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. 2019 Sep;98(Pt A):73-79.
doi: 10.1016/j.yebeh.2019.06.029. Epub 2019 Jul 10.

The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea

Nuria Lacuey  1 , Rita Martins  2 , Laura Vilella  3 , Johnson P Hampson  4 , M R Sandhya Rani  3 , Kingman Strohl  5 , Anita Zaremba  3 , Jaison S Hampson  3 , Rup K Sainju  6 , Daniel Friedman  7 , Maromi Nei  8 , Catherine Scott  9 , Brian K Gehlbach  6 , Norma J Hupp  3 , Stephan Schuele  10 , Jennifer Ogren  11 , Ronald M Harper  12 , Luke Allen  9 , Beate Diehl  9 , Lisa M Bateman  13 , Orrin Devinsky  7 , George B Richerson  6 , Samden Lhatoo  14
Affiliations

The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea

Nuria Lacuey et al. Epilepsy Behav. 2019 Sep.

Abstract

Objective: Ictal (ICA) and postconvulsive central apnea (PCCA) have been implicated in sudden unexpected death in epilepsy (SUDEP) pathomechanisms. Previous studies suggest that serotonin reuptake inhibitors (SRIs) and benzodiazepines (BZDs) may influence breathing. The aim of this study was to investigate if chronic use of these drugs alters central apnea occurrence in patients with epilepsy.

Methods: Patients with epilepsy admitted to epilepsy monitoring units (EMUs) in nine centers participating in a SUDEP study were consented. Polygraphic physiological parameters were analyzed, including video-electroencephalography (VEEG), thoracoabdominal excursions, and pulse oximetry. Outpatient medication details were collected. Patients and seizures were divided into SRI, BZD, and control (no SRI or BZD) groups. Ictal central apnea and PCCA, hypoxemia, and electroclinical features were assessed for each group.

Results: Four hundred and seventy-six seizures were analyzed (204 patients). The relative risk (RR) for ICA in the SRI group was half that of the control group (p = 0.02). In the BZD group, ICA duration was significantly shorter than in the control group (p = 0.02), as was postictal generalized EEG suppression (PGES) duration (p = 0.021). Both SRI and BZD groups were associated with smaller seizure-associated oxygen desaturation (p = 0.009; p ≪ 0.001). Neither presence nor duration of PCCA was significantly associated with SRI or BZD (p ≫ 0.05).

Conclusions: Seizures in patients taking SRIs have lower occurrence of ICA, and patients on chronic treatment with BZDs have shorter ICA and PGES durations. Preventing or shortening ICA duration by using SRIs and/or BZD in patients with epilepsy may play a possible role in SUDEP risk reduction.

Keywords: Benzodiazepines; Ictal central apnea; SUDEP; Seizures; Serotonin reuptake inhibitors.

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Figures

Figure 1.
Figure 1.. Flowchart for study population
SRI: serotonin reuptake inhibitor, BZD: benzodiazepine, GCS: generalized convulsive seizures, NCS: non-convulsive seizures, ICA: ictal central apnea, PCCA: post-convulsive central apnea. *Thoraco-abdominal excursions signal not obscured by movement and/or acquisition artifact and unobstructed video.
Figure 2.
Figure 2.. SRI and BZD influences on peri-ictal respiration
A and B) Bar plots for data from non-convulsive seizures (NCS) grouped with the pre-convulsive phase of generalized convulsive seizures (GCS), showing the association between A) SRI and ICA incidence and B) SRI and SpO2 drop (percentage). In the BZD group, C) ICA duration was significantly shorter and D) SpO2 drops were smaller than in control. There was a positive correlation between ICA duration and SpO2 drop as shown by a robust simple linear regression line and 95% confidence intervals. For parts A-C values are mean +/− SEM. ICA: ictal central apnea, No: number, SpO2: peripheral capillary oxygen saturation, SRI: serotonin reuptake inhibitor, BZD: benzodiazepine.
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