Combination Medications for Depression Not Effective as First-Line Treatment Plan


Nineteen million Americans each year suffer from major depressive disorder, but for as many as one-third, the most frequently prescribed medications fail to adequately treat the symptoms. In an effort to hasten recovery, physicians may prescribed a combination of two different-acting medications, however, a new study from UT Southwestern Medical Center find this may not be the best first-line treatment plan for most.

Taking Two Medications Not Significantly Beneficial Over Just One

The research team, led by Dr. Madhukar H. Trivedi, a professor of psychiatry and chief of the division of mood disorders, used data from the CO-MED study, which stands for “Combining Medication to Enhance Depression Outcomes.” Over 600 patients between the ages of 18 and 75 were enrolled at 15 sites across the country from March 2008 to February 2009.

The participants were divided into three treatment groups and all were prescribed medications already approved by the US Food and Drug Administration (FDA). Because the many available antidepressant drugs work on the brain using different pathways, the study volunteers were given different combinations of those most commonly prescribed.


Read: Antidepressant Failure May Be Due to NSAID Use

The first group received escitalopram, a selective serotonin reuptake inhibitor (SSRI) known as Lexapro, plus a placebo. The second group received Lexapro paired with bupropion, a non-tricyclic antidepressant marketed under the name Wellbutrin. The third group was prescribed venlafaxine (Effexor), a tetracyclic antidepressant and mirtazapine (Remeron), a norepinephrine reuptake inhibitor.

After twelve weeks of treatment, remission and response rates were similar across the three groups. Dr. Trivedi notes that only about 33 percent of depressed patients go into remission in the first three months after taking one antidepressant, but those receiving treatment with two drugs achieved between 38 and 39% remission – not a significant improvement says Dr. Trivedi.

Read: The Magic Drug for Depression and Anxiety - Exercise

After seven months, the rates remained similar, but side effects were more frequent in the group receiving the Effexor/Remeron combination.

“Clinicians should not rush to prescribe combinations of antidepressant medication as first-line treatment for patients with major depressive disorder,” said Dr. Trivedi. “The extra cost and burden of two medications is not worthwhile as a first treatment step.”

Journal Reference:
Rush, A. John, Trivedi, Madhukar H., et al. Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and Long-Term Outcomes of a Single-Blind Randomized Study Am J Psychiatry 2011 0: appi.ajp.2011.10111645