Lack of significant toxicity after mirtazapine overdose: A five-year review of cases admitted to a regional toxicology unit
ABSTRACT Mirtazapine is a comparatively new antidepressant that selectively blocks central alpha2-adrenergic autoreceptors and postsynaptic 5-HT2 and 5-HT3 receptors, causing reduced neuronal norepinephrine and serotonin reuptake. The prevalence of mirtazapine prescribing has steadily risen; however, comparatively little information is available regarding the clinical features associated with mirtazapine overdose.
To characterize the toxic features that result from mirtazapine overdose.
We performed a retrospective case analysis of patients admitted to the Toxicology Unit of the Royal Infirmary of Edinburgh between January 2000 and December 2004 after stated mirtazapine overdose. Casenotes were examined for clinical, laboratory, and electrocardiographic safety data.
There were 117 mirtazapine cases where the median (interquartile range) stated dose ingested was 450 mg (240-785 mg). Conscious level was reduced in 27.2% of patients and there was a higher incidence of tachycardia (30.4%) than predicted from normal reference range values (p < 0.001). There was no evidence of any other significant clinical, laboratory, or electrocardiographic abnormality.
Severe toxic features could be attributed to other co-ingested drugs or alcohol. The adverse clinical effects attributable to mirtazapine overdose appeared mild and predictable. Mirtazapine overdose appears to be associated with fewer features of severe toxicity than previously reported for other antidepressants.
Full-textDOI: · Available from: W. Stephen Waring, Sep 28, 2015
- SourceAvailable from: Ingrid Berling
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- "No patient ingesting mirtazapine alone had a seizure, developed delirium or serotonin toxicity, required respiratory support, or had an abnormal QT. This is consistent with previous studies of mirtazapine overdose.12,13,18,19 In the few cases of large single-agent mirtazapine ingestions (> 1000 mg) there appeared to be an association with reduced GCS, but none of these cases required any intervention (Fig. 2). "
ABSTRACT: Objective. There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. Methods. This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. Results. From 267 mirtazapine overdoses, there were 89 single-agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26–49 years; Range: 15–81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270–750 mg; Range: 150–1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80–120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8–18.2 h; Range:2.2–75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co-ingestants had more severe toxicity depending on the co-ingested drug. Conclusion. Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention.Clinical Toxicology 11/2013; 52(1). DOI:10.3109/15563650.2013.859264 · 3.67 Impact Factor
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- "Mirtazapine appears capable of causing only minor cardiovascular effects, and toxic doses have been reported to cause inconsistent effects on heart rate and mild hypotension.81–83 Trazodone may be associated with orthostatic hypotension, particularly in high doses, and QTcB prolongation has been reported as a feature of trazodone toxicity.84–86 "
ABSTRACT: A number of different psychotropic agents have been associated with an increased risk of cardiovascular disease, and these relationships have been difficult to interpret due to the presence of confounding factors. Recently, there has been renewed interest in the potential for certain antidepressants to cause QT prolongation, which is a predisposing factor for arrhythmia. However, the optimum means of determining QT remains contentious due to discrepancies between methods that may be readily applied in a clinical setting versus more detailed techniques during regulatory assessment. A number of different pharmacological mechanisms might explain the occurrence of adverse cardiac effects, and these differ according to the type of antidepressant agent. Emerging data indicate that citalopram exhibits a dose-effect relationship for QT prolongation. Whereas cardiotoxicity is readily apparent in the context of intentional antidepressant overdose, the occurrence of cardiac effects as a result of therapeutic administration is less certain. Pre-existing cardiac disease and other factors that independently predispose to arrhythmia are important considerations. Therefore, clinical judgment is needed to evaluate the overall risk or benefit of a particular antidepressant in any patient. Close monitoring should be considered for those at greatest risk of QT prolongation and arrhythmia.Drug, Healthcare and Patient Safety 08/2012; 4(1):93-101. DOI:10.2147/DHPS.S28804
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- "Adenosine causes hypotension by inducing the A 2 receptors (Lerman and Belardinelli, 1991). Sinus tachycardia is a common anticholinergic effect in humans after tricyclic antidepressant poisoning (Whyte et al., 2003; Waring et al., 2007; Klasco, 2009). In our study, amitriptyline infusion did not cause any significant change in HR. "
ABSTRACT: We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P < 0.05, respectively). There was no statistically significant difference in the results of arterial blood-gas analyses among the groups (P > 0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.Drug and Chemical Toxicology 10/2010; 34(1):53-60. DOI:10.3109/01480545.2010.495947 · 1.23 Impact Factor