The Association of Serotonin Reuptake Inhibitors and Benzodiazepines with Ictal Central Apnea

Overview

Journal Epilepsy Behav

Specialties Neurology
Psychology
Social Sciences

Date 2019 Jul 14

PMID 31301453

Citations 18

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.

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Sudden death in epilepsy: the overlap between cardiac and neurological factors.

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Can intravenous lorazepam prevent postictal generalized EEG suppression? A case report.

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5-HT receptors exert differential effects on seizure-induced respiratory arrest in DBA/1 mice.

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Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure-induced mortality in Dravet mice.

Guo J, Min D, Farrell E, Zhou Y, Faingold C, Cotten J Epilepsia. 2024; 65(6):1791-1800.

PMID: 38593237 PMC: 11166528. DOI: 10.1111/epi.17966.

References

Brownstein C, Goldstein R, Thompson C, Haynes R, Giles E, Sheidley B . SCN1A variants associated with sudden infant death syndrome. Epilepsia. 2018; 59(4):e56-e62. PMC: 6453530. DOI: 10.1111/epi.14055. View

Kuo J, Zhao W, Li C, Kennedy J, Seyal M . Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction. Epilepsia. 2016; 57(3):412-7. PMC: 4783192. DOI: 10.1111/epi.13312. View

Tupal S, Faingold C . Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice. Epilepsia. 2006; 47(1):21-6. DOI: 10.1111/j.1528-1167.2006.00365.x. View

Josephson C, Gonzalez-Izquierdo A, Denaxas S, Fitzpatrick N, Sajobi T, Engbers J . Serotonin reuptake inhibitors and mortality in epilepsy: A linked primary-care cohort study. Epilepsia. 2017; 58(11):2002-2009. DOI: 10.1111/epi.13904. View

van der Lende M, Hesdorffer D, Sander J, Thijs R . Nocturnal supervision and SUDEP risk at different epilepsy care settings. Neurology. 2018; 91(16):e1508-e1518. DOI: 10.1212/WNL.0000000000006356. View

Vilella L, Lacuey N, Hampson J, Rani M, Sainju R, Friedman D . Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP). Neurology. 2018; 92(3):e171-e182. PMC: 6340388. DOI: 10.1212/WNL.0000000000006785. View

ORegan M, Brown J . Abnormalities in cardiac and respiratory function observed during seizures in childhood. Dev Med Child Neurol. 2005; 47(1):4-9. DOI: 10.1017/s0012162205000022. View

Feldman J, Mitchell G, Nattie E . Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci. 2003; 26:239-66. PMC: 2811316. DOI: 10.1146/annurev.neuro.26.041002.131103. View

Pattinson K . Opioids and the control of respiration. Br J Anaesth. 2008; 100(6):747-58. DOI: 10.1093/bja/aen094. View

10.

Lacuey N, Zonjy B, Hampson J, Rani M, Zaremba A, Sainju R . The incidence and significance of periictal apnea in epileptic seizures. Epilepsia. 2018; 59(3):573-582. PMC: 6103445. DOI: 10.1111/epi.14006. View

11.

Schneider H, Grote L, PETER J, Cassel W, Guilleminault C . The effect of triazolam and flunitrazepam--two benzodiazepines with different half-lives--on breathing during sleep. Chest. 1996; 109(4):909-15. DOI: 10.1378/chest.109.4.909. View

12.

Kinney H, Richerson G, Dymecki S, Darnall R, Nattie E . The brainstem and serotonin in the sudden infant death syndrome. Annu Rev Pathol. 2009; 4:517-50. PMC: 3268259. DOI: 10.1146/annurev.pathol.4.110807.092322. View

13.

Gigli G, Diomedi M, Troisi A, Baldinetti F, Marciani M, Girolami E . Lack of potentiation of anticonvulsant effect by fluoxetine in drug-resistant epilepsy. Seizure. 1994; 3(3):221-4. DOI: 10.1016/s1059-1311(05)80192-x. View

14.

Ogren J, Tripathi R, Macey P, Kumar R, Stern J, Eliashiv D . Regional cortical thickness changes accompanying generalized tonic-clonic seizures. Neuroimage Clin. 2018; 20:205-215. PMC: 6073085. DOI: 10.1016/j.nicl.2018.07.015. View

15.

Lacuey N, Zonjy B, Londono L, Lhatoo S . Amygdala and hippocampus are symptomatogenic zones for central apneic seizures. Neurology. 2017; 88(7):701-705. PMC: 5317387. DOI: 10.1212/WNL.0000000000003613. View

16.

Keller H, SCHAFFNER R, Haefely W . Interaction of benzodiazepines with neuroleptics at central dopamine neurons. Naunyn Schmiedebergs Arch Pharmacol. 1976; 294(1):1-7. DOI: 10.1007/BF00692778. View

17.

Masneuf S, Buetler J, Koester C, Crestani F . Role of α1- and α2-GABA(A) receptors in mediating the respiratory changes associated with benzodiazepine sedation. Br J Pharmacol. 2011; 166(1):339-48. PMC: 3415658. DOI: 10.1111/j.1476-5381.2011.01763.x. View

18.

Devinsky O, Hesdorffer D, Thurman D, Lhatoo S, Richerson G . Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol. 2016; 15(10):1075-88. DOI: 10.1016/S1474-4422(16)30158-2. View

19.

Abdala A, Dutschmann M, Bissonnette J, Paton J . Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2010; 107(42):18208-13. PMC: 2964253. DOI: 10.1073/pnas.1012104107. View

20.

Macdonald R, Young A . Pharmacology of GABA-mediated inhibition of spinal cord neurons in vivo and in primary dissociated cell culture. Mol Cell Biochem. 1981; 38 Spec No(Pt 1):147-62. DOI: 10.1007/BF00235693. View