Successful Treatment of Amoxapine-Induced Intractable Seizures With Intravenous Lipid Emulsion.

BACKGROUND: Amoxapine is a second-generation tricyclic antidepressant with a greater seizure risk than other antidepressants. If administered in large amounts, amoxapine can cause severe toxicity and death. Therefore, it is necessary to terminate seizures immediately if amoxapine toxicity occurs. However, intractable seizures often occur in these patients. We describe a case of intractable seizures caused by amoxapine poisoning, in which intravenous lipid emulsion (ILE) was used successfully. CASE REPORT: A 44-year-old woman with a history of depression ingested 3.0 g of amoxapine during a suicide attempt. Although she was initially treated with intravenous diazepam, her seizures persisted. Levetiracetam and phenobarbital were then administered, but seizures persisted. Hence, ILE was injected for over 1 min. At 2 min after ILE administration, the patient's status seizures ceased. Recurrence of seizures was observed 30 min after ILE, and the seizures disappeared after re-administration of ILE. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ILE may be effective in amoxapine intoxication. Emergency physicians may consider ILE as an adjunctive therapy for amoxapine poisoning with a high mortality rate. ILE should be implemented carefully with monitoring of total dosage and adverse events.

Randomized Crossover Trial of Amoxapine Versus Vitamin B12 for Retrograde Ejaculation.

OBJECTIVE: To compare the efficacy and safety of amoxapine and vitamin B12 for treating retrograde ejaculation (RE). MATERIALS AND METHODS: Between May 2009 and November 2012, this open-label, randomized, crossover study enrolled 26 men suffering with RE at Department of Reproductive Medicine, Omori Hospital. Patients were randomly allocated into two groups (n=13 each). The amoxapine-B12 group received amoxapine (50 mg daily for 4 weeks, orally) followed (after a 1-week washout period) by vitamin B12 (500 µg three-times daily for 4 weeks). The B12-amoxapine group received the opposite regimen. All pa-tients masturbated to ejaculation at least twice during each treatment period. The primary outcome was antegrade ejaculation of semen, as reported by the patient, on more than one occasion during either treatment period (defined as treatment success). Any adverse events were noted. Success rates were compared between treatments using Fisher's exact test. RESULTS: One patient (B12-amoxapine group) withdrew for personal reasons (breakdown of marital relations); all other patients completed the study. Overall success rate was 88% (22/25). Success rate was higher for amoxapine than for vitamin B12 (80%, 20/25 vs 16%, 4/25; P<0.0001). 18 patients were responsive to amoxapine but not to vitamin B12, 2 patients were responsive to vitamin B12 but not amoxapine, 2 patients were responsive to both drugs, and 3 patients had no response to either drug. One patient (4%) reported sleepiness and 2 (8%) reported constipation while receiving amoxapine. No adverse events were reported during vitamin B12 treatment. CONCLUSIONS: Amoxapine may be an effective, safe and well-tolerated therapy for RE.

Amoxapine-associated acute respiratory distress.

A 37-year-old woman was admitted to our hospital because of acute respiratory distress. Two weeks previously, amoxapine (75 mg/day) had been administered for the first time. Ten days later she developed a high fever, severe hypoxaemia and pulmonary infiltrates on chest CT, including patchy areas of ground-glass opacity, thickening of the interlobular septae and bronchial walls and pleural effusions. BAL showed a predominance of neutrophils, lymphocytes and erythrocytes but not eosinophils. Amoxapine was stopped, resulting in complete resolution of the pulmonary infiltrates. When the patient was re-exposed to amoxapine (52.5 mg total dose), high fever, reduced SaO(2) and pulmonary infiltrates reappeared. We concluded that acute respiratory distress may be associated with amoxapine treatment.

Amoxapine as an atypical antipsychotic: a comparative study vs risperidone.

