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Ask the Expert: Which Cognitive Medication Delivery is More Effective? A Patch or Pill?

By Howard Hurtig, MD, Chair, Department of Neurology, Co-Director, Parkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, Frank and Gwladys Elliott Professor, University of Pennsylvania School of Medicine

Patch or Pill? This is a frequently asked question by Lewy body dementia patients and caregivers who are considering a trial of medication to treat impaired memory and cognitive function. Lewy body dementias include dementia with Lewy bodies (DLB) and its close relative, dementia associated with Parkinson’s disease (PDD).

The first drugs for this purpose targeted a chemical neurotransmitter in the brain called acetylcholine. In the 1980’s this neurotransmitter was found in reduced levels in the autopsied brains of Alzheimer patients (and later in Parkinson brains). Clinical trials of medications that boosted the activity of acetylcholine (by blocking the degrading enzyme knows as acetylcholinesterase) showed benefit, and the FDA approved three of these cholinesterase inhibitors for therapeutic use in Alzheimer’s disease. These medications are donepezil, rivastigmine and galantamine. A fourth drug, memantine, which works in the brain on a different chemical system, has also been approved for use in treating Alzheimer’s disease.

Later clinical trials in patients with DLB and PDD who were treated with the cholinesterase inhibitors showed modest improvement. One of these trials, headed by Dr. Murat Emre from Istanbul and published in the prestigious New England Journal of Medicine in 2005, showed that rivastigmine was effective in patients with PDD. The evidence was robust enough that the FDA approved rivastigmine in 2006 as an effective treatment for PDD.

Since patients with a clinical diagnosis of DLB were not included in the Emre trial, rivastigmine was not approved for DLB. However, many doctors who treat DLB consider its symptoms similar enough to PDD that rivastigmine is now widely used for both disorders.

Rivastigmine was given to patients in the Emre clinical trial in pill form, administered several times a day. A patch or transdermal (through the skin) delivery system had not been developed when the study was launched over a decade ago. The rivastigmine patch was developed and approved in 2007 as a once a day alternative to pills for people who had trouble remembering to take pills multiple times a day and for those for whom swallowing was difficult. None of the other cognitive enhancers is available in patch form.

Studies of the effectiveness of the two formulations of rivastigmine—pill vs. patch—have not shown a difference in benefit. Both were more effective than placebo. The patch was declared in one of these trials to be more effective than the pill. The occurrence of side effects, mainly nausea and vomiting, was lower in patients using the patch because the drug was delivered through the skin and not taken by mouth.

All of the clinical trials of cholinesterase inhibitors have shown a low but definite risk of mild worsening of Parkinson symptoms, particularly tremor. Other side effects include diarrhea and irritation of the skin at the site of patch application.

Each of the four available drugs currently on the market for treating cognitive symptoms in AD, DLB and PDD, donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne) and memantine (Namenda), has been shown to provide some benefit to patients who participated in clinical trials. Only 25 percent of patients in the Emre trial of rivastigmine were rated moderate or markedly improved.

We can assume that there are no practical differences among the three cholinesterase inhibitors, so if one is not helpful then the other two may not be effective either. On the other hand, if a patient can’t tolerate one cholinesterase inhibitor because of side effects, a trial of one of the other two is worthwhile. There have been no clinical trials comparing each of these drugs with the others to see if one stands out as more effective.

It is well known that the results of clinical trials must be interpreted cautiously because people who enter clinical trials are carefully selected and may not represent the population of patients at large who were not selected for a trial. It is also important to know that the results of these trials reflect average responses of the entire group of participants and could easily hide a positive effect of the drug on an individual patient, especially if the study shows no difference between the drug and a placebo.

Thus, in practice, it is vital for doctors treating patients with DLB and PDD to try one of the cholinesterase inhibitors to see if that particular patient might have a positive response. The same is true for memantine either alone or in combination with a cholinesterase inhibitor, since memantine has a different pharmacologic mechanism and the combination can sometimes give a positive response when either drug given alone has no effect.