Abstract: A few Parkinson patients develop a disabling pattern of compulsive dopaminergic drug use ("dopamine dysregulation syndrome"-DDS). DDS patients commonly identify aversive dysphoric "OFF" mood-states as a primary motivation to compulsively use their drugs. We compared motoric, affective, non-motor symptoms and incentive arousal after overnight medication withdrawal and after levodopa in DDS and control PD patients. Twenty DDS patients were matched to 20 control PD patients for age, gender, and disease duration and underwent a standard levodopa challenge. Somatic symptomatology, positive and negative affective states, drug effects, reward responsivity, motor disability, and dyskinesias were tested in the "OFF"-state after overnight withdrawal of medications, and then after a challenge with a standard dose of levodopa, after a full "ON"-state was achieved. In the "OFF"-state, DDS patients reported lower positive affect, and more motor and non-motor disability. In the "ON"-state, DDS patients had higher expressions of drug "wanting," reward responsivity, and dyskinesias. Positive and negative affect, non-motor symptomatology, and motor disability were comparable. These findings suggest that affective, motivational, and motoric disturbances in PD are associated with the transition to compulsive drug use in individuals who inappropriately overuse their dopaminergic medication.
Abstract: OBJECTIVE: A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients. METHODS: We used a two-scan positron emission tomography protocol to calculate the percentage change in (11)C-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS. RESULTS: PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopa-treated patients with PD not compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug "wanting" but not "liking" and was related to heightened psychomotor activation (punding). INTERPRETATION: This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use.
Abstract: BACKGROUND: In the course of treatment, a small group of patients with Parkinson disease (PD) develop a harmful pattern of compulsive dopaminergic drug use, called the dopamine dysregulation syndrome (DDS). Individual factors may influence susceptibility. OBJECTIVES: To identify predisposing factors to DDS in a population of outpatients with PD. METHODS: The authors compared clinical features, impulsive sensation seeking (ISS) personality traits, past experimental drug use, alcohol consumption, smoking behaviors, and depressive symptoms in 25 patients with DDS to an outpatient sample of 100 patients with PD who were not compulsively overusing dopaminergic medication. RESULTS: Patients with DDS had a significantly younger age at disease onset, higher dopaminergic drug intake, greater past experimental drug use, more depressive symptoms, scored higher on ISS ratings, and tended to have higher alcohol intake. Using logistic regression analysis, we found that novelty seeking personality traits, depressive symptoms, alcohol intake, and age at PD onset were significant predictors of DDS. CONCLUSIONS: These factors may help to identify early patients who are more vulnerable to developing a pattern of compulsive dopaminergic drug use and help minimize its consequences.
Abstract: Punding is a term that was coined originally to describe complex prolonged, purposeless, and stereotyped behaviour in chronic amphetamine users. A structured interview of 50 patients with higher dopamine replacement therapy requirements (>800 levodopa equivalent units/day) from 123 unselected patients with Parkinson's disease (PD) from a PD clinic identified 17 (14%) patients with punding. Punding was acknowledged as disruptive and unproductive by the patients themselves, but forcible attempts by family to interrupt the behaviour led to irritability and dysphoria. Punding was associated with very high doses of dopamine replacement therapy often related to a pattern of chronic inappropriate overuse of dopaminergic medication. We believe that this is an underreported, socially disabling phenomenon that is commonly associated with the syndrome of dopamine dysregulation and is phenomenologically distinct from both obsessive-compulsive disorder and mania.
