Riluzole, an inhibitor of glutamate release, is approved by the FDA for the treatment of amyotrophic lateral sclerosis. This agent, at a dosage of 50 to 200 mg/d, was evaluated in an 8-week add-on study in combination with lithium in 14 adults with bipolar depression, 6 of whom had bipolar I disorder, and 8 of whom had bipolar II disorder. Eight patients completed the 8-week trial.6 Significant improvement in depressive symptoms was noted in weeks 5 through 8 as measured by the Montgomery Asberg Depression Rating Scale (MADRS).
Ketamine is a noncompetitive NMDA antagonist that has been evaluated in subanesthetic doses in persons with bipolar disorder.7 Results from a double-blind, randomized, placebo-controlled, crossover study indicate that a single intravenous infusion of ketamine combined with lithium or valproate was capable of alleviating depressive symptoms within 40 minutes of administration when compared with placebo.7 The benefit of ketamine was sustained through day 3. Overall, 71% of patients responded to ketamine and 6% responded to placebo at some point during the trial. Ketamine was not associated with significant increases in hypomania or mania but was associated with dissociative symptoms.
Several case reports and case series suggest that insulin sensitizers (eg, rosiglitazone) may offer an antidepressant effect in persons with major depressive disorder. Studies are currently under way in bipolar disorder. For example, several studies are evaluating the antidepressant effects of intranasal insulin and insulin secretagogues (eg, incretins) in bipolar disorder. Moreover, there is ongoing research to determine whether weight loss, bariatric surgery, and dietary modification (eg, ketogenic diet) improve depressive symptoms in persons with bipolar disorder.
Novel Treatment Avenues for Bipolar Depression
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