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

Nuria Lacuey; Rita Martins; Laura Vilella; Johnson P. Hampson; M. R.Sandhya Rani; Kingman Strohl; Anita Zaremba; Jaison S. Hampson; Rup K. Sainju; Daniel Friedman; Maromi Nei; Catherine Scott; Brian K. Gehlbach; Norma J. Hupp; Stephan Schuele; Jennifer Ogren; Ronald M. Harper; Luke Allen; Beate Diehl; Lisa M. Bateman; Orrin Devinsky; George B. Richerson; Samden Lhatoo

doi:10.1016/j.yebeh.2019.06.029

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

Nuria Lacuey^*, Rita Martins, Laura Vilella, Johnson P. Hampson, M. R.Sandhya Rani, Kingman Strohl, Anita Zaremba, Jaison S. Hampson, Rup K. Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Brian K. Gehlbach, Norma J. Hupp, Stephan Schuele, Jennifer Ogren, Ronald M. Harper, Luke Allen, Beate Diehl, Lisa M. BatemanOrrin Devinsky, George B. Richerson, Samden Lhatoo

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Pages (from-to)	73-79
Number of pages	7
Journal	Epilepsy and Behavior
Volume	98
DOIs	https://doi.org/10.1016/j.yebeh.2019.06.029
State	Published - Sep 2019

Keywords

Benzodiazepines
Ictal central apnea
SUDEP
Seizures
Serotonin reuptake inhibitors

ASJC Scopus subject areas

Clinical Neurology
Neurology
Behavioral Neuroscience

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10.1016/j.yebeh.2019.06.029

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Lacuey, N., Martins, R., Vilella, L., Hampson, J. P., Rani, M. R. S., Strohl, K., Zaremba, A., Hampson, J. S., Sainju, R. K., Friedman, D., Nei, M., Scott, C., Gehlbach, B. K., Hupp, N. J., Schuele, S., Ogren, J., Harper, R. M., Allen, L., Diehl, B., ... Lhatoo, S. (2019). The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea. Epilepsy and Behavior, 98, 73-79. https://doi.org/10.1016/j.yebeh.2019.06.029

@article{33455931b1cc4018a94ae9183e57ef7c,

title = "The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea",

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",

author = "Nuria Lacuey and Rita Martins and Laura Vilella and Hampson, {Johnson P.} and Rani, {M. R.Sandhya} and Kingman Strohl and Anita Zaremba and Hampson, {Jaison S.} and Sainju, {Rup K.} and Daniel Friedman and Maromi Nei and Catherine Scott and Gehlbach, {Brian K.} and Hupp, {Norma J.} and Stephan Schuele and Jennifer Ogren and Harper, {Ronald M.} and Luke Allen and Beate Diehl and Bateman, {Lisa M.} and Orrin Devinsky and Richerson, {George B.} and Samden Lhatoo",

note = "Funding Information: Samden Lhatoo is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090405 and NIH/NINDS U01-NS090407 . Funding Information: Lisa Bateman, Daniel Friedman, Maromi Nei, Ronald M. Harper, Beate Diehl, Laura Vilella, M.R. Sandhya Rani, Anita Zaremba, Jaison S. Hampson, Brian K. Gehlbach, Norma J. Hupp, Rup K. Sainju, Jennifer Ogren, Luke Allen, and Orrin Devinsky are funded by the Center for SUDEP Research: NIH/NINDS U01-NS090407 . Funding Information: George Richerson is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090414 and NIH/NINDS U01-NS090407 . Funding Information: Stephan Schuele is on the speaker's bureau for Sunovion and Eisai. He receives grant support from NINDS ( RFA-NS-14-004 ), NIH/NINDS U01-NS090407 and the Danny Did Foundation . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = sep,

doi = "10.1016/j.yebeh.2019.06.029",

language = "English (US)",

volume = "98",

pages = "73--79",

journal = "Epilepsy and Behavior",

issn = "1525-5050",

publisher = "Academic Press Inc.",

}

Lacuey, N, Martins, R, Vilella, L, Hampson, JP, Rani, MRS, Strohl, K, Zaremba, A, Hampson, JS, Sainju, RK, Friedman, D, Nei, M, Scott, C, Gehlbach, BK, Hupp, NJ, Schuele, S, Ogren, J, Harper, RM, Allen, L, Diehl, B, Bateman, LM, Devinsky, O, Richerson, GB & Lhatoo, S 2019, 'The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea', Epilepsy and Behavior, vol. 98, pp. 73-79. https://doi.org/10.1016/j.yebeh.2019.06.029

TY - JOUR

T1 - The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea

AU - Lacuey, Nuria

AU - Martins, Rita

AU - Vilella, Laura

AU - Hampson, Johnson P.

AU - Rani, M. R.Sandhya

AU - Strohl, Kingman

AU - Zaremba, Anita

AU - Hampson, Jaison S.

AU - Sainju, Rup K.

AU - Friedman, Daniel

AU - Nei, Maromi

AU - Scott, Catherine

AU - Gehlbach, Brian K.

AU - Hupp, Norma J.

AU - Schuele, Stephan

AU - Ogren, Jennifer

AU - Harper, Ronald M.

AU - Allen, Luke

AU - Diehl, Beate

AU - Bateman, Lisa M.

AU - Devinsky, Orrin

AU - Richerson, George B.

AU - Lhatoo, Samden

N1 - Funding Information: Samden Lhatoo is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090405 and NIH/NINDS U01-NS090407 . Funding Information: Lisa Bateman, Daniel Friedman, Maromi Nei, Ronald M. Harper, Beate Diehl, Laura Vilella, M.R. Sandhya Rani, Anita Zaremba, Jaison S. Hampson, Brian K. Gehlbach, Norma J. Hupp, Rup K. Sainju, Jennifer Ogren, Luke Allen, and Orrin Devinsky are funded by the Center for SUDEP Research: NIH/NINDS U01-NS090407 . Funding Information: George Richerson is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090414 and NIH/NINDS U01-NS090407 . Funding Information: Stephan Schuele is on the speaker's bureau for Sunovion and Eisai. He receives grant support from NINDS ( RFA-NS-14-004 ), NIH/NINDS U01-NS090407 and the Danny Did Foundation . Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Benzodiazepines

KW - Ictal central apnea

KW - SUDEP

KW - Seizures

KW - Serotonin reuptake inhibitors

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SN - 1525-5050

VL - 98

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JO - Epilepsy and Behavior

JF - Epilepsy and Behavior

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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