FORMULARY ADDITION

Mirtazapine (Remeron®)

15 mg, 30 mg, 45 mg Tablets

            Mirtazapine is indicated as an antidepressant and has a tetracyclic chemical structure unrelated to the tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) or monoamine oxidase inhibitors (MAOIs). Contrary to the SSRIs, mirtazapine has a dual mode of action similar to that of the TCAs.  Mirtazapine acts as an antagonist at central presynaptic a2-adrenergic receptors as well as postsynaptic serotonin (5HT2 and 5HT3) receptors, thus resulting in an increase in norepinephrine and serotonin release.  It is also a potent histamine (H1) antagonist and a moderate peripheral a1-adrenergic antagonist.  It has minimal activity at muscarinic and dopaminergic receptors.

            Mirtazapine should be initiated at 15 mg once daily at bedtime.  The dose may be increased if needed every 2 weeks up to a maximum of 45 mg daily.  Elderly patients and patients with severe renal or hepatic impairment have a reduced mirtazapine clearance and may require smaller dosages.

            The adverse event profile of mirtazapine is favorable compared to the TCAs and equally favorable as the SSRIs.  Adverse events reported in comparative trials show that mirtazapine is less likely than TCAs to cause anticholinergic adverse events and less likely than SSRIs to cause serotonin-related adverse events, including sexual dysfunction. The most commonly observed adverse events reported with mirtazapine use included somnolence, increased appetite, weight gain, and dizziness. Since more somnolence is seen at lower therapeutic doses (15-30 mg) lessens the incidence of somnolence.

            Since mirtazapine is a weak inhibitor of the cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4, significant interactions are unlikely. Coadministration of mirtazapine and diazepam does not affect the pharmacokinetics of either drug.  Mirtazapine does not affect the absorption rate of alcohol.  However, coadministration of mirtazapine with either ethanol or diazepam can result in additive cognitive and motor performance impairment. Although there is no data with mirtazapine, coadministration of MAOIs with other antidepressants has caused severe adverse events, including nausea, vomiting, tremor, rigidity, seizures, and mental status changes.  Patients should be cautioned not to combine mirtazapine with other central nervous system depressants, especially diazepam, alcohol, and MAOIs.

            Mirtazapine is a FDA pregnancy category rating of C.  It is unknown if mirtazapine is excreted in breast milk.

FORMULARY BOOK 1999-2000 UPDATES

Formulary Additions Not Listed in 1999-2000 Formulary Book (as of 9/28/99)

Formulary Deletions Not Listed in 1999-2000 Formulary Book (as of 9/28/99)

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