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document
Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone : preliminary findings and a discussion of therapeutic mechanisms . OBJECTIVES Attenuation of protein kinase C ( PKC ) is a mechanism common to both established ( lithium , valproate ) and some novel ( tamoxifen ) antimanic agents . Verapamil , although primarily known as a calcium channel blocker , also has PKC inhibitory activity . Verapamil has shown antimanic activity in some but not all studies . Therefore , we investigated verapamil , used alone or as an adjunctive treatment , in manic patients who did not respond to an initial adequate trial of lithium . METHODS Each study phase lasted three weeks . Subjects were treated openly with lithium in Phase 1 ( n = 45 ) . Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil ( n = 10 ) or continued-lithium ( n = 8 ) . Phase 2 nonresponders ( n = 10 ) were assigned to combined verapamil/lithium in Phase 3 . RESULTS Response in Phase 2 did not differ significantly between verapamil and continued-lithium . During Phase 3 , response to combined treatment was significantly better than overall response to monotherapy in Phase 2 ( Fisher 's Exact test , p = 0.043 ) . Mania ratings improved during combined treatment in Phase 3 by 88.2 % ( linear mixed model analysis , F = 4.34 , p = 0.013 ) , compared with 10.5 % improvement during Phase 2 . CONCLUSIONS In this preliminary investigation , verapamil monotherapy did not demonstrate antimanic efficacy . By contrast , the combination of verapamil plus lithium was highly efficacious . Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium . This effect may be mediated by additive actions on PKC inhibition , which may be an important mechanism for antimanic agents in general .
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Intervention_Pharmacological
Verapamil
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Intervention_Pharmacological
lithium
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Intervention_Pharmacological
lithium
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Intervention_Pharmacological
( lithium , valproate )
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Intervention_Pharmacological
some novel ( tamoxifen ) antimanic agents
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Intervention_Pharmacological
Verapamil
41108
Intervention_Pharmacological
Verapamil
41109
Intervention_Pharmacological
verapamil , used alone or as an adjunctive treatment
41110
Intervention_Pharmacological
lithium
41111
Intervention_Pharmacological
lithium
41112
Intervention_Pharmacological
verapamil
41113
Intervention_Pharmacological
continued-lithium
41114
Intervention_Pharmacological
combined verapamil/lithium
41115
Intervention_Pharmacological
verapamil
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Intervention_Pharmacological
continued-lithium
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Intervention_Pharmacological
verapamil
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Intervention_Pharmacological
verapamil plus lithium
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Intervention_Pharmacological
verapamil
41120
Intervention_Pharmacological
lithium
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Outcome_Mental
Fisher 's Exact test
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Outcome_Mental
Mania ratings