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Augmentation/Combination Strategies for Bipolar Disorder

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While monotherapy with lithium was the standard treatment for bipolar disorder in 1970, the availability of many newer agents and the limited efficacy of lithium in a large percentage of patients have resulted in polypharmacy as the new standard of care in many, if not most, bipolar patients. Lithium may be combined with anticonvulsants in the treatment of patients with refractory mania. There are few prospective data using such combinations; however, a number of reports indicated that lithium-carbamazepine combinations are effective with patients who have failed to respond to these two agents given separately (see Chapter 5: "Mood Stabilizers"). Retrospective reviews have generally found the combination of lithium and carbamazepine to be useful and synergistic (Lipinski and Pope 1982; Peselow et al. 1994). However, at least one retrospective study (Fritze et al. 1994) failed to find any benefit from combining lithium and carbamazepine in bipolar patients. There is also evidence that the combination of lithium and carbamazepine may be particularly useful in rapid-cycling bipolar disorder. The combination of lithium and carbamazepine appears to be well tolerated. There is one report of increased risk of sinus node dysfunction with this combination (Steckler 1994), but this effect appears to be rare. In addition, the combination of lithium and carbamazepine may have a cumulative antithyroid effect (Kramlinger and Post 1990). There is no evidence of increased neurotoxicity or blood dyscrasias with this combination. Dosing schedules of the lithium and carbamazepine should parallel regimens used for prescribing each drug alone. The therapeutic serum levels of both drugs should be monitored and maintained.

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