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Treatment-Resistant Bipolar Disorder: Page 3 of 3

Treatment-Resistant Bipolar Disorder: Page 3 of 3

Several novel approaches have been suggested for treatment-resistant bipolar maintenance (either depression or cycling) including clozapine, at either low or standard doses, and maintenance ECT.35-38 Other approaches include augmentation with hypermetabolic thyroid supplementation, diltiazem, aripiprazole, topiramate, gabapentin, mexiletine, levetiracetam, and chromium, as well as vagus nerve stimulation.19,39-46 Efficacy has also been reported for levetiracetam monotherapy and a combination of topiramate and clozapine.47,48


Bipolar disorder is associated with significant morbidity. Numerous evidence-based treatments exist for all phases of bipolar disorder, and these should be optimized and fully explored before resorting to treatments with limited evidence of efficacy. Medication dosage should be titrated to response and emergence of adverse effects.

Combinations of evidence-based treatments are often used. When a treatment has failed, careful consideration should be made about whether it should be discontinued before adding another. Comorbidities such as substance abuse that complicate treatment must be minimized. Often, lithium or an anticonvulsant is used initially and an antipsychotic is added if response is not adequate. However, antipsychotics have been shown to be efficacious in nonpsychotic moderately ill bipolar manic and depressed patients. If evidence-based treatments are truly unsuccessful, clozapine and ECT have some evidence of efficacy as an augmentation to standard treatments. If these too fail, then novel treatments may be considered.




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