Parkinson's Disease
Aripiprazole: A new risk factor for pathological gambling? A report of 8 case reports
Abstract
Objective
It is commonly accepted that pathological gambling results from the interaction of multiple risk factors. Among these, dopamine replacement therapy (DRT) prescribed for Parkinson disease can be cited. Another dopamine agonist, aripiprazole, could be a new risk factor. We decided to explore this potential adverse drug reaction (ADR).
Method
Based on a cohort of 166 pathological gamblers starting treatment in our department, data of each of the 8 patients treated by aripiprazole at inclusion were analyzed.
Results
The patients involved were schizophrenic or bipolar, mostly young men with a history of addictive disorders and regular gambling prior to the prescription of aripiprazole. For each one of them, the causality of aripiprazole was considered, using an algorithm. The probability that pathological gambling is actually due to aripiprazole is “possible” in 7 cases out of 8, and “doubtful” in one.
Conclusions
Adverse drug reactions were confronted with other already published case reports. Dopamine partial agonist mechanism of aripiprazole could explain the occurrence of pathological gambling.
Source : Addictive Behaviour
Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs
Thomas J. Moore, AB1,2; Joseph Glenmullen, MD3; Donald R. Mattison, MD, MS4
Abstract
Importance Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia.
Objectives To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs.
Design, Setting, and Participants We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System.
Main Outcomes and Measures Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.
Results We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3receptor (n = 37; PRR = 8.6, P < .001).
Conclusions and Relevance Our 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.
Source : JAMA Network
Mirapex (pramipexole): Drug Safety Communication - Ongoing Safety Review, Possible Risk of Heart Failure
ISSUE: FDA notified healthcare profesionals about a possible increased risk of heart failure with Mirapex (pramipexole). Results of recent studies suggest a potential risk of heart failure that needs further review of available data. Because of the study limitations, FDA is not able to determine whether Mirapex increases the risk of heart failure. FDA is continuing to work with the manufacturer to clarify further the risk of heart failure with Mirapex and will update the public when more information is available.
FDA evaluated a pooled analysis of randomized clinical trials and found that heart failure was more frequent with Mirapex than with placebo; however, these results were not statistically significant. FDA also evaluated two epidemiologic studies that suggested an increased risk of new onset of heart failure with Mirapex use. However, study limitations make it difficult to determine whether excess heart failure was related to Mirapex use or other influencing factors (see FDA Drug Safety Communication Data Summary for a detailed discussion of the studies).
BACKGROUND: Mirapex (pramipexole) is a prescription medicine used to treat the signs and symptoms of Parkinson's disease and moderate to severe symptoms of primary restless legs syndrome, in a class of medicines called dopamine agonists.
RECOMMENDATION: At this time, FDA has not concluded that Mirapex increases the risk of heart failure. Healthcare professionals should continue to follow the recommendations in the drug label when prescribing Mirapex. Patients should continue to take their Mirapex as directed and should contact their health care professional if they have any questions or concerns.
Source : FDA
Link to Source
FDA Drug Safety Communication: Ongoing Safety Review of Stalevo (entacapone/carbidopa/levodopa) (Parkinson's Disease Medication) and possible development of Prostate Cancer
The U.S. Food and Drug Administration (FDA) is evaluating clinical trial data that may suggest that patients taking Stalevo, a Parkinson's disease medication, may be at an increased risk for developing prostate cancer. In this trial, patients taking Stalevo were compared to those taking carbidopa and levodopa (sold as Sinemet), a combination medication also used to treat Parkinson's disease. At this time, FDA's review of Stalevo is ongoing and no new conclusions or recommendations about the use of this drug have been made.
Stalevo contains a combination of the active ingredients entacapone, carbidopa, and levodopa. Entacapone is also available as a single-ingredient product sold under the brand name Comtan. Both Stalevo and Comtan are used to treat symptoms of Parkinson's disease.
The data being reviewed are from a long-term clinical trial called Stalevo Reduction in Dyskinesia Evaluation – Parkinson's Disease (STRIDE-PD). STRIDE-PD evaluated the time to onset of dyskinesia (difficulty controlling voluntary movement) in patients with Parkinson's disease taking Stalevo compared to those taking only carbidopa/levodopa. An unexpected finding in the trial was that a greater number of patients taking Stalevo were observed to have prostate cancer compared to those taking carbidopa/levodopa.
The agency is exploring additional ways to better understand if Stalevo actually increases the risk of prostate cancer. Previous controlled clinical trials of shorter duration evaluating Stalevo in Parkinson's disease have not found an increased risk of prostate cancer, and prostate cancer is most commonly diagnosed in men who are of the same age as men included in the STRIDE-PD trial.
