The effect of anti-inflammatory drugs in protecting the nerve cells involved in Parkinson's Disease

Different agents have been examined for their effects in protecting the nerve cells that die in Parkinson's disease (PD). These are often called neuroprotective or disease-modifying agents. They can act by preventing the onset of the disease itself (called primary prevention) or by halting the progression of PD once it has been established (called secondary prevention). Inflammation in the nervous system is thought to be one of the possible mechanisms of nerve cell death in PD, which has led investigators to look at the potential of anti-inflammatory drugs in PD. The current review aimed to look at the effects of anti-inflammatory drugs on both preventing the onset of PD and also on symptoms and the progression of disease in people who already have PD.

Epidemiological or observational studies were used to see if taking an anti-inflammatory drug reduces the risk of developing PD in the general population. We found fourteen studies. Investigators looked at both aspirin and non-aspirin anti-inflammatory drugs and also the individual drug ibuprofen. We pooled results from the included studies. Overall, there was no benefit seen with taking aspirin, but a slight reduction in the risk of developing PD in people taking non-aspirin anti-inflammatory drugs. Ibuprofen was examined in isolation in four of the included studies. Larger benefits were seen when taking this drug.

Clinical trials were used to see if taking an anti-inflammatory drug when you already have PD reduces symptoms or slows disease progression. We found no trials from the extensive searching. As no clinical trials were found, there is also a lack of information about any adverse effects of taking anti-inflammatory drugs in people with PD.

Non-aspirin anti-inflammatory drugs appear to reduce the risk of developing PD, particularly ibuprofen. However, more research is needed to determine which individual drugs work best, what dose to take and over what period, in whom (those at high risk for PD or the general population) before any recommendations can be made about their use in preventing PD onset. These studies will also help to identify possible drugs to be examined further in early trials of safety in those who already have PD, to see if they could potentially halt disease progression or improve symptoms.

Authors' conclusions: 

There is currently no evidence for the use of NSAIDs in the secondary prevention of PD. Non-aspirin NSAIDs, particularly ibuprofen, may reduce the risk of developing PD. However, little is known of the effects of other individual drugs and at present no recommendations can be made regarding their use in primary prevention.

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Background: 

Neuroinflammation may play a key role in the neurodegeneration associated with Parkinson's disease (PD). Non-steroidal anti-inflammatory drugs (NSAIDs) may be beneficial in the primary and secondary prevention of PD.

Objectives: 

1) Do NSAIDs prevent the onset of PD?

2) Are NSAIDs neuroprotective in PD - do they slow the progression of disease once PD is established?

3) What are the adverse effects of taking NSAIDs in PD?

Search strategy: 

We searched electronic databases, including trial registers, complemented with handsearching of conference proceedings and citation searching on key articles. All searching was updated in May 2011. We contacted authors to provide additional information where necessary.

Selection criteria: 

For the primary prevention review, we sought primary prevention trials and observational studies (cohort and case-control studies). Participants were free of PD when exposure to NSAIDs was assessed. For the secondary prevention review, we sought clinical trials in patients with a well-defined definition of PD. Two people independently selected studies for inclusion using predetermined criteria.

Data collection and analysis: 

Two review authors abstracted data from the source papers and assessed methodological quality independently. No studies met the inclusion criteria for the secondary prevention review. For the primary prevention review only observational studies were found. We combined data where appropriate using the inverse variance method. We assessed methodological quality using the Newcastle Ottawa Scales and by examining the period of exposure assessed prior to PD onset (or the index date in controls).

Main results: 

Fourteen observational studies met the inclusion criteria for the primary prevention review (five cohort, nine case-control studies). Exposure to any NSAIDs or aspirin had no effect on the risk of developing PD. Exposure to non-aspirin NSAIDs reduced the risk of developing PD by 13% (effect estimate 0.87 (95% CI 0.73 to 1.04 - random-effects model), but this did not reach statistical significance. We found similar results for the most robust studies. Ibuprofen in isolation was examined in four studies and was associated with a 27% reduction in risk (effect estimate 0.73, 95% CI 0.63 to 0.85). There was a lack of information on adverse effects.

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