Although there are many medications on the market approved for the treatment of depression, such as Prozac and Zoloft to name a few, they have been shown to be effective for major depression, a more serious condition. For milder but persistent depression (called "dysthymia" or "minor depression") it isn't clear exactly what treatments (pills or psychotherapy) are most appropriate. At Columbia University/New York State Psychiatric Institute, our research team has been studying alternative treatments for mild depression, and are now exploring the effects of the hormone DHEA for people with HIV/AIDS.

What Is Clinical Depression?

Psychiatrists generally refer to three main categories of depressive disorder which differ in severity and duration. Major depression includes more different kinds of symptoms that are more severe than "minor" depression. "Dysthymia" is a term used for a more chronic and generally milder set of depressive symptoms.

For people who are HIV-positive and also have depressive symptoms, the first task is to sort out whether they are likely due to HIV, medication side effects, or are "psychological." For example, one of the standard psychiatric symptoms of depression is fatigue. In HIV/AIDS, fatigue also may be due to an HIV-related condition, or HIV-related medications such as AZT or interleukin-2. Such distinctions generally can be made but require familiarity with psychiatric criteria for depression, characteristics of HIV illness and also side effects associated with HIV-related medications.

Some symptoms of depression are more closely related to thoughts and feelings (such as feeling sad most of the day, most days; loss of interest in all or nearly all usually pleasurable activities; feeling guilty, problems with concentration or indecisiveness, recurrent thoughts of death) while others are considered "somatic" and represent physical changes such as loss of appetite (or overeating), insomnia (or sleeping too much), fatigue, and slowed or overactive activity level. However, the term depressive "disorder" is only made when these symptoms cluster together, last at least two weeks at a time, and also interfere with everyday events and activities.

What Are Conventional Treatments?

The condition most often studied in clinical trials is major depression. Antidepressant medication has been shown to be effective for most people, most of the time; while many are marketed, they differ primarily in terms of side effects and in general are all equally effective. It is estimated that about 60 to 70 percent of patients with major depression experience improved mood after 6 to 8 weeks of antidepressant medication. Similar response rates have been reported with interpersonal psychotherapy and cognitive-behavioral therapy, both of which are standardized and have been systematically studied.

The diagnosis of major depression requires the presence of at least four kinds of symptoms (in addition to depressed mood), including loss of interest in most activities, disturbances of sleep and eating/weight, guilt, thoughts of suicide, impaired concentration and either slowed-down or agitated behavior.

Minor depression and dysthymia require fewer of the same symptoms and tend to be more chronic, in contrast to major depression which sometimes has a more clearcut onset and end. HIV-positive people who have some symptoms of depression that do not represent major depression often are troubled by low energy, are less interested in other people or in activities that used to be enjoyable. They may also experience reduced sexual desire and loss of muscle mass (the last two problems are not included in the official psychiatric diagnosis of depression).

Steroids as Treatment for Depression

For several years, our group has studied the effects of testosterone, an anabolic steroid, for problems such as loss of sexual desire, low energy, loss of muscle mass and depressed mood. We continue to conduct a study comparing the effects on mood of testosterone and Prozac for men with major depression. We have found testosterone to be helpful and well accepted among the more than 200 men we have studied so far.

Testosterone does have limitations, however. First, it is approved for use only with men. Second, for men with prostate problems it is not safe. For men with naturally high levels of testosterone, it may not be indicated. Finally, it is classified as a controlled substance and some doctors and hospitals are reluctant to prescribe testosterone for this reason.

Because we wanted to identify a treatment that is appropriate for women as well as for men, and is more readily accessible, we became interested in DHEA (dehydroepiandrosterone), which is also a steroid but in this country is not considered a drug at all. It is classified as a nutritional supplement which does not require any prescription.

DHEA is a hormone produced in abundance in the body. Despite several hundred animal and human studies conducted over the past 20 years, the major biologic functions of DHEA remain unclear. Declining levels of DHEA have been associated with aging and a variety of chronic diseases including cardiovascular disease and autoimmune diseases.

