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.

Off-Label Use of Second-generation Antipsychotics in Bipolar Disorder: A Survey of Italian Psychiatrists.

Bipolar disorder (BD) is characterized by recurrent depressive and manic episodes. Lithium, valproate, lamotrigine, and some second-generation antipsychotics (SGAs) are the most typical pharmacological treatments for BD, the main goal being mood stabilization. However, despite these treatments, most patients continue to experience recurrent mood episodes and residual symptoms. Findings from several studies suggest that some SGAs may be beneficial beyond approved indications. The goal of the survey presented in this article was to examine Italian psychiatrists' attitudes concerning the off-label use of SGAs in depressive and maintenance phases of BD. A questionnaire about the off-label prescription of SGAs was e-mailed to 300 psychiatrists from Northern, Central, and Southern Italy affiliated with the Italian Society of Psychopharmacology (SINPF) to investigate the frequency of and motivation for off-label use of SGAs and evaluate the psychiatrists' attitude toward use of specific SGAs in BD; 202 questionnaires were completed. The respondents were equally distributed in terms of sex, and the mean age of respondents was 44.1 years. The majority of the sample reported use of SGAs for off-label indications either very often (16.7%), often (33.7%), or occasionally (34.7%). The main motivation for off-label use of the SGAs was the presence of published evidence (51.5%), followed by patients' nonresponse to previous treatment (37.1%). With regard to the use of specific SGAs in BD, off-label aripiprazole was considered appropriate for depressive episodes by 46% of the psychiatrists, followed by olanzapine which was considered appropriate by 33.7%. For maintenance treatment of BD, off-label asenapine was considered appropriate by 45% of the psychiatrists, followed by long-acting aripiprazole and olanzapine pamoate, which were considered appropriate by 37.1% and 23.8%, respectively. In summary, ~50% of Italian psychiatrists frequently (very often or often) prescribe SGAs for off-label indications. Given the relatively limited number of indicated effective treatments for BD, the use of some SGAs off-label may be considered appropriate when dealing with patients whose BD is resistant to medications with labeled indications for BD.

Long-acting injectable antipsychotics as maintenance treatments for bipolar disorder-A critical review of the evidence.

The maintenance phase of bipolar disorder is arguably the most important. The aim of management during this time is to maintain wellness and prevent future episodes of illness. Medication is often the mainstay of treatment during this phase, but adherence to treatment is a significant problem. In recent years, long-acting injectable (LAI) solutions have been proposed, but these too have limitations. This paper discusses the options that are currently available and critically appraises the effectiveness of this strategy. The authors reviewed the small number of open-label and randomised studies on LAI medications in bipolar disorder and evaluated the efficacy and safety of these medications. The studies reviewed show benefit of LAIs for the management of bipolar disorder but have several key limitations to the generalisability of findings to routine practice. LAIs have an emerging role in the management of bipolar disorder and, although it is not without limitations, this strategy addresses some issues of long-term treatment and medication. Patients with bipolar disorder that are non-adherent or have an unstable illness with a predilection towards mania are possibly better suited to the use of LAIs, though more research is required to fully assess the effectiveness of this approach.

Outcomes of patient education practices to optimize the safe use of lithium: A literature review.

Introduction:Lithium is commonly used to treat various psychiatric disorders and is particularly effective in the maintenance phase of bipolar disorder. Unfortunately, this drug has a narrow therapeutic index and, if not monitored regularly, can result in toxicity. Therefore, for lithium to be prescribed safely, clinicians must ensure that patients are well educated on lithium toxicity, its prevention, and symptom recognition. This article summarizes studies that investigated lithium education strategies to help promote the safe use of lithium.Methods:Four electronic databases were searched using key terms and subject headings. Reference lists of relevant papers were also reviewed. The search was limited to literature published in English, without year limits. Eligible studies examined lithium patient education and the impact on patients' knowledge of safe lithium use.Results:Of a total of 517 citations that were retrieved from the electronic database search, 12 were selected for inclusion in this review. Most of the studies included assessed the effect of lithium education on various aspects of patients' knowledge, including but not limited to, lithium toxicity. Of the studies assessing the correlation between lithium knowledge and lithium levels, most demonstrated a positive correlation between lithium knowledge and lithium levels that were more stable and within the higher end of the recommended therapeutic range.Conclusions:Studies evaluating lithium patient education and its effect on improving the safe use of lithium are limited. Nevertheless, this literature review highlights that lithium patient education is critical to promote its safe use.

