Type I bipolar disorder is a severe and usually chronic mood disorder that causes significant illness and life disruption and is characterized by recurring episodes of mania and depression.

The goals of pharmacological treatment for bipolar disorder are to stabilize mood and achieve remission from manic and depressive episodes and, after completing an acute phase of treatment, maintain remission and prevent the recurrence of episodes. In practice, these goals are often achieved by treatment with traditional mood-stabilizing agents, such as lithium, valproate, and/or lamotrigine, with addition of an antipsychotic or other psychotropic agents 1. In randomized, placebo-controlled trials, lithium has been observed to reduce the risk of relapse by 41% and increase the time to requirement of additional medication for a manic or depressive episode (median survival time of 170 days versus 93 days for placebo 234. When compared with placebo, lamotrigine also increased the time to intervention for a manic or depressive episode (median survival time of 200 days versus 93 days), but was notable for its superiority to lithium in preventing depressive relapse (57% versus 46% of patients were intervention-free for depression over 1 year 4. Ideally, the risk of drug interactions, adverse events, and potential benefit for the individual patient must be evaluated for each additional medication and combination.

Although many combinations of these therapies are in common usage, longitudinal studies of patients with bipolar disorder in the community indicate that a large proportion of individuals remain ill or have serious symptoms for significant periods of time, despite treatment with several different medications during the course of the studies 5678. These observations suggest there is a continuing need for systematic investigations of therapeutic options for patients, particularly those with refractory disease.

Quetiapine has been shown to be effective either as combination therapy or monotherapy for the treatment of bipolar mania 91011, and as monotherapy for the treatment of bipolar depression 12. These studies have demonstrated that even in the absence of psychotic symptoms, patients benefit from quetiapine therapy during mania and depression. In general, atypical agents such as quetiapine are recommended for patients with bipolar disorder over conventional antipsychotic agents due to the more benign side-effect profile associated with atypicals 1.

In open-label trials, quetiapine has been found to reduce symptoms, with a well-tolerated side-effect profile for patients with poorly controlled bipolar and schizoaffective mood disorders 13, as well as rapid-cycling type I bipolar disorder 14. These studies were carried out for 12 to 20 weeks with patients whose previous dose of mood-stabilizing medication was either discontinued or maintained. Large, randomized, clinical studies demonstrated the efficacy and tolerability of quetiapine as short-term (3 months) monotherapy and combination therapy during episodes of mania 111516. However, the effects of longer-term therapy with quetiapine for patients with refractory disease are less well understood. This study was designed to determine the long-term clinical efficacy of adding quetiapine to ongoing medications in patients who were responding inadequately to these medications. Symptomatology and relapse rates were evaluated during combination therapy for 26 to 78 weeks.

Patients with bipolar I disorder who have inadequate responses to standard pharmacological therapy remain a common problem, despite the wide array of psychotropic agents that may be utilized 20. This open-label study has demonstrated that long-term therapy with quetiapine may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of depressive relapses as well as manic/mixed relapses. In this study, treatment with quetiapine for 26–78 weeks of treatment was associated with significant improvements in relapse rates and symptoms that were achieved with 26 weeks of treatment in 21 patients and maintained for more than 52 weeks in a subset of 13 patients. These results, while in agreement with a recent large, randomized, double-blind study that established significant improvements in bipolar depressive symptoms 12 as well as several clinical trials showing efficacy for patients with symptoms of mania 111516, also suggest that the treatment effect observed with quetiapine is maintained in the long-term.

For each patient, long-term quetiapine treatment was added to ongoing medication, which included several classes of psychotropic therapies, such as traditional mood stabilizers and anticonvulsants, typical antipsychotic agents, and atypical antipsychotic agents. While polypharmacy with several kinds of psychotropic therapies is common in adults and children with bipolar disorder in the community 521, systematic studies of long-term antipsychotic therapy have generally used only traditional mood stabilizers as adjunctive therapy 22232425. This study showed that adding quetiapine to a variety of ongoing therapies was well tolerated and associated with a low incidence of adverse events over the long term.

Although the cause is unknown, several studies have suggested an increased rate of antipsychotic-induced tardive dyskinesia and extrapyramidal symptoms (EPS) in patients with affective disorders compared with patients with schizophrenia 26272829. Of particular importance for patients with affective disorders, no increase in tardive dyskinesia or EPS was reported during quetiapine therapy in this study.

Similar results have been reported in a small, open-label, 88-week study of 10 adolescents with schizoaffective disorder or bipolar disorder 30, indicating that quetiapine treatment is effective and well tolerated for long-term treatment in this population as well.

This study has a number of limitations, including small sample number and lack of a comparator. Furthermore, the design of an open-label study does not include randomization techniques and blinding of investigators to patient status, which may introduce selection bias. However, albeit a different study population, similar observations with quetiapine were reported in a study of comparable design 30. Nevertheless, large, randomized, double-blind, placebo-controlled studies are needed to explore the benefits of adding long-term quetiapine to standard therapies for bipolar disorder.

The author(s) declare that they have no competing interests.

MCH, MGC conceived of the study, participated in the design of the study, coordinated the study, performed the statistical analysis and drafted the manuscript. AG, BC, JRC participated in its design and coordination. All authors read and approved the final manuscript.