J Neurol Neurosurg Psychiatry 63:421-428 doi:10.1136/jnnp.63.4.421
  • Paper

Catechol-O-methyltransferase inhibition with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients

  1. H Baasa,
  2. A G Beiskeb,
  3. J Ghikac,
  4. M Jacksond,
  5. W H Oertele,
  6. W Poewef,
  7. G Ransmayr on behalf of the study investigators (see )f
  1. aKlinik fur Neurologie, Klinikum der Johann-Wolfgang-Goethe-Universitaet, Frankfurt, Germany, bDepartment of Neurology, Akershus Central Hospital, Nordbyhagen, Norway, cDepartment de Neurologie, CHUV, Lausanne, Switzerland, dDepartment of Neurology, Radcliffe Infirmary, Oxford, UK, eNeurologische Klinik, Klinikum der Philipps-Universitaet, Marburg, Germany, fAbteilung fur Neurologie, Virchow Klinikum, Berlin, Germany, and Universitaetsklinik fur Neurologie, Innsbruck, Austria
  1. Professor W H Oertel, Neurologische Klinik, Zentrum fur Nervenheilkunde, Philipps Universitat Marburg, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany. Telephone ++ 49 6421 286 279; fax: ++ 49 6421 288 955; e-mail: oertelw{at}
  • Received 28 January 1997
  • Revised 23 June 1997
  • Accepted 30 June 1997


BACKGROUND More than 50% of patients with Parkinson’s disease develop motor response fluctuations (the “wearing off” phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa.

OBJECTIVES The primary objective was to evaluate the efficacy of tolcapone in reducing “wearing off” in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients’ clinical status, duration of improvements, and tolerability of tolcapone.

METHODS In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide.

RESULTS After three months with 200 mg tolcapone tid, “off” time decreased by 26.2% of the baseline value, “on” time increased by 20.6% (P<0.01 v placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (P<0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, “off” time decreased by 31.5% (P<0.05), “on” time increased by 21.3% (P<0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (P<0.05). With 200 mg tolcapone tid, unified Parkinson’s disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhoea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhoea.

CONCLUSION Tolcapone prolongs “on” time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.


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