JAMA Neurology: COMT inhibitors are ineffective in adjunctive levodopa therapy for Parkinson's

Is adding a dopamine reuptake inhibitor (DRI) (a monoamine oxidase type B (MAO-B) inhibitor or a catechol-o-methyltransferase (COMT) inhibitor) to levodopa therapy better than adding a dopamine agonist More effective, and if DRI is more effective, which DRI class (MAO-B or COMT) is more beneficial for improving the quality of life of patients with motor complications of Parkinson's disease uncontrolled by levodopa therapy
.

Is adding a dopamine reuptake inhibitor (DRI) (a monoamine oxidase type B (MAO-B) inhibitor or a catechol-o-methyltransferase (COMT) inhibitor) to levodopa therapy better than adding a dopamine agonist More effective, and if DRI is more effective, which DRI class (MAO-B or COMT) is more beneficial for improving the quality of life of patients with motor complications of Parkinson's disease uncontrolled by levodopa therapy
.

Quality of Life

Many patients with Parkinson's disease experience motor complications that cannot be controlled by levodopa dose adjustment
.

In these patients, it is unclear which drug is more effective as adjunctive therapy

Many patients with Parkinson's disease experience motor complications that cannot be controlled by levodopa dose adjustment

Richard Gray et al compared the effect of adding a dopamine agonist and a dopamine reuptake inhibitor (DRI) to levodopa therapy on long-term quality of life in patients with motor complications of PD .

This practical semi-factorial randomized clinical trial was recruited from 64 neurology and geriatrics clinics (62 in the UK, 1 in the Czech Republic, and 1 in Russia) between 23 February 2001 and 15 December 2009
.

A total of 500 patients with idiopathic PD who developed uncontrollable motor complications without dementia were randomly assigned to a 1:1:1 group

This practical semi-factorial randomized clinical trial was recruited from 64 neurology and geriatrics clinics (62 in the UK, 1 in the Czech Republic, and 1 in Russia) between 23 February 2001 and 15 December 2009

Intervening factors were open-label dopamine agonists, MAO-B inhibitors, or COMT inhibitors
.

The primary outcome measures were the 39-item Parkinson's Disease Questionnaire (PDQ-39) activity domain and cost-effectiveness score

Intervening factors were open-label dopamine agonists, MAO-B inhibitors, or COMT inhibitors

The mean age (SD) of the 500 participants was 73.

At a median follow-up of 4.

Regarding DRIs, participants in the MAO-B group had a mean PDQ-39 activity score of 4.

The EuroQol 5 -dimensional 3-level (EQ-5D-3L) utility score of 0.

Estimated mean differences in prognostic indicators between treatment groups

There was no significant improvement in the PDQ-39 pooled index (mean difference 2.
2 points; 95% CI, 0.
2 to 4.
5 points; P=.
07), while the incidence of dementia (ratio [RR], 0.
70; 95% confidence interval, 0.
47 to -1.
03) ; P = 0.
07) and mortality (RR, 0.
76; 95% confidence interval, 0.
56 to -1.
03; P = .
07) were not significantly reduced
.

Dopamine agonists compared with MAO-B inhibitors with similar results
.

There was no significant improvement in the PDQ-39 pooled index (mean difference 2.
2 points; 95% CI, 0.
2 to 4.
5 points; P=.
07), while the incidence of dementia (ratio [RR], 0.
70; 95% confidence interval, 0.
47 to -1.
03) ; P = 0.
07) and mortality (RR, 0.
76; 95% confidence interval, 0.
56 to -1.
03; P = .
07) were not significantly reduced
.
Dopamine agonists compared with MAO-B inhibitors with similar results
.

In PD patients whose motor complications cannot be controlled by levodopa therapy, COMT inhibitors as adjuvant therapy have a lower quality of life than MAO-B inhibitors or dopamine agonists
.
MAO-B inhibitors produced equivalent disease control, suggesting that these drugs may not be adequately used in adjuvant therapy
.

In PD patients whose motor complications cannot be controlled by levodopa therapy, COMT inhibitors as adjuvant therapy have a lower quality of life than MAO-B inhibitors or dopamine agonists
.
MAO-B inhibitors produced equivalent disease control, suggesting that these drugs may not be adequately used in adjuvant therapy
.
In PD patients whose motor complications cannot be controlled by levodopa therapy, COMT inhibitors as adjuvant therapy have a lower quality of life than MAO-B inhibitors or dopamine agonists
.
MAO-B inhibitors produced equivalent disease control, suggesting that these drugs may not be adequately used in adjuvant therapy
.

 original source

 original source

Gray R, Patel S, Ives N, et al.
Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy : The PD MED Randomized Clinical Trial .
  JAMA Neurol.
 Published online December 28, 2021.
doi:10.
1001/jamaneurol.
2021.
4736

Gray R, Patel S, Ives N, et al.
Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy : The PD MED Randomized Clinical Trial .
  Gray R, Patel S, Ives N, et al.
Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy JAMA Neurol.
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