Pharmacologic Treatment Options for Bipolar Disorder in Children and Adolescents

Purpose of review Bipolar disorder is a chronic and disabling condition that often presents in adolescence and leads to significant functional impairment, especially in the areas of emotional, cognitive, and social development. Pharmacotherapy is a vital component of the complex treatment of this disorder.The purpose of this review is to provide an overview of the available data on the management of bipolar disorder and the most common comorbid conditions in youth. Recent findings Several medications such as lithium and second-generation antipsychotics (risperidone, aripiprazole, olanzapine, quetiapine, and asenapine) are currently approved by the FDA for the management of acute mixed or manic phases of pediatric bipolar disorder. Very limited data are available on continuation treatment and management of depressive phases of bipolar disorder. There is some evidence that supports the use of a combination of an antipsychotic with lithium or an anticonvulsant for treatment of resistant cases. Summary Monotherapy with an atypical antipsychotic or lithium is the preferable initial treatment of acute manic or mixed episodes. The available evidence supports the use of an olanzapine/fluoxetine combination for the treatment of bipolar depression, which has also been approved by the FDA for this purpose. Additional studies are needed to evaluate safety and efficacy of psychopharmacological interventions, especially focusing on treatment of the depressive and maintenance phases of bipolar disorder.

Prophylactic efficacy of lithium, valproic acid, and carbamazepine in the maintenance phase of bipolar disorder: a naturalistic study.

Mood stabilizers are used clinically for the management of bipolar disorder. Prophylactic therapy with mood stabilizers is the primary treatment for preventing depressive and manic relapses in bipolar patients once they are stabilized. In this study, we examined the relative efficacy of the three most commonly used mood-stabilizing agents: lithium (Li), valproic acid (VPA), and carbamazepine (CBZ), in preventing relapse episodes. A total of 225 patients with bipolar disorder were included in the present analysis. Patients taking Li, VPA, or CBZ were followed up for up to 124 months, until suffering a manic, mixed, or depressive episode (relapse), or until the end of the study/study termination (no relapse), whichever came first. The median unadjusted survival time was 36 months for patients taking VPA, 42 months for patients taking CBZ, and 81 months for patients taking Li. These results indicate that patients stayed longer on Li, suggesting that it might have been better tolerated than either CBZ or VPA. χ-Analysis showed that patients taking Li were significantly less likely to experience relapse during the observational period than patients taking either VPA or CBZ (P<0.05). A Cox regression model showed that the hazard of experiencing relapse was significantly predicted by the total number of depressive (P=0.007) and manic symptoms (P=0.02) assessed before the observation period. In addition, after controlling for symptom covariates, the hazard of experiencing relapse was 1.66 times (95% confidence interval 1.03-2.67) or 66% higher for patients taking VPA compared with patients taking Li (P=0.037). Although the hazard of experiencing relapse was higher for patients taking CBZ compared with those taking Li, the risk was not elevated by a significant amount. Notwithstanding the limitations of the naturalistic design of this study, the differences in relapse prevention and survival time observed in these medications show Li fairing relatively better in prophylactic therapy.

Asenapine for bipolar disorder.

Asenapine (Saphris®) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.

Is Valproate Depressogenic in Patients Remitting from Acute Mania? Case Series.

Valproate is an effective antimanic agent and is recommended as a first-line medication in the treatment of acute mania. Current evidence based guidelines recommend that valproate should be given as a loading dose as it produces a rapid antimanic and antipsychotic response with minimal side-effects. However, no clear guidelines are available on the appropriate dosing or serum levels of valproate in the continuation or maintenance phase of bipolar disorder. We present 4 clinical cases to hypothesize that the higher doses of valproate, such as those used in the treatment of acute mania, may cause a depressive switch. So consideration should be given to reducing the dose of valproate if a patient develops depressive symptoms following recovery from the manic episode, as a therapeutic strategy. The cases also indicate that relatively lower doses and serum levels of valproate are effective in the maintenance phase compared to those needed in the acute manic phase of bipolar disorder. This is the first set of case series that questions the depressogenic potential of valproate in patients remitting from an acute manic episode. It highlights that different doses and serum levels of valproate may be therapeutic in different phases of bipolar disorder.

The use of antipsychotics in maintenance treatment of bipolar disorder

Antipsychotics are often used in the treatment of the acute phase of bipolar disorder; however, once the acute phase has resolved and patients enter the maintenance phase, there is some debate as to whether or not to continue the antipsychotic. This article reviews studies examining the use of antipsychotics in the maintenance phase of bipolar disorder.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

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.

Risperidone long-acting injection as monotherapy and adjunctive therapy in the maintenance treatment of bipolar I disorder

Importance of the field: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern.Areas covered in this review: This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder.What the reader will gain: The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research.Take home message: The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.

Depressive relapse during lithium treatment associated with increased serum thyroid‐stimulating hormone: results from two placebo‐controlled bipolar I maintenance studies

To assess the relationship between depressive relapse and change in thyroid function in an exploratory post hoc analysis from a controlled maintenance evaluation of bipolar I disorder. Mean thyroid-stimulating hormone (TSH) and outcome data were pooled from two 18-month, double-blind, placebo-controlled, maintenance studies of lamotrigine and lithium monotherapy. A post hoc analysis of 109 subjects (n = 55 lamotrigine, n = 32 lithium, n = 22 placebo) with serum TSH values at screening and either week 52 (+/-14 days) or study drop-out was conducted. Lithium-treated subjects who required an intervention for a depressive episode had a significantly higher adjusted mean TSH level (4.4 microIU/ml) compared with lithium-treated subjects who did not require intervention for a depressive episode (2.4 microIU/ml). Lithium-related changes in thyroid function are clinically relevant and should be carefully monitored in the maintenance phase of bipolar disorder to maximize mood stability and minimize the risk of subsyndromal or syndromal depressive relapse.

