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 the pharmaceutical company have chosen to promote the drug using the acronym noradrenergic and specific serotonergic antidepressant (NaSSA), although there is only modest evidence from their research department to support its claimed effects. Indeed, recent work by researchers independent of Organon International has failed to replicate much of the original data. Also the difference in receptor profile from the 'parent' drug, mianserin, appears to be non-existent, at least in respect of those properties that are hypothesised to be relevant . So the rationale for supposing it to be different to mianserin rests on poor, or non-existent, evidence. Due to its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic effects, serotonin-related side effects, and adrenolytic effects (orthostatic hypotension and sexual dysfunction). As such it may be preferable to SSRIs. 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.

Indications

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 has been reported to be effective in the prophylactic treatment of chronic tension 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

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®).

At lower dosages, such as 7.5 mg, mirtazapine is primarily antihistaminergic, causing sedation, which can be beneficial in depressed patients who have difficulty falling asleep. At doses higher than 15 mg, its effect is primarily in blocking reuptake of norepinephrine, and is thus less sedating.

Side effects occurring commonly:

  • Increased appetite
  • Weight gain
  • Drowsiness, especially at lower doses and 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

    • Dangerous side effects

    If you experience any of these, tell your doctor immediately. You will need to consult your doctor for taper-off instructions. Sudden withdrawal from antidepressants can cause serious symptoms.

  • 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).
  • Agranulocytosis

    • Dosage

    The usual starting dose for mirtazapine is 7.5 - 15 mg once daily, usually at bedtime (due to its sedative nature and the possibility of disturbed visual perception). Doses may be increased, following medical advice, 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 (SolTab® orally disintegrating 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, excessive sedation may result when it is used with other sedating substances, such as alcohol or benzodiazepines. According to official prescribing information from Organon, mirtazapine should not be used within 14 days of the use of an MAOI due to the risk of serious effects such as hypertensive emergency and hyperthermia.

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