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Background: Most people treated with antidepressants drugs for mild-to-moderate depression may not benefit from ongoing pharmacotherapy. Over time, adverse effects often outweigh benefits. Yet many, especially women, take antidepressants for much longer than clinical guidelines recommend. Therefore, when prescribers recommend starting an antidepressant, they also need to know how to stop it. Antidepressant withdrawal is a common but under-recognized clinical issue. At least half of people who stop antidepressants experience significant withdrawal symptoms, particularly from higher doses or after longterm treatment. Aims: Therapeutics Letter 157 discusses the rationale for stopping antidepressants, and provides guidance on safe and effective deprescribing. It recommends dose tapering tailored to a patient’s individual risk, and adjusting an individualized care plan to the clinical response. Successful deprescribing also includes distinguishing withdrawal symptoms from possible relapse of a mental health condition. This Letter offers suggestions from physicians experienced in stopping antidepressants to manage challenging cases such as antidepressant withdrawal-induced akathisia or protracted withdrawal. Recommendations: To reduce the likelihood or severity of withdrawal symptoms, avoid abrupt discontinuation. For high risk patients, consider very gradual tapering over months or even years. Hyperbolic dose tapering can be facilitated by liquid formulations or compounding pharmacies. Monitor patients every two to four weeks after each dose reduction, with the option to pause or reverse a dose taper as needed. Patient education, shared decision-making, and informed consent to deprescribing should minimize harms and improve outcomes.