Pharmacotherapy Update: Quetiapine use in Bipolar Disorder—What does the evidence tell us?

Bipolar disorder is a common and serious illness usually requiring long term medication. We critically review the available evidence surrounding the increasing use of quetiapine, a second generation antipsychotic, in both the acute and maintenance phases of bipolar disorder. Large scale, randomized controlled data supports the use of quetiapine in both acute mania and acute bipolar depression, as a safe and effective treatment and probably best used in combination with a traditional ‘mood stabiliser’ such as lithium or divalproex. Also, quetiapine monotherapy has been shown to be effective in bipolar depression. Two recently published studies also confirm that quetiapine in combination with either lithium or divalproex ‘adds value’ to the maintenance treatment of bipolar disorder in terms of delaying relapse compared to either lithium or divalproex alone. Quetiapine is generally well tolerated, although further work on long term weight gain and emergent diabetes would be helpful.

Comparison of carbamazepine and lithium in treatment of bipolar disorder: A systematic review of randomized controlled trials

To review data from randomized controlled trials (RCTs) assessing the comparative efficacy of carbamazepine and lithium in treatment of acute manic and maintenance phase of bipolar disorder (BD). RCTs were identified through a search strategy that included: electronic databases, reference cross-checking, hand search of non-indexed publications, and book chapters on the treatment of BD comparing carbamazepine with lithium. Outcomes investigated were antimanic effect, trial withdrawal, relapse, hospitalization, need for rescue medication, and presence of adverse effects. Selection of studies and data analysis were performed independently by authors. Whenever possible, data from trials were combined through meta-analyses. Relative risks (RR) were estimated for dichotomous data. In acute mania, carbamazepine was similar to lithium on the following outcomes: trial withdrawal due to adverse effects, number of participants with at least one adverse effect, improvement in the Clinical Global Impression (CGI). In acute mania, carbamazepine was associated with fewer trial withdrawals. In maintenance treatment, carbamazepine was similar to lithium in relapses and hospitalization, but there were fewer trial withdrawals due to adverse effects on lithium. This review suggests that carbamazepine might be comparable to lithium in terms of efficacy and safety, and therefore a valuable option in the treatment of both manic and maintenance phases.

Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53-0.86] for lithium, 0.68 (95% CI = 0.55-0.85) for lamotrigine, and 0.82 (95% CI = 0.57-1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49-0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35-0.79 and RR = 0.37; 95% CI = 0.24-0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46-0.91 and RR = 0.40; 95% CI = 0.20-0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34-0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12-2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08-3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31-3.70). There were few data for carbamazepine or medications given as adjunct therapy. Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.

Historical Review of Carbamazepine for the Treatment of Bipolar Disorder

The management of bipolar disorder has seen significant evolution in terms of the number of treatment options now approved for both the acutely manic phase and the maintenance stages of the illness. In addition, new formulations of traditional agents are available for clinicians to use in their treatment approach. One such example is carbamazepine, which has approval by the United States Food and Drug Administration for the treatment of acute and mixed mania in an extended-release formulation that uses a three-bead delivery system. Although the parent compound has been available for decades, its approval for bipolar disorder is recent despite numerous clinical trials that have supported its use in both the acute and maintenance phases of bipolar disorder. Advantages of the new formulation include less fluctuation in plasma concentration and, in general, improved tolerability. However, issues remain with regard to cytochrome P450 drug-related interactions and the need for therapeutic drug monitoring (e.g., drug concentrations, epoxide metabolite concentrations, hematology, and liver function tests) as part of the treatment and monitoring process. We review the current body of literature describing the use of carbamazepine in bipolar disorder during both the acute and maintenance phases of the disorder, including trials of both monotherapy and combination therapy, as well as findings from trials that included patients with rapid cycling and mixed episodes.

The role of quetiapine in the treatment of bipolar disorder

Through a review of randomised, controlled trials, this article evaluates the efficacy and tolerability of quetiapine in the acute and maintenance phases of bipolar disorder. In trials involving mania patients, quetiapine was found to be effective as adjunctive therapy in combination with lithium or valproate, significantly superior to placebo, and equal to lithium or haloperidol as monotherapy. With regard to the prevention of relapses in bipolar disorder, quetiapine seems to differ from other atypical antipsychotics in its characteristics as a mood stabiliser, which are associated with a promising efficacy in the treatment of bipolar depressive episodes. However, further larger controlled long-term prospective studies are needed to confirm the efficacy of quetiapine for the prevention of relapses in bipolar disorder. Quetiapine seems to have a satisfactory safety and tolerability profile, with a low prevalence of extrapyramidal symptom-related adverse events, treatment-emergent depression and weight gain. Sedation is the main side effect of treatment with quetiapine.