Incidence of tricyclic antidepressant-like complications after cyclobenzaprine overdose

Abstract

Background: The cyclobenzaprine structure is similar to amitriptyline; however, tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been reported. Our objective was to determine the incidence of TCA-like effects in cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We compared the incidence of these effects to amitriptyline overdoses collected during the same period. Methods: We performed a retrospective review of 2 years of cases as reported to the Texas Poison Center Network. We identified sole ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical outcome and clinical effect. A trained reviewer used a standard data collection sheet within a secured electronic database. One investigator audited a random sample of charts. Results: We identified 3974 cases of cyclobenzaprine calls. Of these, we collected 209 cases of acute overdoses without coingestions. There were no deaths. No cases of cyclobenzaprine ingestions were reported to have died or have a wide QRS or ventricular dysrhythmia. Seizures were reported in 2 cases; however, both were unrelated to cyclobenzaprine. Hypotension was reported in 1.4% (3/209) of cases, and a vasopressor was used in one case (0.5%). Patients with an amitriptyline overdose were more likely to have seizure, coma, tachycardia, a wide QRS or ventricular dysrhythmia, and have received sodium bicarbonate or be intubated. Conclusions: Cyclobenzaprine overdoses were not reported to cause widened QRS, ventricular dysrhythmias, or seizures, and hypotension was rarely reported. Tricyclic antidepressant-related effects occurred more often in our comparison group of amitriptyline overdoses.

Comment on “Treatment of comatose patient from cyclobenzaprine overdose with therapeutic plasma exchange”

“…3 The authors also allude to effects of cyclobenzaprine toxicity resembling tricyclic antidepressants; in fact, these effects are sparsely reported, and their existence is disputed. 4 Regardless, this patient is described as having a benign electrocardiogram, and did not otherwise demonstrate evidence of cyclic antidepressant toxicity. Although the team appropriately initiated supportive treatment for coma with mechanical ventilation, patients with coma related to cyclobenzaprine overdose are expected to improve with time regardless of extracorporeal removal.…”

The Skeletal Muscle Relaxer Cyclobenzaprine Is a Potent Non-Competitive Antagonist of Histamine H1 Receptors

“…The current study explains the molecular mechanisms of the potential sedative effects of cyclobenzaprine, but also demonstrates the need to utilize cyclobenzaprine with caution in patients on other antihistamines, particularly over-the-counter antihistamines and combination cough and cold products. In this regard, there are an abundance of case reports of cyclobenzaprine toxicities and overdoses when the agent is combined with other centrally acting depressants, including GABAergics such as benzodiazepines and alcohol (Winek et al, 1999;Spiller and Cutino, 2003;Bebarta et al, 2011). Given that histamine plays a role in the maintenance of systemic, arterial, and pulmonary blood pressure, as well as its role in regulating seizure susceptibility, there are also concerns on the effects of additive effects of cyclobenzaprine and other antihistamines on blood pressure and convulsions (Bebarta et al, 2011).…”

“…In this regard, there are an abundance of case reports of cyclobenzaprine toxicities and overdoses when the agent is combined with other centrally acting depressants, including GABAergics such as benzodiazepines and alcohol (Winek et al, 1999;Spiller and Cutino, 2003;Bebarta et al, 2011). Given that histamine plays a role in the maintenance of systemic, arterial, and pulmonary blood pressure, as well as its role in regulating seizure susceptibility, there are also concerns on the effects of additive effects of cyclobenzaprine and other antihistamines on blood pressure and convulsions (Bebarta et al, 2011). A recent case report documenting the fatal interaction between cyclobenzaprine and the OTC H1R antagonist chlorpheniramine is illustrative of the cautions of combining these agents (Shihata, 2021).…”