Duration of new antidepressant use and factors associated with discontinuation among community-dwelling persons with Alzheimer\u2019s disease

Reetta Kettunen,Heidi Taipale,Anna-Maija Tolppanen,Sirpa Hartikainen,Marjaana Koponen,Antti Tanskanen,Jari Tiihonen

doi:10.1007/s00228-018-2591-5

Abstract

PurposeTo study how long antidepressants initiated after diagnoses of Alzheimer’s disease (AD) were used and factors associated with discontinuation of use among persons with Alzheimer’s disease (AD). In addition, differences in duration of use between the antidepressants groups were compared.MethodsRegister-based Medication use and Alzheimer’s disease (MEDALZ) cohort included 70,718 community-dwelling people with AD who were diagnosed during the years 2005–2011. For this study, the new antidepressant users were included after 1-year washout period (N = 16,501; 68.6% females, mean age 80.9). The duration of antidepressant use was modeled with the PRE2DUP method. Factors associated with treatment discontinuation were assessed with Cox proportional hazard models and included age, gender, comorbid conditions and concomitant medications.ResultsMedian duration of the new antidepressant use period was 309 days (IQR 93–830). For selective serotonin reuptake inhibitor (SSRI) use, the median duration was 331 days (IQR 101–829), for mirtazapine 202 days (IQR 52–635), and for serotonin and norepinephrine reuptake inhibitors (SNRIs) 134 days (IQR 37–522). After 1-year follow-up, 40.8% had discontinued antidepressant use, 54.6% after 2 years and 64.1% after 3 years. Factors associated with treatment discontinuation were age over 85, male gender, diabetes, and use of memantine, opioids, and antiepileptics whereas benzodiazepines and related drugs and antipsychotic use were inversely associated with discontinuation.ConclusionsAntidepressants are used for long-term among people with AD. Need and indication for antidepressant use should be assessed regularly as evidence on their efficacy for behavioral and psychological symptoms of dementia is limited.

Highlights

Over the last two decades, prevalence of antidepressant use has increased and treatment duration has prolonged in older people [1]
Antidepressant use is associated with an increased risk of adverse effects and events, such as falls, fractures, cardiovascular events, all-cause mortality, and upper gastrointestinal bleeding among older persons [8, 9]
Among people with Alzheimer’s disease (AD), antidepressant use has been associated with an increased risk of hip fractures and head injuries, and the risks remained elevated in long-term use [11, 12]

Summary

Introduction

Over the last two decades, prevalence of antidepressant use has increased and treatment duration has prolonged in older people [1]. Main indications for antidepressant use are depression and anxiety disorders [5]. These drugs are used for other indications such as neuropathic pain, insomnia, and migraine. Among persons with AD, antidepressants are used for treatment of behavioral and psychological symptoms of dementia (BPSD) their effectiveness in this indication is modest [6, 7]. Antidepressant use is associated with an increased risk of adverse effects and events, such as falls, fractures, cardiovascular events, all-cause mortality, and upper gastrointestinal bleeding among older persons [8, 9]. Discontinuation of antidepressant use may be problematic as withdrawal symptoms may emerge [14]

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Results

Conclusion