Brexpiprazole (Rexulti) is the most likely cause of new bradykinesia in this patient and should be discontinued immediately.
Most Likely Culprit: Brexpiprazole
The new bradykinesia is almost certainly drug-induced parkinsonism from brexpiprazole, an atypical antipsychotic with dopamine D2 receptor partial agonist activity. While brexpiprazole has lower extrapyramidal symptom (EPS) rates than traditional antipsychotics, EPS-related adverse events still occur in 5.3% of patients versus 3.1% on placebo 1. In elderly dementia patients, even partial dopamine antagonism can precipitate parkinsonian symptoms 2.
- Brexpiprazole's mechanism involves dopamine D2 receptor partial agonism, which can still block dopamine signaling sufficiently to cause extrapyramidal symptoms including bradykinesia 3
- The temporal relationship—new bradykinesia after starting brexpiprazole—strongly suggests causation 1
- Neither memantine nor ranolazine are associated with parkinsonian side effects, making them unlikely culprits 4
Immediate Management Algorithm
Step 1: Discontinue Brexpiprazole
- Stop brexpiprazole immediately as the risk-benefit ratio no longer favors continuation when significant motor side effects emerge 5
- Bradykinesia represents an intolerable side effect that warrants medication discontinuation per Canadian consensus guidelines 5
- Do not taper—brexpiprazole can be stopped abruptly when serious adverse effects occur 1
Step 2: Monitor for Symptom Resolution
- Bradykinesia should improve within 1-2 weeks after discontinuation, though complete resolution may take 4-6 weeks
- If symptoms persist beyond 6 weeks, consider alternative diagnoses including underlying Lewy body dementia or Parkinson's disease dementia 5
Step 3: Reassess Need for Antipsychotic
- Determine if brexpiprazole was treating agitation or psychosis 3
- If agitation has resolved or was never severe, do not restart any antipsychotic 5
- If severe agitation persists with risk of harm, consider non-pharmacologic interventions first 6
Alternative Management for Agitation (If Needed)
Non-Pharmacologic First-Line Approach
- Prioritize environmental modifications including safety locks, predictable routines, and distraction techniques before considering any psychotropic medication 6
- Optimize lighting to reduce confusion, particularly at night 6
- Reduce environmental stimuli including television noise and household clutter 6
- Consider adult day care programs for structured activities 6
Pharmacologic Considerations (Only If Non-Pharmacologic Fails)
- All antipsychotics carry black box warnings for increased mortality in elderly dementia patients and should only be used for severe agitation with risk of harm 6
- Brexpiprazole should not be restarted given the development of bradykinesia 1
- If antipsychotic treatment is absolutely necessary, use the lowest effective dose of an alternative agent with close monitoring for EPS 7
Optimize Existing Alzheimer's Medications
Verify Memantine Dosing
- Ensure memantine is at target dose of 20mg daily (current 10mg BID is appropriate) 4
- Continue memantine as it does not cause parkinsonian symptoms and may help with behavioral symptoms 4
Assess for Underlying Triggers
- Evaluate for pain, constipation, urinary retention, or infections that may worsen behavioral symptoms 6
- Rule out delirium or other acute medical conditions contributing to agitation 5
Critical Pitfalls to Avoid
- Do not add anticholinergic medications (e.g., benztropine) to treat the bradykinesia while continuing brexpiprazole—this worsens cognitive function in dementia patients and does not address the root problem 8
- Do not switch to another antipsychotic unless absolutely necessary for severe agitation with risk of harm, as all carry similar EPS risks in this population 7
- Do not attribute bradykinesia to disease progression without first discontinuing the offending medication and observing for improvement 1
- Do not restart brexpiprazole even at a lower dose, as the patient has demonstrated susceptibility to EPS 2