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Tolerability of clobazam as add-on therapy in patients aged 50 years and older with drug-resistant epilepsy

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Abstract

Objective

To evaluate the tolerability of clobazam in patients with drug-resistant epilepsy aged 50 years and older.

Methods

We performed a single center, retrospective chart review of patients at least 50 years of age with drug resistant epilepsy of any type who started clobazam as an add on therapy. Retention rate, safety, and tolerability at 6 and 12 months and last follow-up, and the discontinuation rate due to side effects were analyzed.

Results

A total of 26 patients met inclusion criteria. Mean age was 62 ± 7.1 years, and 69.2% of patients were female. The mean baseline seizure frequency before initiation of clobazam was 2 (range 1–30) seizures per month. The mean total daily dose of clobazam administered was 13 (range 5 to 30) mg/day. At the 12-month follow-up visit after clobazam initiation, 40% of patients were seizure-free and an additional 45% of patients had > 50% reduction in seizure frequency. The mean seizure frequency at 12-month follow-up was 1.5 (range 0–24) seizures per month. The mean total dose of clobazam at 12-month follow-up was 14.25 (range 5 to 25) mg/day. The mean duration of clobazam at last follow was 55.2 ± 27.02 (mean ± SD months) and 18 (69.2%) patients remained on clobazam. Twenty out of 26 (76.9%) patients reported at least one side effect and 6/26 (23%) discontinued the medication within a month of initiation. At last follow-up, 40% remained seizure free on stable dosing.

Conclusion

Clobazam can be a safe and tolerable, add-on treatment older adults with drug-resistant epilepsy. Those who responded tolerated the medication well. Discontinuation due to side effects occurred soon after initiation of therapy.

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Data Availability

The data that support the findings of this study are available from the corresponding author [EN], upon reasonable request.

Abbreviations

EEG:

Electroencephalogram

FDA:

Food and Drug Administration

DEA:

Drug Enforcement Administration

VNS:

Vagal nerve stimulator

LGS:

Lennox Gastaut Syndrome

SD:

Standard deviation

GABA:

Gamma-aminobutyric acid

References

  1. Thurman DJ, Beghi E, Begley CE, Berg AT, Buchhalter JR, Ding D et al (2011) Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia 52. https://doi.org/10.1111/j.1528-1167.2011.03121.x

  2. Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342. https://doi.org/10.1056/NEJM200002033420503

  3. Sillanpää M, Schmidt D (2006) Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain 129. https://doi.org/10.1093/brain/awh726

  4. Sankar R (2012) GABAA receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs 26. https://doi.org/10.2165/11599020-000000000-00000

  5. Purcarin G, Ng Y-T (2014) Experience in the use of clobazam in the treatment of Lennox–Gastaut syndrome. Ther Adv Neurol Disord 7. https://doi.org/10.1177/1756285614521314

  6. Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA (2011) Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology 77. https://doi.org/10.1212/WNL.0b013e318232de76

  7. Conry JA, Ng Y-T, Paolicchi JM, Kernitsky L, Mitchell WG, Ritter FJ et al (2009) Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia 50. https://doi.org/10.1111/j.1528-1167.2008.01935.x

  8. Schmidt D (1986) Clobazam for Refractory Focal Epilepsy. Arch Neurol 43. https://doi.org/10.1001/archneur.1986.00520080064023

  9. Koeppen D, Baruzzi A, Capozza M, Chauvel P, Courjon J, Favel P et al (1987) Clobazam in therapy-resistant patients with partial epilepsy: a double-blind placebo-controlled crossover study. Epilepsia 28. https://doi.org/10.1111/j.1528-1157.1987.tb03678.x

  10. Allen JW, Oxley J, Robertson MM, Trimble MR, Richens A, Jawad SS (1983) Clobazam as adjunctive treatment in refractory epilepsy. BMJ 286. https://doi.org/10.1136/bmj.286.6373.1246

  11. American Geriatrics Society (2015) 2015 Updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 63. https://doi.org/10.1111/jgs.13702

  12. Barker M (2004) Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis. Arch Clin Neuropsychol 19. https://doi.org/10.1016/S0887-6177(03)00096-9

  13. American Geriatrics Society (2019) 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am GeriatrSoc 67. https://doi.org/10.1111/jgs.15767

