Mirtazapine and Levetiracetam (Keppra) Interaction
There is no clinically significant pharmacokinetic or pharmacodynamic interaction between mirtazapine and levetiracetam, and these medications can be safely co-administered without dose adjustment.
Pharmacokinetic Profile of Levetiracetam
Levetiracetam has an exceptionally favorable drug interaction profile that makes it compatible with most medications:
Levetiracetam undergoes minimal hepatic metabolism through hydrolysis of the acetamide group rather than cytochrome P450 pathways, with primarily renal elimination 1, 2.
It lacks cytochrome P450 enzyme-inducing or inhibiting potential and is not associated with clinically significant pharmacokinetic interactions with other drugs 1, 2.
Studies specifically demonstrate no pharmacokinetic interaction even with highly protein-bound drugs like valproic acid, where levetiracetam did not affect steady-state pharmacokinetics 3.
Mirtazapine Metabolism
Mirtazapine is metabolized primarily via CYP2D6, CYP1A2, and CYP3A4 pathways. Since levetiracetam does not interact with cytochrome P450 enzymes, there is no mechanism for a pharmacokinetic interaction between these two agents.
Clinical Implications
No dose adjustment is required when initiating either medication in patients already taking the other 3.
No additional monitoring beyond standard clinical assessment for each medication's individual side effects is necessary.
The combination does not increase risk of sedation synergistically, as levetiracetam causes only mild somnolence and does not potentiate CNS depression 1, 2.
Important Caveat
While levetiracetam generally has minimal drug interactions, clinicians should be aware that it can cause psychiatric adverse events including irritability, aggression, anxiety, and mood changes in up to 45% of patients 4. In patients taking mirtazapine for depression or anxiety, monitor for behavioral changes when adding levetiracetam, though this represents an additive effect profile rather than a true drug interaction.