What is the recommended protocol for switching a patient from Thorazine (chlorpromazine) to Zyprexa (olanzapine)?

Switching from Thorazine (Chlorpromazine) to Zyprexa (Olanzapine)

Use a gradual cross-titration protocol over 1-2 weeks, starting olanzapine at 2.5-5 mg daily while simultaneously reducing chlorpromazine by 50%, then titrating olanzapine to a target dose of 5-10 mg daily while discontinuing chlorpromazine completely by week 2. 1

Recommended Switching Protocol

Week 1: Initiation Phase

• Start olanzapine at 2.5-5 mg orally once daily, preferably at bedtime due to its sedating properties 2
• Simultaneously reduce chlorpromazine by 50% of the current dose on the same day you initiate olanzapine 1, 3
• Monitor closely for withdrawal symptoms from chlorpromazine discontinuation and emerging side effects from olanzapine 1

Week 2: Completion Phase

• Increase olanzapine to target therapeutic dose of 5-10 mg daily based on symptom response and tolerability 2
• Discontinue chlorpromazine completely by the end of week 2 1, 3
• Continue monitoring for orthostatic hypotension, drowsiness, and metabolic changes 2

Dose Equivalency Considerations

Chlorpromazine 100 mg is approximately equivalent to olanzapine 5 mg, which helps guide the cross-titration 4. For example, if your patient is on chlorpromazine 200 mg daily, the equivalent olanzapine dose would be approximately 10 mg daily.

Critical Monitoring Parameters

During the Switch (Weeks 1-2)

• Assess psychotic symptoms weekly using standardized scales to detect any symptom exacerbation during the transition 1
• Monitor orthostatic vital signs at each visit, as both medications can cause orthostatic hypotension, though chlorpromazine carries higher risk 2
• Watch for extrapyramidal symptoms (EPS), noting that olanzapine has lower EPS risk than chlorpromazine 2
• Evaluate sedation levels, as both agents are sedating but olanzapine may cause less severe sedation 2

Post-Switch Monitoring (Weeks 3-4 and Beyond)

• Assess metabolic parameters including weight, fasting glucose, and lipid panel, as olanzapine carries significant metabolic risk with long-term use 2
• Monitor for anticholinergic effects, though olanzapine is less anticholinergic than chlorpromazine 2
• Evaluate for drowsiness and orthostatic hypotension, which are common with olanzapine 2

Special Considerations and Adjustments

For Older or Frail Patients

• Start olanzapine at the lower end of the dosing range (2.5 mg daily) and titrate more gradually 2
• Reduce doses in patients with hepatic impairment 2
• Use a slower cross-titration closer to 2-3 weeks rather than 1-2 weeks to minimize risk of decompensation 1

Route of Administration

• Olanzapine is available as oral tablets and orally disintegrating tablets (ODT), which may improve adherence 2
• Olanzapine can also be given intramuscularly if needed, though this is typically reserved for acute agitation 2

Common Pitfalls to Avoid

• Do not switch too abruptly: Stopping chlorpromazine suddenly without overlap increases risk of psychotic relapse and withdrawal symptoms including insomnia, nausea, and agitation 1, 5
• Do not combine olanzapine with benzodiazepines at high doses: Fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine due to oversedation and respiratory depression 2
• Do not ignore metabolic monitoring: Olanzapine carries significant risk of weight gain and metabolic syndrome with long-term use, requiring baseline and ongoing metabolic parameter assessment 2
• Do not underdose olanzapine: The therapeutic range is typically 5-10 mg daily for most patients; inadequate dosing may lead to perceived treatment failure 2

Expected Timeline for Response

Symptom improvement should be evident by week 4 after completing the switch 1. If symptoms worsen during the cross-titration or fail to improve by week 4 post-switch, reassess diagnosis, confirm medication adherence, and consider alternative strategies 1.