Amoxapine

What it is used for

Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation.

How to take it

Effective dosage of amoxapine may vary from one patient to another. Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily. Hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have dosage raised cautiously up to 600 mg daily in divided doses.

Amoxapine may be given in a single daily dose, not to exceed 300 mg, preferably at bedtime. If the total daily dosage exceeds 300 mg, it should be given in divided doses.

Side effects, and when to stop

Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class.

Who should not take it

Amoxapine is contraindicated in patients who have shown prior hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants and monoamine oxidase inhibitors simultaneously. When it is desired to replace a monoamine oxidase inhibitor with amoxapine, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amoxapine should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. The drug is not recommended for use during the acute recovery phase following myocardial infarction.

Other medicines and interactions

See CONTRAINDICATIONS about concurrent usage of tricyclic antidepressants and monoamine oxidase inhibitors. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic drugs. Amoxapine may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Serum levels of several tricyclic antidepressants have been reported to be significantly increased when cimetidine is administered concurrently. Although such an interaction has not been reported to date with amoxapine, specific interaction studies have not been done, and the possibility should be considered.

Drugs Metabolized by P450 2D6

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

General

In prescribing the drug it should be borne in mind that the possibility of suicide is inherent in any severe depression, and persists until a significant remission occurs; the drug should be dispensed in the smallest suitable amount. Manic depressive patients may experience a shift to the manic phase. Schizophrenic patients may develop increased symptoms of psychosis; patients with paranoid symptomatology may have an exaggeration of such symptoms. This may require reduction of dosage or the addition of a major tranquilizer to the therapeutic regimen. Antidepressant drugs can cause skin rashes and/or “drug fever” in susceptible individuals. These allergic reactions may, in rare cases, be severe. They are more likely to occur during the first few days of treatment, but may also occur later. Amoxapine should be discontinued if rash and/or fever develop. Amoxapine possesses a degree of dopamine-blocking activity which may cause extrapyramidal symptoms in <1% of patients. Rarely, symptoms indicative of tardive dyskinesia have been reported.