Codeine Allergy and ECT: A Potential Marker of Treatment Resistance
Location
LSUHSC-NO
Publication Date
April 2026
Start Date
9-4-2026 10:00 AM
End Date
9-4-2026 2:00 PM
Description
Background: Electroconvulsive therapy (ECT) is an effective treatment for many psychiatric conditions but is typically reserved for patients with treatment-resistant illness, commonly defined as failure of two adequate medication trials [l]. One proposed contributor to treatment resistance is pharmacogenetic variability, particularly involving cytochrome P450 2D6 (CYP2D6), a highly polymorphic enzyme responsible for metabolizing 20-25% of commonly prescribed medications. Abnormal CYP2D6 activity may result in subtherapeutic medication response or increased rates of adverse effects [2]. One commonly used medication that is metabolized by CYP2D6 is codeine, which is a prodrug that is converted to the opioid analgesic morphine by this pathway. Both poor and ultrarapid CYP2D6 metabolizers have been shown to experience higher rates of adverse effects with codeine exposure, which may be documented as an allergy [3,4]. Given the association of CYP2D6 variability with both treatment resistance and documented codeine allergies, we hypothesized that patients undergoing ECT would have a higher-than-expected rate of codeine allergies.
Methods: Using deidentified data from the Epic SlicerDicer tool, we evaluated documented allergy rates for patients over a 15-year period at a single center. The comparison groups were all patients who underwent ECT over that time and a control group of all patients who underwent any procedure under anesthesia over that same period. The 10 most common allergies and contraindications, including codeine, were compared between these two groups.
Results: Patients undergoing ECT were found to have a significantly higher rate of codeine allergies, with a prevalence of9.57% compared to 5.05% among patients undergoing all procedures (p < 0.005). Rates of sulfa allergy (12.23% vs. 5.97%, p < 0.005) and adhesive allergy (5.85% vs. 2.21%, p <0.001) were also significantly higher in the ECT group.
Discussion: These findings support the hypothesis that documented codeine allergies are more prevalent among patients undergoing ECT, potentially reflecting underlying abnormal CYP2D6 metabolism contributing to treatment resistance. Future studies using matched controls, multi-institutional data, and medication-level analysis are needed to confirm this association and clarify contributing factors. Additionally, further exploration is necessary regarding whether this association is consistent among other treatments for treatment-resistant depression. While we hypothesize that the increased rate of adhesive allergies likely reflects an increase in exposure associated with serial ECT treatments, the association between ECT and sulfa allergies is unexpected and warrants further study.
Recommended Citation
Mercante, Andrew MD; Moazzam, Muhammad BS; Knight, Michael MD; and Galarneau, David MD, "Codeine Allergy and ECT: A Potential Marker of Treatment Resistance" (2026). Dept. of Psychiatry Research Symposium. 1.
https://digitalscholar.lsuhsc.edu/psych_rd/2026/posters/1
Codeine Allergy and ECT: A Potential Marker of Treatment Resistance
LSUHSC-NO
Background: Electroconvulsive therapy (ECT) is an effective treatment for many psychiatric conditions but is typically reserved for patients with treatment-resistant illness, commonly defined as failure of two adequate medication trials [l]. One proposed contributor to treatment resistance is pharmacogenetic variability, particularly involving cytochrome P450 2D6 (CYP2D6), a highly polymorphic enzyme responsible for metabolizing 20-25% of commonly prescribed medications. Abnormal CYP2D6 activity may result in subtherapeutic medication response or increased rates of adverse effects [2]. One commonly used medication that is metabolized by CYP2D6 is codeine, which is a prodrug that is converted to the opioid analgesic morphine by this pathway. Both poor and ultrarapid CYP2D6 metabolizers have been shown to experience higher rates of adverse effects with codeine exposure, which may be documented as an allergy [3,4]. Given the association of CYP2D6 variability with both treatment resistance and documented codeine allergies, we hypothesized that patients undergoing ECT would have a higher-than-expected rate of codeine allergies.
Methods: Using deidentified data from the Epic SlicerDicer tool, we evaluated documented allergy rates for patients over a 15-year period at a single center. The comparison groups were all patients who underwent ECT over that time and a control group of all patients who underwent any procedure under anesthesia over that same period. The 10 most common allergies and contraindications, including codeine, were compared between these two groups.
Results: Patients undergoing ECT were found to have a significantly higher rate of codeine allergies, with a prevalence of9.57% compared to 5.05% among patients undergoing all procedures (p < 0.005). Rates of sulfa allergy (12.23% vs. 5.97%, p < 0.005) and adhesive allergy (5.85% vs. 2.21%, p <0.001) were also significantly higher in the ECT group.
Discussion: These findings support the hypothesis that documented codeine allergies are more prevalent among patients undergoing ECT, potentially reflecting underlying abnormal CYP2D6 metabolism contributing to treatment resistance. Future studies using matched controls, multi-institutional data, and medication-level analysis are needed to confirm this association and clarify contributing factors. Additionally, further exploration is necessary regarding whether this association is consistent among other treatments for treatment-resistant depression. While we hypothesize that the increased rate of adhesive allergies likely reflects an increase in exposure associated with serial ECT treatments, the association between ECT and sulfa allergies is unexpected and warrants further study.