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

ABSTRACT 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 patients 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.

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.

Detection and treatment of akathisia in advanced cancer patients during adjuvant analgesic therapy with tricyclic antidepressants: case reports and review of the literature.

OBJECTIVE: There is substantial evidence that tricyclic antidepressants are effective in the management of chronic pain, including cancer pain. In oncological settings, these agents are used as adjuvant analgesic drugs. However, cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic therapy have not previously been reported. CASE REPORTS: Two cancer patients experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for neuropathic pain. These patients developed inner restlessness and restless physical movements after amoxapine was prescribed. Although symptoms were atypical, akathisia was suspected and discontinuation of amoxapine resolved the symptoms. RESULTS AND SIGNIFICANCE OF RESULTS: Akathisia should be considered in patients receiving adjuvant analgesic therapy with tricyclic antidepressants. Early detection and appropriate treatment will relieve this distressing symptom. Restless movements involving parts of the body other than the legs may be the clue to the diagnosis.

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.

Photo-distributed neutrophilic drug eruption and adult respiratory distress syndrome associated with antidepressant therapy.

Drug reactions are well-known complications of antidepressant therapy, often related to photosensitization. Herein is reported a singular case of antidepressant (amoxapine and citalopram) and anxiolytic related (perphenazine) photo-distributed neutrophilic dermatosis and adult respiratory distress syndrome (ARDS). The clinicopathologic findings displayed overlapping features with drug-induced Sweet's syndrome, acute generalized exanthematous pustulosis (AGEP), and so-called sterile neutrophilic folliculitis with perifollicular vasculopathy. Of the three medications, only amoxapine has been associated with AGEP. Treatment with high-dose systemic corticosteroids and cessation of drug therapy was followed by rapid resolution of the cutaneous eruption and respiratory distress. The possibility that neutrophil infiltration of the lung and/or accumulation of neutrophils in the skin and blood served as a source for reactive oxygen species, leading to lung injury and subsequent ARDS, is discussed.

Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study.

OBJECTIVE: Amoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of amoxapine in acutely psychotic patients with schizophrenia. METHODS: Seventeen patients were enrolled and 15 completed a prospective open-label 6-week study of amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments. RESULTS: Amoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p<0.001), with a trend towards improvement in mood symptoms and no treatment-emergent extrapyramidal side-effects, akathisia or weight gain. Prolactin elevation was observed. CONCLUSION: These clinical data lend support to the pre-clinical suggestions that amoxapine may be an atypical antipsychotic. Given its lack of weight gain and that it is considerably less expensive than current options, amoxapine could be a valuable alternative for some patients. These considerations strongly call for more systematic, double-blind studies of amoxapine as an atypical antipsychotic.

[Unexpected drug-interaction].

The case of a male patient suffering from chronic normal pressure hydrocephalus is outlined. Antidepressant and pravastatin were administered because of the patient's abulia and hypercholesterolemia, but neuroleptic malignant syndrome-like conditions developed. All physicians should suppose the occurrence of such an "unexpected drug-interaction" in any case. The author considered that a good sense of careful discernment and rapid reference system of medical information are "essential tools" for clinical management.

[A case of amoxapine-induced tardive dystonia successfully treated with a low dose anti-cholinergic agent].

We report a 63-year-old man who presented with amoxapine-induced tardive dystonia. At 49 years of age, he developed depression and was administrated 50 mg amoxapine, 4 mg cloxazoram and 3 mg biperiden per day. The daily dose of amoxapine was gradually increased up to 150 mg at 58 years of age. At 61 years of age and after having been taking amoxapine for twelve years, he noticed a rotating left arm and muscle pain in his left shoulder and arm while walking. At 62 years of age, he stopped taking these three drugs. However, the dystonic movements and pain both continued to get worse. Neurological findings revealed no abnormality except for a dystonic posture and movements in the neck and bilateral arms while sitting, standing and walking. Positron emission tomography with C-11 raclopride revealed a mild decrease in the dopamine D 2 receptor numbers in the bilateral striatum. However, two dopamine agonists, pergolide and bromocriptine, worsened his dystonia. In contrast, the daily administration of 2 mg of trihexyphenidyl, an anti-cholinergic agent, markedly ameliorated the dystonia symptoms. As a result, the long-term co-administration of biperiden, an anti-cholinergic agent, may mask the toxicity of amoxapine, which may induce tardive dystonia.

