Calcium Channel Inhibitors

For a more detailed discussion of this topic, see Calcium Channel Inhibitors, Sec. 31.13, p. 3065 in Comprehensive Textbook of Psychiatry, 9th Edition.

The intracellular calcium ion regulates activity of multiple neurotransmitters such as serotonin and dopamine, and that action may account for its role as a treatment in mood disorders. Calcium channel inhibitors are used in psychiatry as antimanic agents for persons who are refractory to, or cannot tolerate, treatment with first-line mood-stabilizing agents such as lithium (Eskalith), carbamazapine (Tegretol), and divalproex (Depakote). Calcium channel inhibitors include nifedipine (Procardia, Adalat), nimodipine (Nimotop), isradipine (DynaCirc), amlodipine (Norvasc, Lotrel), nicardipine (Cardene), nisoldipine (Sular), nitrendipine, and verapamil (Calan). They are used for control of mania and ultradian bipolar disorder (mood cycling in less than 24 hours).

Pharmacologic Actions

The calcium channel inhibitors are nearly completely absorbed after oral use, with significant first-pass hepatic metabolism. Considerable intraindividual and interindividual variations are seen in the plasma concentrations of the drugs after a single dose. Peak plasma levels of most of these agents are achieved within 30 minutes. Amlodipine does not reach peak plasma levels for about 6 hours. The half-life of verapamil after the first dose is 2 to 8 hours; the half-life increases to 5 to 12 hours after the first few days of therapy. The half-lives of the other calcium channel blockers (CCBs) range from 1 to 2 hours for nimodipine and isradipine to 30 to 50 hours for amlodipine (Table 11-1).

The primary mechanism of action of CCBs in bipolar illness is not known. The calcium channel inhibitors discussed in this section inhibit the influx of calcium into neurons through L-type (long-acting) voltage-dependent calcium channels.

Therapeutic Indications

Bipolar Disorder

Nimodipine and verapamil have been demonstrated to be effective as maintenance therapy in persons with bipolar illness. Patients who respond to lithium appear to also respond to treatment with verapamil. Nimodipine may be useful for ultradian cycling and recurrent brief depression. The clinician should begin treatment with a short-acting drug such as nimodipine or isradipine, beginning with a low dosage and increasing the dosage every 4 to 5 days until a clinical response is seen or adverse effects appear. When symptoms are controlled, a longer-acting drug, such as amlodipine, can be substituted as maintenance therapy. Failure to respond to
verapamil does not exclude a favorable response to one of the other drugs. Verapamil has been shown to prevent antidepressant-induced mania. The CCBs can be combined with other agents, such as carbamazepine, in patients who are partial responders to monotherapy.

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