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Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
A number of behavioural disorders have been described in advanced PD after prolonged exposure to dopaminergic medications. These include the dopamine dysregulation syndrome (DDS), punding and impulse control disorders. DAs are most often implicated but these presentations can occur following levodopa exposure alone. The prevalence of DDS is estimated to be 3–4% among people with PD attending movement disorder services.54 However, figures may be inaccurate given the wide range of potential behavioural problems and a reluctance to talk openly about some of them. They are also more common in those with a younger age of onset.55
The Current Status of the Incentive Sensitization Theory of Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Mike J. F. Robinson, Terry E. Robinson, Kent C. Berridge
Sensitization has also been demonstrated in the brains of ordinary people, as direct elevation of the amount of mesolimbic dopamine released in response to an addictive drug. For example, significantly greater amphetamine-induced ventral striatal dopamine release was observed two weeks and again one year after the administration of three drug doses over a one-week period (Boileau et al. 2006). Compelling evidence for neural sensitization of dopamine release has also been shown in Parkinson patients with dopamine dysregulation syndrome (DDS) (Evans et al. 2006). This leads to compulsive use of dopaminergic drug medications, with increased reports of drug wanting but not drug liking, and increased dopamine release in the ventral striatum especially in the combined presence of cues and the dopamine-stimulating drug. Consequent incentive-sensitization may also manifest itself by pathological gambling, hypersexuality, food bingeing and punding (a form of complex behavioral stereotypy). Conversely, there was no apparent sensitization to how much subjects liked amphetamine or other dopamine-stimulating drugs in the aforementioned studies.
Drug therapy
Published in Jeremy Playfer, John Hindle, Andrew Lees, Parkinson's Disease in the Older Patient, 2018
Both levodopa and dopamine agonists have limitations in long-term use and require adjunct therapy. Both COMT inhibitors and MAO-B inhibitors are now well established at supporting levodopa treatment in the longer term. The tolerability of both entacapone and rasagaline in older patients has been demonstrated with a low rate of psychiatric side effects. Dopamine agonists, however, are very effective in supplementing levodopa for motor problems. Maintenance therapy, as far as drugs are concerned, usually involves combinations of medication and the objectives of treatment shift from purely symptomatic relief of symptoms to avoiding complications of medication. Once again the recommendations of NICE fairly reflect current practice. ‘It is not possible to identify a universal first choice of adjunct drug therapy with late PD. The choice of adjuvant drug first prescribed should take into account clinical and lifestyle characteristics and patient preference after the patient has been informed of the short- and long-term benefits and drawbacks of drug classes.’ NICE also warns against sudden withdrawal and the need to replace dopaminergic therapy when patients are admitted with emergencies into hospital, often using parenteral treatment such as apomorphine to cover surgery. Dopamine dysregulation syndrome, an uncommon disorder in which dopaminergic medication misuse (particularly that of dopamine agonists), is associated with abnormal behaviours including hyper-sexuality, pathological gambling and stereotypic motor acts, and it needs to be recognised. While this syndrome was originally felt to be much more frequent in younger patients, it is now being described in older patients.
Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson’s disease
Published in Expert Opinion on Drug Safety, 2023
Angela M Richmond, Kelly E Lyons, Rajesh Pahwa
DAs are a good adjunctive treatment option for PD patients due to the variety of available formulations (e.g., ER tablets, transdermal system, SC injection, etc.). However, special attention should be given to AEs associated with DAs, including excessive daytime sleepiness, SOOS, hallucinations, psychosis, and ICD behavior. The elderly and those at risk of cognitive changes, hallucinations, or psychosis should avoid DAs unless otherwise indicated. ICD behavior including pathological gambling, compulsive shopping, compulsive eating, and hypersexuality have been seen in up to 18% of PD patients taking DAs [78]. The risk appears to be higher in younger male patients, those with a longer exposure history to DAs, taking higher doses of DAs, a personal or family history of substance abuse or bipolar disorder, and a prior history of ICD behavior [76]. For these reasons, patients should be informed about the risks associated with DAs before initiating treatment. When initiating treatment with a DA, dosing should be titrated up slowly and used at the lowest possible dose to control symptoms. Patients taking DAs should be screened for these potential side effects at each visit and if present, dose reduction or medication discontinuation should be strongly considered. If discontinued, patients need to be monitored for symptoms of dopamine dysregulation syndrome, especially with chronic use or use of higher doses.
An evaluation of the efficacy and value of CVT-301 for the treatment of Parkinson’s disease
Published in Expert Opinion on Pharmacotherapy, 2021
Fabrizio Stocchi, Laura Vacca, Andrea Grassi, Margherita Torti
CVT-301 was generally safe and well tolerated. In each CVT-301 trial, the most common adverse event reported with an incidence >5% was cough, which was usually mild and not associated with other respiratory symptoms like dyspnea, wheezing, or bronchospasm. Dizziness and nausea were the other common adverse events reported. In the CVT 301–004 study, two serious adverse events were judged to be possibly related to the investigational product: one case of hypotension, reported in the CVT-301 60 mg group, and one case of atrial fibrillation in CVT-301 84 mg group [31–34]. No serious adverse events were judged to be related to CVT-301, and no clinically significant change was observed in safety parameters. In all clinical trials performed, there was no worsening of psychiatric symptoms or new onset of dopamine dysregulation syndrome. It must be noted though that in all CVT-301 trials the enrollment of subjects with hallucinations or major psychiatric disorders was not allowed and therefore a definitive conclusion about the incidence of these complications cannot be drawn.
Complications of levodopa therapy in Parkinson’s disease
Published in Expert Opinion on Orphan Drugs, 2019
Jordan Dubow, C. Warren Olanow
Neuropsychiatric complications are less common but can be troublesome. Levodopa can cause punding which is the Swedish term for similar activities observed in amphetamine users. Punding is a complex, stereotyped behavior characterized by intense, purposeless, and repetitive activities such as the continual handling, examining, and sorting of common objects, grooming, hoarding, pointless driving or walkabouts, and the engagement in extended monologues devoid of content [49]. Punding tends to be associated with very high doses of levodopa; in one study pudding was observed in 14% of PD patients taking more than 800 mg levodopa per day [50]. PD patients can also develop compulsive and repeated levodopa use, known as the dopamine dysregulation syndrome. These patients repeatedly take levodopa because it is associated with a ‘high’. In that regard it is noteworthy that dopamine is taken up by the cocaine receptor. Sensitization of brain dopamine systems mediating reward is proposed to underlie its development [51]. Uncontrolled data showed that continuous delivery of levodopa may improve punding and dopamine dysregulation syndrome. One study looking at risk factors found that patients with dopamine dysregulation syndrome had a younger age at disease onset, high dopaminergic drug intake, a history of experimental drug use, more depressive symptoms, scored high on impulsive sensation-seeking behaviors and tended to have higher alcohol intake [52]. Physicians should be on guard for this syndrome and prevent patients from taking excess and unnecessary levels of levodopa.