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Drugs Affect Serotonin Receptor Site Occupancy in Depressed Patients

Clinical doses of paroxetine or citalopram result in occupancy of approximately 80 percent of serotonin transporter (5-HTT) sites in patients with major depression.

These levels of site occupancy may be necessary to allow for some therapeutic effects, say United States researchers led by Dr. Jeffrey H. Meyer of the VA Greater Los Angeles Healthcare System in California. "This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential," they point out.

Investigators note that selective serotonin reuptake inhibitors are commonly used as therapy for depressed patients. Prior to this study, the percentage of 5-HTT sites occupied during clinical dosing was unknown.

They measured the proportion of 5-HTT sites blocked when 12 medication-free depressed patients completed a six-week trial of either paroxetine (eight patients) or citalopram (four patients).

Researchers measured striatal 5-HTT binding potential with [11C] DASB and positron emission tomography (PET) at baseline and after four weeks of treatment. They measured binding potential twice in six healthy patients and once in 11 patients.

"A significant decrease in striatal 5-HTT binding potential was found after either treatment, compared to changes found over a four-week period in healthy subjects," they report.

"For patients treated with 20 milligrams per day of paroxetine, the mean proportion of 5-HTT sites occupied was 83 percent.

"For patients treated with 20 mg/d of citalopram, the mean 5-HTT occupancy was 77 percent."
American Journal of Psychiatry, 2001; 158: 1843-1849. "Occupancy of Serotonin Transporters by Paroxetine and Citalopram During Treatment of Depression: A [ 11 C]DASB PET Imaging Study"

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