Quetiapine fumarate is used for the symptomatic management of psychotic disorders (e.g., schizophrenia). Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to sustain symptom remission or control and to minimize the risk of relapse. Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia. Patient response and tolerance to antipsychotic agents are variable, and patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.
Short-term efficacy of quetiapine for the management of schizophrenia has been established by placebo-controlled studies of 6 weeks' duration principally in hospitalized patients with schizophrenia. Schizophrenia is a major psychotic disorder that frequently has devastating effects on various aspects of the patient's life and carries a high risk of suicide and other life-threatening behaviors. Manifestations of schizophrenia involve multiple psychologic processes, including perception (e.g., hallucinations), ideation, reality testing (e.g., delusions), emotion (e.g., flatness, inappropriate affect), thought processes (e.g., loose associations), behavior (e.g., catatonia, disorganization), attention, concentration, motivation (e.g., avolition, impaired intention and planning), and judgment. The principal manifestations of this disorder usually are described in terms of positive and negative (deficit) symptoms, and more recently, disorganized symptoms. Positive symptoms include hallucinations, delusions, bizarre behavior, hostility, uncooperativeness, and paranoid ideation, while negative symptoms include restricted range and intensity of emotional expression (affective flattening), reduced thought and speech productivity (alogia), anhedonia, apathy, and decreased initiation of goal-directed behavior (avolition). Disorganized symptoms include disorganized speech (thought disorder) and behavior and poor attention.
In clinical studies in patients with schizophrenia, quetiapine was more effective than placebo in reducing the severity of symptoms associated with this disorder. Quetiapine appears to improve both positive and negative manifestations of schizophrenia. Results from comparative clinical studies and meta-analyses suggest that quetiapine is at least as effective as chlorpromazine or haloperidol in reducing positive and negative symptoms of schizophrenia.
The American Psychiatric Association (APA) considers certain atypical antipsychotic agents (i.e., quetiapine, aripiprazole, olanzapine, risperidone, ziprasidone) first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes), principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of conventional and atypical antipsychotic agents remain controversial. The APA states that, with the possible exception of clozapine for the management of treatment-resistant symptoms, there currently is no definitive evidence that one atypical antipsychotic agent will have superior efficacy compared with another agent in the class, although meaningful differences in response may be observed in individual patients. Conventional antipsychotic agents may be considered first-line therapy in patients who have been treated successfully in the past with or who prefer conventional agents. The choice of an antipsychotic agent should be individualized, considering past response to therapy, adverse effect profile (including the patient's experience of subjective effects such as dysphoria), and the patient's preference for a specific drug, including route of administration.
Although the efficacy of quetiapine for long-term use has not been established in controlled studies, the manufacturer states that beneficial effects of the drug were maintained for up to 4 years in some patients during an open-label extension study in patients who achieved an initial response to treatment during double-blind clinical studies. If quetiapine is used for extended periods, the need for continued therapy should be reassessed periodically on an individualized basis.
(See Dosage and Administration: Dosage.)
For additional information on the symptomatic management of schizophrenia, including treatment recommendations and results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research program,
Quetiapine is used alone or in conjunction with lithium or divalproex sodium for the management of acute manic episodes associated with bipolar I disorder. Efficacy of quetiapine monotherapy in the treatment of acute manic episodes has been demonstrated in 2 placebo-controlled studies of 12 weeks' duration in patients who met the DSM-IV criteria for bipolar disorder and who met diagnostic criteria for an acute manic episode (with or without psychotic features). Patients with rapid cycling and mixed episodes were excluded from these studies. The principal rating instrument used for assessing manic symptoms in these studies was the Young Mania Rating Scale (YMRS) score, an 11-item clinician rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score). In these studies, quetiapine was shown to be superior to placebo in reduction of the YMRS total score after 3 and 12 weeks of treatment.
Efficacy of quetiapine when used in combination with lithium or divalproex sodium in the management of acute manic episodes has been demonstrated in a placebo-controlled study of 3 weeks' duration in patients who met the DSM-IV criteria for bipolar I disorder with acute manic episodes (with or without psychotic features). Patients with rapid cycling and mixed episodes were excluded from enrollment and patients included in the study may or may not have received an adequate course of therapy with lithium or divalproex sodium prior to randomization. Quetiapine was shown to be superior to placebo when added to lithium or divalproex sodium alone in the reduction of YMRS total score. However, in a similarly designed study, quetiapine was associated with an improvement of YMRS scores but did not demonstrate superiority to placebo.
For the initial management of less severe manic or mixed episodes in patients with bipolar disorder, current APA recommendations state that monotherapy with lithium, valproate (e.g., valproate sodium, valproic acid, divalproex), or an antipsychotic (e.g., olanzapine) may be adequate. For more severe manic or mixed episodes, combination therapy with an antipsychotic and lithium or valproate is recommended as first-line therapy. For further information on the management of bipolar disorder,
Quetiapine also is used for the treatment of depressive episodes associated with bipolar disorder. Efficacy of quetiapine in the treatment of depressive episodes has been demonstrated in 2 randomized, double-blind, placebo-controlled studies of 8 weeks' duration in patients with bipolar I or II disorder (with or without a rapid cycling course). Patients in these studies received fixed daily quetiapine dosages of 300 or 600 mg once daily. The principal rating instrument used for assessing depressive symptoms in these studies was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale with scores ranging from 0 to 60. In both studies, quetiapine was found to be superior to placebo in reduction of MADRS scores at week 8, with improvements in scores evident within one week of treatment. In addition, patients receiving 300 mg of quetiapine daily demonstrated significant improvements compared to placebo recipients in overall quality of life and satisfaction related to various areas of functioning.