Calcium Channel Blockers for
verapamil, isradipine ( and nimodipine)
Verapamil has been around a long time, and as a result there are multiple generics around (thus no trade name above). It's in the class of blood pressure medications called "calcium channel blockers".
While all that follows is still largely appropriate, one new study reaffirms a possible role for verapamil -- not necessarily by itself, but in combination with lithium.Mallinger Patients who had not responded to lithium alone were switched to verapamil alone. There was no significant improvement. However, when they were instead switched to a combination of the two agents, there was substantial improvement. This was a difficult challenge, you see: patients who had already improved on lithium were weeded out. Only those who were more difficult to treat progressed on in this study.
However, this is just one more study, added to the mixture of results below. The role of verapamil in the treatment of bipolar disorder is still not clear.
A long time ago several randomized trials were done which confirmed that verapamil had "mood stabilizing" properties. This may be related to it's action on calcium channels, the small pores in cells that allow calcium to move in and out. Calcium seems to be part of the story of what causes bipolar disorder (for more on that subject, go to that heading from the Diagnosis Details page). However, there were two "negative" trials later, meaning that the data did not show verapamil had mood stabilizing effects.
As a result of this "mixed" evidence, interest in verapamil has been very limited (in addition, because it is available in multiple generics, there is no manufacturer willing to pump money into research and advertising for this medication, so it "looks" less attractive than it really is). I tried it with several patients and was not particularly impressed myself.
Then I met Dr. Steve Dubovsky, an eminent researcher from University of Colorado, who had done much of the original work on this medication. He said "you have to use the non-slow-release version!" So, I've since tried it again in that form, and sure enough, I'm pretty sure I've seen people respond to it, as with other recognized mood stabilizers. Then, a recent surge in interest has come along from several researchers concerned about the effects of conventional mood stabilizers on women's hormones. They point out that verapamil may also be safe to use in pregnancy, which is not true for any of the "big three" (lithium, Depakote, Tegretol/Trileptal). And they have just published a study showing further support (although in "open trial" design, there were actually quite a few more patients in this study than in Dubovsky's original workDubovsky; not conclusive, but strongly supportive evidence) for verapamil's effectiveness in women with bipolar disorder. Some of these women were pregnant.Wisner et al They used the non-slow-release form, if I am interpreting their methods correctly.
There is some concern about immediate-release versions of verapamil having a negative effect on heart function. American Academy... But this issue is still being studied (e.g. Hilleman) and does not appear to be an issue in terms of the use of this medication as a bipolar disorder treatment. For a patient who has known heart disease, or for a patient who is already on a blood pressure medication, a discussion with her/his doctor prior to starting verapamil in either form would probably be wise.
Where verapamil fits in the list of mood stabilizers is unclear because we have so little information on it, and that which we have is conflicting (e.g. see a review by Janicak, 2000). However, it carries relatively few risks compared to other commonly used mood stabilizers and must be kept in mind for cases in which the better-studied medications have not been effective or tolerable. It is also a consideration for a woman contemplating pregnancy, if it can be established before the pregnancy that this is an effective agent, which can take months or even years depending on the woman's usual course of bipolar symptoms.
Isradipine is another calcium channel blocker. There is one observation that has been published by Bob Post and colleagues at the NIMH which apparently represents the entire literature base for use of this agent:
When verapamil was blindly substituted for nimodipine, two BP patients failed to maintain improvement but responded again to nimodipine and remained well with a blind transition to another dihydropyridine L-type calcium channel blocker (CCB), isradipine.Pazzaglia
There are no other articles found searching "isradipine bipolar" on PUB MED or Google (7/2004).
Both isradipine and verapamil are in the FDA's Pregnancy Category C, which means that the medication is neither clearly safe, nor clearly unsafe.
Nimodipine was the main calcium channel blocker used in the study described immediately above. But it is extremely expensive -- $1200 for a 21-day course, several years ago -- and must be taken every four hours, which may be why we don't see it in regular use in bipolar disorder. I have never seen it used outside a research study, even on the lists of "other medications" being used by bipolar specialty clinics when they report on some new treatment. Many unusual medications turn up on those lists, but I've never seen nimodipine there.
In one thorough review, multiple individual case descriptions of very good results are presented.Goodnick Better yet, the study above by Pazzaglia (from Bob Post's group) is a "randomized trial" of sorts, in that patients were switched between two drugs (no placebo group, but a plausible comparison drug was used as the comparator), remaining "blind" to what medication they were taking. In this and other small series of patients, nimodipine does indeed appear to work, sometimes extremely well. But at that cost -- no wonder Post's NIMH group tried to switch patients to a different calcium channel blocker to see if it would work as well! (I just found a version online: at $37 for 30 of the 30 mg pills, to reach the dose often used in these studies (360 mg) would cost $150 per day.)