Stress Hormone Lowering Drug Doesn’t Benefit Depression

A drug that works to lower levels of the stress hormone cortisol does not necessarily provide any benefit in treating depression as once thought, according to researchers at Newcastle University in England.

Hamish McAllister-Williams, MD, PhD, and colleagues enrolled 165 patients with depression who were under treatment by a clinician. Patients were randomly selected to receive either the drug metyrapone, which works to block production of cortisol, or a placebo, in addition to their antidepressant regimen. The goal was to determine the efficacy, tolerability and safety of metyraphone as an adjunctive therapy.

Prior work done by researchers at the Northern Centre for Mood Disorders in rats showed that those with high levels of stress saw reduced effectiveness of antidepressants. A number of small studies using drugs that block the effect of cortisol or inhibit its production as treatments for depression have been conducted, and some showed positive results.

However, the latest research by McAllister-Williams, published in Lancet Psychiatry, questions the efficacy of metyrapone as an adjunctive treatment for treatment-resistant depression.

“While stress may well play a role in the development of depression in some individuals, using a drug to decrease the potential negative effects of stress hormones in those whose depression has not responded to conventional antidepressants does not work,” he said in a statement.

“Our findings suggest that in people who have not responded to several conventional antidepressants and been depressed for some time, either stress plays less of a role in the development of their depression or these effects wears off over time,” McAllister-Williams added.

The next steps for researchers is to identify if different groups of depressed patients would respond to drugs acting on their stress hormone system, as well as identifying treatments targeting different systems within the brain for patients not responding to standard antidepressants.