Deprescribing of antidepressants: development of indicators of high-risk and overprescribing using the RAND/UCLA Appropriateness Method
Authors: Brisnik Vita , Vukas Jochen , Jung-Sievers Caroline , Lukaschek Karoline , Alexander G Caleb , Thiem Ulrich , Thürmann Petra , Schüle Cornelius , Fischer Sebastian , Baum Erika , Drey Michael , Harder Sebastian , Niebling Wilhelm , Janka Ulrike , Krause Olaf , Gensichen Jochen , Dreischulte Tobias ,   for the POKAL-Group, Falkai Peter , Henningsen Peter , Bühner Markus , Krcmar Helmut , Pitschel-Walz Gabriele , Schneider Antonius , Biersack Katharina , Brand Constantin , Ebert Christopher , Eder Julia , Gökce Feyza , Haas Carolin , Hattenkofer Lisa , Kaupe Lukas , Raub Jonas , Reindl-Spanner Philipp , Schillok Hannah , Schönweger Petra , Teusen Clara , Vogel Marie , von Schrottenberg Victoria , Younesi Puya 
Published: May 2024

Abstract
Background
Antidepressants are first-line medications for many psychiatric disorders. However, their widespread long-term use in some indications (e.g., mild depression and insomnia) is concerning. Particularly in older adults with comorbidities and polypharmacy, who are more susceptible to adverse drug reactions, the risks and benefits of treatment should be regularly reviewed. The aim of this consensus process was to identify explicit criteria of potentially inappropriate antidepressant use (indicators) in order to support primary care clinicians in identifying situations, where deprescribing of antidepressants should be considered.

Methods
We used the RAND/UCLA Appropriateness Method to identify the indicators of high-risk and overprescribing of antidepressants. We combined a structured literature review with a 3-round expert panel, with results discussed in moderated meetings in between rounds. Each of the 282 candidate indicators was scored on a 9-point Likert scale representing the necessity of a critical review of antidepressant continuation (1–3 = not necessary; 4–6 = uncertain; 7–9 = clearly necessary). Experts rated the indicators for the necessity of review, since decisions to deprescribe require considerations of patient risk/benefit balance and preferences. Indicators with a median necessity rating of ≥ 7 without disagreement after 3 rating rounds were accepted.

Results
The expert panel comprised 2 general practitioners, 2 clinical pharmacologists, 1 gerontopsychiatrist, 2 psychiatrists, and 3 internists/geriatricians (total N = 10). After 3 assessment rounds, there was consensus for 37 indicators of high-risk and 25 indicators of overprescribing, where critical reviews were felt to be necessary. High-risk prescribing indicators included settings posing risks of drug-drug, drug-disease, and drug-age interactions or the occurrence of adverse drug reactions. Indicators with the highest ratings included those suggesting the possibility of cardiovascular risks (QTc prolongation), delirium, gastrointestinal bleeding, and liver injury in specific patient subgroups with additional risk factors. Overprescribing indicators target patients with long treatment durations for depression, anxiety, and insomnia as well as high doses for pain and insomnia.

Conclusions
Explicit indicators of antidepressant high-risk and overprescribing may be used directly by patients and health care providers, and integrated within clinical decision support tools, in order to improve the overall risk/benefit balance of this commonly prescribed class of prescription drugs.