Parkinsons disease Recurrent Off periods

Effective treatments for reducing "off" periods in Parkinson's disease include carbidopa/levodopa enteral suspension (Duopa), levodopa inhalation powder, sublingual apomorphine film, and add-on medications like safinamide and istradefylline, all of which have demonstrated significant improvements in managing off-periods.

The following treatment modalities are proven effective to decrease “off” periods and prolong the efficacy of antiparkinson medicine.

Carbidopa/Levodopa Enteral Suspension (Duopa):

In a multicentre trial, the enteric suspension at maximum daily dose of 2000 mg daily administered over 16 hours (reduced the mean off- period by 4.04 hours. (1)

Levodopa Inhalation Powder:

In a phase 3 trial; compared to placebo, the inhaled powder of Levodopa showed improvement in mean motor score change by a median of -5·91 and hence “off” periods. Treatment was safe and well tolerated. (2)

Sublingual Film Formula of Apomorphine:

Recently, in 2020, a sublingual film formula of apomorphine was introduced as an on- demand formula for sudden "off" periods in patients with advanced Parkinson disease. (3)

Add-On Treatments to Levodopa/Carbidopa:

A-Safinamide (Xadago), which is a MAOB inhibitor. Trials showed that safinamide at 50 mg per day, as add- on treatment to levodopa/ carbidopa provided a significant reduction in off- periods. (4) B-Istradefylline (Nourianz) which is a selective adenosine A2A antagonist was approved in late 2019. Four randomized, placebo controlled trials showed statistically significant decrease in “off” periods with the addition of istradefylline at 20 mg daily.(5)

References

1-Schapira AH; Fox SH; Hauser RA; Jankovic J; Jost WH; Kenney C; Kulisevsky J; Pahwa R; Poewe W; Anand R: Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and

Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol. 2017; 74(2):216-224 (ISSN: 2168- 6157)

2- LeWitt PA, Hauser RA, Pahwa R, et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol 2019; 18:145.

3-Olanow CW, Factor SA, Espay AJ, Hauser RA, Shill HA, Isaacson S, Pahwa R, Leinonen M, Bhargava P, Sciarappa K, Navia B, Blum D, CTH-300 Study investigators Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo -controlled phase 3 study. Lancet Neurol. 2020;19(2):135. Epub 2019 Dec 7.

4-Borgohain R; Szasz J; Stanzione P; Meshram C; Bhatt M; Chirilineau D; Stocchi F; Lucini V; Giuliani R; Forrest E; Rice P; Anand R: Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Mov Disord. 2014; 29(2):229-37 (ISSN: 1531-8257)

5-Mizuno Y; Kondo T: Adenosine A2A receptor antagonist istradefylline reduces daily OFF time in Parkinson's disease. Mov Disord. 2013; 28(8):1138-41 (ISSN: 1531-8257)