Objective: To demonstrate that patients with drug-induced parkinsonism (DIP) can remain symptomatic beyond 6 months, what majority of literature suggests, after withdrawal of causative agents.

Background: DIP in most literature sources is documented to persist for approximately 6 months after discontinuation of causative agent. In our observation, we followed two patients longitudinally for about two years after removal of causative agents with continual parkinsonian symptoms.

Method: We report 2 cases of DIP followed longitudinally, with normal ioflupane iodine-123 (DaT) single-photon emission computed tomography (SPECT) scans.

Results: Our first patient developed acute onset rest and action tremors after beginning aripiprazole for depression. During our initial evaluation, he was diagnosed with DIP and switched to quetiapine, which has a lower risk of extrapyramidal symptoms, with marked improvement. Normal DaT scan was completed 16 months after switch of medications but with symptoms still present. Symptoms continued to improve but persisted at our last visit 27 months since discontinuation of aripiprazole but on quetiapine. Our second patient reports developing symptoms of parkinsonism 3 months after beginning risperidone and valproic acid for bipolar disorder. About 57 months after symptom onset, patient discontinued all causative agents. DaT scan performed 8 months after discontinuation of all causative agents was normal despite continual parkinsonian symptoms. Our last visit, 22 months after discontinuation of all causative agents, revealed that the patient’s symptoms were improving but still present.

Conclusion: Our cases demonstrate that symptoms of DIP can persist beyond the accepted 6 months since stopping the causative agents, and in our case beyond 22 and 27 months. Parkinsonism persisted at our last visit but improved during longitudinal follow-up, going against a progressive degenerative disorders such as Parkinson’s disease. DaT scans showing normal dopamine transporters at 8 and 16 months since discontinuation of causative agents persuade us that the patients did not evolve or concurrently suffer from neurodegenerative causes of parkinsonism. An updated consensus regarding timeline for when to pursue other etiologies of parkinsonism in patient’s diagnosed with DIP after discontinuation of causative agents is needed.

References: Lim, T.T., et al. (2013). Is 6 Months of Neuroleptic Withdrawal Sufficient to Distinguish Drug-Induced Parkinsonism From Parkinson’s Disease? International Journal of Neurosciences, 123(3), 170-174.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/drug-induced-parkinsonism-may-persist-beyond-two-years-after-discontinuation-of-dopamine-transmission-blocking-agents/