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DATATOP

Effect of deprenyl on the progression of disability in early Parkinson's disease: The Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial

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Year of Publication: 1989

Authors: Ira Shoulson, Stanley Fahn, Carolyn Lang, ..., J. Timothy Penney

Journal: The New England Journal of Medicine

Citation: N Engl J Med. 1989 Sep 14;321(20):1364–1371. doi:10.1056/NEJM198911163212002

Link: https://doi.org/10.1001/archneur.1989.00520460028009

Clinical Question

Do deprenyl (selegiline) and tocopherol delay the need for levodopa therapy in early Parkinson's disease?

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	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

Content summarized and formatted by NeuroTrials.ai.

DATATOP

(1989)

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.

Inclusion Criteria

Idiopathic PD, Hoehn and Yahr stage I–II, no need for levodopa, age ≥30

Study Design

Arms: Deprenyl, Tocopherol, Deprenyl + Tocopherol, Placebo

Patients per Arm: 200 per arm

Outcome

• Time to levodopa: 667 vs 491 days (P<0.001)
• Deprenyl improved UPDRS and ADL scores
• No increase in serious adverse events

Bottom Line

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.

Study Design

Study Type: Randomized, double-blind, placebo-controlled, 2x2 factorial trial
Randomization: Yes
Blinding: Patients, investigators, and outcome assessors were blinded to treatment assignment
Sample Size: 800
Follow-up: Up to 2 years or until levodopa needed
Centers: 28
Countries: USA, Canada

Primary Outcome

Definition: Time from randomization to disability requiring levodopa

Control	Intervention	HR/OR	P-value
Mean 491 days	Deprenyl group: mean 667 days	-	<0.001

Limitations & 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

Citation

N Engl J Med. 1989 Sep 14;321(20):1364–1371. doi:10.1056/NEJM198911163212002

View Original Publication →

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

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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