Once Daily Cabergoline Successfully Controls Sleep Disturbances

Up to 96 percent of patients with Parkinson's disease (PD) experience serious sleep disturbances caused by many factors,1 however, these symptoms are often overlooked by doctors. As a consequence many patients suffer from excessive daytime sleepiness, impaired cognitive ability and an overall diminished quality of life, warned researchers presenting at the International Congress of the European Federation of Neurological Societies (14th-18th October, 2000; Copenhagen).

To improve PD management, researchers presented encouraging findings on new ways of monitoring PD symptoms, including sleep disturbance and motor problems. In two separate presentations, researchers presented data using a newly designed Parkinson's Disease Sleep Scale (PDSS), a patient-administered questionnaire which could help clinicians diagnose nocturnal disability quickly and provide a useful tool to monitor response to treatment. Actigrapy, the second test discussed, measures limb motor activity and circadian variations by use of a special device called an Actigraph. Using both testing methods, investigators evaluated the efficacy of the long-acting dopamine agonist cabergoline (CABASER/CABASERIL tablets) on sleep disturbances in PD patients and found cabergoline offers important benefits, possibly due to its long duration of action, in achieving significant improvement of the symptoms underlying PD during the night as well as the day.

Dr K. Ray Chaudhuri, Consultant and Honorary Senior Lecturer at Kings College Hospital, London, explained that current methods lack quantitative aspects, thereby making them inadequate for the precise assessment of symptoms and treatment. The most commonly employed sleep questionnaire that is traditionally used in clinical practice is the Epworth Sleepiness Scale (ESS). Although motor disturbances are an important cause of sleep disturbance, the ESS scale only gives a general indication of daytime sleepiness and does not address the nature of the sleep disruption common in patients with PD.

Dr Chaudhuri advised, "Sleep disturbance, insomnia and its implications such as excessive daytime sleepiness are a major cause of morbidity and impaired quality of life for patients with PD. We need to be aware of the impact of sleep disturbance on PD patients' lives, and should treat them with therapies shown to improve this problem".

He presented results in a group of patients who used the PDSS. The PDSS measures the level of sleep disturbance by asking patients to assess the severity of 15 commonly reported symptoms associated with sleep disturbance in PD, with an easy-to-use visual scale. The PDSS has demonstrated the ability to objectively quantify the effects of drug therapy in the management of sleep symptoms.

Results from 62 patients (mean age 65.9 years), diagnosed with PD an average of 6.1 years, showed that the mean total PDSS score was 92.0 out of a maximum score of 150 (range 46-150, with a lower score indicating more sleep disturbance). A group of 16 patients in the study were tested before and after treatment with cabergoline, given for a mean period of eight months. Dr Chaudhuri reported that the mean total PDSS for this subgroup increased from 76.3 before treatment, to 99.1 post-therapy.

Explaining the results Dr Chaudhuri said, "Cabergoline therapy achieved statistically significant improvements in patients' quality of sleep over six of the 15 key symptoms of sleep disturbance. There were improvements in the patients' subjective rating of their sleep quality and a reduction in nocturnal awakenings". He suggested, "These improvements are likely due to the very long half-life of cabergoline (more than 65 hours) which allows improved symptom and fluctuation control throughout the night as well as the day".

Actigraphy -- Improving the assessment of movement disorders in PD Professor Soichi Katayama, Professor Emeritus of Neurology at Southern Tohoku General Hospital in Tokyo, Japan, presented findings using the second new assessment technique - actigraphy - which has been developed to more accurately measure motor limb activity occurring in PD. PD is characterised by a delay in starting movements, increased time to carry out movements and difficulty in sustaining activity to reach a goal. These symptoms - called akinesia - are accompanied by sudden acceleration of movement which can be measured quantitatively by actigraphy. A group of patients with advanced PD were monitored using actigraphy over 24 hours for several days before and after cabergoline was added as adjuvant therapy to levodopa.

Professor Katayama explained, "Results from actigraphic studies demonstrated that cabergoline significantly improved motor function, activities of daily living and fluctuations of response to long-term levodopa use in patients with PD". He also advised, "Actigraphy will be useful in helping doctors determine the least effective dose of dopamine agonist necessary to achieve optimal improvement in akinesia which previously has been difficult to assess accurately".

