Parkinson’s disease. The most extensive evidence for treating movement disorders with clozapine involves patients with Parkinson’s disease (PD). Geriatric psychiatrists commonly use clozapine, particularly at low doses, to treat psychotic symptoms in patients with PD. Because of a relatively low likelihood of extrapyramidal side effects, clozapine and quetiapine are the 2 antipsychotics most often used to treat dopamimetic psychosis in PD.49 In a randomized, placebo-controlled study, low-dose clozapine showed benefits in treating dopamimetic psychosis in PD, without worsening overall motor function.50 (The recent approval of pimavanserin for PD psychosis likely will impact off-label use of clozapine for this condition.)
A retrospective review of patients with PD and Lewy body dementia described benefits of treating psychosis with clozapine.51 Benefits also have been reported in using clozapine to address levodopa-induced dyskinesia (LID) absent psychotic symptoms. In an evidence-based review, the Movement Disorder Society described clozapine for LID as “efficacious and possibly useful.”52
Tardive syndromes. In a retrospective review of clozapine use for tardive dyskinesia, 43% of the 30 patients showed improvement, particularly those with concomitant dystonia.53 Another retrospective analysis reported similar outcomes for 48 patients with tardive dyskinesia treated with clozapine.54 Case series and case reports show support for clozapine as monotherapy for tardive dystonia.55
Huntington’s disease. A randomized, double-blind study found little benefit in using clozapine for patients with Huntington’s disease. The authors concluded that, although individual patients may be able to tolerate sufficiently high dosages to improve chorea, clinicians should use restraint when considering clozapine for this population.56
Precautions in older patients. Caution is advised when using clozapine for movement disorders in older individuals, particularly those with concurrent dementia. All antipsychotics, including clozapine,57 carry a “black-box” warning of increased mortality in older adults with dementia.
We hope that this series, “Rediscovering clozapine,” has helped you get reacquainted with this effective medication, employ appropriate caution, and explore off-label uses.
Bottom Line
Clozapine generally is most appropriate for refractory cases, regardless of the primary condition being treated. Prescribing clozapine for refractory bipolar disorder is the off-label use with the strongest available scientific support.
