Management of treatment-related behavioral disturbances in Parkinson’s disease

Introduction: Primum non nocere meaning “first, do no harm” is a fundamental ethical basis of medical practice. As conscientious physicians, we strive to provide our patients with safe and effective treatments free of permanent or even transient adverse effects. The management of Parkinson’s disease (PD) may be complicated by unwanted behavioral effects of treatment with dopamine replacement therapy (DRT) and/or neurosurgery [1]. The decision to reduce or alter treatment may not always be a welcome one by the patient with PD for fear of losing motor benefits gained by the intervention. These psychiatric and behavioral disturbances pose significant morbidity and negatively impact the quality of life for patients with PD, as well as contributing to higher caregiver burden [2]. The treatment of PD has greatly advanced since George Cotzias’ discovery of levodopa’s seemingly miraculous benefits in PD. Since this discovery, dopamine (and, in turn, dopamine replacement) has naturally been at the center of the treatment approach. With time and further investigation, it is becoming clearer that nondopaminergic neurotransmitter systems and pathways may be vitally important in the pathogenesis of PD, particularly with regard to the production of psychiatric and behavioral manifestations [3]. This has been supported by pathological evidence of serotonin and norepinephrine degeneration in PD [1]. It has been suggested that a mesocorticolimbic variant of PD may exist that renders some patients more susceptible to adverse psychiatric and behavioral effects than others [4].These disturbances are likely the effect of DRT exposure in the setting of frontal-subcortical dysfunction, coexisting conditions, environmental catalysts and individual personal factors (Figure 14.1). The need for vigilance in detecting these emerging behaviors is therefore essential. Unfamiliarity with the delicate nuances of DRT can predispose patients to dramatic motor and nonmotor consequences when doses are purposefully or inadvertently adjusted. The extensive therapeutic options, sometimes in multiple delivery preparations, added to the seemingly infinite number of combinations, can create confusion for even the best medical providers. The options for management of motor symptoms in PD include: (i) levodopa (l-DOPA): in combination with carbidopa (available as standard-release [with or without entacapone] or controlled-release preparation, orally disintegrating tablet and intestinal gel); (ii) dopamine agonists: nonergot- and ergot-derivative tablets, transdermal patch and subcutaneous injection; (iii) catechol-O-methyltransferase (COMT) inhibitors; (iv) monoamine oxide type B (MAO-B) inhibitors: standard-release tablet, orally disintegrating tablet and transdermal patch; (v) glutamate antagonists;[…].