Anti-Depressant Research Must Safely Include Suicidal People

By DeQuincy A. Lezine, Ph.D.

Patients in antidepressant drug trials are not representative of patients in the United States who might need antidepressant medication. That is the conclusion of a recent study by Dr. Madhukar Trivedi of the University of Texas Southwestern Medical Center and colleagues appearing in the May issue of the American Journal of Psychiatry. The report comes from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, funded by the National Institute of Mental Health (NIMH). The $35 million study included 2,855 patients with depression and lasted six years.

MedPage Today senior editor John Gever writes in a May 14 article that pharmaceutical drug trials for antidepressants generally exclude many potential participants, such as those with "more than one concurrent general medical condition or Axis I psychiatric disorder in addition to depression, or current episodes lasting more than two years." A May 12 article in The Medical News notes that potential participants "who have previously tried treatment, have suicidal thoughts or have other psychiatric illnesses" would have been excluded. In fact, nearly 80 percent (4 out of 5) of the patients included in STAR*D would have been excluded from other antidepressant clinical trials.

The problem of excluding suicidal individuals from research studies has been noted for some time, with some solutions initially covered in a 2001 article by by Jane Pearson (NIMH) and colleagues. This research issue will only intensify as we continually recognize and treat depression and other mental illnesses earlier, especially if we continue to find that comorbidity is the norm rather than the exception.

While prior studies have noted that patients in drug trials differed from other patients based on demographics and clinical characteristics, the current study also documented differences in outcomes. According to the MedPage Today article, findings from drug trials probably "paint a rosier picture than should be expected in ordinary practice" because patients who would have been excluded from drug trials
These findings call into question whether the information provided to patients who receive antidepressant medications overstates the potential benefits, including response rates, and understates the potential side effects and risks. Can patients truly give informed consent without accurate information?

According to Dr. Trivedi, "We are basing our judgment of clinical care in the United States on samples of patients that are totally different than the patient population actually treated in primary care and mental health facilities." The patients who would have been included in drug trials had "shorter bouts of depression, quicker response to medication, less severe side effects and fewer adverse events compared with those people with depression who would have been excluded from such a trial."

Dr. Trivedi notes that the people who would be excluded are "the patients impacted by depression the most--highest suicide potential, highest unemployment rates, highest social impairment--and they are likely to produce poorer outcomes."

For clinicians, Dr. Trivedi recommends prescribing antidepressants with realistic expectations about the long-term nature of depression. Many clinicians, having recognized this trend years ago, will find validation in the study results. Other clinicians prescribe antidepressants liberally, in attempts to treat conditions that may be better suited for psychotherapy.

In a May 11 column in the Los Angeles Times, Dr. Valerie Ulene notes that the number of antidepressant prescriptions has increased over the years, "but it's not always the right people taking them. Some who probably have very little to gain from their use are on SSRIs; others who stand to benefit are not."

The L.A. Times article is partially based on a RAND Corporation survey of 700 adults who were prescribed antidepressant medications. Only 20% (1 in 5) had clinical depression based on a screening instrument. Less than 30% (1 in 3) had any depressive symptoms. As the article points out, "roughly half of all people with depression go untreated, and the vast majority in treatment aren't adequately medicated."

The implication for research, as Dr. Trivedi indicates, is that antidepressant drug trials must include representative samples of patients, including those at risk of suicide. Of course, this will require careful monitoring of research participants because there may be more side effects and adverse events. However, the end result will be more accurate profiles for antidepressant medications, improving patient care. On the treatment side, as noted in the LA Times article, there must be better training for primary care physicians who are prescribing the majority of antidepressants--training in appropriately prescribing antidepressant medications, following up with high-risk patients, and recommending psychotherapy and other alternatives for patients who would benefit from those treatments.

People suffering from depression are counting on us to get it right.

Created on ... May 17, 2009