Ropinirole: A Second-Choice Drug for Parkinson’s Disease

Ropinirole (REQUIP, REQUIP XL) is approved by the Food and Drug Administration (FDA) for the treatment of symptoms of Parkinson’s disease (PD), a neurological condition that produces tremors (shaking); rigid muscles; and disturbances in posture, walking, balance, speech, swallowing and muscle strength. It is a member of the drug family called dopamine agonists.

Ropinirole is prescribed as initial single-drug treatment for earlystage PD and as add-on therapy for advanced PD that is no longer adequately controlled with the combination drug levodopa-carbidopa (SINEMET, SINEMET CR).[1]

For many years before the availability of newer dopamine agonists such as ropinirole, levodopa-carbidopa was the first choice for initial treatment for PD patients with significant symptoms. But since the late 1990s, physicians have increasingly favored initial treatment with dopamine agonists, especially in patients younger than age 60, because the drugs are less likely to cause dyskinesia (involuntary muscle movements, such as sudden flailing of an arm or a leg), a well-known side effect of long-term treatment with levodopa-carbidopa.
[2],[3]
However, more recent research shows that levodopa-carbidopa has a more favorable benefit-risk balance than dopamine agonists such as ropinirole for initial treatment of early Parkinson’s disease. Therefore, Public Citizen’s Health Research Group designates ropinirole as a Limited Use drug for PD.

Research comparing different PD drugs

In 2008, researchers analyzed data from multiple randomized clinical trials that compared dopamine agonists with levodopa-carbidopa in patients with early PD.[4] They found that dopamine agonists indeed were less likely to cause dyskinesia and other movement complications seen with levodopa-carbidopa. However, dopamine agonists were less effective than levodopa-carbidopa for controlling the primary symptoms of PD. More importantly, patients receiving dopamine agonists were more likely to experience a variety of nonmovement side effects, including swelling, drowsiness, constipation, dizziness, hallucinations and nausea. Dopamine- agonist-treated patients also were much more likely to stop treatment due to such side effects.

More recently, researchers reported similar findings from a large randomized clinical trial published in the medical journal Lancet in 2014.[5] In the trial — known as the PD MED study — 1,620 patients with newly diagnosed PD were randomly assigned to long-term treatment with either levodopa-carbidopa, a dopamine agonist such as ropinirole, or one of the monoamine oxidase (MOA) type B inhibitors, another family of PD medications. Patients were enrolled from 2000 to 2009 and followed for a median of three years.

PD MED study patients receiving levodopa-carbidopa scored better than those assigned to other treatments on measures of mobility-related quality of life. Furthermore, patients assigned to either a dopamine agonist or an MOA type B inhibitor stopped their assigned treatment due to side effects more than 10 times as frequently as those assigned to levodopa-carbidopa.

Rates of long-term PD complications — including dementia, admission to a nursing home or other institution, and death — were not different between groups. Importantly, the mobility-related quality-of-life advantage of levodopa-carbidopa over the other drugs was similar in patients younger than 70 and those older than 70.

An editorial commenting on the PD MED study noted that, since the study was launched in 2000, many neurologists — encouraged by aggressive marketing by companies that make dopamine agonists — have promoted dopamine agonists over levodopa-carbidopa as initial treatment for PD.[6] It further stated that the result of the study should persuade physicians and reassure patients that fears about using levodopa as initial treatment for PD are unfounded.

Adverse effects warnings

The FDA-approved label for ropinirole contains several warnings about the drug (see box, below).

Impulse control problems and compulsive behaviors are among the most notable adverse effects of ropinirole and other dopamine agonists. Patients taking these drugs can lose control of their behavior, leading to pathological gambling, hypersexuality, and compulsive shopping or eating. Affected patients often do not recognize these behaviors as abnormal.

In their more severe cases, these drug-induced behaviors can have devastating, life-altering effects: Divorces, financial ruin, criminal charges and suicide attempts have all been reported in patients using these drugs. In 2016, we petitioned the FDA to require the addition of a black-box warning to the labels of all dopamine agonist drugs describing these risks.[7] FDA action on our petition is still pending.

What You Can Do

If you have PD, you should use levodopa-carbidopa as initial treatment and begin taking ropinirole or another dopamine agonist only when you are no longer responding adequately to levodopa-carbidopa alone.

You also should try to engage in vigorous daily exercise, which has been shown to improve motor fitness and gait in PD patients.

You should never stop taking ropinirole abruptly, because doing so commonly causes a withdrawal syndrome characterized by anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness and drug craving. These symptoms improve only upon resuming the drug.[8] Sudden stopping or rapid dose reduction of ropinirole also can cause a rare but life-threatening condition with symptoms including confusion, muscle rigidity and fever.[9]

Promptly talk to your prescribing doctor if you or your family notices that you are developing any unusual compulsive behaviors while taking ropinirole.

Finally, if you have symptoms of PD, there is some chance that they are caused by a drug you are taking. Review all of your medications with your doctor and discuss whether any of them could be causing your symptoms. A list of drugs that can cause such symptoms is available online to subscribers of WorstPills.org.

References

[1] Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: A review. JAMA. 2014;311(16):1670-1683.

[2] Stowe R, Ives N, Clarke CE, et al. Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database of Systematic Reviews. 2008, Issue 2. Art. No.: CD006564. DOI:10.1002/14651858.CD006564.pub2.

[3] Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: A review. JAMA. 2014;311(16):1670-1683.

[4] Stowe R, Ives N, Clarke CE, et al. Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database of Systematic Reviews. 2008;(2). Art. No.: CD006564. DOI:10.1002/14651858.CD006564.pub2.

[5] PD MED Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet. 2014; 384:1196-1205.

[6] Lang AE, Marras C, Initiating dopaminergic treatment in Parkinson’s disease. Lancet. 2014; 384:1164-1166.

[7] Public Citizen. Petition to the FDA to require the addition of a boxed warning to the product labeling for all dopamine agonist drugs currently approved in the U.S. describing the risk of developing certain impulse-control problems and compulsive behaviors. June 29, 2016. http://www.citizen.org/documents/2328.pdf. Accessed July 10, 2016.

[8] Tarsy D. Pharmacologic treatment of Parkinson disease. UpToDate. Updated April 16, 2015.

[9] GlaxoSmithKline. Label: REQUIP XL (ropinirole hydrochloride). August 2014. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c1859eee-b5b9-401e-34ac-254a30218555&type=pdf&name=c1859eee-b5b9-401e-34ac-254a30218555. Accessed June 25, 2016.