Ires Ghielen

12 Chapter 1 The interplay between anxiety and motor symptoms Anxiety in PD can also occur in the context of fluctuations in PD symptoms and is often dependent on available dopamine related to the timing of PD medication. First line treatment for PD symptoms is dopamine replacement therapy (DRT), e.g., levodopa [34]. In reaction to chronic DRT and due to the progressive nature of PD, patients eventually develop response fluctuations, including wearing-off. Wearing-off refers to the re-emergence of PD symptoms while transitioning from an ‘on’ state to an ‘off’ state, and typically occurs prior to the next scheduled dose of dopaminergic medication taking effect [35]. About 75% of patients with motor fluctuations experience fluctuations in mood and/or anxiety in parallel [36, 37]. Wearing-off related anxiety is characterized not only by subjective feelings of anxiety but also by physical complaints, such as sweating, abdominal distress and shortness of breath, and can include panic attacks [16]. Just like wearing-off related anxiety, fear of falling is a PD specific anxiety phenomenon associated with motor fluctuations [19, 35, 38]. Anxiety itself can worsen motor symptoms, such as tremor and freezing [39, 40] and a vicious cycle can emerge, in which motor symptoms trigger anxiety or distress, which can in turn exacerbate motor symptoms. As one can imagine, this interplay between motor and anxiety symptoms considerably complicates diagnosing and treating anxiety in PD. Treatment of anxiety in PD Evidence for the treatment of anxiety in PD patients is extremely limited [41-43]. No randomized controlled trials (RCTs) with anxiety as primary outcome measure have been performed. Only two studies, without control conditions, have been performed to investigate the effect of psychotherapy on anxiety in PD [44, 45]. Psychotherapy includes cognitive behavioral therapy (CBT) and mindfulness based treatments. Their effects on psychological distress (including anxiety) are reviewed and analyzed in chapter 6 [46]. Similar to psychotherapy, pharmacological treatments of anxiety in PD have not been investigated using RCT research designs. Non-RCT studies using serotonergic antidepressants have reported marginal secondary benefits for anxiety symptoms in PD, and treatment with benzodiazepines should be used with caution because of their propensity to increase cognitive impairment and risk of falling [8]. For patients who experience anxiety as part of an ‘off’ state, or as non-motor fluctuation, dopaminergic medication adjustments can be made in an attempt to decrease the duration and severity of these ‘off’ episodes [8, 43, 47]. However, the risk of