Tolerability and adherence issues
in antidepressant therapy

Masand PS.
Program for Continuing Medical Education,
Duke University Medical Center,
Durham, North Carolina, USA
Clin Ther. 2003 Aug;25(8):2289-304


BACKGROUND: Despite the availability of effective antidepressants, recurrence and relapse rates for depression are high (up to 80%), treatment failures are common (40% to 60%), and as many as 20% of patients remain inadequately treated. Depression treatment guidelines are often not followed, and rates of nonadherence to treatment are high, with 28% of patients discontinuing antidepressant treatment within the first month and 44% discontinuing within 3 months of initiating therapy.OBJECTIVE: The aim of this article was to summarize research on antidepressant therapy nonadherence and examine the limitations of strategies used to minimize adverse events (AEs) and improve treatment duration.METHODS: A thorough search of the published literature from 1990 to the present was performed on MEDLINE and other search engines. The following search terms were used: tolerability, antidepressants, patient compliance, adherence, therapy, SSRIs, tricyclics, and other related terms focusing on specific agents.RESULTS: Physician-specific issues represent some of the most important obstacles to adequate antidepressant therapy. Inadequate patient education, prescription of inappropriate medications or inadequate dosages, and lack of follow-up care are all issues the physician can control to improve patient adherence. Patient-specific issues include poor motivation (due to symptoms of depression) to continue therapy, failure to perceive a benefit, and concerns about cost of therapy. Medication-specific issues such as treatment-related AEs, delayed onset of action, complicated dosing or titration schedule, and subtherapeutic dosing also contribute to treatment discontinuation. Therapy with >/=I antidepressant and/or atypical antipsychotic may improve symptom control, but little evidence exists regarding efficacy and safety. Dosage reduction has been attempted to reduce events that may lead to patient discontinuation, but this may increase the risk of recurrent depressive episodes.CONCLUSIONS: To maximize patient adherence to antidepressant therapy, it is necessary to combine adequate treatment duration, realistic patient expectations, and the right dose of an agent capable of treating the full range of symptoms while controlling for AEs.
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