Amoxapine is marketed as an antidepressant. However, its in-vitro profile, receptor occupancy and preclinical effects are very similar to atypical antipsychotics. Amoxapine has also shown efficacy as an atypical antipsychotic in open trials. The objective of this study was to compare the antipsychotic and side effect profile of amoxapine and risperidone in a randomised assignment, standardized dosing, double-blind trial of acutely psychotic patients with schizophrenia. A total of 48 schizophrenic patients were enrolled and randomized in a double-blind 6-week trial to receive either risperidone (up to 5 mg/day) or amoxapine (up to 250 mg/day). Positive, negative, affective symptoms and motor side effects were measured using standardized weekly assessments. Prolactin levels were also determined at baseline and at the end of the study. A total of 39 patients (amoxapine, n=22; risperidone, n=21) completed the trial. Both pharmacological treatments, amoxapine 228.0 mg/day (SD=34.6) and risperidone 4.5 mg/day (SD=0.7), showed equivalent improvement in positive, negative, and depressive symptoms. Amoxapine was associated with less EPS and less prolactin elevation than risperidone. These data support previous reports about the efficacy of amoxapine as an atypical antipsychotic. Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics.

Case report of withdrawal dyskinesia associated with amoxapine.

The antidepressant amoxapine is structurally related to the neuroleptic loxapine and can cause side effects related to hypothesized dopamine receptor blockade. This case of withdrawal dyskinesia after amoxapine discontinuation further demonstrates its potential for causing side effects associated with neuroleptics.

Case report of withdrawal dyskinesia associated with amoxapine.

The authors describe a case of oral-facial dyskinesia that occurred after discontinuation of amoxapine, and antidepressant which may also have neuroleptic effects. Occurrence of withdrawal dyskinesia indicates that the neuroleptic effects of amoxapine may be clinically significant.

A case of akinesia induced by amoxapine.

A depressed woman who was treated with amoxapine developed akinesia, which was mistaken for depression. This extrapyramidal syndrome has not previously been linked with this widely used antidepressant, and clinicians should be aware of the association.

Case report of tardive dyskinesia and parkinsonism associated with amoxapine therapy.

The authors describe a case of tardive dyskinesia and parkinsonism associated with amoxapine. Patients who develop acute parkinsonism while taking amoxapine may be at higher risk for tardive dyskinesia. The authors recommend that amoxapine be prescribed as carefully as other neuroleptics.

Amoxapine: neuroleptic as well as antidepressant?

Amoxapine, a new antidepressant, is the N-desmethyl analog of loxapine, a neuroleptic. There have been reports suggesting that amoxapine itself or its metabolites have neuroleptic as well as antidepressant properties. With in vitro studies using a radioreceptor assay for neuroleptics, the authors found that amoxapine--and one of its metabolites in particular (7-hydroxyamoxapine)--have potent neuroleptic-like activity. Furthermore, blood specimens from patients receiving amoxapine showed the presence of neuroleptic activity in the same assay. The authors note the implications of these findings for gauging the benefits and risks of treatment with amoxapine, including the risk of neurologic effects.

Amoxapine and imipramine in the treatment of depressed outpatients: a controlled study.

In a double-blind, controlled study 158 outpatients with unipolar depression were treated for six weeks with amoxapine, imipramine, or placebo to assess the antidepressant effects of the new dibenzooxazepine compound, amoxapine. Forty-five amoxapine, 43 imipramine, and 27 placebo patients completed at least four weeks of treatment. Active drugs produced significantly more improvement at treatment endpoint, according to several physician-rated measures, but patient-rated measures failed to differentiate among treatments. Both active drugs at daily doses up to 200 mg produced an equal amount of moderate and marked global improvement, and both produced significantly more side effects than did placebo.

Reversal by bethanechol of sexual dysfunction caused by anticholinergic antidepressants.

The anticholinergic properties of currently available antidepressants sometimes cause sexual dysfunction. Bethanechol, a cholinergic drug, was found to give total relief of impotence in two men and of anorgasmy in one woman; none of the subjects suffered side effects.

Atrial flutter with amoxapine: a case report.

The author describes a patient with preexisting heart disease who rapidly developed cardiac arrhythmia in association with the use of amoxapine. He calls attention to the potential for serious cardiac toxicity with this new drug.

