TCR: My readers would be in interested in knowing a little bit about your background and how you came to be interested in natural medications for psychiatry.
Dr. Mischoulon: It was kind of serendipitous. I went to medical school at Boston University School of Medicine, where I got my M.D. and also a PhD in biochemistry. I did my residency in psychiatry at Mass General, and as chief resident, one of the duties was to run a lecture series on a particular subject of interest. Jerry Rosenbaum, who was then outpatient director and my supervisor as chief resident, had been recently given a book about herbal remedies for various medical indications. The book had a small chapter on psychiatric drugs, and Jerry thought that would be a great focus for a lecture series. At the time, I was also thinking about fellowship applications for continued work in depression research, and Maurizio Fava suggested that we do something with natural remedies. He and Jerry already had a grant on St. John's Wort for major depression and Maurizio thought that it might be a good niche for me. So, I did some more research on the topic and that is what I have been focusing on ever since.

TCR: Interesting. Have you found that you have been using natural medications in your practice?
Dr. Mischoulon: I use them, but I am careful about who I recommend them for. Since I work in a tertiary care center, I see more severely ill patients, and most of the research on these natural and complementary remedies suggests that they are most effective for people with milder illness. On the other hand, there are some very ill patients who have tried just about everything that is approved by the FDA, and either they just didn't respond to it or they couldn't tolerate the drugs because of side effects. Those are individuals that I might consider as candidates to use alternatives remedies.

“The theory is that humans, in order to function at their best, require a critical ratio of omega-3 to omega-6 fatty acids and perhaps the reason why there is so much depression in this country is because this ratio is skewed.”
- David Mischoulon

TCR: I know you've done some writing on omega-3 fatty acids. Can you explain what they are and how we should use them?
Dr. Mischoulon: The omega-3s are a family of essential fatty acids. They have a well-established body of evidence about their cardiovascular benefits. But more recently, there have been a number of studies suggesting that they may be effective for a number of different psychiatric conditions. Initially, Andrew Stoll found that a mixture of the omega-3s called EPA and DHA was effective for bipolar disorder (Arch Gen Psychiatry 1999; 56:407-412) and a couple of other groups have been looking at omega-3s for treatment of depression, borderline personality disorder, and schizophrenia. The preliminary results are encouraging and suggest that omega-3s may have a wide application in psychiatry, so I think it will be of much interest to psychiatrists to learn more about them.

TCR: There is also omega-6, isn't there?
Dr. Mischoulon: omega-6 fatty acids are found primarily in vegetable oils. In fact, one of the theories about the use of Omega-3's is that the American diet, the Western diet in general, tends to be very heavy on the Omega-6 fatty acids relative to the omega-3 fatty acids. For example, Americans tend to eat a lot of foods that contain highly processed vegetable oils, but relatively little fish. Historically, our primitive ancestors tended to eat more fish, so their diet was richer in omega-3's than omega-6's. So the theory is that humans, in order to function at their best, require a critical ratio of omega-3 to omega-6 and perhaps the reason why there is so much depression in this country is because this ratio is skewed. In theory, by correcting this imbalance, by giving omega-3 supplements, we might help to reverse some of these psychiatric disorders.

TCR: Are there any significant side effects of omega-3s?
Dr. Mischoulon: Yes, some patients have reported stomach upset and a fishy taste in the mouth when taking omega-3s. There have been some anecdotal reports of bipolar patients who take omega-3s without a concomitant mood stabilizer who have cycled into mania. In Dr. Stoll's study, he gave the omega-3 primarily as an adjunct to treatment. These patients were already taking mood stabilizers. In fact, most of the research on the omega-3s is as adjunct treatment, not as monotherapy. So, one of the things we emphasize is that bipolar patients who are interested in omega-3s should use them under a physician's supervision and should probably be on a mood stabilizer as well.

TCR: Given that there has been some evidence for omega-3's effectiveness in depression, bipolar disorder, borderline personality disorder, and schizophrenia, some clinicians would be inclined to recommend it to most of their patients, since those groups make up the majority of most psychiatric practices.
Dr. Mischoulon: Yes, a very good argument can be made for that. I find myself encouraging more of my patients to take omega-3 supplements because there is already the well-documented cardiovascular benefit. So just by taking omega-3 you are potentially improving your general health status. Most of the recent evidence on the omega-3s is that low doses (500 mg to 1000 mg) are effective.

TCR: And how much fish would you have to eat to get your daily dose of omega-3?
Dr. Mischoulon: If you are taking a gram a day of omega-3, that is probably equivalent to eating a salmon dinner three or four times a week. So, I tell my patients, "If you like fish, you certainly can benefit by eating more of it, but if we are looking at it from the standpoint of trying to attack a serious depression, then probably the supplementation is the way to go." It is easier to get a depressed patient to take a pill than to make a lifestyle change.

TCR: On the subject of depression, what's your opinion on St. John's Wort?
Dr. Mischoulon: There are thirty or so European studies that say it is effective, and there are about probably a half dozen or so American studies that are not very positive.

TCR: So the jury is still out?
Dr. Mischoulon: Yes. But to understand St. John's Wort in context, we have to know something about the FDA. For the FDA to approve an antidepressant, it requires two well-designed studies showing that it is truly better than placebo. Now that doesn't mean that there can't be studies saying that it is no better than placebo. Take Paxil (paroxetine), for example. Of the first nine controlled studies that were done, only two of them suggested that Paxil was better than placebo; the other seven showed that it was no better than placebo. The problem is that many negative studies don't get published, either because the manufacturer sponsored it and doesn't want to publish it, or because most journals don't think negative studies are "sexy" enough. So a lot of drugs that are widely considered to be effective may not be as effective as we think. So, what I think may be going on with St. John's Wort is the same thing -- that we happen to be getting some studies that are saying that it is not as effective as the earlier studies suggested. I think we have to take all of it with a grain of salt.

TCR: What about the controversial kava?
Dr. Mischoulon: Well, a couple of years ago there were at least two dozen reports of severe liver toxicity, including a couple of cases so extreme that a liver transplant was required. So that caused an uproar in the media and as a result of that kava has been banned in number of countries in Europe and I believe in Canada as well.

TCR: But it appears to still be available here.
Dr. Mischoulon: Yes, kava is still available in the U.S., and the FDA is investigating it. While the FDA does not formally regulate natural medications, if they have enough evidence that a certain medication could be harmful, whether it be natural or synthetic, they have the authority to remove it from the market. So, the FDA, could in theory, ban kava the way they banned ephedra earlier this year.

TCR: So, what do you tell your patients about kava?
Dr. Mischoulon: In general, I am not recommending it to anyone. What I do tell someone, if they have a compelling reason to take kava, is they should first always do so under a doctor's supervision. And, secondly, no one who has any history of liver disease or alcoholism or who is taking any drugs that are potentially toxic to the liver, like Depakote, should take kava; I think it is just too dangerous. Until we know more about the extent of this toxicity, I encourage people to be extremely careful.

TCR: Any parting words of wisdom on natural medications?
Dr. Mischoulon: Generally, what I say to everyone is that these medications are promising, and with time they will probably have an established niche in psychopharmacology. But for the time being, it is very important that people who use them do so under a doctor's supervision because we still don't know enough about their efficacy, as well as safety and drug-drug interactions. To prevent any tragic consequences like those we have seen with Kava or with some of the St. John's Wort interactions, it is always better to have a doctor on your team. That is what I recommend to everyone.