Discontinuation of antidepressants in people with dementia and neuropsychiatric symptoms (DESEP study): double blind, randomised, parallel group, placebo controlled trial

OBJECTIVE: To determine the effect of discontinuing antidepressant treatment in people with dementia and neuropsychiatric symptoms. DESIGN: Double blind, randomised, parallel group, placebo controlled trial. SETTING: Norwegian nursing homes; residents recruited by 16 study centres in Norway from August 2008 to June 2010. PARTICIPANTS: 128 patients with Alzheimer's disease, dementia or vascular dementia, and neuropsychiatric symptoms (but no depressive disorder), who had been prescribed escitalopram, citalopram, sertraline, or paroxetine for three months or more. We excluded patients with severe somatic disease or terminal illness, or who were unable to take tablets or capsules as prescribed. INTERVENTIONS: Antidepressant treatment was discontinued over one week in 63 patients, and continued in 68 patients. We assessed patients at baseline, four, seven, 13, and 25 weeks. MAIN OUTCOME MEASURES: Primary outcomes were score differences between study groups in the Cornell scale of depression in dementia and the neuropsychiatric inventory (10 item version) after 25 weeks. Secondary outcomes were score differences in the clinical dementia rating scale, unified Parkinson's disease rating scale, quality of life-Alzheimer's disease scale, Lawton and Brody's physical self maintenance scale, and severe impairment battery. RESULTS: Using a linear multilevel model analysis, we found that the discontinued group had significantly higher scores on the Cornell scale after 25 weeks than the continuation group (difference -2.89 (95% confidence interval -4.76 to -1.02); P=0.003). We saw a similar result in the mean total score for the neuropsychiatric inventory after 25 weeks, but this difference was non-significant (-5.96 (-12.35 to 0.44); P=0.068). We confirmed these results by non-response analysis (>30% worsening on the Cornell scale)--significantly more patients worsened in the discontinuation group than in the continuation group (32 (54%) v 17 (29%); P=0.006). We found no significant differences between the groups for secondary outcomes. Forty seven (37%) patients withdrew from the study early. CONCLUSIONS: Discontinuation of antidepressant treatment in patients with dementia and neuropsychiatric symptoms leads to an increase in depressive symptoms, compared with those patients who continue with treatment. TRIAL REGISTRATION: ClinicalTrial.gov NCT00594269, EudraCT 2006-002790-43.