Certain calcium channel blockers are also being studied for use in the treatment of bipolar disorder as mood stabilizers. One reason for the interest in this application is that calcium channel blockers are far safer for use during pregnancy than lithium or any of the anticonvulsants commonly used to stabilize moods and treat mania. Some of these medications may also be effective in treating neuroleptic-induced tardive dyskinesia, a side effect of many antipsychotics.
The calcium channel blocking agents that are being used to treat bipolar disorder include:
- Verapamil - brand names Calan, Isoptin
- Nimodipine - brand name Nimotop
- Diltiazem - brand names Cardizem, Cartia, Dilacor, Tiazac
- Nifedipine - brand names Procardia, Adalat (mentioned, but no clinical studies found for BP treatment)
Verapamil is readily available in generic form for a reasonable price. Dr. Jim Phelps of PsychEducation.org reports that he had no success using verapamil until Dr. Steve Dubovsky, who had done extensive research on verapamil for bipolar disorder, told him it was necessary to use the non-slow-release version. Using that version, he says he is "pretty sure" he has seen people respond to it. A study of 37 women by Wisner, et al, showed a 94 percent response rate for mania, but there was far less response for depression. The researchers concluded, "A definitive randomized clinical trial [of verapamil] for patients with bipolar disorder is compelling and urgently needed."
Nimodipine
Dr. Phelps refers to a study by Goodnick that concluded: "These two properties - calcium channel blockade and anticonvulsant benefits have been applied with success to mood disorder treatment. Although found helpful nearly a decade ago for uncomplicated mania, nimodipine may have particular benefits for those diagnostic subclasses of bipolar disorder most resistant to therapy, e.g., ultra-rapid-cycling bipolars and brief recurrent depressions." However, as Dr. Phelps points out, the high cost of this medicine, even in generic form, makes it difficult to prescribe, especially since a high dosage is needed for effectiveness and the drug must be taken four times a day. I can't follow his math (where he calculates it would cost $150 per day), but I did find that to achieve a dosage of 360 mg, four times a day, would take 48 pills per day. These would, at the lowest cost I found ($174 for 240 pills), cost $1,044 for a 30-day supply.
Diltiazem
Diltiazem has not been studied in depth, but Silverstone and Birkett, in a small study using a slow-release form of the drug as additional therapy along with other, non-specified medications, reported: "There was a statistically significant decrease in the frequency and severity of both manic and depressive episodes in these patients after they started treatment with diltiazem, compared with the period before they started treatment with diltiazem (p < 0.001). There was no evidence of side effects requiring patient withdrawal or of drug interactions."
Precautions
- The effects of Tegretol (carbamazepine) may be increased when used with some calcium channel blockers.
- Extended release capsules or tablets should be swallowed whole, without crushing or chewing.
- Rarely, some patients may experience tender, swelling or bleeding gums. Regular brushing and flossing are important, as is seeing a dentist on a regular basis.
- Diltiazem and verapamil: learn to check your pulse and do so regularly. If it is much slower than your usual rate, or drops below 50 beats per minute, check with your doctor.
- Elderly patients may need a lower dose when being treated with one of these medications.
A 1993 study found mixed results from using calcium channel blockers to reduce the symptoms of tardive dyskinesia. The researchers reported, "Positive findings have been reported for nifedipine, verapamil, and diltiazem; nifedipine may be the most efficacious treatment and diltiazem the least. It appears that patients with TD who can tolerate higher doses of calcium-channel blockers may respond more favorably to treatment." A small 1997 double-blind study found that "[g]lobal TD ratings during nifedipine treatment were significantly improved from baseline." It is perhaps surprising that so little research has been done in this area, given the low rate of side effects from calcium channel blockers compared to some other medications used to treat tardive dyskinesia.
References:
Mayo Clinic. Calcium Channel Blockers 2005, updated 2008. 1/5/07.
PsychEducation.org. Calcium Channel Blockers for Bipolar Disorder: verapamil, isradipine (and nimodipine) 2006. 1/5/07.
Wisner, K.L., et al. Verapamil treatment for women with bipolar disorder. Biological Psychiatry 1 May 2002: 745-52. 1/5/07.
Goodnick, P.J. The use of nimodipine in the treatment of mood disorders. Bipolar Disorders 2 Sept 2000: 165-73. 1/5/07.
Silverstone, P.H., and L. Birkett. Diltiazem as augmentation therapy in patients with treatment-resistant bipolar disorder: a retrospective study. Journal of Psychiatry and Neuroscience May 2000: 276-280. 1/5/07.
Cates, M., Lusk, K. and Wells, B.G. Are calcium-channel blockers effective in the treatment of tardive dyskinesia? The Annals of Pharmacotherapy 27 Feb 1993: 191-6. 1/7/07.
McCarthy, M.F., et al. "The effect of nifedipine on tardive dyskinesia: a double blind study in eighteen patients." Schizophrenia Research March 1997: 271. 1/7/07.
