The place of anticonvulsant therapy in bipolar illness

Abstract

With the increasing recognition of lithium's inadequacy as an acute and prophylactic treatment for many patients and subtypes of bipolar illness, the search for alternative agents has centered around the mood stabilizing anticonvulsants carbamazepine and valproate. In many instances, these drugs are effective alone or in combination with lithium in those patients less responsive to lithium monotherapy, including those with greater numbers of prior episodes, rapid-cycling, dysphoric mania, co-morbid substance abuse or other associated medical problems, and patients without a family history of bipolar illness in first-degree relatives. Nineteen double-blind studies utilizing a variety of designs suggest that carbamazepine, or its keto-congener oxcarbazepine, is effective in acute mania; six controlled studies report evidence of the efficacy of valproate in the treatment of acute mania as well. Fourteen controlled or partially controlled studies of prophylaxis suggest carbamazepine is also effective in preventing both manic and depressive episodes. valproate prophylaxis data, although based entirely on uncontrolled studies, appear equally promising. Thus, both drugs are widely used and are now recognized as major therapeutic tools for lithium-nonresponsive bipolar illness. The high-potency anticonvulsant benzodiazepines, clonazepam and lorazepam, are used adjunctively with lithium or the anticonvulsant mood stabilizers as substitutes or alternatives for neuroleptics in the treatment of manic breakthroughs. Preliminary controlled clinical trials suggest that the calcium channel blockers may have antimanic or mood-stabilizing effects in a subgroup of patients. A new series of anticonvulsants has just been FDA-approved and warrant clinical trials to determine their efficacy in acute and long-term treatment of mania and depression. Systematic exploration of the optimal use of lithium and the mood-stabilizing anticonvulsants alone and in combination, as well as with adjunctive antidepressants, is now required so that more definitive treatment recommendations for different types and stages of bipolar illness can be more strongly evidence based.

Vagus Nerve Stimulation for Epilepsy and Depression

“…17 Moreover, AEDs such as carbamazepine, valproate and gabapentin, have been shown to play a major role in the pharmacologic treatment of mood disorders. 73,74 Findings such as these have paved the way for FDA approval in 2005 of adjunctive VNS in the United States for patients who are at least 18 years of age with treatment-resistant major depression (TRMD) (unipolar and bipolar), which is defined as a failure to respond to Ն4 antidepressant trials. 75 Those with bipolar disorder should either be resistant, intolerant, or have a medical contraindication to lithium.…”

Behavioral, Psychotic, and Anxiety Disorders in Epilepsy: Etiology, Clinical Features, and Therapeutic Implications

“…Carbamazepine, valproate, and lamotrigine, have all demonstrated a beneficial effect in some psychotic factors and particularly in rapid cyclic bipolar disorders that are strictly related to kindling phenomena (108,109).…”

Beyond Lithium in the Treatment of Bipolar Illness

“…Thus, rational combination therapy seems to be a requirement for clinical stabilization in many instances . Defining the principles for optimum combination of these agents (Post et al 1996b;Post et al 1997) remains a very important task for future research.…”

“…Perhaps most revealing is the clear documentation of responsivity in individual patients using double-blind, placebo substitution designs that demonstrate efficacy, reconfirmed with placebo-related exacerbation and re-responsiveness after drug institution on a blind basis (Ballenger and Post 1978;Post et al 1984a;Post et al 1996a). Antidepressant effects are much less well documented and require further controlled study (Post et al 1994).…”