________________________________________________________________________ Behavioral Addictions
PATIENTS WITH PARKINSON DISEASE Patients with Parkinson disease receiving dopaminergic therapy can develop behavioral side effects that include impulse control disorders. A multi-center study in 2010 found that gambling disorder, compulsive shopping, compulsive sexual behav- iors, or binge eating developed in 17% of patients receiving dopaminergic medications. Other behaviors associated with impulse control disorders included compulsive medication use (dopamine dysregulation syndrome) and punding (repetitive non-goal-directed simple or complex behaviors, including hob- byism) [355]. Hypersensitivity to rewards has been suggested as a contributing factor to the development of impulse control disorders in Parkinson disease [356]. Another study of patients with Parkinson disease identified addictive behaviors in 14% of patients receiving any dopami- nergic medication and 17% of patients receiving dopamine agonists. Behaviors included compulsive gambling (5%), com- pulsive sexual behavior (3.5%), compulsive shopping (6%), and binge-eating disorder (4%). Compulsive behaviors were more common with dopamine agonists than levodopa and other medications (17.1% vs. 6.9%). The prevalence was similar with the two most commonly used dopamine agonists, pramipexole (17.7%) and ropinirole (15.5%) [357]. Underlying susceptibil- ity factors are suggested by the relatively small proportion of patients with Parkinson disease exposed to dopamine agonists who develop impulse control disorders. In these patients, risk factors for impulse control disorder during dopamine agonist therapy include levodopa treatment, age younger than 65 years, being unmarried, high caffeine use, family history of gambling problems, and current cigarette smoking. Other associated factors were functional impairment, depression, anxiety, obsessive-compulsive symptoms, impulsivity, and novelty-seeking. These risk factors show similarity to those reported in substance use disorders and gambling disorder and suggest common neurobiologic substrates [357].
OTHER DISORDERS Restless legs syndrome is a common sensorimotor disorder treated with levodopa or a dopamine agonist. A case study of patients with restless legs syndrome and new-onset addictive behaviors linked to dopamine agonist therapy found that patients developed pathologic gambling, kleptomania, com- pulsive shopping, and hypersexuality; other adverse behavioral effects included criminality, suicidality, and marital discord. The behaviors developed over a wide range of levodopa/dopa- mine agonist exposures and latencies and, in some patients, persisted despite discontinuation. Some of these patients suf- fered devastating financial, social, and marital consequences, and the authors concluded dopamine agonist use in restless legs syndrome requires careful consideration [358]. OTHER MEDICATIONS Aripiprazole, an atypical antipsychotic drug, has been linked to treatment-emergent pathologic gambling in eight adult male patients with schizophrenia or bipolar disorder [359]. All had histories of substance use disorders and non-pathologic gambling before taking aripiprazole. Patient histories showed aripiprazole initiation coincided with intensified urges to gamble or loss of control over gambling; discontinuation of aripiprazole coincided with cessation of severe gambling urges or loss of control [359]. While acknowledging this association, the authors of one analysis caution that since Parkinson disease is itself associated with pathologic gambling, further studies are warranted [360]. PATHOPHYSIOLOGY When titrated to alleviate dorsal striatal motor neuron loss, dopaminergic agonist therapy may overload intact dopamine circuits in ventral cortico-striatal cognitive and limbic path- ways, explaining the development of treatment-emergent addictive behaviors with these medications [361; 362]. Patients with Parkinson disease who develop impulse control disorders show impairments in decisional but not motor impulsivity. Dopaminergic medications are thought to enhance learning from reward (positive feedback) and impair learning from consequences (negative feedback); this relative imbalance presents as impulsivity [357]. A 2014 report addressed the role of dopamine-3 receptor (D3R) agonist medications in impulse control disorders. This report emphasized the significantly greater link between addictive behaviors and dopamine agonists with higher D3R selectivity (pramipexole, ropinirole) compared with dopamine agonists with lower D3R selectivity (aripiprazole) [363]. D3R is impli- cated in motivation, physiologic and behavioral responses to drug cues, and novelty-seeking behaviors [357].
When starting dopamine agonist therapy, patients with Parkinson disease and their family members and carers (as appropriate) should be given oral and written information about the increased risk of developing impulse control disorders
(e.g., compulsive gambling, hypersexuality, binge eating, obsessive shopping) when taking dopamine agonist therapy and that these may be concealed by the person affected. (https://www.nice.org.uk/guidance/ng71. Last accessed April 19, 2024.) Level of Evidence : Expert Opinion/Consensus Statement
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