Caffeinated beverages and decreased seizure control

  • KENNETH R KAUFMAN
    Correspondence
    Correspondence to: Dr Kenneth R. Kaufman, M.D., M.R.C.Psych., Departments of Psychiatry and Neurology, 125 Paterson Street, Suite #2200, New Brunswick, NJ 08901, USA.
    Affiliations
    Department of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, Suite #2200, New Brunswick, NJ 08901, USA

    Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, Suite #2200, New Brunswick, NJ 08901, USA
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  • RAJESH C SACHDEO
    Affiliations
    Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, Suite #2200, New Brunswick, NJ 08901, USA
    Search for articles by this author

      Abstract

      Seizure control is often affected by seizure threshold lowering behaviours. In this case report, the authors address excessive caffeine ingestion from tea with increased seizure frequency. When decaffeinated beverages were substituted for the tea, seizure frequency returned to baseline. Similar findings occurred when the patient was re-challenged. The authors recommend avoidance of excessive caffeine in patients with epilepsy.

      Keywords

      INTRODUCTION

      Lack of seizure control can be related to a series of issues: complexity of seizure disorder, inappropriate anticonvulsant for the particular seizure disorder, and concomitant medical illnesses with fevers
      • Perucca E.
      The management of refractory idiopathic epilepsies.
      • Boggs J.G.
      Seizures in medically complex patients.
      • Delanty N.
      • Vaughan C.J.
      • French J.A.
      Medical causes of seizures.
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Delanty N.
      • French J.A.
      • Labar D.R.
      • Pedley T.A.
      • Rowan A.
      Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients.
      . With the plethora of recently released anticonvulsants, uncontrolled seizure frequency often leads to a change in prescribed anticonvulsant. What may be overlooked in this rush to use the newer agents are the fundamentals in seizure control—compliance, therapeutic anticonvulsant blood levels, and the avoidance of threshold lowering behaviours
      • Perucca E.
      The management of refractory idiopathic epilepsies.
      .
      Seizure threshold is decreased by: decreased sleep
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Mendez M.
      • Radtke R.A.
      Interactions between sleep and epilepsy.
      ; excessive stress
      • Frucht M.M.
      • Quigg M.
      • Schwaner C.
      • Fountain N.B.
      Distribution of seizure precipitants among epilepsy syndromes.
      • Spector S.
      • Cull C.
      • Goldstein L.H.
      Seizure precipitants and perceived self-control of seizures in adults with poorly-controlled epilepsy.
      ; threshold lowering medications
      • Delanty N.
      • French J.A.
      • Labar D.R.
      • Pedley T.A.
      • Rowan A.
      Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients.
      • Trimble M.R.
      Epilepsy, antidepressants, and the role of nomifensine.
      • Czuczwar S.J.
      • Ikonomidou C.
      • Kleinrok Z.
      • Tursk L.
      • Turski W.
      Effect of aminophylline on the protective action of common antiepileptic drugs against electroconvulsions in mice.
      • Kaufman K.R.
      • Kaufman E.R.
      Psychotropic management of seizure duration during electroconvulsive therapy: trazodone, a case report.
      • Stern L.
      • Dannon P.N.
      • Hirschmann S.
      • et al.
      Aminophylline increases seizure length during electroconvulsive therapy.
      • Miura T.
      • Kimura K.
      Theophylline-induced convulsions in children with epilepsy.
      ; medications with pharmacokinetic interactions with anticonvulsants
      • Ebert U.
      • Thong N.Q.
      • Oertel R.
      • Kirch W.
      Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects.
      • Yamamura N.
      • Imura-Miyoskhi K.
      • Naganuma H.
      Panipenum, a carbapenem antibiotic, increases the level of hepatic UDP-glucuronic acid in rats.
      or threshold lowering substances
      • Carrillo J.A.
      • Benitez J.
      Clinically significant pharmacokinetic interactions between dietary caffeine and medications.
      • Randinitis E.J.
      • Alvey C.W.
      • Koup J.E.
      • et al.
      Drug interactions with clinafloxacin.
      ; and caffeine
      • Coffey C.E.
      • Figiel G.S.
      • Weiner R.D.
      • Saunders W.B.
      Caffeine augmentation of ECT.
      • Czuczwar S.J.
      • Gasior M.
      • Janusz W.
      • Szczpanik B.
      • Wlodarczyk D.
      • Kleinrok Z.
      Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice.
      • Francis A.
      • Fochtmann L.
      Caffeine augmentation of electroconvulsive seizures.
      • Shum S.
      • Seale C.
      • Hathaway D.
      • Chucvich V.
      • Beard D.
      Acute caffeine ingestion fatalities: management issues.
      .
      Literature suggests that patients with epilepsy should avoid caffeinated beverages
      • Carrillo J.A.
      • Benitez J.
      Clinically significant pharmacokinetic interactions between dietary caffeine and medications.
      • Gasior M.
      • Borowicz K.
      • Kleinrok Z.
      • Czuczwar S.J.
      Chronic caffeine and the anticonvulsant potency of antiepileptic drugs against maximal electroshock.
      , but the only report concerning the proconvulsive effect of tea was a study with mice
      • Gomes A.
      • Das M.
      • Vedasiromoni J.R.
      • Ganguly D.K.
      Proconvulsive effect of tea (Camellia sinensis) in mice.
      . In this case report, accidental increase in seizure frequency associated with excessive tea ingestion is noted that resolved when decaffeinated beverages were substituted. This finding was duplicated when the patient was re-challenged with the caffeinated beverage.

