Simultaneous determination of 5 psychotropic drugs of various types in an autopsy case of acute multiple drug poisoning.

We attempted the simultaneous determination of 5 drugs, mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem, detected in a gas chromatography-mass spectrometry screening test in an autopsy case. The solid-phase extraction of the analytes from biological samples was achieved using Oasis(®)HLB cartridges (Waters, Milford, MA, USA). Gas chromatography was performed on a HP-5MS fused silica capillary column (30 m × 0.25 mm i.d., 0.25 µm film thickness, Agilent Technologies). The mass spectrometer was operated with an electron energy of 70 eV in electron impact mode. The qualitative and quantitative analyses were performed in full-scan mode and the selected ion monitoring mode, respectively. The total ion chromatogram showed good separation of these drugs. Linear graphs were obtained with good correlation coefficients for these drugs from 0.001 to 2.0 µg/mL (r(2)=0.9909-0.9986) using imipramine-d6 as an internal standard. The recoveries of these drugs were found to be 62.8-88.0% in spiked whole blood. Mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem were found in post-mortem samples of the deceased at concentrations of 2.67, 0.07, 0.25, 0.32 and 0.68 µg/mL, respectively. The concentration of mirtazapine was within the lethal level and those of amoxapine and zolpidem were within the toxic level. We diagnosed that the cause of death was acute multiple drug poisoning. The simple and practical procedure used in this study is useful for the simultaneous determination of psychotropic drugs of various types in post-mortem biological samples.

An autopsy case of poisoning with ethanol and psychotropic drugs.

A case of fatal poisoning involving ethanol with psychotropic drugs is presented. Quantitative toxicological analysis showed that the concentrations of ethanol, amoxapine and phenobarbital in the femoral blood were 2.86 mg/ml, 0.41 microg/ml and 6.80 microg/ml, respectively. We concluded that the cause of death was due to the combination use of ethanol, amoxapine and phenobarbital.

A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.

A 43-year-old woman was found dead in a car in the supine position. She had been suffering from depression for 2 years and hesitation wounds on the left forearm and wrist were observed. On microscopic examination, pulmonary congestion and edema were observed with heart failure cells in many alveoli, thereby suggesting not only acute but also chronic heart failure. Drug screening in the blood by gas chromatography-mass spectrometry (GC-MS) revealed the presence of amoxapine and levomepromazine, and their concentrations in tissues were determined by GC-MS with three-step solvent extraction followed by acetylation. The concentration of amoxapine in the blood and liver was 0.86-1.77 and 18.76microg/ml, respectively; the levels were much higher than the therapeutic level but did not reach the lethal level. The concentrations of levomepromazine in tissues were within the therapeutic level. Based on the pathological and toxicological findings, the cause of death was determined to be amoxapine poisoning on the basis of chronic heart failure due to the chronic use of psychotropic drugs.

Amoxapine overdose in a young man: a transient mitochondrial abnormality?

Amoxapine is a second-generation tricyclic antidepressant structurally related to the neuroleptic loxapine. It was previously marketed as an alternative to traditional tricyclic antidepressants because of alleged shorter onset of action and fewer cardiotoxic effects. However, various adverse reactions, including cardiac dysrhythmias, renal failure, coma, seizures, and neuroleptic malignant syndrome, were reported during therapy or after acute overdose. A 14-year-old boy ingested 1900 mg of amoxapine and developed seizures, hypertension, hyperpyrexia, altered mental status, myoglobinuria, renal failure, and transient magnetic resonance imaging (MRI) changes suggestive of hypertensive encephalopathy and neuroleptic malignant syndrome. Since mitochondrial disorders can cause multisystem failure, including encephalopathy, renal tubular dysfunction, and myopathy, a transient, toxic disorder of mitochondrial function was considered as the basis for the patient's clinical and MRI changes.

[Acute amoxapine poisoning with rhabdomyolysis and acute renal insufficiency]. / Intoxication aiguë à l'amoxapine avec rhabdomyolyse et insuffisance rénale aiguë.

Acute renal failure and rhabdomyolysis are reported in a 33 year old man who had taken 6 g of amoxapine. Different possible levels for the toxic action of amoxapine are discussed and compared with literature data.

Diagnostic pitfalls associated with amoxapine overdose: a case report.

Amoxapine is a second-generation antidepressant that has been reported to cause seizures, severe acidosis, cardiac dysrhythmias, hypotension, renal failure, coma, and cardiorespiratory arrest in poisoning exposures. This is a report of a previously normal 9-year-old child who presented with generalized tonic clonic seizures that led to an extensive workup for primary generalized epilepsy. Nothing in the patient's history or laboratory test results suggested ingestion of a toxin. It was not until 48 hours after admission, when the child admitted taking several of her mother's amoxapine tablets, that the correct diagnosis was made. Because of the risks and the diagnostic pitfalls associated with ingestion of amoxapine, clinicians should be mindful of the lessons taught by this case.

