Mirtazapine

Mirtazapine is an antidepressant introduced by Organon International in 1996  used for the treatment of mild to severe depression. Although Mirtazapine has a tetracyclic chemical structure it is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). Mirtazapine may be used in preference to an SSRI due to the fact that it causes fewer sexual dysfunction problems. Due to its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic, adrenolytic, and serotonin-related side effects. Mirtazapine is relatively safe if an overdose is taken.

Trade Names
Mirtazapine is marketed under the tradenames Remeron® in the U.S. and Finland, Avanza® and Axit® in Australia, Zispin® in the UK & Ireland, Norset® in France, Remergon® in Belgium, Remergil® in Germany and Mirtabene® in Austria.

Approved
Mirtazapine is primarily used to treat the symptoms of mild to severe depression.

Unapproved/Off-label/Investigational
There is also eveidence that mirtazapine can be used to treat panic disorder (PD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post traumatic stress disorder (PTSD) and pruritus. Mirtazapine is thought to be effective in the prophylactic treatment of chronic tension-type headache.

Mechanism of action
It is thought to work by blocking presynaptic alpha-2 adrenergic receptors that normally inhibit the release of the neurotransmitters norepinephrine (noradrenaline) and serotonin, thereby increasing active levels in the synapse. Mirtazapine also blocks post-synaptic 5-HT2 and 5-HT3 receptors—an action which is thought to enhance serotonergic neurotransmission while causing a low incidence of side effects.

Side effects
The side effects that do occur are thought to be primarily related to the blockage of histamine receptors, which decreases with higher dosages.

Side effects occurring commonly:

 * Increased appetite
 * weight gain
 * Drowsiness, especially at lower doses during the first few weeks of treatment
 * Dizziness
 * Headache
 * General or local swelling
 * Visual hallucinations (when taken during the day)

Side effects occurring rarely:

 * Mania
 * nightmares and vivid dreams
 * Seizures
 * Tremor
 * Muscle twitching and Restless Legs Syndrome
 * Pins and needles
 * Rash and skin eruptions
 * Pain in the joints or muscles
 * Low blood pressure
 * Agranulocytosis

Side effects to tell your doctor about and stop taking mirtazapine immediately

 * An allergic reaction; signs of swelling of the lips, face and tongue, difficulty in breathing, rash or itching (especially affecting the whole body) or feeling faint.
 * Signs of infection such as fever, sore throat, mouth ulcers or stomach upset.
 * Jaundice (yellowing of the skin and/or eyes).

Interestingly, its side effect profile can be used for benefit in certain clinical situations. The drowsiness, increased appetite, and weight gain it causes are useful in patients with depressive disorders with prominent sleep and appetite disturbances. In addition, it is quite useful in inpatient situations in which patients suffer from nausea since it also antagonizes the 5-HT3 receptor, the target of the popular anti-emetic ondansetron (Zofran®).

Dosage
The usual starting dose for mirtazapine is 7.5 - 15 mg once daily, usually at bedtime (Due to the sedative nature and disturbed visual perception). Doses may be increased every 1-2 weeks up to a dose of 45 mg, the maximum daily dose is 90 mg. It may be taken with or without food. Dissolving tablets can even be taken without water.

Pregnancy and Lactation

 * Pregnancy : Sufficient data in humans is lacking. The use should be justified by the severity of the condition to be treated.
 * Lactation : Sufficient data in humans is also lacking. Additionally, Mirtazapine may be found in the maternal milk in significant concentrations. The use in breastfeeding women should be carefully weighed against possible risks.

Drug-Drug Interactions
Due to the sedative effects of Mirtazapine, alcohol should not be taken. Excessive sedation may result when it is used with other sedating drugs, such as benzodiazepines. Mirtazapine should not be used within 14 days of the use of a monoamine oxidase inhibitor because of the possibility that a hypertensive emergency will be triggered.