Antidepressants are commonly prescribed with usual care for dementia patients with depression. But such use should now be reconsidered following the results of the HTA-SADD trial, that show sertraline and mirtazapine provided no benefit yet increased side effects in these patients. The findings are reported in an Article published Online First by The Lancet. The Article is by Professor Sube Banerjee, Institute of Psychiatry, King's College London, UK, and colleagues.
Patients for study were recruited from nine centres in England, and were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a dementia-related depression score above a certain level. Patients were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The patients were assigned to receive sertraline (target dose 150 mg per day; 107 patients), mirtazapine (45 mg; 107 patients), or placebo (control group; 111 patients), all with standard care. The primary outcome was reduction in depression at 13 weeks.
The researchers found decreases in depression scores at 13 weeks did not differ between the groups, a finding that persisted to 39 weeks. Fewer controls had adverse reactions (26%) than did participants in the sertraline group (43%) or mirtazapine group (41%) and fewer serious adverse events rated as severe in the placebo group. Five patients in each group had died by week 39.
The authors conclude: "The two classes of antidepressants most likely to be prescribed for depression in Alzheimer's disease are no more effective than placebo. In our study, there were more adverse reactions in individuals treated with antidepressants than there were with placebo. Clinicians and investigators need to reframe the way they think about the treatment of people with Alzheimer's disease who are depressed, and reconsider routine prescription of antidepressants."
In a linked Comment, Dr Henry Brodaty, Brain and Ageing Research Program and Primary Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia, concludes: "The HTA-SADD trial1 has underscored the need for clinicians to think about creative alternatives to drug treatment for management of depression in people with dementia, and to use evidence-based techniques and partnerships with family carers."
Professor Sube Banerjee, Institute of Psychiatry, King's College London, UK. T) + (0) 7734681599. E) s.banerjee@kcl.ac.uk
Dr Henry Brodaty, Brain and Ageing Research Program and Primary Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia. Contact via email E) h.brodaty@unsw.edu.au
Journal
The Lancet