Fatal Intoxication With a Selective Serotonin Reuptake Inhibitor, Lorazepam, and Codeine

Filter, Emily R.; Gorczynski, Laura Y.; Fernandes, John

doi:10.1097/paf.0b013e31815b4c37

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…The control group was treated with lorazepam 0.5 mg, with the same presentation and posology as the experimental group. The patients were assigned weekly appointments at study initiation and during the withdrawal period (weeks 1 and 2, as well as weeks [12][13][14][15]; during the remainder of the treatment, patients were seen every 2 weeks. At each appointment, we assessed the following: primary therapeutic-effectiveness outcome (reduction ≥ 50% of the baseline HAM-A); tolerability (the absence of undesirable effects that would merit treatment suspension), and treatment compliance (administration of 80 % or more of the indicated doses).…”

Section: Study Proceduresmentioning

confidence: 99%

“…Pharmacological treatment of GAD consists of the chronic administration of some drug from the following groups: SSRI, SNRI, tricyclic antidepressants, partial GABA agonists, azapirones, and, mainly, benzodiazepines [8][9][10]. The latter are widely prescribed due to their high anxiolytic effectiveness, but they cause multiple known and predictable secondary effects, prominently exhibiting pharmacological interaction with other drugs and with commonly used substances, sedation, abstinence syndrome, dependence, and tolerance, which in many cases limit and contraindicate their prescription [11][12][13][14][15][16]. Galphimia glauca Cav.…”

mentioning

confidence: 99%

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Therapeutic Effectiveness of Galphimia glauca vs. Lorazepam in Generalized Anxiety Disorder. A Controlled 15-Week Clinical Trial

et al. 2012

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tolerability and safety. One hundred ninety-one patients initiated the study with 94 in the experimental group. One hundred four patients concluded the study, 51 of these in the experimental group. Anxiolytic effectiveness, measured as 0 in a negative case and as 1 in a positive case, was assessed 593 times in the experimental group and 631 in the control; the mean effectiveness observed was 0.686 ± 0.019 vs. 0.588 ± 0.019 (repeated-measures ANOVA; p = 0.0003). In the same way, G. glauca-herbal medicinal product diminished the score in the Hamilton anxiety scale to 11.51 ± 8.27 points and lorazepam to 12.40 ± 8.07 points (repeated-measures ANOVA; p = 0.05). The tolerability analysis, which comprised patients who concluded the treatment plus 11 patients who withdrew due to adverse reactions did not show differences between treatments (p = 0.35), nor did therapeutic safety demonstrate differences between groups (p = 0.21). There were no cases of tolerance, intoxication, dependence, or suppression syndrome. We concluded that G. glauca herbal medicinal product, standardized in 0.175 mg of galphimine-B and administered for 15 weeks to patients with generalized anxiety disorder, showed greater anxiolytic effectiveness than that obtained with lorazepam, with high percentages of therapeutic tolerability and safety.

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Section: Study Proceduresmentioning

confidence: 99%

mentioning

confidence: 99%

Therapeutic Effectiveness of Galphimia glauca vs. Lorazepam in Generalized Anxiety Disorder. A Controlled 15-Week Clinical Trial

et al. 2012

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“…Symptoms might last several days due to the long half‐life of some benzodiazepines (up to 70 hr for diazepam). When part of a multi‐drug intoxication with other drugs or ethanol, prognosis is worse, and there are several reports of deaths due to multi‐drug intoxications where benzodiazepines were involved .…”

