From the Guidelines
Antipsychotics that most severely worsen Parkinsonism are first-generation (typical) antipsychotics, with haloperidol, fluphenazine, and chlorpromazine ranking as the worst offenders. These medications have high dopamine D2 receptor blocking potency, which directly interferes with the dopaminergic pathways already compromised in Parkinson's disease, as noted in a study from 1. Second-generation (atypical) antipsychotics generally cause less Parkinsonism, with clozapine and quetiapine having the lowest risk, as suggested by research from 1 and 1. Risperidone and olanzapine fall in the middle range, still causing significant extrapyramidal symptoms at higher doses.
Some key points to consider when prescribing antipsychotics to patients with Parkinsonism include:
- Starting with the lowest effective dose to minimize the risk of worsening Parkinsonian symptoms
- Selecting atypical antipsychotics, such as quetiapine or clozapine, which have a lower risk of extrapyramidal side effects
- Monitoring patients closely for worsening tremor, rigidity, and bradykinesia, especially during the first few weeks of treatment or after dose increases
- Being aware of the potential for drug interactions and adjusting doses accordingly, as noted in 1
The mechanism behind this ranking relates to receptor binding profiles - medications with higher D2 receptor affinity and longer receptor occupancy cause more Parkinsonian symptoms by blocking dopamine transmission in the nigrostriatal pathway. According to a study from 1, the suggested starting doses for some antipsychotics are:
- Quetiapine: 25 mg (immediate release) p.o. stat
- Risperidone: 0.5 mg p.o. stat
- Olanzapine: 2.5–5 mg p.o. or s.c. stat
It's essential to weigh the benefits and risks of antipsychotic treatment in patients with Parkinsonism and to consider alternative treatments when possible, as noted in 1. By prioritizing the patient's morbidity, mortality, and quality of life, clinicians can make informed decisions about antipsychotic treatment and minimize the risk of worsening Parkinsonian symptoms.
From the Research
Antipsychotics that Worsen Parkinsonism
- The following antipsychotics have been reported to worsen parkinsonism:
- Risperidone: has been shown to deteriorate motor function in some Parkinson's disease studies 2
- Olanzapine: initial studies showed it to be effective without deterioration of motor function, but succeeding reports demonstrated a deleterious effect on motor functioning 2
- Typical antipsychotics: are recommended against in patients with Parkinson's disease due to their potential to worsen motor symptoms 3
- High-potency antipsychotics: have been associated with worsening parkinsonism, and their use is not uncommon in patients with Parkinson's disease and psychosis 4
Comparison of Antipsychotics
- Clozapine: does not induce deterioration of motor function, but has the potential to cause agranulocytosis 2
- Quetiapine: may induce mild deterioration of motor function, but is generally well tolerated and effective in Parkinson's disease patients 2, 5
- Pimavanserin: is a novel therapeutic option with a more favorable adverse effects profile, but requires careful postmarketing monitoring to establish its long-term safety and efficacy 6, 5
Prescribing Practices
- Potentially inappropriate antipsychotic prescribing practices are common in the neuropsychiatric management of patients with parkinsonism 3
- There is a need for education and improvement in prescribing practices to minimize the risk of worsening parkinsonism in patients with Parkinson's disease and psychosis 3, 4