Antidepressants in the elderly: challenges for study design and their interpretation

Abstract

Drug treatment of depressive illness in the elderly differs from that in younger patients and there is no clear consensus as to ®rst line treatment in the former. Nor is it possible to extrapolate directly from studies in younger patients to the elderly with these agents. Whilst there are over two dozen antidepressants currently marketed in the U.K., most studies have been on younger adults and have excluded very old and frail patients. Design short-comings of the few trials conducted in elderly patients do not allow accurate interpretation of differences in ef®cacy or safety between drugs.This paper identi®es key de®ciencies in the evidence currently available in support of both older and newer antidepressant agents and makes the proposal that speci®c studies are required in the elderly to determine the ef®cacy and safety of antidepressants in the treatment of depressive illness. It outlines a Phase II and III clinical trial programme which could be used to provide adequate evidence of ef®cacy and safety of new agents and which conforms to current European guidelines. Dose ®nding studies, short-term ef®cacy, prevention of relapse (continuation therapy) and prevention of recurrence (maintenance therapy) studies are discussed as are key issues to be addressed in the trial protocol.

Antidepressant use and functional limitations in U.S. older adults

“…The efficacy of antidepressant treatment was unconfirmed for that patient population. Parikh (2000) summarized the challenges in study design and result interpretation for evaluating the efficacy of antidepressant treatment in older adults [21]. Most Phase II and III clinical trials on antidepressants had been on younger adults and excluded very old and frail patients.…”

Pharmacological treatment of neuropathic pain in older persons

“…For example, the inclusion of at least 25% of subjects aged 75 years and over in studies of drugs that will be registered for use in the elderly. Due to the fact that the majority of studies of antidepressants use a highly selective trial population, without signifi cant co-morbidity and with minimum numbers of elderly subjects, there are fundamental problems extrapolating the results to the elderly population as a whole (Parikh 2000). However, despite the lack of evidence, there are some recommendations in the literature relating to the use of antidepressants in the elderly.…”

“…However, despite the lack of evidence, there are some recommendations in the literature relating to the use of antidepressants in the elderly. It is widely reported that older patients are more prone to side-effects and have greater diffi culty tolerating doses of antidepressants that are likely to be of therapeutic value (Parikh 2000;ANZCA 2005). Older adults often require lower initial doses with slow titration and the initial dose should be one-half or lower than the normal starting dose (Antai-Otong 2006).…”

“…Due to the risk of potential life-threatening side-effects some authors recommend baseline and follow-up electrocardiograms (ECGs) throughout treatment with tricyclic antidepressants (Dworkin, Backonja et al 2003). In Parikh's (2000) advice on the posology of antidepressants in the elderly a lower starting and maintenance dose is advised for amitriptyline, but no specifi c recommendations are made for nortriptyline.…”

Pharmakotherapie im Alter

“…Es sind Studien bei älteren Patienten vonnöten, um optimale Dosen, z.B. von Antidepressiva, zu ermitteln (4). Folge ist häufig eine Anwendung von Medikamenten außerhalb der Zulassung ("off-label-use"), so z.B.…”