SOURCE : FDA
LINK TO PRESS RELEASE
- L. Gaboriaua,
- C. Victorri-Vigneaua, b,
- M. Gérardina, b,
- G. Allain-Veyraca,
- P. Jolliet-Evina, b,
- M. Grall-Bronnecb, c,
Abstract
Objective
It is commonly accepted that pathological gambling results from the interaction of multiple risk factors. Among these, dopamine replacement therapy (DRT) prescribed for Parkinson disease can be cited. Another dopamine agonist, aripiprazole, could be a new risk factor. We decided to explore this potential adverse drug reaction (ADR).
Method
Based on a cohort of 166 pathological gamblers starting treatment in our department, data of each of the 8 patients treated by aripiprazole at inclusion were analyzed.
Results
The patients involved were schizophrenic or bipolar, mostly young men with a history of addictive disorders and regular gambling prior to the prescription of aripiprazole. For each one of them, the causality of aripiprazole was considered, using an algorithm. The probability that pathological gambling is actually due to aripiprazole is “possible” in 7 cases out of 8, and “doubtful” in one.
Conclusions
Adverse drug reactions were confronted with other already published case reports. Dopamine partial agonist mechanism of aripiprazole could explain the occurrence of pathological gambling.
Source : Addictive Behaviour
Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs
Thomas J. Moore, AB1,2; Joseph Glenmullen, MD3; Donald R. Mattison, MD, MS4
Abstract
Importance Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia.
Objectives To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs.
Design, Setting, and Participants We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System.
Main Outcomes and Measures Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.
Results We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3receptor (n = 37; PRR = 8.6, P < .001).
Conclusions and Relevance Our 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.
Source : JAMA Network
Mirapex (pramipexole): Drug Safety Communication - Ongoing Safety Review, Possible Risk of Heart Failure
ISSUE: FDA notified healthcare profesionals about a possible increased risk of heart failure with Mirapex (pramipexole). Results of recent studies suggest a potential risk of heart failure that needs further review of available data. Because of the study limitations, FDA is not able to determine whether Mirapex increases the risk of heart failure. FDA is continuing to work with the manufacturer to clarify further the risk of heart failure with Mirapex and will update the public when more information is available.
FDA evaluated a pooled analysis of randomized clinical trials and found that heart failure was more frequent with Mirapex than with placebo; however, these results were not statistically significant. FDA also evaluated two epidemiologic studies that suggested an increased risk of new onset of heart failure with Mirapex use. However, study limitations make it difficult to determine whether excess heart failure was related to Mirapex use or other influencing factors (see FDA Drug Safety Communication Data Summary for a detailed discussion of the studies).
BACKGROUND: Mirapex (pramipexole) is a prescription medicine used to treat the signs and symptoms of Parkinson's disease and moderate to severe symptoms of primary restless legs syndrome, in a class of medicines called dopamine agonists.
RECOMMENDATION: At this time, FDA has not concluded that Mirapex increases the risk of heart failure. Healthcare professionals should continue to follow the recommendations in the drug label when prescribing Mirapex. Patients should continue to take their Mirapex as directed and should contact their health care professional if they have any questions or concerns.
Source : FDA
Link to Source
FDA Drug Safety Communication: Ongoing Safety Review of Stalevo (entacapone/carbidopa/levodopa) (Parkinson's Disease Medication) and possible development of Prostate Cancer
The U.S. Food and Drug Administration (FDA) is evaluating clinical trial data that may suggest that patients taking Stalevo, a Parkinson's disease medication, may be at an increased risk for developing prostate cancer. In this trial, patients taking Stalevo were compared to those taking carbidopa and levodopa (sold as Sinemet), a combination medication also used to treat Parkinson's disease. At this time, FDA's review of Stalevo is ongoing and no new conclusions or recommendations about the use of this drug have been made.
Stalevo contains a combination of the active ingredients entacapone, carbidopa, and levodopa. Entacapone is also available as a single-ingredient product sold under the brand name Comtan. Both Stalevo and Comtan are used to treat symptoms of Parkinson's disease.
The data being reviewed are from a long-term clinical trial called Stalevo Reduction in Dyskinesia Evaluation – Parkinson's Disease (STRIDE-PD). STRIDE-PD evaluated the time to onset of dyskinesia (difficulty controlling voluntary movement) in patients with Parkinson's disease taking Stalevo compared to those taking only carbidopa/levodopa. An unexpected finding in the trial was that a greater number of patients taking Stalevo were observed to have prostate cancer compared to those taking carbidopa/levodopa.
The agency is exploring additional ways to better understand if Stalevo actually increases the risk of prostate cancer. Previous controlled clinical trials of shorter duration evaluating Stalevo in Parkinson's disease have not found an increased risk of prostate cancer, and prostate cancer is most commonly diagnosed in men who are of the same age as men included in the STRIDE-PD trial.
SOURCE : FDA
LINK TO PRESS RELEASE