Neuroleptic malignant syndrome associated with amoxapine and lithium in an older adult.

This report describes the presentation of neuroleptic malignant syndrome (NMS) in the primary care setting in an older adult with major depression with psychosis. This patient had been stable on a regimen of amoxapine, lithium carbonate, lorazepam, and benztropine. The patient had rigidity, altered sensorium, diaphoresis, autonomic instability, elevated WBC count and urine myoglobin, and creatine phosphokinase (CPK) reaching 1331 U/I. He was successfully treated with bromocriptine.

A case of neuroleptic malignant syndrome in a patient with hemodialysis.

A 63-year-old man with chronic renal failure who had received hemodialysis three times per week for 4 years developed neuroleptic malignant syndrome 10 days after taking amoxapine. His condition was characterized by muscle rigidity, elevation of body temperature and altered consciousness. Although he was treated with dantrolen and supportive care as well as discontinuation of amoxapine, his condition rapidly deteriorated, resulting in death. Because the pharmacokinetics of drugs, especially those such as antidepressants, in patients with chronic renal failure has not been fully clarified, one should be careful about giving such patients these drugs.

Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice.

The use of antidepressant drugs (ADs) in patients with epilepsy still raises uncertainties because of the widespread conviction that this class of drugs facilitates seizures. A detailed knowledge of this issue in its various aspects may help in optimal management of patients suffering concurrently from epilepsy and depression. This article reviews the available data in vitro in animals and humans concerning the known potential of various ADs to induce epileptic seizures. Emphasis has been placed on those variables that may generate confusion in interpreting the results of the various studies. Most ADs at therapeutic dosages exhibit in nonepileptic patients a seizure risk close to that reported for the first spontaneous seizure in the general population (i.e., <0.1%). In patients taking high AD doses, seizure incidence rises markedly and may reach values up to 40%. With a patient history of epilepsy and/or concomitant drugs that act on neuronal excitability, low or therapeutic AD doses may be sufficient to trigger seizures. Experimental data are in partial conflict with human data on the relative potential seizure risk of the various ADs. Therefore, a reliable scale for assigning a relative value to an individual AD or to single AD classes cannot be made. It appears fair to say that maprotiline and amoxapine exhibit the greatest seizure risk, whereas trazodone, fluoxetine, and fluvoxamine exhibit the least. Some ADs may also display antiepileptic effects, especially in low doses, in experimental models of epilepsy and in humans, but the mechanism of this action is largely unknown. The available data suggest that ADs may display both convulsant and anticonvulsant effects and that the most important factor in determining the direction of a given compound in terms of excitation/inhibition is drug dosage. It is probable that drugs that increase serotonergic transmission are less convulsant or, even, more anticonvulsant than others. Because of mutual pharmacokinetic interactions between antiepileptic drugs and ADs, with consequent marked changes in plasma concentrations, it remains to be established whether or not plasma AD levels that are effective against depression also facilitate seizures. Finally, exploring the mechanisms through which ADs modulate neuronal excitability might open new possibilities in antiepileptic drug development.

Repeated propofol anesthesia for a patient with a history of neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is the most serious side effect produced by the administration of antipsychotic drugs. NMS shares many clinical similarities with malignant hyperthermia (MH), but the etiology of NMS and the relation between NMS and MH remain unknown. Anesthetic regimens for patients with NMS are not well established. We gave repeated anesthesia to a patient with a history of NMS undergoing electroconvulsive therapy for the treatment of depression. Propofol and vecuronium were used in twelve consecutive ECT sessions without complications. In this case report, we describe the safe and satisfactory repeated use of propofol in a patient with a history of NMS, and outline NMS and its questionable relation to MH.

[A case of allergic cross reaction between tricyclic antidepressants and maprotiline].

Although a 76-year-old woman with a diagnosis of depression began a course of maprotiline, the drug was discontinued after 14 days when she developed a rash. She was started on lofepramine in substitution for maprotiline. Four years later, lofepramine treatment was stopped and to amoxapine treatment introduced due to the aggravation of depressive symptoms. On the second day of this regimen, she developed a pruritic rash. She stopped the medication immediately. Because the rash disappeared gradually, lofepramine treatment was restarted. But her recovery was restrained and new skin lesions developed. Again, she stopped the medication, and the rash cleared within several days. This case suggests the existence of cross-allergenicity between tricyclic antidepressants and maprotiline.