Procyclidine (Kempro) Should NOT Be Used to Treat Olanzapine-Induced Anticholinergic Side Effects
You have a fundamental misunderstanding: procyclidine is an anticholinergic medication that would worsen, not treat, anticholinergic side effects from olanzapine. Procyclidine is used to treat extrapyramidal symptoms (EPS) like dystonia, parkinsonism, and akathisia—not anticholinergic effects like dry mouth, constipation, urinary retention, or cognitive impairment.
Understanding the Problem
Olanzapine itself has anticholinergic properties 1. The FDA label explicitly warns that "concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility" 1. Research confirms olanzapine has measurable serum anticholinergic levels, though significantly lower than clozapine 2.
Adding procyclidine to olanzapine would compound the anticholinergic burden, potentially causing:
- Severe constipation or ileus
- Urinary retention
- Cognitive impairment
- Confusion or delirium
- Increased risk of falls (especially in elderly)
What Procyclidine Actually Treats
Procyclidine is an anticholinergic agent used specifically for extrapyramidal side effects (EPS) from antipsychotics 3, 4:
For Acute Dystonia:
- Procyclidine is appropriate and effective for sudden muscle spasms, oculogyric crisis, or torso contractions 3
- These respond well to anticholinergic medications 3
For Drug-Induced Parkinsonism:
- Procyclidine can be used for bradykinesia, tremors, and rigidity 3
- The APA guideline suggests three options: lowering antipsychotic dose, switching antipsychotics, or adding an anticholinergic 4
For Akathisia:
- Procyclidine is NOT consistently helpful 3
- Better options include dose reduction, switching to quetiapine/olanzapine, propranolol (10-30 mg 2-3 times daily), or benzodiazepines 3, 5
Critical Clinical Pitfall
Olanzapine causes relatively few EPS compared to typical antipsychotics 6. The 2018 ESMO guidelines note olanzapine "may cause drowsiness, orthostatic hypotension" but do not list EPS as a primary concern 6. Research shows olanzapine-treated patients require significantly fewer anticholinergic agents than those on typical antipsychotics 7.
If your patient on olanzapine has what appears to be anticholinergic side effects, do not add procyclidine. Instead:
- Review the anticholinergic burden of all medications 5
- Consider dose reduction of olanzapine if clinically feasible 5
- Switch to an antipsychotic with lower anticholinergic activity (aripiprazole, risperidone, quetiapine) if symptoms are severe 8, 5
- Manage specific symptoms:
- Constipation: laxatives, increased fluids/fiber
- Dry mouth: sugar-free gum, saliva substitutes
- Urinary retention: may require catheterization and medication review
When Anticholinergics Should Be Discontinued
The 2009 AACAP guideline explicitly states: "if an anticholinergic medication is added to an antipsychotic to reduce the risk for extrapyramidal symptoms during initial treatment, it may be possible to discontinue anticholinergic medication after the child is stabilized on the antipsychotic" 9. This principle applies to adults as well—anticholinergics should be tapered once acute EPS resolves 3.
Research demonstrates that procyclidine itself impairs cognitive function (prepulse inhibition, critical flicker fusion threshold) even in healthy volunteers at 15 mg doses 10, 11, 12, further supporting minimizing anticholinergic use.
The Bottom Line
Procyclidine treats extrapyramidal symptoms (muscle rigidity, tremor, dystonia), not anticholinergic side effects. Using procyclidine for anticholinergic symptoms from olanzapine is pharmacologically incorrect and potentially dangerous. If EPS occur with olanzapine (uncommon), procyclidine may be appropriate. For anticholinergic symptoms, reduce the anticholinergic burden—never add more anticholinergic medication.