Two antidepressants commonly prescribed to people with dementia appear to be no better than a sugar pill at easing the symptoms of depression in Alzheimer's patients, according to a new study.

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By Amanda Gardner

MONDAY, July 18, 2011 ( — Two antidepressants commonly prescribed to people with dementia appear to be no better than a sugar pill at easing the symptoms of depression in Alzheimer’s patients, according to a new study published today in the Lancet.

Zoloft (sertraline) and Remeron (mirtazapine), which are both available as generics, also generated more—and more severe—side effects than placebo, leading the researchers to suggest that these and other antidepressants should be reserved for dementia patients whose depression fails to respond to more conservative treatments, such as psychotherapy.

Although it included just 326 patients, the study is the largest placebo-controlled trial to date on antidepressants in people with dementia. In fact, it is nearly as large as all the previous studies on this topic combined, according to an editorial accompanying the study.

More than one-fifth of the 35 million people around the world who have dementia are estimated to also suffer from depression. Despite the limited evidence for the use of antidepressants in this population, some doctors have begun using the drugs—especially sertraline—as a first-line treatment, the researchers say.

Alan Manevitz, MD, a psychiatrist at Lenox Hill Hospital, in New York City, agrees with the authors' conclusion that doctors should consider nondrug treatments before prescribing antidepressants to depressed dementia patients.

"You don't want to make prescription of antidepressants routine. You should always be thoughtful about why you're introducing [a medication]," says Manevitz, who was not involved in the new study. "This raises the question of whether treatments that don't cause side effects...might have a role in treating depression."

Led by a team at King's College London, researchers randomly assigned people with a diagnosis of depression and a "probable" or "possible" diagnosis of Alzheimer's disease to receive 150 milligrams of sertraline, 45 milligrams of mirtazapine, or placebo, in addition to their usual care.

Depression symptoms had declined in all three groups after 13 weeks, and again at 39 weeks, but there were no measurable differences between the drug and placebo groups, or between the two drug groups.

Side effects, however, were considerably worse among those taking the drugs. Roughly one-quarter of the people in the placebo group experienced side effects such as nausea or drowsiness, compared with about 40 percent of the people taking antidepressants. And the side effects in the drug groups were more likely to be considered severe.

"The practical implications of this study are that we should reframe the way we think about the treatment of people with dementia who are depressed, and reconsider the routine prescription of antidepressants," the authors write.

The study is hardly the last word on the subject. It was small, and the findings can't be applied to certain subgroups of patients who were excluded from the study (such as those with severe depression who may be suicidal), to primary care settings, to forms of dementia other than Alzheimer's, or to other types of antidepressants.

Moreover, depression and dementia are both complicated conditions that resist one-size-fits-all treatment and can interact with each other.

Depression—which can impair memory and concentration—sometimes masquerades as dementia, and in some cases may even contribute to dementia, Dr. Manevitz says.