Effects of antidepressants on longevity and dementia onset among adults with Down syndrome: a retrospective study

To investigate the effects of antidepressants on longevity, age at dementia onset, and survival after onset among adults with Down syndrome, controlling for late-onset seizures, trisomy 21 mosaicism, and cholinesterase inhibitor use.

The charts of 357 adults with Down syndrome (mean age at first visit = 46.3 years, SD = 9.0) evaluated in a metropolitan diagnostic and research clinic between 1990 and 2008 were reviewed. Seventeen patients had trisomy 21 mosaicism; 155 patients were diagnosed with depressive disorders using DSM-III-R and IV criteria, 78 of whom received antidepressants for over 90 days. Of 160 patients who developed dementia, the estimated mean age at onset was 52.8 years. Fifty-six patients (demented and nondemented) had late-onset seizures. Longevity and age at estimated onset among those receiving and not receiving antidepressants were compared. Cox proportional hazards models examined risks for dementia onset and death.

The mean age at dementia onset among those receiving antidepressants before onset was 53.75 years versus 52.44 years among others. Proportional hazards models showed a significant delay of onset among those taking antidepressants (hazard ratio = 0.69; 95% CI, 0.48-0.98; P = .038). Mean age at death or at end of study for those receiving antidepressants was 54.71 years; among others, it was 52.60 years (hazard ratio = 0.63; 95% CI, 0.42-0.94; P = .024). Among the 35 adults with late-onset seizures and dementia who died, mean survival after seizure onset was 4.23 years.

The findings in this retrospective study revealed that antidepressant use was associated with delayed dementia onset and increased longevity in adults with Down syndrome; mean survival after late-onset seizures was longer than previously reported. Further studies, however, are needed to confirm these associations, optimally in a clinical trial to confirm causality.