Effectiveness of Escitalopram and Nortriptyline on Depressive Symptoms in Parkinson's disease: the ADepT-PD RCT pilot.

Background: There is insufficient evidence on the effectiveness of different antidepressants in Parkinson's disease. This trial was commissioned to provide robust evidence regarding the effectiveness of a tricyclic and a selective serotonin reuptake inhibitor on depression in people with Parkinson's disease. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the tricyclic nortriptyline and the selective serotonin reuptake inhibitor escitalopram in addition to standard psychological care in the National Health Service in the treatment of depression in Parkinson's disease. Design: Forty-seven-month, multisite, three-arm, placebo-controlled, double-blind, randomised controlled trial, with an internal pilot phase. Four hundred and eight patients with a 1 : 1 : 1 randomisation between placebo, nortriptyline and escitalopram. The pilot study aimed to recruit 46 participants in the first 6 months from 10 sites to decide whether the trial is feasible. Interventions: Participants were treated with nortriptyline (target dose 100 mg in patients 65 and under, or 50 mg in patients over 65 or those with hepatic impairment), escitalopram (target dose 20 mg in patients 65 and under, or 10 mg in patients over 65 or those with hepatic impairment) or placebo, in addition to available standard psychological care. Outcomes: The primary outcome measure was the Beck Depression Inventory-II at 8 weeks. Secondary outcomes included clinician- and patient-reported outcomes, with safety summaries. Results: Fifty-two patients were recruited and randomised to receive either nortriptyline, escitalopram, or a placebo-matched tablet. This was effectively the internal pilot period, with the trial being truncated at this point. There was a reduction in Beck Depression Inventory-II scores between baseline to week 8 in all arms. In the placebo arm, this was from a mean of 24.3 (SD 7.8) at baseline to 15.7 (SD 5.8) at week 8, in the nortriptyline arm from 20.5 (SD 3.8) to 12.6 (SD 8.1), and in the escitalopram arm from 23.3 (SD 8.0) to 14.6 (SD 8.4). The reduction in Beck Depression Inventory-II scores was not significantly different between either of the two active arms and the placebo arm, with a mean change of -3.1 (95% confidence interval -8.66 to 2.53, p = 0.28) in the nortriptyline versus placebo comparison, and a mean change of -0.7 (-6.11 to 4.70, p = 0.80) in the escitalopram versus placebo comparison. There was however a statistically significant difference in reduction of Patient Health Questionnaire-9 items scores between the nortriptyline and the placebo arm (p = 0.01) but not the escitalopram compared to the placebo arm (p = 0.33). There were no differences in adverse events, Movement Disorders Society Unified Parkinson's Disease Rating Scale scores or Montreal Cognitive Assessment scores. Descriptive analysis of health economic outcomes suggested no significant differences across time periods or groups. Limitations: This trial was limited by low number of patients with depression in Parkinson's disease who could be recruited. Future work: Future trials should concentrate on one rather than two medications to reduce the number of ineligible patients as well as the sample size. Alternatively, a three-arm comparison with a compound not currently available but with potential added benefit may also increase recruitment rate. Conclusions: The ADepT-PD trial was terminated at the end of the pilot phase due to low recruitment. Only limited conclusions can be drawn as to the efficacy and safety of the active treatments. Trial registration: This trial is registered as NCT03652870. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/145/01) and is published in full in Health Technology Assessment; Vol. 29, No. 57. See the NIHR Funding and Awards website for further award information.