Depression Symptoms Treatment

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

Pharmacopoeias. In Japan and US.

The United States Pharmacopeia 31, 2008 (Amoxapine). A white to yellowish crystalline powder. Practically insoluble in water slightly soluble in acetone freely soluble in chloroform sparingly soluble in methyl alcohol and in toluene soluble in tetrahydrofuran. Store in airtight containers.

Adverse Effects, Treatment, and Precautions

As for tricyclic antidepressants in general (see Amitriptyline).

Rare cases of tardive dyskinesias and the neuroleptic malignant syndrome have been reported with amoxapine.

Antidopaminergic effects. Amoxapine is a derivative of the antipsychotic and possesses some antipsychotic activity. It also has dopamine-receptor blocking properties as do its hydroxylated metabolites. Adverse effects that are symptoms of such blockade have been reported and reviewed’ and include akinesia, akathisia, withdrawal dyskinesia, reversible tardive dyskinesia, persistent dyskinesia, elevated serum concentration of prolactin, and galactorrhoea. Chorea and oculogy-ric crisis have also been reported.

Antimuscarinic effects. Amoxapine therapy has been reported to produce adverse effects associated with antimuscarinic activity (such as constipation, blurred vision, and dry mouth), but

such reports did not reflect in-vitro findings that amoxapine had considerably less affinity for muscarinic binding sites than amitriptyline this was supported by results in healthy subjects. The adverse effects described as antimuscarinic could possibly be explained by amoxapine affecting noradrenergic mechanisms.

Breast feeding. For comments on the use of tricyclic antidepressants in breast feeding patients, see under Precautions for Amitriptyline.

Effects on the endocrine system. Reversible nonketotic hy-perglycaemia developed in a 49-year-old woman with no history of diabetes mellitus within 5 days of oral therapy with amoxapine 50 mg three times daily. She had previously had nonketotic hyperglycaemic coma after loxapine 150 mg daily. 7-Hydroxyamoxapine, a metabolite common to both amoxapine and loxapine, was implicated.

See also Antidopaminergic Effects, above, for mention of galactorrhoea andhyperprolactinaemia.

Overdosage. In overdosage, amoxapine is reported to cause acute renal failure with rhabdomyolysis, coma, and seizures. Although there has been some debate as to whether the incidence of seizures and death is higher with overdosage of amoxapine than with other tricyclic antidepressants, some consider that evidence does seem to favour increased neurological consequences.

It has been reported that amoxapine is not cardiotoxic in overdosage but later evidence would suggest that there is cardiotoxic potential.

Interactions

For interactions associated with tricyclic antidepressants, see Amitriptyline.

Pharmacokinetics

Amoxapine is readily absorbed from the gastrointestinal tract. It bears a close chemical relationship to loxapine and is similarly metabolised by hydroxylation. It is excreted in the urine, mainly as its metabolites in conjugated form as glucuronides.

Amoxapine has been reported to have a plasma half-life of 8 hours and its major metabolite, 8-hydroxyamoxapine, has been reported to have a biological half-life of 30 hours 7-hydroxyamoxapine has been identified as another metabolite. Both metabolites are pharmacologically active. Amoxapine is about 90% bound to plasma proteins.

Amoxapine and its metabolite 8-hydroxyamoxapine are distributed into breast milk.

Uses and Administration

Amoxapine, the N-desmethyl derivative of loxapine, is a dibenzoxazepine tricyclic antidepressant with actions and uses similar to those of amitriptyline. Amoxapine is one of the less sedating tricyclics and its antimuscarinic effects are mild it also inhibits the reuptake of dopamine.

In the treatment of depression amoxapine is given in oral doses of 50 mg two or three times daily initially, gradually increased up to 100 mg three times daily as necessary. In the USA, higher doses of up to 600 mg daily may also be given, if required, in severely depressed patients in hospital. A suggested dose for the elderly is 25 mg two or three times daily initially, increased after 5 to 7 days to up to 150 mg daily as necessary in the USA further increases to a maximum of 300 mg daily are permitted, if required.

Once-daily dosage regimens, usually given at night, are suitable for amoxapine up to 300 mg daily divided-dosage regimens are recommended for doses above 300 mg daily. It has been claimed that, in the treatment of depression, amoxapine has a more rapid onset of action than amitriptyline or imipramine with a clinical effect possibly appearing 4 to 7 days after starting therapy, although this has been disputed. Amoxapine should be withdrawn gradually to reduce the risk of withdrawal symptoms.

Amoxapine has also been investigated for its potential as an antipsychotic.

Preparations

The United States Pharmacopeia 31, 2008: Amoxapine Tablets.

Proprietary Preparations

Denmark: Demolox

France: Defanyl

India: Demolox

Indonesia: Asendin

United Kingdom: Asendis

USA: Asendin