Amoxapine (pronounced: a-mox-a-peen. Notable brand names include: Asendin, Asendis, Defanyl, Demolox. See here for more brand name information) is a tetracyclic antidepressant of the dibenzoxazepine family, though it is often classified as a secondary aminetricyclic antidepressant. It is the N-demethylated metabolite of loxapine. It first received marketing approval in the US in 1992 (approximately thirty to forty years after most of the other tricyclic antidepressants were introduced in the US).
Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within a fortnight of the beginning of treatment. It also has properties similar to those of the atypical antipsychotics, and may behave as one and may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to exacerbate motor symptoms in patients with Parkinson's disease psychosis.
Adverse effects by incidence: Note: Serious (that is, those that can either result in permanent injury or are irreversible or are potentially life-threatening) are written in bold text. Very common (>10% incidence) adverse effects include:
Agranulocytosis a drop in white blood cell counts. The white blood cells are the cells of the immune system that fight off foreign invaders. Hence agranulocytosis leaves an individual open to life-threatening infections.
Leukopaenia the same as agranulocytosis but less severe.
Neuroleptic malignant syndrome (a potentially fatal reaction to antidopaminergic agents, most often antipsychotics. It is characterised by hyperthermia, diarrhoea, tachycardia, mental status changes [e.g. confusion], rigidity, extrapyramidal side effects)
Tardive dyskinesia a most often irreversible neurologic reaction to antidopaminergic treatment, characterised by involuntary movements of facial muscles, tongue, lips, and other muscles. It develops most often only after prolonged (months, years or even decades) exposure to antidopaminergics.
Thrombocytopenia a significant drop in platelet count that leaves one open to life-threatening bleeds.
Eosinophilia an elevated level of the eosinophils of the body. Eosinophils are the type of immune cell that's job is to fight off parasitic invaders.
Jaundice yellowing of the skin, eyes and mucous membranes due to an impaired ability of the body to clear the by product of haem breakdown, bilirubin, most often the result of liver damage as it is the liver's responsibility to clear bilirubin.
As with all FDA-approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25. Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations. Its use is also recommended against in the following disease states:
Severe cardiovascular disorders (potential of cardiotoxic adverse effects such as QT interval prolongation)
It is considered particularly toxic in overdose, with a high rate of renal failure (which usually takes 2–5 days), rhabdomyolysis, coma, seizures and even status epilepticus. Some believe it to be less cardiotoxic than other tricyclic antidepressants in overdose, although reports of cardiotoxic overdoses have been made.
- t1/2 is the elimination half life of the compound.
- tmax is the time to peak plasma levels after oral administration of amoxapine.
- CSS is the steady state plasma concentration.
- protein binding is the extent of plasma protein binding.
- Vd is the volume of distribution of the compound.
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