A five-year persistence of antidepressant polypharmacy and associated pharmacological risk in a community cohort

Introduction

Antidepressant polypharmacy is increasingly encountered in clinical practice, particularly in individuals with complex or treatment-resistant affective disorders. While combination therapy may be employed in cases of partial or inadequate response, the evidence supporting its long-term use remains limited. Concerns persist regarding cumulative pharmacological burden, drug–drug interactions, and adverse effects. In particular, the use of multiple serotonergic agents may increase the risk of toxicity, including Serotonin Syndrome, and contribute to increased healthcare utilisation through adverse effects and clinical instability [1,2]. Despite these concerns, there remains a relative lack of real-world longitudinal data examining the persistence of such prescribing patterns and their clinical trajectory over time.

Aims

To examine the persistence of antidepressant polypharmacy over a 5-year period and to evaluate its clinical implications, including specialist follow-up and hospital admissions, in a community cohort.

Methods

This was a retrospective cohort study derived from a comprehensive survey of prescribing patterns in a complete community-based population. Baseline medication data were collected, with follow-up conducted at 5 years. Antidepressant polypharmacy was defined as the concurrent use of two or more antidepressants. Demographic and clinical variables, including age, diagnosis, follow-up status, and hospital admissions over the follow-up period, were recorded. Diagnostic categories were grouped pragmatically to reflect routine clinical practice. Descriptive statistical analysis was performed using Microsoft Excel, with results reported as frequencies, percentages, and measures of central tendency.

Results

Of 244 individuals, 140 (57%) were prescribed at least one antidepressant at baseline. Thirty-one patients were receiving antidepressant polypharmacy (≥2 agents). At 5-year follow-up, 19 (61.3%) remained on polypharmacy, 8 (25.8%) had reduced to monotherapy, and 2 (6.5%) were no longer prescribed antidepressants; 1 (3.2%) was lost to follow-up and 1 (3.2%) had died. The mean age of the cohort was 48.9 years (SD 15.7). Affective-spectrum conditions (12/31) and mixed depressive/anxiety presentations (11/31) predominated, with additional diagnoses including personality disorders (7/31) and one case of schizoaffective disorder. At 5 years, 12 individuals (38.7%) had been discharged from specialist services, while 17 (54.8%) remained under ongoing specialist follow-up; one patient had died and one had transferred to another service. Over the follow-up period, 9 patients (29.0%) experienced at least one hospital admission. Recurrent admissions were observed in a subset, including three patients admitted twice and one patient admitted ten times, indicating a group with higher healthcare utilisation.

Conclusions

Antidepressant polypharmacy frequently persists over a 5-year period, with a majority of patients remaining on combination therapy. This persistence is associated with ongoing specialist care involvement and, in a subset, significant healthcare utilisation including recurrent hospital admissions. These findings suggest prolonged exposure to cumulative pharmacological burden, including recognised risks such as Serotonin Syndrome. In the context of limited evidence supporting long-term combination therapy, this highlights the importance of regular medication review, rationalisation, and careful monitoring in patients receiving multi-drug antidepressant regimens [1,2].

References

1. National Institute for Health and Care Excellence. Depression in adults: treatment and management (NG222). 2022.
2. Henssler J, Heinz A, Brandt L, Bschor T. Antidepressant polypharmacy for the treatment of depression: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73(10):1014–1022.