Older patients not always helped by antidepressants

Nutrition Health Review, Winter, 2002

Observing the effect of antidepressant medications on brain metabolism may give doctors new insight into why 25 percent of depressed older patients gain little benefit from a widely prescribed class of antidepressants that focus on the brain chemical serotonin, according to a study reported in the American Journal of Geriatric Psychiatry (October 31, 2002).

Over the past decade, treatment of depression has been greatly enhanced by the development of a relatively new class of drugs, such as fluoxetine (Prozac[R]) and sertraline (Zoloft[R]). The effectiveness of these agents appears to involve the ability to restore a patient's capacity to produce or retain the neurotransmitter serotonin. Scientists have linked diminished serotonin levels to depression and to a host of other mental disorders as well.

Scientists have confirmed that drugs that target serotonin function, known as selective serotonin reuptake inhibitors (SSRIs), can be very effective in fighting depression, but it is still not known precisely how they work or why they sometimes provide no relief.

The study, led by Gwenn Smith, Ph.D., of the Albert Einstein College of Medicine, and Bruce G. Pollock, M.D., Ph.D., of the University of Pittsburgh School of Medicine, sought what scientists have thus far lacked: a biological "marker" that corresponds with successful use of SSRIs in depressed elderly people.

Dr. Smith hopes that one day positron emission tomography (PET) scans may help doctors identify which patients will benefit from drugs that affect the serotonin system and which patients might require additional medications or another type of therapy.

She explains, "For example, if the individual failed to respond, if we fail to see a change in brain metabolism after administering an SSRI, we might want to consider that a different neurochemical is involved." Serotonin might not be the only problem. The patient might need a different selection of drugs. So rather than starting out with an SSRI, we might choose a drug with mixed effects that increases dopamine or norepinephrine, in addition to serotonin."

Because the study involved such a small group of patients who responded well to treatment, Dr. Smith said that this is only the "first step" in developing a marker for serotonin function. The next step would be to conduct a similar study with a larger group of patients.

The experimental approach used in the study could apply to younger patients with depression, she added. However, the results in the elderly population might be different, because younger depressed patients typically do not have evidence of elevated cortical brain metabolism, as has been observed in older adults.