Vol.:(0123456789) 1 3 Journal of Neural Transmission https://doi.org/10.1007/s00702-020-02257-0 NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE Comparison of efectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson’s disease Lulup Kumar Sahoo 1  · Vikram Venkappayya Holla 1  · Dhruv Batra 1  · Shweta Prasad 1,2  · Amitabh Bhattacharya 1  · Nitish Kamble 1  · Ravi Yadav 1  · Pramod Kumar Pal 1 Received: 4 July 2020 / Accepted: 22 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020 Abstract Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson’s disease (PD), the mecha- nism of action and exact beneft is unclear. This study compared the efectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was signifcantly bet- ter compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS- III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS- III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had signifcantly milder base- line tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed signifcant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not signifcantly diferent to that obtained by LD. Those with better tremor response on THP had milder tremor severity. Keywords Parkinson’s disease · Trihexyphenidyl · Levodopa · UPDRS-III · Tremor Introduction Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Its incidence is around 1% in persons aged 65 years or older with an estimated preva- lence of 6.2 million worldwide in 2016, and is expected to double by 2040 (Dorsey and Bloem 2018; Dorsey et al. 2018). PD is characterized by muscle rigidity, rest- ing tremor, bradykinesia, and postural instability. From a biochemical perspective, it is caused by degeneration of dopaminergic neurons in the basal ganglia. Dopaminergic medications like levodopa (LD) and dopamine agonists remain the primary and most commonly used pharma- cological agents in the treatment of PD (Orayj and Lane 2019; Surathi et al. 2017). However, anti-cholinergic med- ications were the frst drugs used. (Brocks 1999; Rober- son 2017) The basis of therapeutic action in PD is incom- pletely understood. Anti-cholinergics appear to improve symptoms by modulating the central anti-cholinergic efect exerted within the neostriatum, and ameliorates the state of cholinergic hypersensitivity which occurs secondary to dopamine depletion (Roberson 2017). Despite the addition of newer medications for PD, anti-cholinergic drugs still Lulup Kumar Sahoo, Vikram Venkappayya Holla contributed equally to this work. * Pramod Kumar Pal palpramod@hotmail.com 1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru 560029, India 2 Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru 560029, India