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Medication. For years, lithium has been the "gold standard" pharmacological treatment for bipolar disorder. When taken regularly, lithium can effectively control mania and depression in many patients and can reduce the likelihood of episode recurrence. However, scientists still do not know exactly how it works, nor do they understand why it works well for some people but not others. In attempt to answer these questions, NIMH researchers are investigating the biochemical mechanisms of action of lithium. This and future work will inform the development of new and better treatments.For patients who either do not respond to lithium or cannot tolerate its side effects, which can include weight gain, tremor, and excessive urination, there are several anticonvulsant medications that may serve as alternative mood stabilizers. Valproate and carbamazepine have been used for the past two decades for treatment of acute mania and prevention of cycling. However, valproate is the only anticonvulsant approved by the U.S. Food and Drug Administration (FDA) for use with bipolar disorder - specifically, for the acute treatment of mania. NIMH researchers are currently investigating the efficacy of newer anticonvulsant drugs, including lamotrigine and gabapentin, as mood stabilizers for treatment refractory bipolar disorder. Topiramate is also receiving attention in clinical studies.
Treatment of Bipolar Depression
Antidepressant medications have long been used to treat the depressive phase of bipolar disorder. However, research has shown that antidepressants, when taken without a mood-stabilizing medication, can increase the risk of switching into mania or hypomania, or of developing rapid cycling, in people with bipolar disorder. Therefore, mood-stabilizing medications are generally required, alone or in combination with antidepressants, to protect patients with bipolar disorder from this switch. Lithium and valproate are the most commonly used mood stabilizing drugs today. Research studies are evaluating the potential mood stabilizing properties of newer medications.
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NIMH-funded research has evaluated the efficacy of atypical antipsychotic medications in the treatment of bipolar disorder. One recent NIMH study demonstrated mood stabilizing and antimanic effects of clozapine in patients with treatment-resistant bipolar disorder. Another NIMH study found olanzapine to help relieve psychotic depression in patients with a diagnosis of major depression or bipolar I disorder. Other research has supported the efficacy of olanzapine for acute mania, an indication that has recently received FDA approval. The efficacy of risperidone is also under study.
A nutritional approach under investigation for maintenance treatment of bipolar disorder involves omega-3 fatty acids found in fish oil. Preliminary research has found a combination of the two main omega-3 fatty acids to be better than placebo, when added to ongoing conventional medications, in avoiding an acute illness episode and in improving a variety of symptoms over four months. However, due to several limitations in this preliminary study, more definitive research is required to validate the appeal of a naturally occurring, apparently safe substance in the treatment of bipolar disorder.
Psychotherapy. Interest in using psychotherapy in combination with medication for bipolar disorder has grown in recent years with the recognition of the continuing high rate of relapse, some of which appears preventable, during pharmacological maintenance treatment. NIMH researchers are conducting studies to evaluate the benefits of specific types of adjunctive psychotherapy in the long-term management of bipolar disorder. These psychotherapies include Psychoeducation (PE), Cognitive-Behavioral Therapy (CBT), Family Focused Therapy (FFT), and Interpersonal and Social Rhythm Therapy (IPSRT). PE involves teaching patients with bipolar disorder about their illness and its treatment. Emphasis is placed on recognizing early signs of relapse so that patients can seek medical care before a full-blown illness episode develops. CBT helps patients modify detrimental or inappropriate thought patterns and behaviors associated with bipolar disorder. FFT employs strategies to reduce the level of distress within the family that may either contribute to or result from the ill person's symptoms. IPSRT uses techniques aimed at regularizing daily routines and improving interpersonal relationships. Research indicates that regular daily routines and sleep schedules may protect against manic episodes. A large-scale NIMH study (called STEP-BD, described below) will compare the effectiveness of intensive CBT, FFT, and IPSRT, each in combination with medication, for treatment of acute depressive episodes and for prevention of recurrent episodes in people with bipolar disorder.
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