Objective: To describe a patient with Lewy Body Dementia (LBD) who developed profound worsening of parkinsonism and an accelerated neuroleptic withdrawal dyskinesia on aripiprazole.
Background: Patients with LBD present a treatment challenge: with spontaneous psychosis and parkinsonism, they are highly sensitive to motor worsening with neuroleptics. Aripiprazole is a new antipsychotic. Unlike all other antipsychotics it is not a dopamine receptor blocking agent but is rather a partial D2 agonist. This offers several theoretical advantages. In schizophrenia a partial agonist might treat both positive symptoms (hallucinations, delusions) as well as the more refractory negative symptoms (anhedonia, apathy). In the reported clinical trials incidence of EPS did not differ from placebo [Medical Letter 2003], and tardive dyskinesia has not been previously reported with this agent. However, hopes for greater efficacy over other atypical neuroleptics for either negative or positive symptoms were not borne out in clinical trials [Potkin 2003]. Despite theoretical advantages of a partial dopamine agonist antipsychotic, there are no reports of aripiprazole use in parkinsonian disorders.
Case Report: Mr. H developed a rapidly progressive dementia at age 57. Initially, he noticed memory difficulties; shortly thereafter he developed frightening visual and auditory hallucinations. He became child-like, irritable, paranoid, and displayed compulsive grooming. His gait worsened, he developed seizures, and became progressively dependent in ADLs. At our initial evaluation, 13 months after symptom onset, he was variably attentive with no spontaneous speech. All verbal responses were perseverative. He was bradykinetic and rigid, with a course rest tremor and shuffling gait. Neither his mental nor his motor state changed with stopping the risperidone 0.25 mg which he was on at that time. Difficult to redirect, Mr. H began to wander around the house handling objects he came across, responding to internal stimuli. A trial of quetiapine did not worsen his parkinsonism but minimally helped his psychotic symptoms. Aripiprazole 10 mg/day (smallest dose available) was added to a regimen which at that point included galantamine, phenytoin (which decreases aripiprazole levels) and paroxetine (which increases aripiprazole levels). At the next visit 4 weeks later, Mr. H was wheelchair bound, unable to walk or talk. When lifted from the wheelchair he remained frozen in the seated position. Aripiprazole was discontinued. Within days following discontinuation he developed continuous orobuccal dyskinesias with prominent tongue protrusions and grimacing. Within a month his rigidity was less severe and he was once again able to walk, using a rolling walker most of the time. Nonetheless, he progressed to frozen mutism over the coming months. The dyskinesias, however, continued unabated until his demise under home hospice care, 8 months after discontinuation of aripiprazole and 2 years after symptom onset.
Conclusion: Despite promising theoretical advantages, aripiprazole can cause severe motor worsening and persistent withdrawal dyskinesia in LBD.