      CASE

      A 49-year-old white male with a 36-year history of mixed seizure disorder (grand mal seizures with intermittent auras, absence seizures, atonic seizures, and myoclonic seizures) who had been well controlled on phenytoin 400 mg once daily and primidone 500 mg once daily developed a sharp increase in myoclonic and atonic seizure frequency. Anticonvulsant compliance had been maintained with therapeutic blood levels. A pill count revealed that no anticonvulsants had been missed. There had been no change in sleep patterns or level of stress. Further, the patient had no concurrent illnesses or addition of medications. Change in anticonvulsants to newer agents was contemplated. Prior to doing such, a review of the patient’s diet revealed a recent increase in caffeinated beverages. In an effort to avoid caloric beverages, the patient was drinking 4 pints of “Peach diet Snapple Iced Tea” daily. Further, this was typically consumed within 180 minutes. The increased seizure frequency continued over a 2-month time period until the patient’s wife commented upon the potential influence of the additional caffeinated beverages. When the “Peach diet Snapple Iced Tea” was changed to the decaffeinated “Kiwi Strawberry Cocktail diet Snapple”, the patient’s seizure frequency returned to baseline. This simple change in diet obviated the need to change anticonvulsants to control seizure frequency.
      The patient thereafter found that he could drink 1 pint of “Peach diet Snapple Iced Tea” without any effect on seizure frequency. When 4 years later he re-challenged himself briefly with 4 pints of “Peach diet Snapple Iced Tea”, the blinded wife again commented on the return of myoclonic activity and queried his compliance. Again with immediate reduction to 1 pint or use of decaffeinated beverages, no further myoclonus was noted.

