Thursday October 23 2014
Dopamine agonists are used to treat Parkinson’s disease
“Drugs for restless leg syndrome cause gambling, hypersexuality and compulsive shopping,” Metro reports.
Researchers in the US have looked at serious drug side effects reported to the FDA over a 10-year period. In particular, they were interested to see how often reports of impulsive behaviours such as gambling were linked to a group of drugs called dopamine receptor agonists.
These drugs (such as pramipexole) mimic the effect of dopamine on the brain. They are most commonly used to treat Parkinson’s disease and other conditions such as restless legs syndrome and acromegaly.
The drugs have sometimes been known to trigger extremely severe patterns of compulsive behaviours, so the researchers wanted to estimate exactly how common this side effect was.
The study found that 710 events – just under half of all impulse control disorders reported during this 10-year period – were attributed to dopamine receptor agonists. Given the number of prescriptions of these drugs that are likely to be prescribed every year in the US, this would suggest that the compulsive side effect – or at least the reporting of it – is quite rare. We would expect to see a similar pattern in the UK.
The risk of mental health-related adverse effects with these drugs, including impulse control disorders, is already recognised by the UK's medical profession. You or your carer should seek medical advice if there are any changes to your behaviour after taking a dopamine receptor agonist.
Where did the story come from?
The study was carried out by researchers from The George Washington University and Harvard Medical School in the US, and University of Ottawa and Risk Sciences International in Ottawa, Canada. No sources of funding are reported. Two of the authors declare being consultant or expert witnesses in civil and criminal litigation involving many psychiatric drugs, though none involving the drugs that are at the centre of this research. This article is also reported to be based in part on data obtained under license from the National Prescription Audit.
The study was published in the peer-reviewed medical journal JAMA International Medicine.
The Mail Online’s headline that, “Drugs for Parkinson’s disease can turn patients into gamblers, sex addicts and compulsive shoppers” is not justified by this study alone because – as the study authors acknowledge – the results did “not prove a causal relationship, only that such a relationship was suspected”. The study also only looked at one group of drugs, so the study results do not apply to all Parkinson’s treatments.
What kind of research was this?
This was an analysis of adverse drugs events (more commonly known as side effects) reported to the US Food and Drug Administration (FDA) involving six FDA-approved dopamine receptor agonist drugs.
These drugs are used in the initial treatment of Parkinson’s disease – a neurological condition with an unknown cause, where not enough of the chemical dopamine is produced in the brain. This causes the three classic symptoms of tremor, with stiff, rigid muscles and slow movements, as well as a range of other effects, including dementia and depression. While there is no cure, treatments that aim to control this dopamine imbalance are used to try and control symptoms.
Dopamine receptor agonists act directly on dopamine receptors, effectively taking the place of dopamine and stimulating the receptor in the same way. There are a group of these drugs licensed in the UK, including drugs called pramipexole, ropinirole and rotigotine. Dopamine receptor agonists are a different group of treatments from the well-known Parkinson’s treatment Levodopa, which works in a different way.
Dopamine receptor agonists are also sometimes used in restless legs syndrome if a person is having very frequent symptoms, as well as the hormonal acromegaly.
The drugs are already known to be associated with a risk of adverse mental health issues. This study reports that severe impulse control disorders such as gambling, hypersexuality and compulsive shopping have been reported following the use of these drugs, in both case series and patient surveys. This study aimed to further investigate the potential link between these drugs and this side effect.
What did the research involve?
The researchers looked at all domestic and foreign serious adverse drug events concerning impulse control disorders reported to the FDA between 2003 and 2012. They looked at the number of impulse control disorder events that were associated with the use of dopamine receptor agonists, and with all other drugs, to look for differences.
They specifically looked for 10 impulse control disorders as listed in the Medical Dictionary for Regulatory Activities:
- pathological gambling
- hypersexuality (experiencing extremely frequent sexual urges)
- compulsive shopping
- poriomania (wandering impulses)
- binge eating
- excessive masturbation
- compulsive sexual behaviour
- kleptomania (impulses to steal)
- excessive sexual fantasies
For the individual dopamine receptor agonists, they calculated the proportional reporting ratio (PRR).
This involves calculating the frequency of impulse control adverse events for each dopamine receptor agonist drug, as a proportion of all adverse events reported for that drug.
What were the basic results?
Overall, the researchers identified 1,580 reports of impulse control disorders associated with any drug over the 10-year period. Gambling was the term mentioned in around half of these reports: pathological gambling in 628 (39.7%) and gambling in 186 (11.8%). This was followed by hypersexuality, which accounted for just under a third of impulse control events (465, 29.4%), and then compulsive shopping, which accounted for around an eighth (202, 12.8%).
Just under half of all the impulse control events were related to dopamine receptor agonists (710, 44.9%) and the remainder to other drugs. The reports related to dopamine receptor agonists occurred in people with an average age of 55 years, and over half of whom were male. Most of these prescriptions had been for Parkinson’s disease (61.7%), with most of the remainder prescribed for restless legs syndrome.
The six specific dopamine receptor agonists examined were pramipexole, ropinirole, rotigotine, bromocriptine, cabergoline and apomorphine – all of which are used in the UK.
The PRR was significant for dopamine receptor agonists, meaning that the proportion of impulse control events was significantly higher than all other events with these drugs. For all dopamine receptor agonists, the PRR was 277.6. Most of the impulse control events associated with these drugs had occurred with pramipexole (410 events; PRR 455.9) followed by ropinirole (188 events; PRR 152.5). The number of reported impulse control events with the other four drugs was between 56 for cabergoline and 12 for apomorphine.
How did the researchers interpret the results?
The researchers say that their findings, “confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings”.
This study analysed serious adverse drug events reported to the US FDA over a 10-year period, and found that 710 events (just under half of all impulse control disorders reported during this period) were attributed to dopamine receptor agonists. Most of these disorders involved gambling, followed by hypersexuality and compulsive shopping.
This group of six drugs are used in Parkinson’s disease (and a small number of other conditions) where there is a lack of the chemical dopamine. The drugs act directly on dopamine receptors, effectively taking the place of dopamine and stimulating the receptor in the same way.
Dopamine receptor agonists are known to have mental health-related adverse effects; impulse control disorders are already recognised.
This study further highlights this risk, demonstrating that impulse control disorders account for more serious adverse events than all other events associated with these drugs that have been reported to the FDA.
The study is based on US FDA data only, but it could give a good indication of the data reported to UK medicines regulatory authorities. The study also only covers adverse events that are formally reported, and it is unclear how many impulse control disorders may occur, but are not reported.
As the researchers acknowledge, this study still cannot prove that it is the dopamine receptor agonist that has directly caused the adverse events reported.
UK prescribing information for dopamine receptor agonists advises patients and prescribers of the risk of impulse control disorders. If symptoms develop, doctors are advised to reduce the dose or stop prescribing the drug until symptoms resolve.
People in the grip of a compulsive pattern of behaviour are often unaware that their behaviour has changed and that they are acting strangely, so do not seek medical advice. Therefore friends, family members or carers can help by being vigilant for any strange changes in the behaviour of a person taking these drugs.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.