Additional studies presented confirm efficacy of cabergoline

Additional research presented at the meeting supports the use of cabergoline in the management of PD patients. Presenting the findings, Dr Horst Baas, Head of the Dept. of Neurology and Geriatrics in Hanau/Germany, referred to data from three observational studies. In the studies the therapeutic behaviour of cabergoline in the daily clinical routine use was reviewed in patients with advanced PD. All studies were looking at adverse events, efficacy, dosing and interactions with other medications. The largest study, the Optimised Parkinson's Therapy in Long-Term-Use Study (OPTiL) involved 721 patients with advanced PD, which were insufficiently controlled by their previous therapeutic regimen and requiring additional medication. Three groups, using either cabergoline (n=131) or an other dopamine agonist or other non-dopaminergic co-medication as add on, were observed for up to two years. Among the three groups quality of life was best preserved under cabergoline over two years and investigators concluded that cabergoline therapy is safe and effective in long term use.

A second study of 585 patients with PD, who underwent a planned switch from another dopamine agonist to cabergoline and were observed for 2 to 6 weeks showed that most patients experienced a clear therapeutic improvement in activities of daily living by about a mean 10% on the UPDRS VI scale in 2/3 of the patients. Switch was very well tolerated by almost all patients with a drop out rate of only 3/585 patients. Dr Baas commented, "The new data indicate that the vast majority of patients in this study treated with cabergoline reported an improvement in their symptoms which was achieved with a once-a-day administration."

The most common side effects were gastrointestinal complaints and there were two serious adverse events reported (syncope and diarrhoea).

Cabergoline is currently the only dopamine agonist shown to be effective when administered as a once-a-day dose. It has a longer duration of action than any other treatment for Parkinson's disease, giving proven symptom and fluctuation control over 24 hours.2

For further information and full prescribing information, please contact:
Karen Sutherland, Pharmacia Corporation
Tel: + 1 908 901 8584 (NJ office)

Roseann Ward, Ketchum, London
Tel: + 44 (0) 207 465 8752

References:
1. Chaudhuri KR, et al. The use of cabergoline in nocturnal Parkinsonian disabilities causing sleep disruption: a parallel study with controlled release levodopa. Eur J Neurol 1999:6(suppl 5): S11-15.
2. Musch B, Bonura L. Cabergoline once-a-day as adjunctive therapy to levodopa in Parkinson's disease. Poster presentation, 6th International Congress of Parkinson's Disease and Movement Disorders, June 13 2000, Barcelona, Spain.

Notes to Editors:

Parkinson's disease is a chronic and progressive disorder that results from the death of nerve cells in a critical area of the brain called the substantia nigra. Dopamine is the chemical that allows the brain to send messages to the body, allowing normal muscle movement. The loss of dopamine causes Parkinson's symptoms that include a shuffled walk, shaking hands, drooling, slowed speech and frozen facial expressions.

Dopamine agonists are among the most promising newer treatment approaches for Parkinson's disease. They mimic the action of dopamine by directly stimulating dopamine receptors in the brain.

Levodopa is traditionally regarded as the gold-standard treatment for Parkinson's disease, but after several years of use, it is associated with a number of different problems, reducing both its usefulness and effectiveness. Over time, patients have to increase the dosage of levodopa to maintain control of their symptoms. Levodopa also causes 'on-off' episodes, where patients find they suddenly fluctuate between mobility (an 'on-phase') and immobility (an 'off-phase'). There is also the problem of developing dyskinesia with long-term levodopa therapy, which in itself can be disabling.

CABASER/CABASERIL Tablets can be used for the treatment of Parkinson disease (PD), either as monotherapy in newly diagnosed patients or as adjunctive therapy to levodopa. The licence varies from country to country. Side effects reported during the studies were similar for both treatment groups and included, nausea, vomiting, heartburn and dizziness.

In Denmark, Germany, Japan, Sweden, Australia, Italy, Portugal and Austria cabergoline is licensed for use in Parkinson's disease with or without the addition of levodopa. In Finland, Norway, Ireland, Switzerland, Spain, France and the UK, it is indicated as adjunctive therapy to levodopa to control motor fluctuations. Cabergoline is marketed under the brand name CABASER in Denmark, Finland, Japan, Norway, Sweden, Australia, Switzerland and the UK and as CABASERIL in Germany. Full prescribing information is available upon request.

Pharmacia Corporation is a leading global pharmaceutical company created through the merger of Pharmacia & Upjohn and Monsanto Company with its G.D. Searle & Co. unit. Pharmacia (NYSE: PHA) has a broad product portfolio, a robust pipeline of new drugs, and an annual investment of more than $2 billion in pharmaceutical research and development.

Useful web sites:
� European Parkinson's Disease Association: http://www.shef.ac.uk/misc/groups/epda/home.html
� World Health Organization: http://www.who.org/
� We Move - World education and Awareness for movement disorders: http://www.wemove.org/