How To Treat Parkinson's Disease

An examination of the evidence base for the use of atypical antipsychotic medication in treating Parkinson’s Disease Psychosis

Parkinson’s disease (PD) is a chronic and progressive neurological condition that affects one person in every 500. Parkinson’s disease tends to affect people between the ages of 50 and 60 but the symptoms may start even earlier. Over 127,000 people in the UK are affected by it today (Parkinsons.org.uk, 2015). It is typically caused by low levels of dopamine in the brain ultimately causing the symptoms of Parkinson’s Disease. It occurs when neurons responsible for controlling movement become impaired or die and as such produce less dopamine. Dopaminergic neurons are comparatively few in number (only about 400,000 in

First-generation antipsychotics, more commonly known as typical antispychotics, are dopamine (D2) antagonists. As a result, they reduce dopaminergic neurotransmission in the four dopamine pathways. Dysfunction of the mesocortical pathway is associated with cognitive impairment and emotional disturbances (negative symptoms). Blockade of this pathway by first generation antipsychotics can induce secondary negative symptoms. Overactivity of the mesolimbic pathway is thought to be involved in the pathophysiology of positive symptoms and as such a blockade of the D2 receptors in the mesolimbic pathway has been proposed as a possible mechanism of the antipsychotic action of first generation antipsychotics. Antagonism of the D2 receptors in the nigrostriatal pathway is associated with increased risk of extrapyramidal symptoms. In the tuberoinfundibular pathway, dopamine acts as a prolactin-inhibting factor therefore a D2 receptor blockade increases prolactin levels by promoting its release from the pituitary glands. While second generation antipsychotics, more commonly known as typical antipsychotics, work by blocking both the dopamine D2 receptor and the 5-HT2A receptor. Second generation antipsychotics tend to achieve lower levels of adverse effects (fewer extrapyramidal symptoms etc) than the first generation antipsychotics. One theory used to explain this is the so called ‘fast-off’ theory. It proposes that the atypical antipsychotics achieve a lower incidence of adverse effects b binding more loosely to the D2 receptor than the typical antipsychotic or even dopamine itself. It is suggested that they therefore only bind to the D2 receptor long enough to produce the therapeutic effect but not long enough to produce the extrapyramidal symptoms. This can be seen in the antipsychotic agents that bind loosely to the D2 receptor such as clozapine, melprone, quetiapine and remoxipride are generally