What medications are used to treat post-operative psychosis?

Treatment of Post-Operative Psychosis (Delirium)

Antipsychotics should be reserved exclusively for severe agitation threatening substantial harm to self or others, used at the lowest effective dose for the shortest duration, and only after behavioral interventions have failed. 1

First-Line Approach: Non-Pharmacologic Management

The primary treatment for post-operative psychosis (delirium) is non-pharmacologic intervention, not medication. 1

• Environmental modifications including reducing excessive stimulation, ensuring adequate lighting, and maintaining a quiet environment are essential first steps 2
• Reorientation strategies such as visible clocks, calendars, and familiar objects should be implemented 2
• Address reversible causes including hypoxia, infection, electrolyte imbalances, and medication effects 2
• Ensure basic needs including adequate hydration, nutrition, pain control, and sleep hygiene 2

Pharmacologic Treatment: When and What to Use

For Severe Agitation Only

Antipsychotics (haloperidol or other typical/atypical agents) may be used ONLY when:

• The patient is severely agitated or distressed 1
• There is threat of substantial harm to self and/or others 1
• Behavioral interventions have failed or are not possible 1
• Daily in-person re-evaluation is performed to assess ongoing need 1

Haloperidol is the most commonly used agent in this setting, though no specific antipsychotic has demonstrated superiority over others 1

Critical Contraindications

DO NOT use the following medications:

• Benzodiazepines as first-line treatment - These worsen delirium duration, increase adverse effects, and may precipitate or prolong delirium 1, 2

  • Exception: Alcohol or benzodiazepine withdrawal syndromes 1

• Antipsychotics or benzodiazepines for hypoactive (non-agitated) delirium - Strong recommendation against this practice as pharmacologic treatment has not been shown to modify duration or severity of delirium 1

• Cholinesterase inhibitors - Do not newly prescribe these perioperatively; they are ineffective and may increase mortality 1

• Prophylactic antipsychotics - Insufficient evidence to support prevention strategies, with substantial harm potential including increased mortality even with short-term use 1

Medications to Avoid That Cause Delirium

Strongly avoid these deliriogenic medications postoperatively: 1

• Benzodiazepines (diphenhydramine, midazolam)
• Anticholinergics (cyclobenzaprine, oxybutynin, prochlorperazine, promethazine, tricyclic antidepressants, paroxetine)
• Diphenhydramine and hydroxyzine
• H2-receptor antagonists (cimetidine)
• Meperidine
• Sedative-hypnotics

Important Safety Considerations

Antipsychotic harms are substantial and include: 1

• Cardiovascular: QT prolongation, dysrhythmias, sudden death, hypotension 1
• Neurologic: Extrapyramidal symptoms, neuroleptic malignant syndrome, decreased seizure threshold 1
• Other: Pneumonia, falls, deep venous thrombosis, increased mortality even with short-term use 1

Critical pitfall: 47% of patients continue antipsychotics after ICU discharge and 33% continue as outpatients without clear indication - this inadvertent chronic administration must be avoided 1

Clinical Algorithm

1. Identify and treat underlying causes (infection, hypoxia, metabolic derangements, pain) 2
2. Implement non-pharmacologic interventions (reorientation, environmental modifications) 2
3. If severe agitation threatening harm: Consider low-dose antipsychotic (e.g., haloperidol) 1
4. Daily reassessment with in-person examination to discontinue as soon as possible 1
5. Never use for hypoactive/non-agitated delirium 1

Patients over 75 years are less likely to respond to antipsychotics, particularly olanzapine 1