  14. Marini C, King MA, Archer JS, Newton MR, Berkovic SF (2003) Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry 74. https://doi.org/10.1136/jnnp.74.2.192

  15. Jensen HS, Nichol K, Lee D, Ebert B (2014) Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for α2- versus α1-GABAA–receptor complexes. PLoS One 9. https://doi.org/10.1371/journal.pone.0088456

  16. Klehm J, Thome-Souza S, Sánchez Fernández I, Bergin AM, Bolton J, Harini C et al (2014) Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy. Pediatr Neurol 51. https://doi.org/10.1016/j.pediatrneurol.2014.01.025

  17. Stefan H (2011) Epilepsy in the elderly: facts and challenges. Acta Neurologica Scandinavica 124. https://doi.org/10.1111/j.1600-0404.2010.01464.x

  18. Leppik IE, Birnbaum AK (2010) Epilepsy in the elderly. Ann N. Y. Acad Sci 1184. https://doi.org/10.1111/j.1749-6632.2009.05113.x

  19. Walzer M, Bekersky I, Blum RA, Tolbert D (2012) Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy 32. https://doi.org/10.1002/j.1875-9114.2012.01028.x

  20. Geffrey AL, Pollack SF, Bruno PL, Thiele EA (2015) Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 56. https://doi.org/10.1111/epi.13060

  21. Montenegro MA, Ferreira CM, Cendes F, Li LM, Guerreiro CAM (2005) Clobazam as add-on therapy for temporal lobe epilepsy and hippocampal sclerosis. Can J Neurol Sci / J Can Des Sci Neurol 32. https://doi.org/10.1017/S0317167100016942

  22. Montenegro MA, Cendes F, Noronha ALA, Mory SB, Carvalho MI, Marques LHN et al (2001) Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy. Epilepsia 42. https://doi.org/10.1046/j.1528-1157.2001.31600.x

  23. Mäkinen J, Peltola J, Raitanen J, Alapirtti T, Rainesalo S (2017) Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market. J Neurol 264. https://doi.org/10.1007/s00415-017-8526-8

  24. Jamil A, Levinson N, Gelfand M, Hill CE, Khankhanian P, Davis KA (2020) Efficacy and tolerability of clobazam in adults with drug-refractory epilepsy. Neurol Clin Pract. https://doi.org/10.1212/CPJ.0000000000000992.

  25. Alsfouk BAA, Hakeem H, Chen Z, Walters M, Brodie MJ, Kwan P (2020) Characteristics and treatment outcomes of newly diagnosed epilepsy in older people: a 30‐year longitudinal cohort study. Epilepsia 61. https://doi.org/10.1111/epi.16721

  26. Barcs G, Halász P (2009) Effectiveness and tolerance of clobazam in temporal lobe epilepsy. Acta Neurologica Scandinavica 93. https://doi.org/10.1111/j.1600-0404.1996.tb00180.x

  27. Shimizu H, Kawasaki J, Yuasa S, Tarao Y, Kumagai S, Kanemoto K (2003) Use of clobazam for the treatment of refractory complex partial seizures. Seizure 12. https://doi.org/10.1016/S1059-1311(02)00287-X

  28. Paton C (2002) Benzodiazepines and disinhibition: a review. Psychiatric Bull 26. https://doi.org/10.1192/pb.26.12.460

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Authors and Affiliations

  1. Department of Neurology, Division of Epilepsy, Albany Medical College, Albany, NY, 12208, USA

    Elanagan Nagarajan, Timothy M. Lynch, Bridget Frawley & Marjorie E. Bunch

  2. Department of Neurology, Erlanger Health System, Chattanooga, TN, 47308, USA

    Elanagan Nagarajan

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  1. Elanagan Nagarajan
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  2. Timothy M. Lynch
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Correspondence to Elanagan Nagarajan.

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The authors declare no competing interests.

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IRB for this study was approved on 21-Feb 2022 under Exempt Category (d)(4)(iii) with Waiver of HIPAA Authorization (Secondary research for which consent is not required) (5409).

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Nagarajan, E., Lynch, T.M., Frawley, B. et al. Tolerability of clobazam as add-on therapy in patients aged 50 years and older with drug-resistant epilepsy. Neurol Sci 44, 2883–2888 (2023). https://doi.org/10.1007/s10072-023-06765-1

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