(Celexa) Sex differences seen in response to common antidepressant

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Sex differences seen in response to common antidepressant

Women are 33 percent more likely than men to experience full

remission with citalopram (Celexa), suggesting a biological basis for

difference in response

http://www.eurekalert.org/pub_releases/2008-08/uomh-sds082908.php

Women with depression may be much more likely than men to get relief

from a commonly used, inexpensive antidepressant drug, a new national

study finds. But many members of both sexes may find that it helps

ease their depression symptoms.

The persistence of a gender difference in response to the drug — even

after the researchers accounted for many complicating factors —

suggests that there's a real biological difference in the way the

medication affects women compared with men. The reasons for that

difference are still unclear, but further studies are now examining

hormonal variations that may play a role.

The study involved citalopram, a commonly used antidepressant that is

available both as a generic drug and under the brand name Celexa.

Researchers from the University of Michigan Depression Center and

their colleagues from around the country tested the drug's ability to

help depression patients achieve remission, or total relief from

their symptoms, in a multi-year study called STAR*D.

The gender differences emerged from a detailed analysis of data from

2,876 men and women who had a clear diagnosis of major depression,

and took citalopram over a number of weeks, with the doses increasing

over time.

In the end, women were 33 percent more likely to achieve a full

remission of their depression, despite the fact that women in the

study were more severely depressed than the men when the study began.

The study showed no differences between men and women in side

effects, the amount of time that patients stuck to taking the drug,

or the amount of time it took for them to achieve remission of their

symptoms.

The new findings, which represent the largest and most rigorous

analysis ever of gender differences in response to an antidepressant,

are published online in the Journal of Psychiatric Research.

Young, M.D., a professor and associate chair of psychiatry

at the U-M Medical School and member of the Depression Center, is the

study's lead author. " Other studies have suggested that there are

differences between men and women in response to different

antidepressants, but the evidence has been conflicting, " she

says. " This study is large enough, and we were able to control for

enough complicating factors, that we feel confident there is a true

difference. These results have clear implications for the clinical

treatment of depression. "

Young and her colleagues, including Kornstein, M.D., of

Virginia Commonwealth University, and Rush, M.D., formerly of

the University of Texas Southwestern Medical Center at Dallas,

conducted the analysis of data from men and women between the ages of

18 and 75, many of whom were being treated by primary care physicians

and not psychiatrists. All of the patients had been experiencing

depression for years, with the average length of experience around 12

years.

The study was funded by the National Institute of Mental Health.

Unlike many previous industry-sponsored studies of antidepressants,

it included a " real world " sample of people with major depression,

and did not exclude people who had a history of suicidal thinking.

The study did not include people with bipolar disorder. Participants

in the study could continue with psychotherapy that they had been

undergoing before the start of the study, but could take no other

antidepressants.

Citalopram is one of a class of medicines known as SSRIs, or

selective serotonin reuptake inhibitors. In earlier decades, gender

differences had been seen in studies of patients taking an older

generation of drugs called tricyclics, with men tending to respond

better to such medications. But for more than 15 years, SSRIs have

been the first choice for treating depression.

Although the current study didn't look at hormonal variations between

men and women that might account for the difference in response to

citalopram, Young and her colleagues note that animal studies have

shown that estrogen modifies the brain systems involved in the

activity of serotonin, a key brain chemical.

Kornstein is leading further analysis of the STAR*D results to look

for possible differences among women according to their menopausal

status and their use of hormone replacement therapy. Meanwhile,

Young's research as a member of the U-M Molecular & Behavioral

Neuroscience Institute focuses on the interactions of sex hormones

and stress response in depression and other mood disorders.

Overall, women are more affected by depression than men, with about

12 percent of women suffering from some form of depression in a given

year compared with 6 percent of men. Depression and other mood

disorders are the leading cause of disability among women under the

age of 45.

But the study's authors are quick to caution that their findings

don't mean that citalopram should only be used in women. Raw data

from the study show that 24 percent of men achieved remission with

the drug, compared with 29 percent of women. The difference in

remission rates grew larger once the researchers adjusted for other

factors, but the fact remains that many men were helped.

Rather, they note that STAR*D and other studies have shown that many

people with depression need to try several treatments to find the one

that's right for them and will produce lasting results.

That's why a new study called CO-MED has begun. Young and colleagues

from U-M and around the country are now enrolling people with

depression for this study that will assess the impact of combinations

of medications. One of the medications in that study is escitalopram,

a cousin of citalopram, but it also includes other common SSRI

antidepressants.

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More information on the CO-MED study is available at

www.depressioncenter.org/research/co-med.asp. Information on STAR*D

is available at www.nimh.nih.gov/health/trials/practical/stard.

In addition to Young, Kornstein and Rush, the study's authors include

Sheila Marcus of the U-M Depression Center, Madhukar Trivedi and

Diane Warden of UT-Southwestern, Anne Harvey of Via Christi Research,

Wisniewski and G.K. Balasubramani of the University of

Pittsburgh and Maurizio Fava of Harvard Medical School.

Reference: Journal of Psychiatric Research,

doi:10.1016/j.jpsychires.2008.07.002