Detection of a novel compound after overdoses of aspirin and amoxapine.

The identification of a novel by-product in the tissue and fluid extracts of a victim of fatal overdoses of the tricyclic antidepressant amoxapine and aspirin is presented. Gas chromatography/mass spectrometry suggested that amoxapine was transacetylated by aspirin to form N-acetylated amoxapine. When standard N-acetylated amoxapine was prepared and subjected to the same analytical testing as extracted tissues and fluids, the metabolite was identified as N-acetylamoxapine. Quantitation of N-acetylamoxapine was obtained by gas chromatography. Concentrations of N-acetylamoxapine compared to those of amoxapine and salicylates in blood, liver, stomach, and small bowel are given.

Neuroleptic malignant syndrome following amoxapine overdose.

The case of a patient who developed the neuroleptic malignant syndrome following an overdose of amoxapine is presented. It is suggested that amoxapine, an antidepressant structurally related to the neuroleptic loxapine, be added to the list of medications that can cause this potentially lethal syndrome. This case illustrates the need for careful evaluation and attention to differential diagnosis when psychiatric patients develop physical signs and symptoms.

Amoxapine cardiotoxicity.

Prolongation of the QRS interval, cardiopulmonary arrest, and death in a 31-year-old woman following an overdose of 2 g amoxapine, a tricyclic antidepressant, is reported. The patient's QRS interval prolonged to beyond 100 ms throughout hospitalization. Thirty-three hours after admission she suffered a bradycardiac-hypotensive event, followed by electromechanical dissociation and subsequent death. Cardiotoxicity has not been directly related to amoxapine; a 2-g acute ingestion is the lowest reported lethal dose.

Loss of brainstem and pupillary reflexes in amoxapine overdose: a case report.

A case of severe Amoxapine overdose which presented with unusual neurologic signs and from which a complete recovery was attained is discussed.

Cathartic-induced magnesium toxicity during overdose management.

A 39-year-old women was admitted to the hospital following a large ingestion of a tricyclic antidepressant. The administration of magnesium citrate in repeated doses with activated charcoal resulted in a striking increase in serum magnesium levels followed by acute neuromuscular deterioration and respiratory depression. The patient required dialysis for control of hypermagnesemia. Her clinical condition improved slowly without further complication and she was discharged to a rehabilitation center.

Amoxapine overdose: report of two cases.

Two deaths are described involving amoxapine. Toxicological analysis in Case 1 revealed an amoxapine blood concentration of 5.7 micrograms/mL, and in Case 2, a concentration of 3.2 micrograms/mL. Qualitative analysis of other body fluids were performed.

Relative toxicity of cyclic antidepressants.

To compare the relative central nervous system and cardiac toxicity of amoxapine, maprotiline, and trazodone with the older tricyclic antidepressants, a three-year (1981 through 1983) retrospective review was performed on 1,313 cases involving cyclic antidepressant exposures reported to the Maryland Poison Center. Seizures were more common in the amoxapine (24.5%) and maprotiline (12.2%) groups, compared with either the tricyclic antidepressants (3.0%) or trazodone (0%) (P less than .01). A higher incidence of seizures also was observed in desipramine ingestors (17.9%) compared with other tricyclic antidepressants. No significant differences in the incidence of central nervous system depression or cardiotoxicity was found between the groups. These findings support reports of an increased incidence of seizures in overdoses of amoxapine and maprotiline, but do not substantiate claims of less cardiotoxicity.

Adverse reactions to five new antidepressants.

Postmarketing adverse drug reaction reports for amoxapine, maprotiline hydrochloride, and trazodone hydrochloride and premarketing adverse drug reaction data for bupropion hydrochloride and nomifensine maleate are reviewed, and the role of the new agents in the management of depressive illness is discussed. Nomifensine was withdrawn from markets worldwide because of reports of serious hypersensitivity reactions, especially hemolytic anemia, and marketing of bupropion in the United States was delayed after seizures occurred in bulimic patients in clinical trials. Amoxapine and maprotiline, when taken in overdose attempts, are more toxic and cause more serious central nervous system reactions than the standard tricyclics. Acute renal failure and an increased mortality rate are associated with amoxapine overdose. Amoxapine causes several acute and chronic untoward neurologic and endocrine reactions not commonly associated with the standard tricyclics. For maprotiline and bupropion, maximum doses have been established because of dose-related seizures. Trazodone has minimal effect on cardiac conduction; its main cardiovascular effects are hypotension, orthostasis, and dizziness. The trazodone package insert has been revised to warn of priapism; patients with prolonged or inappropriate penile erections are instructed to discontinue the drug and notify the physician. Serious cardiovascular and neurologic toxicities are rare with trazodone overdose. Of the newly marketed antidepressants, only trazodone offers some advantages over the tricyclic and tetracyclic agents in the areas of side effects and toxicities. The number and type of patients exposed to a new drug during clinical trials is too small for detection of rare but potentially serious adverse effects.