DATATOP
Effect of deprenyl on the progression of disability in early Parkinson's disease: The Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial
Clinical Question
Do deprenyl (selegiline) and tocopherol delay the need for levodopa therapy in early Parkinson's disease?
Study Overview
Objective
DATATOP evaluated whether deprenyl (selegiline) or tocopherol delayed disability progression and the need for levodopa in early Parkinson's disease.
Study Summary
- Deprenyl delayed need for levodopa by ~9 months vs placebo
- Tocopherol showed no significant benefit
- Deprenyl improved UPDRS and functional scores
Intervention
800 patients with early PD randomized to deprenyl, tocopherol, both, or placebo and followed until levodopa was required or 2 years.
Patients per Arm
200 per arm
Bottom Line
Selegiline (deprenyl) 10mg/day significantly delayed the need for levodopa in early PD by ~9 months (HR 0.50; P<0.001). Tocopherol (vitamin E, 2000 IU/day) had no effect. Published NEJM 1993. 800 patients, 28 US/Canadian sites. Landmark trial establishing MAO-B inhibitors as early PD treatment.
Major Points
- Selegiline delayed levodopa need: HR 0.50 (P<0.001). Median delay ~9 months vs placebo.
- Tocopherol (vitamin E) had no effect: HR 0.91 (P=0.52).
- 800 early untreated PD patients. 2×2 factorial: selegiline ± tocopherol ± placebo.
- Primary endpoint: time to disability requiring levodopa initiation.
- Selegiline 10mg/day. Tocopherol 2000 IU/day. Double-blind. 28 US/Canadian sites.
- Debate: symptomatic effect vs neuroprotection. Washout studies suggested some disease modification.
- UPDRS improvement with selegiline was rapid (~3 months) — consistent with symptomatic benefit.
- Long-term follow-up showed selegiline benefit diminished over time — favoring symptomatic mechanism.
- Published NEJM 1993 (Parkinson Study Group). NINDS funded.
- Landmark trial: first large RCT of neuroprotective strategy in PD. Led to MAO-B inhibitor era.
Design
Study Type: Randomized, double-blind, placebo-controlled, 2x2 factorial trial
Randomization: 1
Blinding: Patients, investigators, and outcome assessors were blinded to treatment assignment
Enrollment Period: 1987–1988
Follow-up Duration: Up to 2 years or until levodopa needed
Centers: 28
Countries: USA, Canada
Sample Size: 800
Analysis: Intention-to-treat; Kaplan–Meier survival analysis, log-rank test, proportional hazards model
Inclusion Criteria
- Idiopathic Parkinson's disease
- Mild symptoms not requiring levodopa
- Hoehn and Yahr stage I or II
- Age ≥30 years
Exclusion Criteria
- Use of antiparkinsonian medications
- Significant comorbid illness
- Non-idiopathic Parkinsonism
- Severe depression or cognitive impairment
Arms
| Field | Deprenyl | Tocopherol | Deprenyl + Tocopherol | Control |
|---|---|---|---|---|
| Intervention | 10 mg/day oral selegiline (deprenyl) | 2000 IU/day vitamin E (tocopherol) | Combination of 10 mg/day selegiline and 2000 IU/day tocopherol | Matching placebo capsules |
| Duration | Until endpoint (levodopa initiation or 2 years) | Until endpoint | Until endpoint | Until endpoint |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Time from randomization to disability requiring levodopa | Primary | Mean 491 days | Deprenyl group: mean 667 days | <0.001 | |
| UPDRS score change | Secondary | Greater worsening over time | Improved or stabilized in deprenyl groups | <0.001 | |
| Schwab and England ADL scale | Secondary | Lower scores | Higher scores with deprenyl | <0.001 | |
| Nausea | Adverse | 8% | 11% | ||
| Insomnia | Adverse | 4% | 14% | ||
| Orthostatic symptoms | Adverse | 3% | 8% |
Subgroup Analysis
Effects of deprenyl consistent across age, sex, and baseline disability strata; tocopherol showed no benefit alone or in combination
Criticisms
- Cannot distinguish symptomatic from disease-modifying effect of deprenyl
- No washout period before levodopa initiation
- Limited diversity in study population
- Follow-up limited to need for levodopa, not long-term progression
Funding
National Institute of Neurological Disorders and Stroke (NINDS)
Based on: DATATOP (The New England Journal of Medicine, 1989)
Authors: Ira Shoulson, Stanley Fahn, Carolyn Lang, ..., J. Timothy Penney
Citation: N Engl J Med. 1989 Sep 14;321(20):1364–1371. doi:10.1056/NEJM198911163212002
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