TCPR: Dr. Freeman, you were the chair of a task force organized by the APA several years ago to study complementary and alternative treatments in psychiatry. How did you become interested in this area?
Dr. Freeman: I have done research with omega-3 fatty acids and mood disorders since my residency. I became more involved in the area of complementary and alternative medicine (CAM) because of an interest in perinatal psychiatry. There is a particularly compelling need for non-pharmacologic treatments for women who are trying to conceive, and who are pregnant or breastfeeding.
TCPR: And what was the goal of the APA task force?
Dr. Freeman: We were charged with creating an informative, clinically relevant report for practicing psychiatrists. We focused on major depression because that is the area where there has been the greatest number of systematic and controlled studies of CAM treatments in psychiatry.
TCPR: What qualifies as CAM?
Dr. Freeman: Defining CAM is challenging. One of the things that makes it so hard to have a concrete discussion on CAM is that it means different things to different people. It has a lay definition that basically means “any sort of treatment that is not considered mainstream.” There is an epidemiologic study showing that 40 percent of adults in this country use at least one CAM treatment each year, and that Americans spend about 34 billion dollars out of pocket on CAM treatments (Barnes et al, CDC National Health Statistics Report #12;2007–2008). We need to inquire because patients may not tell their psychiatrists about CAM use, because they just don’t think it is relevant or sometimes patients think we won’t approve. When we ask about what medicines a patient is taking, we might expect patients would tell us about supplements, but if we don’t specifically ask about supplements, they probably won’t mention them.
TCPR: When we ask our patients about these remedies, how do you suggest we phrase the question? Should we ask about “dietary supplements”? Do most patients even know what we mean by that?
Dr. Freeman: I tend to ask this in two different ways, in two different parts of the initial interview. When I ask what medications patients are taking, I ask about any supplements or vitamins. Later in the interview, when I ask about use of alcohol, tobacco, and caffeine, I ask again about any supplements or “herbal remedies” or “nontraditional treatments.” It is interesting because if I phrase the question in a slightly different way, I may get different answers.
TCPR: What are some of the CAM remedies that you feel comfortable enough with the evidence base to recommend them to your patients?
Dr. Freeman: I recommend exercise to almost every patient. It is rare that there is any contraindication to exercise. There haven’t been large scale trials of exercise monotherapy that have been rigorously conducted and controlled for validated major depressive disorder, but the literature is compelling that there appear to be antidepressants effects (see for example Lawlor DA and Hopker SW, BMJ 2001;322:763–767). One of the tough things about getting evidence for exercise in the treatment of any disorder is that it is hard to really have a placebo controlled trial of exercise—some sort of condition where people don’t know they are exercising.
TCPR: Any particular kind of exercise?
Dr. Freeman: It depends on exercise experience, the weather, finances (can they afford a gym membership, equipment, etc). For most patients, walking is doable, and is oftentimes more than they are already doing. I usually recommend, if they are not already exercising, 20 to 30 minutes of walking three to four times a week to start with.
TCPR: What else do you recommend?
Dr. Freeman: I recommend omega-3 fatty acids to most patients with mood disorders. The area where there is the most evidence is using omega-3 fatty acids as augmentation to a standard antidepressant (Lin PY and Su KP, J Clin Psychiatry 2007;68:1056–1061). The evidence for anxiety disorders is much less compelling. Some of the most famous benefits of omega-3 fatty acids are cardiovascular benefits, including decreasing high triglycerides. Considering that some of the medications that we use have metabolic and lipid effects, I think it makes sense for patients who take those drugs to supplement with omega-3 fatty acids (Mozaffarian D and Wu JH, J Am Coll Cardiol 2011;58(20):2047–2067). This is an area in which we are currently conducting research.
TCPR: Which kind of omega-3s should we be recommending?
