Apomorphine: 150-Year-Old Drug Benefits Parkinson's Disease Patients

Apomorphine, a 150-year-old drug for Parkinson’s disease is found to lower ‘off’ time for people at an advanced stage of the disease.

Highlights:

Apomorphine has been in use for many years, but its significance in lowering the ‘off’ time among Parkinson’s disease patients had not yet been understood
The current study highlights the benefits of subcutaneous infusion of apomorphine drug during advanced Parkinson’s disease
71% of patients who received this drug therapy said that they felt better when compared to 18% of patients who were on placebo

Apomorphine, a drug that has been in use for over 150 years has now been found to benefit people with advanced Parkinson’s, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology to be held in Boston between April 22 and 28, 2017.

Levodopa has for long been the gold standard of treatment for Parkinson’s, associated with an increase in the quality of life lead by the patient as well as adding to the number of years. However, as the disease advances in severity, there are times when the drug has been shown to be turned ‘off’ resulting in the immobility of the patient during to the temporary period of unresponsiveness. This is known as ‘off’ time for Parkinson’s patients. Muscle rigidity that slows down a patient with Parkinson’s affects their mobility.

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‘Apomorphine mimics the neurotransmitter dopamine and is used to counteract the deficiency in Parkinson’s disease patients.’

Reducing the 'Off' Time

To improve the quality of life of the patient, it is therefore necessary to lower the number of ‘off’ times that the patient experiences. According to the lead author of the study, Dr. Regina Katzenschlager, who is with the Medical University of Vienna, Austria, some patients who were part of the study showed complete alleviation of the ‘off’ times.

Studying the Effect of Apomorphine

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A phase III study was carried out by the scientists with 107 patients in their advanced stages of Parkinson’s included from 23 centers spread across 7 countries. Patients were either given

Subcutaneous infusion of apomorphine
Subcutaneous saline infusion

Patients were selected at random for the subcutaneous apomorphine injection with the infusion provided for 14 to 18 hours every day, using a small portable pump .

The findings of the study were that

Patients who were administered apomorphine showed a significantly lowered ‘off time’ when compared to people who received the placebo.
Patients on apomorphine had 2.5 hours less of ‘off’ time
Patients on the placebo had 30 minutes less of ‘off’time
Patients who received apomorphine were shown to have had an increase in the amount of ‘on’ time or the time when there were no abnormal involuntary movements. Such movements, called dyskinesias were found to occur with the drug levodopa

Patients were then asked to rate their treatment and how they felt post treatment. The findings of the study revealed that

Patients who received apomorphine provided better scores for the treatment at week 12 than patients who received the placebo.
71% of patients who received apomorphine felt improved after treatment, compared to only 18% in the placebo group.
19% of patients on apomorphine became worse when compared to 45% who became worse on placebo.

The drug tolerance among patients who received apomorphine was good and no serious side effects were reported. Dr. Katzenschlager said that such studies increase evidence in support of the use of apomorphine, and should be utilized by doctors in the United States to offer this drug therapy as a form of treatment for Parkinson’s disease patients.

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Apomorphine

A drug that was developed in 1865, apomorphine, was initially used in the United States in 1950 to treat Parkinson’s. There was an increase in the use of this drug in the 1990s and it was used by European doctors subcutaneously to improve mobility when oral pills did not work. Although this drug has been in use in many countries, there has been a persistent lack of sufficient and high-quality evidence to support its use.

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It is used to treat "off"' episodes, when the patients find it difficult to walk or move. Though this drug does not prevent these episodes, it will help in lowering the intensity. This drug mimics the action of dopamine in the brain, a neurotransmitter that is found to be lacking in patients with Parkinson’s disease.

Dyskinesis and Apomorphine:

Involuntary movement or dyskinesias could occur at peak doses or during the entire period of treatment with the drug. During the initial stages of the disease, the movements may be minor or they may be noticed by caregivers, but not by the patient. The patients prefer mild mobility to the complete absence of mobility. Dyskinesias are usually more prominent during the start and end of a drug dose.

The dyskinesis that occurs during the ‘off’ period are usually associated with the feet and toes and are found to be painful. They generally occur when plasma concentrations of dopamine are very low, which is usually during the early morning hours. In a meta-analysis, it was shown that

There was 40% risk of dyskinesis after five years of being affected by Parkinson’s
In young-onset Parkinson’s, 94% of patients reported dyskinesis

The author concluded that the findings on the efficacy of apomorphine infusion will encourage the doctors to offer treatment to their patients and would also enable them to assess its efficacy in their own clinical practice.

References:

Apomorphine - (https://medlineplus.gov/druginfo/meds/a604020.html)
What is Apomorphine? - (https://pubchem.ncbi.nlm.nih.gov/compound/apomorphine#section=Top)

Source-Medindia