Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality.

Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

[The development from drug to designer drug].

Synthetic "designer drugs" with hallucinogenic properties have become increasingly popular among recreational drug users in recent years. Some of the designer drugs are chemically modified drugs previously used in treatment of depression and chronic fatigue. The drugs are available from a large number of internet distributers. There is very little knowledge of the clinical symptoms and how intoxicated people should be treated. We present a review of published literature (including 284 intoxicated patients) and experiences from the Danish poison centre concerning two chemical derivatives of earlier registered drugs.

Serotonin toxicity involving MDMA (ecstasy) and moclobemide.

The use of MDMA (ecstasy) in Australia is a widespread and growing problem, promoting acute toxicity and disease which can lead to premature death in users. We report four cases of fatal serotonin toxicity caused by the combination of MDMA and moclobemide, a reversible MAO-A inhibitor with potent serotonergic activity. Despite the highly reported toxicity of this drug combination, there are very few reports of fatalities attributed to a MDMA and moclobemide interaction. Pathology and toxicology reports, initial police reports and coroners' findings were examined to determine the circumstances of the deaths. Symptoms of some of the four cases as reported by paramedics and medical staff included hyperthermia, hyperkalemia, profuse sweating, twitching and shaking. Two cases involved moclobemide concentrations consistent with common prescribed doses, while the other two cases involved much higher concentrations often associated with toxicity. Three of these cases presented with some form of heart disease.

Pharmacoresistant convulsions and visual hallucinations around two weeks after selegiline overdose: a case report.

A case of pharmacoresistant convulsions after selegiline overdose is reported. A 50-year-old male having been suffering from bipolar II disorder for 16 years attempted suicide by taking an overdose of 195 mg selegiline with other psychotropics. He developed recurrent pharmacoresistant seizure from 12th day to 19th day after selegiline overdose. He also had visual hallucinations and temporary high blood pressure. The authors suspect that the catecholamine-influenced convulsions and visual hallucinations that manifested during the period increased by the MAO-inhibiting action of selegiline which lasts about 2 weeks.

Death of a female cocaine user due to the serotonin syndrome following moclobemide-venlafaxine overdose.

To our knowledge, the majority of evidence supporting the relationship between the serotonin syndrome and medications that effect 5HT is based on case reports. The justification for taking up this subject has been a fatal outcome of a 21 year-old female following an administration of toxic doses of moclobemide (MAOI) and venlafaxine (SNRI). As a result of complex toxicological investigations including antemortem and postmortem material, antemortem clinical observations and postmortem examinations, the cause of death was identified as overdose with antidepressants--moclobemide and venlafaxine--in the mechanism of the clinically fully developed severe toxic serotonin syndrome. The analysis of a hair strand collected from the victim documented the use of the above-mentioned drugs simultaneously with cocaine in the period of at least 20 months preceding death. The fact is a matter of considerable interest in view of the employed pharmacotherapy, giving rise to suspicion that the woman had not developed the serotonin syndrome during the almost 2-year antemortem period until she took toxic doses of both medications.

Suicidal antidepressant overdoses: a comparative analysis by antidepressant type.

INTRODUCTION: The safety of antidepressants following overdose is critical because of the high risk of suicide attempts in depressed patients. This study was conducted to decrease the fatality rate of antidepressant overdoses by providing data to shift prescribing toward safer antidepressants. METHODS: US poison control data for 2000-2004 were analyzed by 25 antidepressant types. Medical outcome differences were quantified using a hazard index (number of major or fatal outcomes per 1000 reported antidepressant ingestions). RESULTS: Of 82,802 suicidal single-agent ingestions of identifiable antidepressants approved for use in the US, cases occurred predominantly in females and peaked in teens. Fatal cases peaked at 40 to 49 years of age. Suicidal ingestions of the SSRIs, SNRIs, and other antidepressants peaked in teens, lithium in the twenties, tricyclics and tetracyclics in the thirties, and MAO inhibitors in the forties. There were 40 major or fatal outcomes per 1000 cases. Weighted by antidepressant type, the mean hazard index for the 25 antidepressants was 79 (range: 0 to 292). Amoxapine (292), maprotiline (211), and desipramine (187) had the highest hazard indices. The tricyclic antidepressants, MAO inhibitors, maprotiline, and bupropion were in the more severe half of antidepressants, ranked by hazard index. All SSRIs had low hazard indices. Hazard index and exposure frequency were inversely correlated (R = -0.423, p = 0.035), while hazard index and use of critical care were positively correlated for the 25 antidepressant types (R = 0.797, p < 0.001). Clinical effect profiles for each antidepressant type are presented. CONCLUSION: Suicidal overdose severity varied considerably by antidepressant type. Prescribing decisions should be informed by regularly updated comparative overdose severity data.

[Seronin syndrome and cardiac arrest caused by high-dose moclobemide (case report)].

Serotonin syndrome is the syndrome resulting from brain tissue serotonin accumulation and accompanying by central nervous system dysfunction and circulatory collapse, which leads to a serious mortal danger to life. A female patient aged 31 years, diagnosed as having chronic psychosis in the history, was admitted to an intensive care unit in a critical state for having taking an increased moclobemide dose. The patient developed cardiac arrest and cardiopulmonary resuscitation (CPR) was initiated. A 15-minute CPR recovered sinus rhythm and pulse on the peripheral arteries of the limbs. When consciousness and respiration improved, the patient was weaned from resuscitation and extubated on the second day. On day 4, the patient was transferred from the intensive care unit to the department of psychiatry. The authors consider that patients with overdosage of antipsychotic agents at a risk for such serious complications, such as cardiac arrest, should be necessarily monitored in the intensive care unit.

Acute myocarditis after massive phenelzine overdose.

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are uncommonly used due to their high frequency of adverse effects, including tachycardia and hypertension. Recently, there has been renewed interest in the role of this class of drugs in treating a variety of psychiatric disorders. The clinical features of MAOI overdose are poorly characterised. This paper describes a novel cardiac complication of phenelzine toxicity in a previously healthy young adult with no history of cardiovascular disease. METHODS: A 23-year-old woman presented to hospital after massive phenelzine overdose, and the clinical features and pathological findings are discussed in light of existing literature. RESULTS: Clinical features of phenelzine toxicity included reduced consciousness level, seizures, and tachycardia, in keeping with previous reports. Unexpectedly, the patient developed severe and unexplained hypotension and impaired left ventricular function, and died 3 days after initial presentation. Post-mortem examination confirmed high serum phenelzine concentrations (4.1 mg/L) and histopathological features that were consistent with drug-induced acute myocarditis. CONCLUSION: Acute myocarditis was attributed to phenelzine in the absence of any plausible alternative explanation. This possible complication should be considered in patients who develop unexplained hypotension after phenelzine overdose.

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose.

INTRODUCTION: Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. CASE REPORT: A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). DISCUSSION AND CONCLUSION: The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances.

The Internet may represent a new mechanism by which adolescents initiate the use of illicit substances. The existence of multiple partisan websites providing misinformation regarding the safety of these substances may lead to an increase in unsafe behavior among this age group. Adverse outcomes related to Internet-based drug information are rarely identified. We report a case of an adolescent whose use of the Internet to obtain drug information led to severe poisoning from the combination of a monoamine oxidase inhibitor, harmaline, and a hallucinogenic tryptamine, 5-methoxydimethyltryptamine (5-MeO-DMT).

Delayed poisoning emergencies.

The American Association of Poison Control Centers (PCCs) has a nationwide toll-free number for contacting regional poison centers. To be automatically connected to a local poison center, call 800/222-1222. EMS providers should follow local protocols to determine how to contact PCCs, either directly or through on-line medical control. Most experts agree that PCCs are a reliable and current source of information on the assessment and treatment of poisoning emergencies.

Death following ingestion of MDMA (ecstasy) and moclobemide.

Four deaths following the ingestion of moclobemide and MDMA ('ecstasy') are described. The probable cause of death in each case was serotonin syndrome as a result of an interaction between the two drugs. As none of the victims had been prescribed moclobemide it seems that each had taken the drug to enhance the effects of MDMA, with fatal consequences. Warnings are needed against misinformed attempts to potentiate the pharmacological effects of illicit drugs.

[Serotonin syndrome. Several cases of this often overlooked diagnosis]. / Serotoninergt syndrom. Flera allvarliga fall med denna ofta förbisedda diagnos.

During the recent decade an increasing number of inquiries concerning cases of overdoses exhibiting typical signs of the serotonin syndrome have been recorded at the Swedish Poisons Information Centre. Four of these cases are presented together with a review of the literature. All patients had overdosed moclobemide and in one case this was the only drug taken. The other patients had ingested moclobemide together with citalopram (2 cases) and clomipramine (1 case). Moreover, other serotoninergic pharmaceuticals as sertraline and sumatriptan were simultaneously ingested in one case and buspirone in another. Three of the cases had hyperthermia, > 40 degrees C and the same number showed pronounced muscle rigidity, coma and mydriasis. Other severe signs and symptoms upon admission included positive Babinski and trismus in two cases each and seizures in one. All patients received mechanical ventilation. Two were treated with dantrolene sodium and one of them was given cyproheptadine as well. One patient received cyproheptadine treatment alone and another prolonged muscle relaxation. Three patients had a typical short clinical course, whereas one patient developed rhabdomyolysis, DIC and arrhythmias. All patients fully recovered.

[Serotonin syndrome--several cases of this often overlooked diagnosis]. / Serotoninergt syndrom--flera allvarliga fall med denna ofta förbisedda diagnos.

During the recent decade an increasing number of inquiries concerning cases of overdoses exhibiting typical signs of the serotonin syndrome have been recorded at the Swedish Poisons Information Centre. Four of these cases are presented together with a review of the literature. All patients had overdosed moclobemide and in one case this was the only drug taken. The other patients had ingested moclobemide together with citalopram (2 cases) and clomipramine (1 case). Moreover, other serotoninergic pharmaceuticals as sertraline and sumatriptan were simultaneously ingested in one case and buspirone in another. Three of the cases had hyperthermia, > 40 degrees C and the same number showed pronounced muscle rigidity, coma and mydriasis. Other severe signs and symptoms upon admission included positive Babinski and trismus in two cases each and seizures in one. All patients received mechanical ventilation. Two were treated with dantrolene sodium and one of them was given cyproheptadine as well. One patient received cyproheptadine treatment alone and another prolonged muscle relaxation. Three patients had a typical short clinical course, whereas one patient developed rhabdomyolysis, DIC and arrhythmias. All patients fully recovered.

The toxicity of antidepressant poisoning: is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants.

AIM: To compare the clinical features of cyclic antidepressant and newer, non-cyclic, serotonin-specific antidepressant poisoning. METHODS: Comparitive, descriptive study of all antidepressant overdose patients admitted to a hospital toxicology service from February 1997 to April 2001. Patient data were entered prospectively into a dedicated toxicology database for subsequent analysis. RESULTS: There were 256 admissions for antidepressant poisoning (17.5% of all poisoning admissions). Cyclic antidepressant poisoning comprised 43% of antidepressant admissions. Statistically significant differences between the two groups included: cyclic antidepressant group had longer median length of stay (23.1 vs 15.9 h, P = 0.0008), greater need for endotracheal intubation (31%vs 4%, OR = 11.5, P < 0.0001) and higher incidence of seizures (7.2%vs 0.7%, OR = 10.4, P = 0.01), faster median pulse rate, longer QRS-interval on admission, and longer intensive care unit stays. However, non-cyclic, serotonin-specific antidepressant poisonings involved larger doses of antidepressants and were more likely to ingest other medications along with these. Serotonin syndrome was only seen in non-cyclic, serotonin-specific poisoning (10.3%, OR = 26.6, P = 0.0002). Patients with serotonin syndrome had a longer median hospital stay (46 vs 16 h, P < 0.0002) compared to other non-cyclic, serotonin-specific patients. There were no deaths during the study period. CONCLUSIONS: Cyclic antidepressants still comprise a significant proportion of antidepressant poisoning and result in more significant morbidity than non-cyclic, serotonin-specific poisoning. Clinicians should also be aware that non-cyclic, serotonin-specific poisoning may result in the development of serotonin syndrome. This was the most significant toxic effect noted following non-cyclic, serotonin-specific poisoning in this study.

Ping-pong gaze in combined intoxication with tranylcypromine, thioridazine, and clomipramine.

OBJECTIVE: This paper reports the occurrence of ping-pong gaze, a neuro-ophthalmological syndrome usually related to severe structural brain damage, in a patient intoxicated with tranylcypromine, thioridazine, and clomipramine. BACKGROUND: Although there have been some reports about the occurence of Ping-pong gaze after intoxications, it is usually related to severe bilateral hemispheric brain damage following stroke or traumatic injuries. METHOD: We report the case of a 56-year old woman who developed a neurotoxic syndrome with coma, hyperthermia, muscular rigidity, myoclonic jerks and tachycardia following an intoxication. Additionally rhythmic and pendular conjugate horizontal eye movements could be observed for three days, so that the diagnosis of ping-pong gaze was made. RESULTS: A treatment with dantrolene lead to complete remission of the neurotoxic syndrome with no signs of neurological or physical deficits. At the stage of regaining consciousness the eye movements became normal. CONCLUSION: In our case the combined intoxication with an monoamine oxidase inhibitor, a neuroleptic and a tricyclic agent lead to a neurotoxic syndrome and the occurrence of a rare neuro-ophthalmological syndrome usually related to bilateral hemispheric brain dysfunction.

Delayed toxidromes.

Some toxins do not result in clinical manifestations until several hours after exposure. This article reviews those agents that may cause delayed-onset toxicity. They are organized into four classes: specific pharmaceuticals, biologicals, pharmaceutical dosage forms, and chemicals. There are five basic mechanisms for delayed toxicity: delayed absorption, distribution factors, metabolic factors, cellular and organ capacity effects, and unknown. Scientific evidence for delayed-onset of effects varies considerably among the individual toxins.

Serotonin syndrome caused by overdose with paroxetine and moclobemide.

Well known clinical syndromes can be produced by overdose with more commonly ingested substances such as opiates or tricyclic antidepressants. A case of a much more unusual syndrome presenting to the accident and emergency department resulting from overdose with a combination of tablets is reported. The clinical presentation of serotonin syndrome and its management are described. This resulted from acute ingestion of paroxetine, a selective serotonin reuptake inhibitor, and moclobemide, a monoamine oxidase inhibitor.