Placebo-controlled three-armed pilot trial of Escitalopram or Nortriptyline for depressive symptoms in Parkinson’s disease (ADepT-PD)

Pilot randomised-controlled trial of nortriptyline and escitalopram compared to placebo for depressive symptoms in people with Parkinson's disease (PD). Participants with PD and depressive symptoms received either nortriptyline, escitalopram or placebo with assessments at baseline and 8 weeks. Feasibility of the full trial was assessed using recruitment rate, loss to follow up before the 8-week primary endpoint, adherence to trial medication and rate of clinically significant adverse reactions. Intended efficacy outcomes included the BDI-II, Patient Health Questionnaire (PHQ-9), Parkinson Anxiety Scale (PAS), MDS-UPDRS and adverse effects. The aim was to recruit 46 participants to determine feasibility of the full trial. 52 participants were recruited from 24 NHS sites and randomised to nortriptyline (n = 16), escitalopram (n = 17) or placebo (n = 19). However, despite multiple strategies, recruitment took two years, and the study therefore did not reach its feasibility aim. Exploratory analyses showed that at 8 weeks depressive symptoms decreased significantly in all three arms. There was no difference in BDI-II score changes between the nortriptyline or the escitalopram when compared to the placebo arm, but PHQ-9 scores showed a greater reduction compared to placebo with nortriptyline (-3.4, 95% CI -5.75 to -0.95) but not with escitalopram (-1.2, 95% CI -3.54 to -1.17). Persistent Anxiety Scale scores showed a similar pattern (nortriptyline: -2.8, 95% CI -5.5 to -0.01; escitalopram: -2.2, 95% CI -4.9 to 0.05). As the study did not reach its primary aim of feasibility due to recruitment difficulties it did not continue to the full trial. The exploratory results are in keeping with previous studies suggesting a beneficial effect of nortriptyline on symptoms of depression and persistent anxiety. The small sample size however limits conclusions on efficacy and a beneficial effect of escitalopram is not excluded. STUDY DATASET IS AVAILABLE ON CLINICALTRIALS.GOV ID: NCT03652870, registered 29 August 2018.