Treating Psychosis in Parkinson's Disease

Clozapine is the ideal drug for treating the psychotic symptoms of Parkinson’s disease, which include hallucinations, delusions, and thought disorder. Most antipsychotic medication binds to the D2 receptors in the brain, causing a decrease in dopamine in the brain. First generation (typical antipsychotics) bind more tightly to the D2 receptors than second generation (atypical) antipsychotics. This decrease of dopamine in the brain leads to extrapyramidal `(affecting motor control and co-ordination) side effects including Parkinsonian symptoms such as tremor, rigidity and bradykinesia (poverty of movement), so are unsuitable for treating psychosis in Parkinson’s disease, as they will lead to the Parkinson’s motor (movement) symptoms deteriorating.
Clozapine has fewer extrapyramidal side effects than other antipsychotics as it binds more strongly to the D4 receptors than the D2 receptors. It is also a partial 5-HT1A agonist (it activates the receptor serotonin 1a) which also reduces extrapyramidal symptoms.