Is mirtazapine (Remeron) contraindicated in patients with delirium?

Mirtazapine in Delirium Management

Mirtazapine is not recommended for patients with delirium and should be considered contraindicated due to its potential to worsen or induce delirium, particularly in patients with underlying brain disorders. 1

Evidence Against Mirtazapine Use in Delirium

Mirtazapine has been documented to induce delirium in patients with organic brain disorders and even in those with subclinical brain disease. The mechanism appears to be related to its central increase of norepinephrine after acute administration, which can precipitate hallucinations, psychomotor agitation, and cognitive changes 1.

Current guidelines do not include mirtazapine as a recommended agent for delirium management. In fact, the European Society for Medical Oncology (ESMO) guidelines specifically recommend:

• Olanzapine for symptomatic management of delirium [III, C]
• Quetiapine for symptomatic management of delirium [V, C]
• Aripiprazole for symptomatic management of delirium [IV, C] 2

Preferred Pharmacological Approaches for Delirium

When pharmacological management is necessary for distressing delirium symptoms or safety concerns, the evidence supports:

1. Atypical antipsychotics as preferred agents:

   • Olanzapine (2.5-5 mg PO or SC)
   • Quetiapine (25 mg immediate release)
   • Aripiprazole (5 mg PO or IM) 2, 3

2. Avoid haloperidol and risperidone in mild-to-moderate delirium as they have been shown to worsen symptoms [I, D] 2

3. For hypoactive delirium specifically:

   • Methylphenidate may improve cognition when no delusions or perceptual disturbances are present [V, C] 2

4. For severe agitation with safety concerns:

   • Benzodiazepines (midazolam, lorazepam) can be considered for crisis intervention, but should not be first-line except in alcohol or benzodiazepine withdrawal [II, C] 2, 3

Important Clinical Considerations

• Medications should only be used if the patient shows distressing symptoms (like perceptual disturbances) or poses safety risks to themselves or others 3

• Use the lowest effective dose for the shortest time possible and monitor closely for effectiveness and adverse effects 3

• Be aware that mirtazapine's sedating properties might seem appealing for sleep disturbances in delirium, but this potential benefit is outweighed by its risk of inducing or worsening delirium 1, 2

• While mirtazapine may be used safely in cardiovascular disease for depression and can help with sleep and appetite stimulation in that context, it should not be used in patients with delirium 2

Non-Pharmacological Approaches

Before considering any medication for delirium:

• Identify and treat reversible causes
• Implement environmental stability measures (minimize transfers, maintain consistent care teams)
• Provide frequent reorientation, orientation boards, and visible clocks
• Ensure proper sensory support (eyeglasses, hearing aids)
• Encourage early mobilization when possible
• Maintain proper hydration and sleep-wake cycles 3

In conclusion, mirtazapine should be avoided in patients with delirium due to its potential to worsen cognitive symptoms and induce hallucinations and agitation, particularly in those with underlying brain vulnerability.