Is mirtazapine contraindicated in a patient with traumatic brain injury, bilateral subarachnoid hemorrhage, right frontotemporal intraparenchymal hemorrhage, and a pre‑existing seizure disorder?

Mirtazapine Use in Traumatic Brain Injury with Intracranial Hemorrhage and Seizure Disorder

Mirtazapine is not absolutely contraindicated in this clinical scenario, but it should be used with extreme caution given the patient's seizure disorder and acute brain injury with hemorrhage. The FDA label explicitly states that mirtazapine should be "prescribed with caution in patients with a seizure disorder," and the drug has not been systematically evaluated in patients with seizure disorders 1.

Key Safety Considerations

Seizure Risk

• Mirtazapine has a low seizure-inducing potential, with only 1 seizure reported among 2,796 patients in premarketing trials 1.
• However, the FDA label specifically recommends caution in patients with pre-existing seizure disorders 1.
• In a safety review, only one seizure case was recorded in a patient with a history of seizures during previous antidepressant treatment 2.

Acute Brain Injury Context

• Mirtazapine has not been systematically evaluated in patients with recent significant neurological injury 1.
• The drug can cause significant somnolence (54% of patients), which could mask neurological deterioration or complicate assessment of mental status in acute TBI 1.
• One case series documented mirtazapine-induced delirium in patients with organic brain disease, with hallucinations, psychomotor agitation, and cognitive changes that resolved after drug discontinuation 3.

Cardiovascular Concerns with Intracranial Hemorrhage

• Mirtazapine was associated with significant orthostatic hypotension in early clinical trials 1.
• The FDA label recommends caution in patients with cerebrovascular disease that could be exacerbated by hypotension, which includes patients with acute intracranial hemorrhage 1.
• Blood pressure management is critical in SAH (maintain systolic <160 mmHg but avoid <110 mmHg) and intracerebral hemorrhage (reduce if >150 mmHg within 6 hours) 4.

Clinical Decision Algorithm

If depression treatment is urgently needed:

• Consider alternative antidepressants with better-established safety profiles in TBI, such as SSRIs (sertraline showed no detrimental effect on recovery in a TBI trial, though efficacy was not proven) 5.
• If mirtazapine is chosen despite risks, start at the lowest possible dose and monitor closely for:
  • Worsening somnolence that impairs neurological assessment 1
  • Orthostatic hypotension that could compromise cerebral perfusion 1
  • New or worsening seizure activity 1
  • Delirium or cognitive changes 3

Defer treatment if possible:

• Given the acute nature of bilateral SAH and frontotemporal IPH, delaying antidepressant initiation until neurological stabilization is the safest approach.
• The risk-benefit ratio strongly favors waiting until the acute hemorrhagic phase has resolved and seizure control is optimized.

Important Caveats

• Somnolence is a major concern: 54% of patients experience somnolence with mirtazapine, and 10.4% discontinue due to this effect 1. In a patient with acute TBI and hemorrhage, this could dangerously obscure clinical deterioration.
• Drug interactions: Avoid concomitant benzodiazepines and alcohol, which could further impair consciousness 1.
• Monitoring requirements: If used, requires frequent neurological assessments, blood pressure monitoring, and EEG consideration if mental status changes occur 1, 3.