Mirtazapine

Mirtazapine is a tetracyclic antidepressant used to treat major depression. It is particularly commonly used when insomnia or an anxiety disorder are present in addition to depression.

Mirtazapine is used off-label for a variety of conditions, including panic disorder, generalized anxiety disorder, dysthymia, tension headaches, hot flashes, post-traumatic stress disorder, sleep disorders, substance abuse, and sexual dysfunction.

Mirtazapine was first synthesized by Organon and patented in 1989. In 1994, it was approved in the Netherlands for the treatment of major depressive disorder and was introduced in the United States in 1996.

Pharmacodynamics

The mechanism of action of mirtazapine is not fully understood. Both noradrenergic and serotonergic activity have been shown to increase following administration of mirtazapine. Mirtazapine is a potent antagonist of the serotonin receptors 5-HT2 and 5-HT3. An antagonistic effect on presynaptic α2-adrenergic receptors has also been demonstrated. Mirtazapine is also a potent histamine (H1) receptor antagonist, which may explain its potent sedative effects.

Pharmacokinetics

The absolute bioavailability of mirtazapine is approximately 50%. The maximum blood concentration is reached within about 2 hours after an oral dose. A steady-state concentration is reached after approximately 5 days. However, 2 to 4 weeks usually elapse before mirtazapine can exert its palpable effects. The volume of distribution of the substance is approximately 107L ± 42L. Mirtazapine is present bound to serum albumin at approximately 85%. The half-life is between 20 and 40 hours. Mirtazapine is extensively metabolized in the liver and ultimately excreted in the urine.

Side effects

• Constipation
• Dry mouth
• Drowsiness
• Increased appetite
• Weight gain
• Weakness
• Confusion
• Dizziness
• Muscle twitching
• Peripheral edema

Mirtazapine and other antidepressants may cause withdrawal symptoms upon discontinuation. To minimize withdrawal symptoms, gradual and slow dose reduction is recommended. Effects of sudden discontinuation of treatment with mirtazapine may include depression, anxiety, tinnitus, panic attacks, dizziness, agitation, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms, allergy-like symptoms such as itching, headache, and sometimes mania or hypomania.

Toxicological data

LD50, mouse, oral: 830 mg/kg