Amoxapine and neuroleptic side effects: a case report.

A depressed patient developed neuroleptic-like side effects while being treated with amoxapine alone. Elevation of her plasma prolactin level and significant ex vivo neuroleptic activity were found despite therapeutic amoxapine levels.

Amoxapine-associated agranulocytosis with thrombocytosis occurring early during recovery.

Agranulocytosis developed in a 35-year-old woman after she received 18 g of amoxapine, a tricyclic antidepressant, over 57 days. On the fifth day after cessation of amoxapine treatment, her platelet count rose from normal to a peak value of 999,000/mm3 on the 13th day. No cause for this thrombocytosis was apparent. Granulocytes appeared in the peripheral blood on the 15th day, and the thrombocytosis abated with the platelet count returning to a normal level by day 22. This confirms a previous report that amoxapine may be associated with agranulocytosis and suggests that thrombocytosis may occur as an early sign of recovery of the bone marrow in drug-associated toxic agranulocytosis.

Amoxapine: a review of its pharmacology and efficacy in depressed states.

Amoxapine is an N-demethylated dibenzoxazepine closely related in the neuroleptic loxapine. Its tricyclic structure appears to give it antidepressant properties resembling imipramine and amitriptyline. In uncontrolled trials it was shown to have antidepressant activity in usual doses up to 200 to 400mg daily. In placebo and double-blind controlled studies comparing amoxapine with the standard tricyclic antidepressants imipramine and amitriptyline, it was shown to be comparable in efficacy with a possibly somewhat faster onset of improvement of selected symptoms of depression in some studies. Because of the small study groups and lack of placebo control, many reports do not show statistically significant differences of treatment over standard drugs. To date there have been no studies comparing amoxapine with electroconvulsive therapy. Side effects were qualitatively similar to standard drugs with a suggestion that in standard doses or overdose myocardial effects are mild. However, the final place of amoxapine in the therapy of depressed states is still to be decided.

Nonketotic hyperglycemia associated with loxapine and amoxapine: case report.

A case of nonketotic hyperglycemic coma associated with the recent introduction of loxapine is presented. Drug discontinuation led to a return of normal fasting blood glucose. Later challenge with amoxapine was also associated with acute hyperglycemia. Their common metabolite, 7-OH amoxapine, is implicated.

A critical appraisal of amoxapine.

The authors provide a literature review and assess amoxapine's clinical pharmacology, therapeutic efficacy and side effects. They conclude that Amoxapine is indicated for use in moderate to severe depressions, has a favorable side effect profile and probably has an earlier onset of action than other tricyclic antidepressants.

Amoxapine: once versus divided daily doses in neurotic and endogenous depression.

In a six-week, double-blind clinical study of 35 hospitalized patients with the diagnoses of endogenous depression (18 patients) and depressive neuroses (17 patients), two dosage schedules of amoxapine were compared. While no statistically significant difference in overall therapeutic and adverse effects between the groups treated with single daily doses and divided daily doses were found by the end of the six weeks investigational period, onset of therapeutic effect was faster in the group treated with single daily doses. There was a significantly greater improvement in Anxiety-Somatization and Sleep Disturbance (HAM-D factors) in the group with depressive neurosis than in the group with endogenous depression.

Amoxapine-induced cognitive impairment in two patients.

Two patients are described in whom subtle cognitive impairments are associated with therapeutic doses of amoxapine. The implications of this observation for the management of depression, particularly in patients with coexisting dementing illnesses, are discussed.

Serum neuroleptic levels and extrapyramidal side effects in patients treated with amoxapine.

Serum neuroleptic levels were measured by radioreceptor assay in patients treated with the antidepressant amoxapine. When compared to standard neuroleptics, amoxapine produced relatively weak neuroleptic activity. Amoxapine dose correlated significantly with serum neuroleptic level. Three of eight patients developed significant extrapyramidal side effects. Neither dose of amoxapine nor neuroleptic level correlated with the presence or severity of EPS.