Dr. Freeman: The ones that have been studied for depression are eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA). I recommend a supplement that contains EPA plus DHA, in a ratio of at least 2:1 or 3:2 of EPA to DHA. I tell patients to aim for a dose of the EPA plus the DHA to equal at least a gram a day. Some positive studies have used even higher ratios of EPA : DHA. The doses that have been demonstrated most consistently to be helpful are in the lower dose range, so about 1 to 2 grams a day versus some of the studies that have looked at enormous doses like 6 to 9 grams a day (Freeman MP et al, J Clin Psychiatry 2006;67:1954–1067). And I also tell patients to steer away from most of the plant source products, which is what you find in supplemented foods, such as enriched breads. These products contain alpha-linolenic acid, also an omega-3 fatty acid, but not the kind that has been associated with mood benefits.
TCPR: A lot of people say, “Well I eat salmon every day.” Is that enough?
Dr. Freeman: Yes. Salmon is a great source of omega-3 fatty acids, and if someone is eating salmon every day there would be no need to supplement. That is just not typical of the American diet. There have been concerns raised about some fish and mercury, and fish intake has fallen, particularly among women of childbearing potential.
TCPR: So exercise and omega-3 fatty acids. What else do you recommend?
Dr. Freeman: For patients with depression treated with antidepressants, I recommend that they take a standard multivitamin with folate (ie folic acid). There have been augmentation studies showing a benefit from adding folic acid in typical doses to an SSRI (Freeman MP et al, Journal of Clinical Psychiatry 2010;71(6):669–681). This is particularly true among women. There was a randomized controlled trial of patients on fluoxetine who were randomized to get either folate or placebo, and the folate was significantly better than placebo, but the effect was more robust among women (Coppen A and Bailey J, J Affect Disord 2000;60:121–130). For women of reproductive age, it is a good idea to take folic acid to decrease the likelihood of birth defects if they get pregnant.
TCPR: What is a standard dose of folate?
Dr. Freeman: The typical dose in a multivitamin is about 400 to 500 mcg. The study that showed significant benefit (and more robust benefit among women) used 500 mcg.
TCPR: Is there anything else you recommend to patients?
Dr. Freeman: For some patients who prefer not to be on a standard antidepressant, the evidence for SAMe (S-adenosyl L-methionine) as a monotherapy is good. There have been quite a number of studies and meta-analyses showing a benefit of SAMe as a monotherapy compared to placebo, at least equivalent in effectiveness to some of the older antidepressants (S-Adenosyl L-Methionine (SAMe) for Depression, Osteoarthritis, and Liver Disease. Agency for Healthcare Research and Quality, Rockville, MD, August 2002). Like many CAM treatments, insurance is not likely to reimburse for SAMe, and some patients have noted it is expensive, so it may have limited usefulness.
TCPR: Do you recommend anything else that is not an oral supplement?
Dr. Freeman: I recommend light boxes often, especially if there is a history of seasonal mood worsening. The main caution with light therapy is that if there is any underlying bipolar diathesis, the patient has to be carefully monitored for symptoms of hypomania, and all patients should be alerted to stop using if they are feeling too revved up. In Massachusetts, where I practice, there are a lot of patients who get seasonal mood worsening, but light boxes have also been shown to be beneficial for depression that is not seasonal (Golden RN et al, Am J Psych 2005;162:656–662). The data for acupuncture in depression have not been consistent, but there have been a couple of well-designed studies showing benefit for depression in pregnancy (Manber R et al, Obstet Gynecol 2010;115(3):511–520). Sometimes patients have to decide where to invest their time and their resources, among all of the available options. If patients are not in psychotherapy, I usually advise them to pursue that first.
TCPR: And then there is the whole field of relaxation exercises, massages, etc. Do you ever recommend those?
Dr. Freeman: There have been studies of massage for depression during pregnancy that had some really interesting results. There was one study where all the patients got psychotherapy and then half were randomized to also get massage as well. Both groups did well in the study, but the groups that received massage had more adherence to the protocol, which seems like it would be an expected outcome (Field T, J Psychosomatic Obstet Gynaecol 1999;20(1):31–38). Another study showed significant benefit, though there are certainly a lot of variables in that (Field T, J Psychosomatic Obstet Gynaecol 2004;25(2):115–122).
TCPR: Thank you, Dr. Freeman.