ETD

• antidepressants
• anxiety
• depression
• Parkinson

Background: Depression and anxiety are highly prevalent non-motor symptoms in patients with Parkinson’s disease (PD), significantly affecting quality of life and disease outcomes. Despite their clinical relevance, evidence comparing the efficacy and tolerability of different antidepressant classes in PD remains limited and inconsistent.

Objective: This study aimed to retrospectively compare the effectiveness and tolerability of three classes of antidepressants, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin–norepinephrine reuptake inhibitors (SNRIs), in the treatment of depressive and anxiety symptoms in patients with PD.

Methods: We conducted a naturalistic, observational follow-up study of 29 PD patients with clinically significant depressive and/or anxiety symptoms treated with TCAs (n = 12), SSRIs (n = 9), or SNRIs (n = 8) at the University Hospital of Pisa between February 2020 and February 2025. Clinical assessments were performed at baseline, 3 months, and 12 months using the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS, depressive/anxiety subscale). Linear mixed-effects models were used to assess changes over time and between treatment groups.

Results: Baseline characteristics were broadly comparable across groups, although patients prescribed SNRIs exhibited later onset of psychiatric symptoms, fewer lifetime depressive episodes and milder symptoms. At 3 months, patients treated with TCAs showed greater symptom improvement than those receiving SSRIs or SNRIs, both on the CGI (trend-level significance, p = 0.08) and BPRS subscale (p < 0.05). By 12 months, depressive/anxiety symptoms improved significantly in all groups, and between-group differences were no longer significant, suggesting convergence of outcomes over time. Adverse effects were reported in 38% of patients overall, with xerostomia and constipation more common with TCAs, somnolence with SSRIs, and tremor with SNRIs; discontinuation rates were low and comparable across groups.

Conclusions: TCAs were more often prescribed to patients with earlier and more severe psychiatric histories and were associated with greater short-term improvement, while SSRIs showed slower response but good tolerability. SNRIs were used mainly in later-onset, milder cases, with intermediate outcomes. Over one year, all antidepressant classes were associated with significant clinical improvement, supporting individualized treatment strategies that balance efficacy, tolerability, and patient characteristics.