Treatment of progressive supranuclear palsy with amitriptyline: therapeutic and toxic effects

Progressive supranuclear palsy (PSP) is a parkinsonian-like disorder characterized by postural instability, rigidity, bradykinesia, supranuclear ocular palsy, dysarthria, dysphagia, and dementia. There is no satisfactory treatment. Two patients with advanced (PSP) reported here had clinically meaningful improvement in motor function on low dose amitriptyline (AMI) but developed cognitive and behavioral disturbances at higher doses.

During 11 weeks of upward dose titration, a 65-year-old man was partially relieved of severe bradykinesia, dysarthria, and dysphagia at an optimal dose of 40 mg bid (plasma AMI 39 ng/mL) such that he could feed himself, swallow easily, and transfer from wheelchair to toilet. Nocturnal confusion and urinary incontinence appeared at 70 mg bid, then resolved at 40 mg bid. Benefits were sustained during the next 14 months. A 77-year-old man had substantial relief of severe rigidity, bradykinesia, poor balance, and blepharospasm at 10 mg bid, such that he could feed himself and walk independently. At 40 mg bid (plasma AMI 62 ng/mL) 3 weeks later, he became aggressive, irritable, and increasingly confused. He reverted to his untreated state with drug withdrawal, then improved when AMI was reintroduced at 10 mg bid (plasma AMI 17 ng/mL).

Low dose AMI may improve severe motor dysfunction in PSP significantly. Dosing must be individualized for optimal response and minimal toxicity.