      DISCUSSION

      Toxicity and seizures associated with over-the-counter stimulants, including caffeine, have been reported
      • Pentel P.
      Toxicity of over-the-counter stimulants.
      ; however, this case is unique in that seizures associated solely with excessive tea ingestion have not been previously reported. Nonetheless, it is important to realise that numerous beverages contain caffeine and, as such, it is the cumulative caffeine from all beverages ingested that matters.
      As a solitary case, the findings from this case cannot be generalised. Further limitations of this case include the lack of caffeine blood levels and the lack of quantitative myoclonic frequency. However, the fact that the myoclonus returned when the patient was re-challenged is noteworthy and supports the theory that caffeine was the aetiologic factor.
      The total time associated with ingestion of caffeinated beverages may be pertinent to the proconvulsive effect of caffeine. In one rat study of caffeine augmentation of electroconvulsive seizures, the proconvulsive effect was dose dependent and lasted for at least 230 minutes
      • Francis A.
      • Fochtmann L.
      Caffeine augmentation of electroconvulsive seizures.
      . Thus it is important that the patient had ingested the caffeinated beverages within 180 minutes.
      Since caffeine is metabolised by cytochrome P450 1A2, saturation of this enzyme (which could occur with high consumptions of caffeine, and may have occurred in this case) or inhibition of this enzyme will result in increased toxicity from caffeine
      • Carrillo J.A.
      • Benitez J.
      Clinically significant pharmacokinetic interactions between dietary caffeine and medications.
      . This is a critical issue for clinicians as selective serotonin reuptake inhibitors, antiarrhythmics, antipsychotics, and bronchodilators all have been reported to inhibit this enzyme
      • Carrillo J.A.
      • Benitez J.
      Clinically significant pharmacokinetic interactions between dietary caffeine and medications.
      .
      Pharmacokinetic studies have shown that caffeine does not affect standard anticonvulsant blood levels (carbamazepine, valproate, phenobarbitone, and phenytoin) and that protective qualities of these anticonvulsants are progressively reduced with chronic caffeine exposure
      • Czuczwar S.J.
      • Gasior M.
      • Janusz W.
      • Szczpanik B.
      • Wlodarczyk D.
      • Kleinrok Z.
      Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice.
      • Gasior M.
      • Borowicz K.
      • Kleinrok Z.
      • Czuczwar S.J.
      Chronic caffeine and the anticonvulsant potency of antiepileptic drugs against maximal electroshock.
      • Gasior M.
      • Borowicz K.
      • Buszewicz G.
      • Kleinrok Z.
      • Czuczwar S.J.
      Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic administration with caffeine and caffeine discontinuation.
      . In this case, the patient was on phenytoin and primidone (the latter metabolises to phenobarbitone).
      Although this case report has focused on caffeine (1,3,7-trimethylxanthine) in tea, it should be noted that tea also includes theobromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine)
      • Graham H.N.
      Green tea composition, consumption, and polyphenol chemistry.
      • Fernandez P.L.
      • Pablos F.
      • Martin M.J.
      • Gonzalez A.G.
      Study of catechin and xanthine tea profiles as geographical tracers.
      . All three methylxanthines, which are ubiquitous in beverage and food preparations, have been shown to have proconvulsive features
      • De Sarro A.
      • Grasso S.
      • Zappala M.
      • Nava F.
      • De Sarro G.
      Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats.
      . As such, the authors speculate that in addition to caffeine, patients with epilepsy should avoid all unnecessary dietary sources of methylxanthines. In fact, the dietary presence of methylxanthines dates to the preclassic Maya civilisation
      • Hurst W.J.
      • Tarska Jr., S.M.
      • Powis T.G.
      • Valdez Jr., F.
      • Hester T.R.
      Cacao usage by the earliest Maya civilization.
      . Finally, in patients wherein dietary issues (excessive methylxanthines) are felt to contribute to the lack of seizure control, levels of these three methylxanthines should be determined
      • Bispo M.S.
      • Veloso M.C.
      • Pinheiro H.L.
      • De Oliveira R.F.
      • Reis J.O.
      • De Andrade J.B.
      Simultaneous determinations of caffeine, theobromine, and theophylline by high-performance liquid chromatography.
      .

      CONCLUSION

      The authors have observed that the newer anticonvulsants are important to control epilepsy and in many instances have better side effect profiles than the older agents. Nonetheless, the use of these agents does not permit the practitioner and the patient to forget the fundamentals of epilepsy control, specifically minimisation of seizure threshold lowering behaviours including excessive caffeinated beverages. In this case, the simple elimination of excessive caffeinated beverages obviated the need to change anticonvulsants to improve seizure control.

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