In HIV/AIDS, lower levels are found in patients with advanced illness in studies that we and others have conducted. We found that DHEA levels are lower in those with lower CD4 cell counts and higher viral loads, and with more severe illness symptoms. Lower DHEA levels were associated with mortality over a one-year period. In addition, lower levels of DHEA have been found in people with lipodystrophy (i.e., redistribution of fat in the body). It is not now known whether these lower levels of DHEA contribute as a cause or are the consequence of such conditions.

Small studies suggest that DHEA tablets may be helpful with problems such as low libido, loss of muscle mass, and memory problems. DHEA appears to increase testosterone levels in women but not in men, according to the very limited available evidence. However, other studies did not find such associations, so that further research is needed.

Several small studies have shown that DHEA is a useful treatment for depression among people who are HIV-negative, and that it increases psychological well-being even when people are getting DHEA treatment for reasons other than depression. We conducted a pilot study a couple of years ago with HIV-positive people in which all participants were given DHEA to treat symptoms of minor depression. About three-quarters of those who completed the eight-week study reported improved mood and energy, and we also found increased muscle mass using bioelectric impedance analysis. However, the findings are suggestive rather than convincing because of our small sample (32 men and women) and the open-label research design, where everyone knew they were getting DHEA. So the answer is, we're not sure if DHEA is helpful.

An Ongoing Study

To learn more about DHEA and depression, we are currently conducting a more rigorous trial. The study is intended for men and women who have mild but persistent depression including loss of interest in formerly pleasurable activities, sad mood more days than not, and related symptoms which may include fatigue, appetite and sleep problems among others. All participants are offered four months of DHEA treatment, either immediately or after eight weeks. At the beginning, half the participants are randomly assigned to get placebo (inactive) pills for the first eight weeks of this "double blind" trial in which neither the patient nor the doctor knows whether the pills are DHEA or placebo. Additional treatment, as clinically indicated, is provided for up to six months total.

Because DHEA is not an approved treatment for major depression, and there are effective antidepressants available on the market, this study is not meant for people with more serious forms of depression. Other "exclusion criteria" are current use of standard antidepressants, and current problems with recreational drugs.

We are also studying the relation between DHEA serum (blood) levels and other hormones and lipids associated with lipodystrophy, before and after treatment with DHEA. This part of the study is being conducted in collaboration with doctors at Cornell and Beth Isr ael Medical Centers. Our goal is to learn more about how DHEA works, and its relationship to other hormones including testosterone.

DHEA does not require a prescription and is sold in health food stores in low doses (usually 25 or 50mg pills). Because it is not a "drug," the manufacturers do not have to pass inspection about the contents of their pills, which may contain more or less DHEA. In our study, we use higher doses, and have obtained from a pharmacist in Colorado a supply of DHEA approved for purity and safety by the Food and Drug Administration. This pharmacist also sells DHEA by mail.

If found effective in ameliorating depression, DHEA may extend treatment options for groups within the HIV population for whom standard antidepressants or testosterone may be unsuitable or unacceptable. It may be a particularly suitable treatment for HIV-positive people because of the association between lower levels of DHEA and HIV illness progression and lipodystrophy.

How to Participate

Potential participants are first screened over the telephone. Those who appear eligible come to our offices at New York-Presbyterian Medical Center (in uptown Manhattan) for an initial evaluation. If it seems likely that the study will be helpful and you are interested, the study is explained in detail and the initial study visits are scheduled. When you meet with the study psychiatrist, and discuss the study with him, you decide whether to sign the consent form and begin treatment at that time. Visits are first weekly, and then biweekly during the eight-week trial. After that, the frequency of visits is up to you and the study doctor and depends on how well you are doing.

If you are interested in participating in our ongoing study, call me at 212-543-5762.

The Research Notebook section welcomes articles from established HIV/AIDS research programs in the New York City area which may be of interest to Body Positive readers. Please submit article ideas to bpmagazine@bodypos.org.

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