Bipolar disorder valproate

Other drugs used in bipolar disorders valproate... 

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

The total costs are likely to reflect the efficacy of treatment. In one industry-sponsored study (Keck et al, 1996b) treatment with lithium or valproate was compared in relation to classical, mixed and rapid-cycling disorder. Treatment with lithium was associated with lower costs than treatment with valproate for classical bipolar disorder, but treatment with valproate was associated with lower costs than treatment with lithium for mixed and rapid-cycling disorders. This is in keeping with the evidence that valproate is more effective than lithium for certain patients with rapid-cycling disorder and probably also for certain patients with mixed affective states. However, these associations are a guide to predicting response to treatment but are not very specific. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Lithium is the drug of choice for bipolar disorder with euphoric mania, whereas valproate has better efficacy for mixed states, irritable/dysphoric mania, and rapid cycling compared with lithium. 

Divalproex sodium (sodium valproate) is now the most prescribed mood stabilizer in the United States. It is FDA approved only for the treatment of acute manic or mixed episodes, but it is often used as maintenance monotherapy for bipolar disorder. 

Approximately 20% to 50% of women with bipolar disorder relapse postpartum prophylaxis with mood stabilizers (e.g., lithium or valproate) is recommended immediately postpartum to decrease the risk of relapse. 

Valproate is as effective as lithium and olanzapine for pure mania, and it can be more effective than lithium for rapid cycling, mixed states, and bipolar disorder with substance abuse. It reduces the frequency of recurrent manic, depressive, and mixed episodes. 

Mood Stabilizers. Lithium (Eskalith, Lithobid), valproic acid (Depakene), sodium valproate (Depakote), and carbamazepine (Tegretol) are most often used by psychiatrists to treat the bipolar disorders. These so-called mood stabilizers are also used to treat impulsivity and agitation in a variety of psychiatric disorders including dementia, certain personality disorders, and the disruptive behavior disorders of childhood. 

Valproic acid (dipropylacetic acid) is a single branched chain carboxylic acid that is structurally unlike any of the other drugs used in the treatment of bipolar disorder or epilepsy. The amide derivative, valproamide, is available in Europe as a more potent form of valproate. Valproate was first developed in Erance as an antiepileptic agent in 1963. As an antiepileptic agent, it was shown to be active against a variety of epilepsies without causing marked sedation. 

Numerous open studies, and seven controlled studies, have shown that valproate is effective in the treatment of acute mania. It has also been claimed to have an antidepressant action. Recent studies have shown that valproate is effective in the long-term treatment of bipolar disorder. 

Dosage regimen for bipolar disorder The target dose of lamotrigine is 200 mg/day (100 mg/day in combination with valproate and 400 mg/day in combination with carbamazepine or other enzyme-inducing drugs). Doses above 200 mg/day are not recommended. 

West, S.A., Keck P.E., Jr., and McElroy, S.L. (1995) Oral loading doses in the valproate treatment of adolecents with mixed bipolar disorder. / Child Adolesc Psychopharmacol 5 225-231. 

Sovner, R. (1989) The use of valproate in the treatment of mentally retarded persons with typical and atypical bipolar disorders. J Clin Psychiatry 50 40—43. 

Valproate, a simple branched-chain fatty acid, was first reported as a successful treatment for acute mania by Lambert and colleagues in 1966. Following this report, at least 16 uncontrolled trials consistently supported the observation that valproate has acute and long-term mood-stabilizing effects in patients with bipolar disorder (reviewed by Keck et al. 1992a). Recently, five double-blind controlled studies of valproate have been completed that provide definitive evidence of its efficacy in acute mania. 

Lambert 1984 McElroy et al. 1988b] suggested that valproate may be a much better antimanic than antidepressant agent. In a study of 78 consecutively recruited patients with rapid-cycling bipolar disorder treated with open-label valproate alone or in combination with other psychotropic agents, Calabrese and colleagues [Calabrese and Delucchi 1990 Calabrese et al. 1992] reported a 54% valproate response in acute mania, an 87% response in acute mixed states, and a 19% response in acute depression. However, they did observe a prophylactic antidepressant effect in patients subsequently. Additional controlled studies are needed to clarify valproate s antidepressant efficacy. 

EFFICACY OF VALPROATE IN MAINTENANCE TREATMENT OF BIPOLAR DISORDER... 

To our knowledge, there have been no reports of controlled clinical trials of valproate as a prophylactic agent in bipolar disorder. Results from a number of open trials suggest that perhaps half of patients treated with valproate experience prophylactic benefit (reviewed in Keck et al. 1992a]. A placebo-controlled, double-blind study of the efficacy of the divalproex form of valproate is under way and may provide additional information regarding the use of this drug in the maintenance therapy of bipolar disorder. 

Several studies suggest that valproate is effective in patients with a history of lithium treatment failure. In the study by Pope et al. [1991), 71% of patients receiving valproate exhibited an antimanic response, even though all of the patients had a history of lithium treatment failure or intolerance. Sixty-four percent of the patients with rapid-cycling bipolar disorder studied by Galabrese and Delucchi [1990) had a history of lithium failure, and the majority of these subsequently responded to valproate. Similarly, the six patients with rapid-cycling bipolar disorder described by McElroy et al. 

Keck PE Jr, McElroy SL, Nemeroff CB Anticonvulsants in the treatment of bipolar disorder. J Neuropsychiatry 4 395-405, 1992a Keck PE Jr, McElroy SL, Vuckovic A, et al Combined valproate and carbamazepine treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci 4 319-322, 1992b... 

McElroy SL, Keck PE Jr, Pope EIG Jr, et al Valproate in primary psychiatric disorders literature review and clinical experience in a private psychiatric hospital, in Use of Anticonvulsants in Psychiatry Recent Advances. Edited by McElroy SL, Pope HG Jr. Clifton, NJ, Oxford Health Care, 1988b McElroy SL, Keck PE Jr, Pope HG Jr, et al Valproate in the treatment of rapid-cycling bipolar disorder. J Clin Psychopharmacol 8 275-279, 1988c McElroy SL, Sessain EC, Pope HG Jr, et al Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder and schizophrenia. J Clin Psychiatry 52 411-414, 1991a... 

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