mentioning

confidence: 99%

Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials

Penninga

Graudal

Ladekarl

et al. 2015

Basic Clin Pharma Tox

128

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Flumazenil is used for the reversal of benzodiazepine overdose. Serious adverse events (SAEs) including seizures and cardiac arrhythmias have been reported in patients treated with flumazenil, and the clinical advantage of flumazenil treatment has been questioned. The objective was to assess the risk of (S)AEs associated with the use of flumazenil in patients with impaired consciousness due to known or suspected benzodiazepine overdose. Studies included in the meta-analyses were identified by literature search in Medline, Cochrane Library and Embase using combinations of the words flumazenil, benzodiazepines, antianxiety agents, poisoning, toxicity and overdose. Randomised clinical trials (RCTs) in verified or suspected benzodiazepine overdose patients comparing treatment with flumazenil versus placebo were included. Pre-defined outcome measures were AEs, SAEs and mortality. Thirteen trials with a total of 994 randomised (990 evaluable) patients were included. AEs were significantly more common in the flumazenil group (138/498) compared with the placebo group (47/492) (risk ratio: 2.85; 95% confidence interval: 2.11-3.84; p < 0.00001). SAEs were also significantly more common in the flumazenil group compared with the placebo group (12/498 versus 2/492; risk ratio: 3.81; 95% CI: 1.28-11.39; p = 0.02). The most common AEs in the flumazenil group were agitation and gastrointestinal symptoms, whereas the most common SAEs were supraventricular arrhythmia and convulsions. No patients died during the blinded phase of the RCTs. The use of flumazenil in a population admitted at the emergency department with known or suspected benzodiazepine intoxication is associated with a significantly increased risk of (S)AEs compared with placebo. Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient.

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“…There is, however, some theoretical basis to support a direct morphine‐mediated serotonin increase in animal models . In addition, chemically related opioids such as oxycodone, oxymorphone, buprenorphine, hydromorphone (a minor metabolite of morphine), and, to a lesser extent, codeine, were associated with previous reports of serotonin toxicity . The involvement of these morphine‐derived opioids (that share the same phenanthrene structure despite different affinities for opioid receptors) in the cases of serotonin syndrome argues in favor of a morphine‐mediated toxicity through an interaction with phenelzine.…”

Section: Discussionmentioning

confidence: 99%

Serotonin Syndrome Probably Triggered by a Morphine–Phenelzine Interaction

et al. 2015

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Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. Evidence supporting an association between nonserotonergic opiates, such as oxycodone or morphine, and serotonin syndrome is very limited and even contradictory. In this case report, we describe a patient who developed serotonergic-adverse effects likely precipitated by an interaction between morphine and phenelzine. A 57-year-old woman presented to the emergency department with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, confusion, sweating, tachycardia, and nausea over the previous week. On admission, her blood pressure was 185/65 mm Hg, and clonus was noted in the lower extremities. The patient was hospitalized 10 days earlier for cellulitis of the left breast secondary to a left mastectomy 5 months earlier, and a short course of oral morphine was prescribed for pain control. Her routine medications consisted of aspirin, atorvastatin, bisoprolol, clopidogrel, gabapentin, omeprazole, phenelzine, and ramipril. Supportive measures were initiated on admission. Phenelzine and morphine were discontinued immediately, leading to a progressive resolution of symptoms over the next 48 hours. Phenelzine was restarted on discharge without further complications. Use of the Drug Interaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of serotonin syndrome and the combination of morphine and phenelzine. The mechanism underlying this interaction, however, remains unclear and warrants further investigation. Clinicians should carefully weigh the risk and benefits of initiating morphine in patients taking monoamine oxidase inhibitors or any other serotonin-enhancing drugs.

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Fatal Intoxication With a Selective Serotonin Reuptake Inhibitor, Lorazepam, and Codeine

Cited by 7 publications

References 22 publications

Therapeutic Effectiveness of Galphimia glauca vs. Lorazepam in Generalized Anxiety Disorder. A Controlled 15-Week Clinical Trial

Therapeutic Effectiveness of Galphimia glauca vs. Lorazepam in Generalized Anxiety Disorder. A Controlled 15-Week Clinical Trial

Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials

Serotonin Syndrome Probably Triggered by a Morphine–Phenelzine Interaction

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