Quetiapine for Acute Mania in Bipolar Disorder
Quetiapine for Acute Mania in Bipolar Disorder
Purpose: The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed.
Summary: Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug.
Conclusion: While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options.
Bipolar disorder is a diagnostically complex, debilitating illness with the potential to produce significant morbidity and mortality if inadequately treated. Two major community surveys have estimated the lifetime prevalence of bipolar disorder for the U.S. general population to be 1.0-1.6% for adults and 1.2% for children and adolescents age 9-17 years. Bipolar disorder is an episodic illness involving mood disturbances, manic spectrum episodes, and depression, which are typically interspersed with periods of normal mood. Initial mood disorders generally occur during the teens or early 20s, though the age of onset can range from childhood to late life. At this time, two presentations of disorder are recognized: bipolar I and bipolar II. Bipolar I disorder involves episodes of mania, while bipolar II disorder involves episodes of hypomania, which do not typically greatly interfere with a person's functioning. Both types of bipolar disorder involve episodes of depression. At least 25-50% of people with bipolar disorder attempt suicide at some point during their lives. An estimated 10-15% of those with bipolar I disorder eventually complete suicide. Bipolar disorder of any type is a lifelong illness that requires continuous pharmacologic management for optimal outcomes. An estimated 90% of people with one manic episode experience future episodes.
Acute mania is a particularly dangerous component of bipolar disorder and requires prompt psychosocial and pharmacologic intervention to prevent serious ramifications for patients. It may present as classic or mixed mania, both of which are often characterized by increased energy; racing, tangential, possibly disorganized, thoughts; and minimal desire for sleep with no resulting fatigue. Delusions and hallucinations may also occur. In classic mania, the mood is initially euphoric, and delusions are often grandiose. Excessive risk-taking behaviors related to grandiosity are common and may involve such things as excessive spending, unsafe driving, or hypersexuality. Often, the mood in classic mania will progress, or switch in a labile fashion, from euphoric to irritable, particularly when grandiose plans are questioned or thwarted by hospitalization or other interventions. Patients may believe that others are interfering with their potential successes. Mixed mania is a state in which a person meets Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria for both acute mania and depression. Delusions and hallucinations may involve guilt and pessimism; grandiosity is likely less prominent, as the mood is depressed. People suffering from mixed mania have an especially high risk of becoming suicidal because the depressed mood is concurrent with increased energy, a lack of desire to sleep, and a labile mood with resulting impulsive behaviors. Any type of acute mania can be considered a psychiatric emergency, and hospitalization with pharmacotherapy is the usual treatment.
Pharmacotherapy for acute mania typically involves a mood stabilizer, such as lithium or certain anticonvulsants, and often an antipsychotic is given to reduce excessive psychomotor agitation. Combination therapy with these agents during acute mania is quite common because of the need to rapidly stabilize patients, as the goal of treatment is to restore normal or near-normal functioning as quickly as possible and prevent further deterioration. This strategy is supported by consensus guidelines. Antipsychotics have been used primarily during the acute phase of the illness as an adjunct to mood stabilizers to rapidly stabilize patients and often discontinued when a patient's mood has stabilized and the risk for rapid relapse is deemed low. However, new evidence suggests that antipsychotics have a role in the maintenance therapy of some patients with bipolar disorders, particularly atypical antipsychotics, which pose a lower risk for tardive dyskinesia and other movement disorders than do conventional agents such as haloperidol.
In 2004, quetiapine, a second-generation dibenzothiazepine, received Food and Drug Administration (FDA) approval for use as monotherapy or adjunctive therapy for acute mania. Noncontrolled trials may be biased by the natural cyclic nature of bipolar disorder, such that people may improve regardless of drug therapy. This article reviews the safety and efficacy data from randomized, double-blind, placebo-controlled trials of quetiapine as a treatment for acute mania.
Purpose: The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed.
Summary: Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug.
Conclusion: While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options.
Bipolar disorder is a diagnostically complex, debilitating illness with the potential to produce significant morbidity and mortality if inadequately treated. Two major community surveys have estimated the lifetime prevalence of bipolar disorder for the U.S. general population to be 1.0-1.6% for adults and 1.2% for children and adolescents age 9-17 years. Bipolar disorder is an episodic illness involving mood disturbances, manic spectrum episodes, and depression, which are typically interspersed with periods of normal mood. Initial mood disorders generally occur during the teens or early 20s, though the age of onset can range from childhood to late life. At this time, two presentations of disorder are recognized: bipolar I and bipolar II. Bipolar I disorder involves episodes of mania, while bipolar II disorder involves episodes of hypomania, which do not typically greatly interfere with a person's functioning. Both types of bipolar disorder involve episodes of depression. At least 25-50% of people with bipolar disorder attempt suicide at some point during their lives. An estimated 10-15% of those with bipolar I disorder eventually complete suicide. Bipolar disorder of any type is a lifelong illness that requires continuous pharmacologic management for optimal outcomes. An estimated 90% of people with one manic episode experience future episodes.
Acute mania is a particularly dangerous component of bipolar disorder and requires prompt psychosocial and pharmacologic intervention to prevent serious ramifications for patients. It may present as classic or mixed mania, both of which are often characterized by increased energy; racing, tangential, possibly disorganized, thoughts; and minimal desire for sleep with no resulting fatigue. Delusions and hallucinations may also occur. In classic mania, the mood is initially euphoric, and delusions are often grandiose. Excessive risk-taking behaviors related to grandiosity are common and may involve such things as excessive spending, unsafe driving, or hypersexuality. Often, the mood in classic mania will progress, or switch in a labile fashion, from euphoric to irritable, particularly when grandiose plans are questioned or thwarted by hospitalization or other interventions. Patients may believe that others are interfering with their potential successes. Mixed mania is a state in which a person meets Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria for both acute mania and depression. Delusions and hallucinations may involve guilt and pessimism; grandiosity is likely less prominent, as the mood is depressed. People suffering from mixed mania have an especially high risk of becoming suicidal because the depressed mood is concurrent with increased energy, a lack of desire to sleep, and a labile mood with resulting impulsive behaviors. Any type of acute mania can be considered a psychiatric emergency, and hospitalization with pharmacotherapy is the usual treatment.
Pharmacotherapy for acute mania typically involves a mood stabilizer, such as lithium or certain anticonvulsants, and often an antipsychotic is given to reduce excessive psychomotor agitation. Combination therapy with these agents during acute mania is quite common because of the need to rapidly stabilize patients, as the goal of treatment is to restore normal or near-normal functioning as quickly as possible and prevent further deterioration. This strategy is supported by consensus guidelines. Antipsychotics have been used primarily during the acute phase of the illness as an adjunct to mood stabilizers to rapidly stabilize patients and often discontinued when a patient's mood has stabilized and the risk for rapid relapse is deemed low. However, new evidence suggests that antipsychotics have a role in the maintenance therapy of some patients with bipolar disorders, particularly atypical antipsychotics, which pose a lower risk for tardive dyskinesia and other movement disorders than do conventional agents such as haloperidol.
In 2004, quetiapine, a second-generation dibenzothiazepine, received Food and Drug Administration (FDA) approval for use as monotherapy or adjunctive therapy for acute mania. Noncontrolled trials may be biased by the natural cyclic nature of bipolar disorder, such that people may improve regardless of drug therapy. This article reviews the safety and efficacy data from randomized, double-blind, placebo-controlled trials of quetiapine as a treatment for acute mania.
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