General Description

Mirtazapine (Remeron) is a tetracyclic compound unrelated to SSRI?s, TCA?s or MAOI's. It is slightly soluble in water and available as tablets of 15, 30, or 45 mg.

Indications for Medication

Major Depressive Episode according to DSM IV is the primary indication for usage of mirtazapine. In some placebo controlled studies, mirtazapine showed an early onset of antidepressant action, shown as significant reduction in total Hamilton Depression Rating Scale and Montgomery Asberg Depression Rating Scale Scores as early as 1 week after starting treatment. In comparative trials, the antidepressant efficacy of mirtazapine was comparable with TCA?s and in two studies, the efficacy was superior to trazadone and fluoxetine.

Mirtazapine is superior to placebo for the treatment of patients with Major Depression and co-existing symptoms of anxiety/agitation or anxiety/ somatization. Selective antagonism of post synaptic 5HT-2 and 5HT-3 receptors may account for the early relief of anxiety symptoms and this helps to improve prognosis for recovery.

Clinical Guidelines

The recommended starting dose for mirtazapine is 15 mg per day as a single dose in the evening prior to sleep. The effective dose range for depression is 15-45 mg/day. Due to the elimination half life of 20-40 hours, dose changes should not be made in less than 2 weeks. Though there is no evidence from controlled trials, it is generally agreed that treatment with mirtazapine of acute episode of depression should continue for 6 months or longer. At least 14 days should elapse between a switch from mirtazapine to MAOI or vice versa.

Administration of alcohol while prescribing mirtazapine produces additive impairment of cognitive and motor skills with mirtazapine.

Mirtazapine should be used with caution in patients with known cardiovascular, disease, cerebrovascular disease, dehydration, hypovolemia, or taking antihypertensive medications. These conditions exacerbate hypotension from mirtazapine.

Other precautions include 0.2 % increase in ALT (SGPT) in U.S. studies in patients exposed to mirtazapine, 0.2% of mania/hypomania occurring in U.S. studies, one seizure reported in 2,796 U.S. and non-U.S. patients treated with mirtazapine.

Adverse Effects

The most common adverse effects of mirtazapine include somnolence, nausea, increased appetite, weight gain and dizziness. Other side effects include asthenia, flu-like syndrome, back pain, dry mouth, seizures, constipation, peripheral edema, myalgia, abnormal dreams, abnormal thinking, tremors, confusion, dyspnea, urinary frequency. Agranulocytosis is a dangerous adverse effect that should be kept in mind while administering mirtazapine. Antidepressant sexual dysfunction is most likely due to postsynaptic stimulation of 5HT-2 receptors, which explains the reduced sexual dysfunction with mirtazapine.

Since there were no systematic observations except during clinical trials, history of drug abuse should be evaluated and patients should be observed closely for signs of mirtazapine misuse or abuse. Overdose treatment is similar to general antidepressant overdose treatment. Mirtazapine is considered under category ?C? in pregnant females. Caution should be exercised in nursing mothers and decreased clearance is shown in elderly people.

Drug-Drug Interactions

Because of mirtazapine?s weak inhibitory effect on the hepatic CYP System and its relatively low plasma protein binding, the propensity of mirtazapine to interact with co-administered drugs is assessed to be very low.

Though studies claim that mirtazapine does not inhibit the cytochrome system as much as some of the other SSRI?s, mirtazapine is metabolized by 2D6, 1A2, 3A enzymes as mentioned earlier and should be kept in mind while choosing medications for the patient.

Mirtazapine has additive effects with anticholinergics, additive seizure potential with phenothiazines. It enhances cardiotoxicity when given with thyroid hormones. Concomitant administration of mirtazapine to diazepam causes additive impairment of motor skills.

Mirtazapine carries a potential for inducing a serotonin syndrome when combined with a monoanine oxidase inhibitor. Hence the 14 days interval should be allowed when a switch between the two is desired.

The consent form for this medication is "Antidepressant (Anti-Obsessive-Compulsive Medication / Tricyclics & Similarly Acting Medications)."