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• W65928263 abstract "Abstract The calcium channel blocker verapamil has been extensively studied for the treatment of mania, with the evidence suggesting that verapamil is effective for controlling mania. Nimodipine has also shown specific utility in patients with rapid cycles. Clinicians faced with a patient with mania who does not respond to other antimania agents may consider using verapamil as an adjunctive therapy. This article reviews the reasons for a surge of interest in these drugs and their underutilisation in clinical practice. Renewed investigation and more research to assess their efficacy and safety are warranted in the third millennium. Key words: Bipolar disorder, Calcium channel blockers, Nimodipine, Verapamil Introduction For the past 2 decades, there has been a search for an effective treatment for the 20% to 40% of patients with classic mania who do not respond to treatment with lithium. (1) In addition, some patients cannot tolerate the side effects of lithium. (2) The need for regular monitoring of serum lithium concentrations, a narrow therapeutic range, and problems with compliance further complicate long-term treatment with lithium. Lithium is generally not prescribed for pregnant women. (3) Certain diagnostic subtypes (e.g., dysphoric mania, rapid cycle) have shown a poor response to lithium. This situation has necessitated the availability of both adjunctive and alternative treatment options to lithium, some of which have been borrowed from other medical specialties. (4) The relatively incisive and specific affect-modulating action of lithium has instigated a surge of interest in the role of other cations--particularly calcium--in the pathogenesis and therapy of mood disorders. Clinical trials have also generated interest and shown that calcium channel blockers have maintained their role in the treatment of mania. (5,6) Two classes of calcium channel blockers have been extensively studied to elucidate their role in mood disorders. These compounds include widely recognised phenylalkylamines such as verapamil and dihydropyridine types such as nifedipine, isradipine, and nimodipine. These 2 types of calcium channel blockers differ from each other in their biochemical and physiological effects on cardiac cells and neurones. Phenylalkylamines gain access to the calcium channel less rapidly than dihydropyridine types. Dihydropyridines are highly lipid-soluble and associated with dopamine overflow in the nucleus accumbens, whereas phenylalkylamines lack these characteristics. Mood Disturbances with Altered Calcium Metabolism Mood disorder is a frequent complication of a primary disorder of calcium metabolism. Manic illness may arise from disorders in calcium-regulated functions. Calcium metabolism has been reported to be disturbed in various forms of affective disorders. In a study in which calcium metabolism was measured in 29 patients with unipolar disorder, 14 with bipolar depression, 11 with mania, and 10 healthy controls, it was found that the plasma calcium level was lower in patients with unipolar disorder and mania than in the controls. (7) Patients with unipolar and bipolar disorders also showed different types of disturbances in calcium metabolism. Altered intracellular calcium homeostasis in the blood cells of patients with bipolar disorder has been studied. (8) Data suggest that storage-operated calcium channels may be the source of the elevated intracellular calcium level in platelets and lymphocytes of patients with bipolar disorder. Anergy and lethargy occur, almost universally, in hypercalcaemic disorders such as hyperparathyroidism (9) or hypervitaminosis D. (10) Extreme cycles of mood and activity have been described in various hypocalcaemic conditions, which may be idiopathic or induced by surgery, or which may occur with pseudohypoparathyroidism. (11) Prompt resolution of mood symptoms usually follows medical and surgical restoration of normal calcium metabolism. …" @default.
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• W65928263 date "2004-06-01" @default.
• W65928263 modified "2023-09-28" @default.
• W65928263 title "Renewed Interest in Calcium Channel Blockers as Antimania Agents in the Third Millennium" @default.
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