STANFORD, Calif. - Depression is a significant medical problem for about 6 percent of Americans over the age of 65, according to the National Institute of Mental Health. In treating these patients, psychiatrists must balance the patients' increased susceptibility to drug-related side effects and possible adverse drug interactions with the need to treat the depression rapidly and effectively. The stakes are high: Senior citizens are more likely than younger people to commit suicide, and older depressed patients are more likely than their non-depressed peers to suffer from other major illnesses.

Now a multicenter, phase-IV clinical trial headed by Stanford University Medical Center professor Alan Schatzberg, MD, has shown that an antidepressant known as mirtazapine works significantly faster, is more effective and causes fewer adverse side effects in elderly patients than does paroxetine, another commonly prescribed antidepressant. The research is the first direct comparison of the two drugs in treating elderly people suffering from a major depressive illness.

"It's very unusual to see one drug significantly better than another;" said Schatzberg, who chairs the psychiatric and behavioral sciences department at Stanford. "But what we found here is that mirtazapine was faster-acting and produced an overall better result in the first six weeks of treatment than paroxetine." He will present the research May 6 at the annual meeting of the American Psychiatric Association in New Orleans, La.

Having a quick-working medication is critical for people suffering from depression, particularly older patients. However, most types of antidepressants must accumulate in the body for several weeks before they begin relieving depression symptoms.

"One of the big issues in depression treatment is that patients drop out because they experience side effects or they feel they are not getting better - there is a lack of perceived efficacy," said Schatzberg. "Drugs that work more rapidly and are better tolerated tend to be associated with the patient continuing the treatment."

The study showed that after one week of treatment, patients taking mirtazapine were significantly more likely to have experienced some improvement in their symptoms. They were also less likely than patients taking paroxetine to prematurely terminate their treatment.

In addition, mirtazapine was more effective than paroxetine, particularly in alleviating the heightened anxiety and sleep disturbances that are often experienced by older depressed patients. The mirtazapine patients were also less likely to terminate their treatment because of adverse side effects, such as sleepiness, nausea, dry mouth and fatigue.

"Having an antidepressant that works for this population of patients - and works quickly - would be a tremendous plus for the field," said Schatzberg, who noted that mirtazapine was well-tolerated by the study patients. "Mirtazapine's low risk of drug interactions and cardiovascular complications may make it an optimal treatment for depression in older adults."

Mirtazapine works by directly enhancing the release of norepinephrine and indirectly enhancing the release of serotonin in the brain. Norepinephrine and serotonin are key neurotransmitters - chemicals that transmit signals from one neuron to another. In contrast, paroxetine belongs to a class of medications known as selective serotonin reuptake inhibitors, or SSRIs. These drugs potentiate the action of serotonin by increasing the amount of time it remains in the neural synapse. Paroxetine also may be able to modestly enhance norepinephrine release.

Schatzberg and investigators at 17 other centers around the country studied the effect of the two medications on 255 patients who were at least age 65. The study was randomized and double-blinded, and each patient was treated for eight weeks. Mirtazapine is marketed by Organon, Inc., under the trade name REMERON SolTab. Paroxetine is marketed by GlaxoSmithKline under the trade name Paxil. The study was supported by funding from Organon, Inc.

---Stanford University

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