A Pilot Study of Lithium Carbonate Plus Divalproex Sodium for the Continuation and Maintenance Treatment of Patients With Bipolar I Disorder

Da, Solomon; Ce, Ryan; Gi, Keitner; Iw, Miller; Shea, M. Tracie; Kazim, Ali; Mb, Keller

doi:10.4088/jcp.v58n0301

Cited by 156 publications

(52 citation statements)

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“…Lithium and carbamazepine likely do so by downregulating brain cPLA 2 gene expression and activity, while valproate may selectively reduce arachidonoyl-CoA synthesis by inhibiting an Acsl. Because these drugs have different targets, this provides a rationale for studying/evaluating their effectiveness concomitantly 145 and could explain why the efficacy of valproate appears to be independent of prior responsiveness to lithium. 17 Although showing that three effective drugs overlap in an unanesthetized rat model is significant, examining the effects of other proven mood stabilizers in this and other models will be needed to further test and extend the hypothesis.…”

Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

109

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

109

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“…53 Combination treatment was significantly more effective than lithium alone in preventing relapse (0/5 vs 5/7, P = 0.014). Combination treatment was associated with significantly greater side effect burden and a higher study dropout rate due to side effects.…”

Section: Treatment-resistant Bipolar Disorder M Gitlinmentioning

confidence: 92%

“…Over the last decade, only three controlled trials of combination maintenance treatment of bipolar disorder have been published. [52][53][54] In the only large-scale controlled study, olanzapine plus lithium or valproate was compared to lithium or valproate alone over 18 months in 99 patients who had responded to the combination for acute mania. 52 Dropout rates were very high; 69% of those on combination and 90% of those on lithium or valproate alone discontinued the study, with the majority of dropouts occurring for reasons other than relapse.…”

Section: Combination Treatmentsmentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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Despite the remarkable increase in medications validated as effective in bipolar disorder, treatment is still plagued by inadequate response in acute manic or depressive episodes or in long-term preventive maintenance treatment. Established first-line treatments include lithium, valproate and second-generation antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance treatments. Recently validated treatments include extended release carbamazapine for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance treatments. For treatment-resistant mania and as maintenance treatments, a number of newer anticonvulsants, and one older one, phenytoin, have shown some promise as effective. However, not all anticonvulsants are effective and each agent needs to be evaluated individually. Combining multiple agents is the most commonly used clinical strategy for treatment resistant bipolar patients despite a relative lack of data supporting its use, except for acute mania (for which lithium or valproate plus an SGA is optimal treatment). Other approaches that may be effective for treatment-resistant patients include high-dose thyroid augmentation, clozapine, calcium channel blockers and electroconvulsive therapy (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of different techniques, most of which include substantial attention to education and enhancing coping strategies. Only recently, bipolar depression has become a topic of serious inquiry with the dominant controversy focusing on the place of antidepressants in the treatment of bipolar depression. Other than mood stabilizers alone or the combination of mood stabilizers and antidepressants, most of the approaches for treatment-resistant bipolar depression are relatively similar to those used in unipolar depression, with the possible exception of a more prominent place for SGAs, prescribed either alone or in combination with antidepressants. Future work in the area needs to explore the treatments commonly used by clinicians with inadequate research support, such as combination therapy and the use of antidepressants as both acute and adjunctive maintenance treatments for bipolar disorder. With the first report of lithium's efficacy in 1949 by Cade, bipolar disorder has the longest record of treatment efficacy among the major Axis I disorders. Furthermore, after more than half a century of clinical research, multiple agents from many different pharmacological classes have shown at least some efficacy, while many other agents (albeit without a consistent database demonstrating their utility) are prescribed regularly by clinicians. Yet, despite this plethora of choices, treatment of bipolar disorder remains suboptimal from the points of view of clinicians and patients alike. Whether measured by recovery time from manic or depressive episodes or preventive efficacy of maintenance treatments, bipolar disorder is characterized by sluggish responses, inadequate responses, poor compliance and recurrences in controlled cli...

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“…36,39,40,42,43,[47][48][49][50][52][53][54][55][56][57]60,61,[64][65][66][67]69,72,74,77 Two of these studies compared only different doses of lithium and are not considered in the analyses. 52,61 Trial details are summarised in Table 2 and presented in the data extraction tables (Appendix 6).…”

Section: Efficacy Of Pharmaceutical Interventions Lithiummentioning

confidence: 99%

A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder

Soares‐Weiser¹,

Vergel²,

Beynon³

et al. 2007

Health Technol Assess

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A Pilot Study of Lithium Carbonate Plus Divalproex Sodium for the Continuation and Maintenance Treatment of Patients With Bipolar I Disorder

Cited by 156 publications

References 0 publications

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Treatment-resistant bipolar disorder

A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder

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