Among the Parkinson’s patients, one of the most commonly asked questions is – if the blood pressure and diabetes pills need to be taken only once a day, how come there is no such Parkinson’s medications? Most of the patients who asked me this question were those who were taking dopamine agonists (as these medications are usually taken thrice daily). It is not uncommon for patients to forget the second or third dose of medications.
Thus, the expected arrival of the once-daily DAs, namely Extended Release / ER Pramipexole (Sifrol) and Ropinirole (Requip PD) in Malaysia, has been much awaited by many Parkinson’s patients. Unlike the Immediate Release (IR) Pramipexole and Ropinirole which are taken thrice daily, ER Pramipexole and Requip PD need to be taken just once a day. This is good news especially for those who are in the early stage of illness and taking either one of these DAs only – just take one tablet of ER Pramipexole or Requip PD with breakfast and when you leave home for work, you can forget about the Parkinson’s medications for the whole day. As such, the new once-daily DAs are convenient to take, and certainly improve compliance with medications.
In addition, these new DAs provide a more continuous delivery of medication to the brain, and thus may enhance the efficacy of symptomatic control of Parkinson’s over a 24-hour period.
However, ER Pramipexole and Requip PD are not the first DAs which are available in once-daily dosage. Cabergoline, an ergot-derived dopamine agonist, has been around for a long time, and is taken once daily. However, the ergot-derived dopamine agonists have nowadays fallen out of favour due to the risk of thickening of heart valve and lung associated with these medications. Fortunately, the non-ergot dopamine agonists such as Pramipexole and Ropinirole are not associated with heart valve and lung disorders.
ER Pramipexole (Sifrol)
The results of two double-blind studies on ER Pramipexole which were presented at the recent American Academy of Neurology meeting were encouraging.
The first study was carried out on early stage Parkinson’s, and compared the efficacy, safety and tolerability of ER Pramipexole with the currently available Pramipexole (IR or immediate release formulation) and placebo (Hauser R et al, 2009). It was shown that ER Pramipexole was superior to placebo and had comparable efficacy to the IR Pramipexole.
The second study which involved early stage Parkinson’s showed that 85% of patients successfully completed an overnight switch from IR Pramipexole to ER Pramipexole at the same daily dose, i.e. 1:1 conversion ratio (Rascol O et al, 2009).
In fact, ER Pramipexole is beneficial at all stages of Parkinson’s. Another study which was carried out on advanced stage Parkinson’s patients showed that ER Pramipexole was as efficacious as IR Pramipexole in decreasing the “off” periods (Schapira A et al, 2009).
In view of the results of these studies, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a recommendation, stating that ER Pramipexole is indicated for treatment of both early and advanced stage of Parkinson’s.
Anti-depressant effect of Pramipexole
Depression is a common and disabling non-motor symptom in Parkinson’s. What is remarkable is that Pramipexole has been shown to be able to improve depressive symptoms in Parkinson’s patients (Barone P, 2009). Thus, Pramipexole is a reasonable option for Parkinson’s patients who have depression in addition to the typical motor symptoms. It has been shown that the anti-depressant property of Pramipexole is independent of its positive effect in relieving the motor symptoms of Parkinson.
Similar to ER Pramipexole, the results of several studies on Requip PD have been encouraging.
One study on early stage Parkinson’s showed that the efficacy and tolerability of Requip PD were comparable to that of IR Ropinirole (Stocchi F, 2008). In this study, patients were successfully switched overnight from IR Ropinirole to Requip PD with a conversion ratio of 1:1. It was also shown that compliance with medication was better among those who were on Requip PD.
In another study which was carried out on advanced stage Parkinson’s, Requip PD was shown to reduce the duration of “off” periods and the daily dose of levodopa (Pahwa R, 2007).
These studies suggest that Requip PD is beneficial in both early and advanced stages of Parkinson’s.
Requip PD improves nocturnal symptoms
Nocturnal symptoms refer to disturbances which are experienced during sleep such as “off” period cramps and stiffness, which lead to frequent awakening. Sleep disorders are common and disabling non-motor symptoms in Parkinson’s. In the Real Life, Real PD survey which was organized by the European Parkinson’s Disease Association, it was found that three-quarter of patients had difficulties in getting to sleep and 72% wake at least once during the night. A quarter of patients rated their quality of sleep as either poor or very poor.
Requip PD has been reported to be effective in improving the nocturnal symptoms of Parkinson’s (such as sleep disruption and cramps) by 20% (Chaudhuri K, 2009). These findings are attributed to the continuous 24-hours delivery of Ropinirole to the brain, resulting better control of symptoms throughout day and night.
What are the potential side effects of ER Pramipexole and Requip PD?
The side effects of these medications are expected to be the same as the IR Pramipexole and Ropinirole, such as nausea, vomiting, dizziness and hallucination.
Barone P et al. Pramipexole ameliorates depression in Parkinson’s disease: A randomized double-blind vs placebo trial. Abstract S43.004, presented during scientific session ‘Evaluation and Treatment of Parkinson’s Disease’ on 30 April 2009 at AAN 61st Annual Meeting, Seattle, USA.
Chaudhuri RK, et al. “Ropinirole prolonged release improves nocturnal symptoms in patients with advanced Parkinson’s disease with sleep disturbances” ICPDMD 2009; Abstract Mo-192.
Hauser R et al. Double-blind evaluation of pramipexole extended-release (ER) in early Parkinson’s disease. Abstract S43.003 presented on 30 April 2009 at AAN 61st Annual Meeting, Seattle, USA.
Pahwa R, Stacy MA, Factor SA, et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology 2007; 68: 1108–1115.
Rascol O et al. Overnight switching from immediate- to extended-release pramipexole in early Parkinson’s disease. Abstract P06.152 presented on 29 April 2009 at AAN 61st Annual Meeting, Seattle, USA.
Schapira A et al. Efficacy and safety of pramipexole extended-release for advanced Parkinson’s disease. Poster We-199 (presented at MDS International Congress, Paris, France, 9 June 2009).
Stocchi F, Hersh BP, Scott BL, et al. Ropinirole 24-hour prolonged release and ropinirole immediate release in early Parkinson’s disease: a randomized, double-blind, non-inferiority crossover study. Curr Med Res Opin. 2008; 24: 2883–2895.