Authors' objectives: 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. 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. The Antidepressants for depression in people with Parkinson’s Disease (ADepT-PD) trial was a three-armed randomised placebo-controlled trial to test the effectiveness and cost-effectiveness of a tricyclic and a selective serotonin re-uptake inhibitor (SSRI) on depression in people with Parkinson’s disease (PD) with an internal pilot study. The tricyclic nortriptyline (target dose 100 mg), and the SSRI escitalopram (target dose 20 mg) were compared to placebo, in addition to available standard psychological care. Primary objective The aim of the ADepT-PD trial was to determine the clinical effectiveness and cost-effectiveness of an 8-week course of nortriptyline (target dose 100 mg), the SSRI escitalopram (target dose 20 mg) in the treatment of depression in PD. The primary outcome was the Beck Depression Inventory (BDI) II at 8 weeks of treatment.

Authors' results and conclusions: 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. 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. Screening and recruitment A total of 1396 patients were screened for entry onto the trial, but only 52 patients were recruited and randomised into the ADepT-PD trial. Seventeen participants were randomised to the escitalopram group, 16 to the nortriptyline and 19 participants were randomised to the control group. The ADepT-PD trial was terminated at the end of the pilot phase, because it did not meet its go/no-go criteria. The main issues were a low recruitment rate owing to high rate of screen failure and patient interest, difficulties in timely identifying the condition and more widespread use of the medications than expected.

Authors' methods: 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. 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. This trial was limited by low number of patients with depression in Parkinson’s disease who could be recruited. The ADepT-PD trial was funded to be a definitive, multisite, three-arm, placebo-controlled, double-blind, Phase IV randomised controlled trial in response to a commissioning brief set by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme. The trial had an internal pilot phase with prespecified go/no-go criteria. The trial aimed to randomise participants (1 : 1 : 1) into either the nortriptyline group – 12-month course of up to 100 mg of nortriptyline per day; the escitalopram group – 12-month course of up to 20 mg of escitalopram per day; or the control group – 12-month course of matched placebo.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/16/145/01

Year Published: 2025

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/HFDO7575

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/HFDO7575

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk