1/36. Fatal combined intoxication with new antidepressants. Human cases and an experimental study of postmortem moclobemide redistribution.Three cases are presented in which death was caused by suicidal intoxication with moclobemide in combination with a selective serotonin reuptake inhibitor. Both antidepressant drug types are considered to be relatively safe with regard to lethal overdose. However, the combination may cause the serotonin syndrome, a condition with a high mortality rate. In one of the cases, there was clinical information consistent with the serotonin syndrome, in the two other cases, there was no information of the clinical course. Postmortem redistribution of the selective monoamine oxidase inhibitor moclobemide was investigated in a rat model. Postmortem concentrations in blood from the vena cava and the heart were found to be in good accordance with antemortem concentrations. Postmortem concentrations in vitreous humour and various tissues were also measured. The apparent volume of distribution was calculated to be 0.95 /- 0.10 l/kg, which is in the same range as that reported in man.- - - - - - - - - - ranking = 1keywords = drug (Clic here for more details about this article) |
2/36. serotonin syndrome in a child associated with erythromycin and sertraline.serotonin syndrome is an uncommon, serious adverse reaction that is usually associated with the interaction of two or more serotonergic agents. A 12-year-old boy receiving sertraline developed the syndrome after erythromycin was added to his regimen. The proposed mechanism involves erythromycin inactivation of cytochrome P450 3A4 inhibition of sertraline metabolism, accumulation of the drug, and precipitation of the syndrome. It is important for clinicians to consider both pharmacokinetic and pharmacodynamic interactions to minimize the risk of the reaction.- - - - - - - - - - ranking = 1keywords = drug (Clic here for more details about this article) |
3/36. Venlafaxine-induced serotonin syndrome with relapse following amitriptyline.A case of venlafaxine-induced serotonin syndrome is described with relapse following the introduction of amitriptyline, despite a 2-week period between the discontinuation of one drug and the commencement of the other. electroencephalography may play an important part in diagnosis. With the increasing use of selective serotonin re-uptake inhibitors, greater awareness of the serotonin syndrome is necessary. Furthermore, the potential for drug interactions which may lead to the syndrome needs to be recognised.- - - - - - - - - - ranking = 2keywords = drug (Clic here for more details about this article) |
4/36. Possible serotonin syndrome associated with buspirone added to fluoxetine.OBJECTIVE: To report the development of a possible serotonin syndrome in a patient taking buspirone and fluoxetine. CASE SUMMARY: A 37-year-old white man taking fluoxetine 20 mg/d for generalized anxiety disorder developed confusion, diaphoresis, incoordination, diarrhea, and myoclonus after buspirone was added to the drug regimen. DISCUSSION: serotonin syndrome is a potentially lethal condition of serotonin hyperstimulation, which may develop rapidly or over the course of several weeks. Symptoms of serotonin syndrome typically occur following additions or increases of serotonin-enhancing drugs. Although buspirone has variable effects on post- and presynaptic 5-HT1A receptors that may reduce the risk of serotonin syndrome when administered as a single agent, it may cause an adverse reaction when given with other serotonergic drugs. CONCLUSIONS: Symptoms consistent with serotonin syndrome may develop with the concurrent administration of buspirone and fluoxetine.- - - - - - - - - - ranking = 3keywords = drug (Clic here for more details about this article) |
5/36. Possible serotonin syndrome associated with clomipramine after withdrawal of clozapine.OBJECTIVE: To report on the possible development of serotonin syndrome in a patient receiving clomipramine after clozapine was withdrawn from the treatment regimen. CASE REPORT: A 44-year-old white man with a 23-year history of undifferentiated schizophrenia and obsessive-compulsive behavior had been treated with clozapine and clomipramine for several years. He tolerated both agents together well, with the exception of experiencing chronic constipation. clomipramine was tapered and reduced to 50 mg over a period of 10 days. A worsening of ritualistic behavior was noted, and the clomipramine dosage was increased to 150 mg/d over 14 days. Simultaneously with the clomipramine dosage increase, clozapine was tapered and stopped ever a period of 19 days. The day after clozapine was stopped, while he was still receiving clomipramine 150 mg/d, he began behaving oddly, started sweating profusely, shivering, and became tremulous, agitated, and confused. He was diagnosed with possible serotonin syndrome; his symptoms resolved after clomipramine was stopped but before clozapine was restarted eight days later. DISCUSSION: There are similarities in symptoms between serotonin syndrome and clozapine withdrawal. This article discusses the reasons why this case may represent serotonin syndrome rather than clozapine withdrawal and the possible pharmacologic mechanisms involved. CONCLUSIONS: Clinicians should be aware that removing a serotonin-2a (S-HT2a) antagonist 1mm a treatment regimen including an agent that increases serotonin in the synaptic cleft may worsen clozapine withdrawal or potentially result in serious adverse drug reactions, such as serotonin syndrome.- - - - - - - - - - ranking = 1keywords = drug (Clic here for more details about this article) |
6/36. A fatal case of serotonin syndrome after combined moclobemide-citalopram intoxication.We present a case involving a fatality due to the combined ingestion of two different types of antidepressants. A 41-year-old Caucasian male, with a history of depression and suicide attempts, was found deceased at home. Multiple containers of medication, the MAO-inhibitor moclobemide (Aurorix), the SSRI citalopram (Cipramil), and the benzodiazepine lormetazepam (Noctamid) as active substance, as well as a bottle of whiskey were present at the scene. The autopsy findings were unremarkable, but systematic toxicological analysis (EMIT, radioimmunoassay, high-performance liquid chromatography-diode-array detection [HPLC-DAD], gas chromatography-nitrogen-phosphorus detection, and gas chromatography-mass spectrometry) revealed the following: ethanol (0.23 g/L blood, 0.67 g/L urine), lormetazepam (1.65 microg/mL urine), cotinine (0.63 microg/mL blood, 5.08 microg/mL urine), caffeine (1.20 microg/mL urine), moclobemide (and metabolites), and citalopram (and metabolite). There upon, we developed a new liquid chromatographic separation with optimized DAD, preceded by an automated solid-phase extraction, for the quantitation of the previously mentioned antidepressive drugs. The results obtained for blood and urine, respectively, were as follows: Ro 12-5637 (moclobemide N'-oxide) not detected and 424 microg/mL; Ro 12-8095 (3-keto-moclobemide) 2.26 microg/mL and 49.7 microg/mL; moclobemide 5.62 microg/mL and 204 microg/mL; desmethylcitalopram 0.42 microg/mL and 1.22 microg/mL; and citalopram 4.47 microg/mL and 19.7 microg/mL. The cause of death was attributed to the synergistic toxicity of moclobemide and citalopram, both antidepressants, which, by intentional or accidental combined ingestion, can produce a potentially lethal hyperserotoninergic state. Based on the history of the case and pharmacology of the drugs involved, the forensic pathologists ruled that the cause of death was multiple drug intoxication, resulting in a fatal "serotonin syndrome," and that the manner of death was suicide.- - - - - - - - - - ranking = 3keywords = drug (Clic here for more details about this article) |
7/36. serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine.OBJECTIVE: To describe HIV-infected individuals taking antidepressants who developed the serotonin syndrome due to drug--drug or drug--food interactions. DESIGN AND SETTING: Case studies carried out at the HIV Outpatient Clinic, Atlanta veterans Affairs Medical Center. PARTICIPANTS AND INTERVENTIONS: HIV-positive patients who were receiving antiretroviral and antidepressant therapies and presented with symptoms consistent with the serotonin syndrome. Their antidepressants were discontinued or the doses reduced in order to resolve the symptoms. RESULTS: Five cases of serotonin syndrome developed after patients who were taking antidepressants ingested P450 inhibitors. CONCLUSIONS: Serotonin syndrome should be suspected in patients on serotonergic medications who present with mental status change, autonomic dysfunction, and neuromuscular abnormalities. Suspicion should be heightened in those who are ingesting substances known to inhibit P450 enzymes, such as protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and grapefruit juice.- - - - - - - - - - ranking = 3keywords = drug (Clic here for more details about this article) |
8/36. serotonin syndrome induced by fluvoxamine and mirtazapine.OBJECTIVE: To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse drug reaction (ADR). CASE SUMMARY: A 26-year-old white woman with a 12-year history of anorexia nervosa was being treated with fluvoxamine. After mirtazapine was added to her therapy, she developed tremors,restlessness, twitching, flushing, diaphoresis, and nausea,symptoms that are consistent with serotonin syndrome. DISCUSSION: The possible causes of this ADR are discussed, including the effects of fluvoxamine and mirtazapine alone, the possible pharmacodynamic and pharmacokinetic interactions of these two drugs, and the patients underlying anorexia nervosa. CONCLUSIONS: An increasing number of drugs that affect serotonin are available and are indicated for various disorders. Since there is a significant likelihood of these agents being prescribed concomitantly, clinicians must be aware of possible interactions that could lead to serotonin syndrome.- - - - - - - - - - ranking = 3keywords = drug (Clic here for more details about this article) |
9/36. serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction.OBJECTIVE: To report 2 cases of serotonin syndrome with serious extrapyramidal movement disorders occurring when metoclopramide was coadministered with sertraline or venlafaxine. CASE SUMMARY: A 72-year-old white woman was treated with sertraline for depression for 18 months and was then admitted to the hospital with a fractured tibia. She was administered metoclopramide because of nausea and, within 2 hours, developed agitation, dysarthria, diaphoresis, and a movement disorder. These symptoms recurred following 2 subsequent administrations of metoclopramide. Treatment with diazepam led to resolution of symptoms within 6 hours, and there was no recurrence at 6 weeks' follow-up. A 32-year-old white woman with major depression was treated with venlafaxine for 3 years. She was admitted following a fall and, after being given metoclopramide, developed movement disorder and a period of unresponsiveness. After a second dose of metoclopramide, these symptoms recurred and were associated with confusion, agitation, fever, diaphoresis, tachypnea, tachycardia, and hypertension. She improved with administration of diazepam, but needed repetition of this treatment over the next 16 hours. Symptoms resolved within 2 days, and she continued venlafaxine with no further adverse effects. DISCUSSION: Both cases met Stembach's criteria for serotonin syndrome and had serious extrapyramidal movement disorders. The possible pathophysiologic mechanisms for the adverse reactions include a single-drug effect, a pharmacodynamic interaction, and a pharmacokinetic interaction. We believe that a pharmacodynamic interaction is most likely. CONCLUSIONS: Clinicians should be aware of a risk of serotonin syndrome with serious extrapyramidal reactions in patients receiving sertraline or venlafaxine when metoclopramide is coadministered even in a single, conventional dose.- - - - - - - - - - ranking = 1keywords = drug (Clic here for more details about this article) |
10/36. Severe serotonin syndrome induced by mirtazapine monotherapy.OBJECTIVE: To document a case of serotonin syndrome (SS) associated with mirtazapine monotherapy, review the previously reported cases of SS associated with this tetracyclic antidepressant, and discuss the possible pathogenic mechanisms leading to this serious adverse drug reaction. CASE SUMMARY: A 75-year-old man developed agitation, confusion, incoordination, and gait disturbance because of progressive rigidity. Mirtazapine had been started 8 days earlier to control major depression. physical examination revealed diaphoresis, low-grade fever, hypertension, tachycardia, bilateral cogwheel rigidity, hyperreflexia, tremor, and myoclonus, symptoms and signs that are consistent with severe SS. DISCUSSION: A review of the cases of SS with implication of mirtazapine as the cause was performed. The possible pathogenic mechanisms leading to this adverse reaction in this patient are also discussed, and pathophysiologic hypotheses are formulated. CONCLUSIONS: Although mirtazapine offers clinicians a combination of strong efficacy and good safety, we suggest bearing SS in mind when prescribing this drug, especially in frail, elderly patients with underlying chronic conditions. In these patients, it might be more adequate to start mirtazapine therapy at a lower dose (<15 mg/d).- - - - - - - - - - ranking = 2keywords = drug (Clic here for more details about this article) |
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