Effexor: Was the STAR*D Trial Misleading?

September 24, 2010, 8:00AM. By Heidi Turner

Seattle, WAWomen who took the antidepressant Effexor during pregnancy may have done so thinking the benefits outweighed the risk of Effexor side effects, including a risk of birth defects. However, a study examining the effectiveness of antidepressants has yielded misleading results—a fact that suggests that antidepressants are only marginally more effective than a placebo.

The study, called Sequenced Treatment Alternatives to Relieve Depression (STAR*D), was intended to "assess the effectiveness of depression treatments in patients diagnosed with major depressive disorder, in both primary and specialty care settings" (nimh.nih.gov, 9/2006). The study was funded not by the pharmaceutical industry but rather by the government, thereby eliminating the potential for industry bias.

The study included four levels that tested a different medication or combination of medications. Patients who were not considered in remission after each level would move to the next level, which involved either changing medication or increasing the medication dose. A number of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors were analyzed in the study, including Celexa, Wellbutrin, Zoloft and Effexor. Medications from other antidepressant classes, including tricyclics, were also included in the study.

According to the National Institute of Mental Health, approximately half the participants in the STAR*D study were symptom-free after two treatment levels, and approximately 70 percent of participants who stayed through the whole study became symptom-free.

Those results appear to heavily support the use of antidepressants when treating major depressive disorder. The problem is that those results only tell half the story, according to a paper published in Psychotherapy and Psychosomatics (Pigott, et al. 7/09/10).

The paper argues that patients with even mild depressive disorder were included in the study, which was meant only to study major depressive disorder. To be included in the study, according to authors, patients had to have a baseline HRSD (Hamilton Rating Scale for Depression) score of greater than or equal to 14. Yet approximately 600 patients were first excluded from the study and later included in it with a score of less than 14, which signifies minor depression. Furthermore, approximately 320 patients were first excluded from the study but later included in it with no baseline score (initially, 4,041 participants were enrolled in the study).

This means that although the study was meant to determine the effectiveness of antidepressants on major depressive disorder, patients were included in the results who did not meet the criteria for major depressive disorder. Those patients, who were more likely to achieve remission anyhow, should not have been included in the study and likely inflated the number of patients who had positive results with the use of antidepressants.

Pigott and fellow researchers conclude that antidepressants "fail to result in sustained positive effects for the majority of people who receive them." This throws into question whether the benefits of antidepressants, including SSRIs and SNRIs, actually outweigh the risks, which reportedly include a risk of birth defects and congenital heart defects.

Women who are pregnant and taking antidepressants should not discontinue medication without speaking to a medical professional. Although there are some risks linked with the use of antidepressants while pregnant, there are also risks associated with untreated depression.