Abstract

Aims: This meta-analysis aimed to evaluate the efficacy and tolerability of antidepressants monotherapy for behavioral and psychological symptoms of dementia (BPSD), with secondary assessments of agitation, psychosis, and cognition.

Method: We systematically searched 10 databases for randomized controlled trials (RCTs) comparing antidepressants monotherapy versus placebo in BPSD patients. Inclusion criteria encompassed RCTs with dementia diagnoses (Alzheimer’s disease, vascular dementia, etc.) and standardized outcome measures. Risk of bias was assessed using the Cochrane tool. Primary outcomes included changes in neuropsychiatric symptom scales; secondary outcomes comprised agitation, psychosis, cognition, and adverse events. Pooled estimates were calculated using random/fixed-effects models.

Results: Eight RCTs (676 patients) were included. Antidepressants showed a small beneficial effect on overall BPSD (SMD = -0.21, 95% CI [-0.38 to -0.04], p = 0.01), but this disappeared after excluding high-dose citalopram trials (>30 mg/day). Psychosis improved significantly (SMD = -0.49, 95% CI [-0.84 to -0.13], p = 0.007), while agitation and cognition showed no differences (p > 0.05). Antidepressants were well-tolerated, with no increased risk of all-cause discontinuations (RR = 1.17, 95% CI [0.89–1.54]) but higher incidences of dizziness and diarrhea.

Discussion: Antidepressants may modestly improve BPSD, particularly psychosis, potentially serving as alternatives to antipsychotics. Citalopram exhibited notable efficacy, though its cardiac risks at higher doses warrant caution. The lack of agitation improvement contrasts with prior studies, possibly due to exclusion of combination therapies. Limitations include small sample sizes, geographic bias, and short trial durations.

Conclusions: Antidepressants monotherapy demonstrates limited efficacy for overall BPSD but may alleviate psychosis. Citalopram (≤30 mg/day) shows promise, though safety monitoring is critical. Further large-scale, long-term RCTs are needed to clarify optimal agents and dosing.