Depression and anxiety in Parkinson s disease and Multiple system atrophy - Consequences for treatment

Abstract Objective: Parkinson s disease (PD) is a chronic progressive neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Hence, the patients suffer from a dopamine deficiency and this causes the cardinal motor symptoms in PD; bradykinesia, tremor and rigidity. Lately, research has shown that also non-motor symptoms play a major role in PD. Among them are depression and anxiety. Multiple system atrophy (MSA) is a rare, neurodegenerative disorder characterized by poor levodopa responsive parkinsonism, extrapyramidal signs, cerebellar ataxia and autonomic failure in any combination. MSA and PD are both classified as alpha-synucleinopathies due to accumulation of this protein in CNS. Similar to PD, non-motor symptoms as depression and anxiety also seems to be present in MSA. This study compares depression and anxiety in MSA and PD to evaluate the consequences for treatment. A non-systematic search was executed in PUBMED and relevant reviews were included in this study. Results: There is little research on this topic and very few RCTs addressing anxiety and depression in MSA or PD. However, of the existing material, there is more research done on the PD group than on the MSA group. For treating depression in PD, SSRIs are most commonly used. However, TCAs have in some studies been found superior to the SSRIs. Other studies found no greater effect of antidepressants than placebo. Recently dopamine agonists have been suggested as another treatment option, but the evidence was found to be insufficient. Rotigotine, a transdermal dopamine agonist patch, recently was included as a treatment option and may improve depression. Also Mirtazepin (an antidepressant) and Bupropion (norephineprine and dopamine reuptake inhibitor) are two new medications that may have effect, but there is not enough research so far to conclude on this. As for anxiety in PD, benzodiazepines are often used and are found to have some effect. However, due to side effects and possible dependence, this medication should be used with care. Buspirone (a partial 5-HT agonist) may have effect, but there is a lack of RCTs studying this. SSRIs and SNRIs are also used for treating anxiety, but there are no RCTs addressing the use of this medication on anxiety only and therefore insufficient data on this. TCAs were found to be effective, but once again there is the same issue with lack of RCTs. The drug Mirtazepin is also mentioned as a treatment for anxiety, but there is no significant evidence backing this information either. Last, electroconvulsive treatment may also work in drug-resistant anxiety. In the MSA group, very little literature exists, but psychotherapy, SSRIs and levodopa are mentioned as possible treatments. Alternative treatments listed are electroconvulsive therapy and repetitive transcranial magnetic stimulation. Cognitive behavioural therapy is found to be efficient in both anxiety and depression in the PD group. There is no literature on this in the MSA group. Conclusion: As a consequence of low number of studies and a lack of large RCTs addressing the treatment options of anxiety and depression in MSA and PD, practical management is currently based on empirical evidence only. There is insufficient evidence to recommend any treatment for depression and anxiety in the PD and MSA groups. More clinical studies are needed