Indian Journal of Medical Sciences Medknow Publications on behalf of Indian Journal of Medical Sciences Trust ISSN: 0019-5359 EISSN: 1998-3654 Vol. 57, Num. 11, 2003, pp. 508

Indian Journal of Medical Sciences, Volume 57, Number 11, November 2003, pp. 508

Letter to editor

Topiramate induced Somnabulism and Automatic behaviour

B M Varkey, L M Varkey

Indo-American Hospital, Brain & Spine centre, Chemmanakary, Vaikom, Kerala, India.
E-mail: bobvarkey@vsnl.com

Code Number: ms03041

Sir,

Topiramate (TPM) is a relatively new antiepileptic drug (AED) that has been in use, primarily as an add on treatment for partial and secondarily generalized seizures that are otherwise refractory to treatment.¹ It is also being increasingly used for the prophylaxis of migraine.^2,3 Topiramate has been associated with a wide variety of CNS side effects including dizziness, ataxia, diplopia, somnolence, weight loss and paresthesias.⁴ No cases of Somnabulism or automatic behaviour have been reported to our knowledge. This report presents an unusual adverse effect of topiramate on sleep and behaviour in a patient with migraine.

A 27-year-old male presented to us with intractable common migraine of 5 years duration. He experienced 1 attack a week associated with severe nausea, vomiting, photophobia and phonophobia. His elder brother suffered a similar headache with lesser frequency and was not taking any medications. His neurological examination was within normal limits and a CT Scan of the brain was also normal. He had been tried on Propranolol, Sodium Valproate, Amitryptiline & Flunarizine in varying combinations, without effect. He was then started on Topiramate 100 mg/day. After 2 weeks he developed two episodes, both on waking up from sleep, during which he got up, removed his clothes and walked out of the room. In the first episode, he regained awareness while standing in the compound of his house. During the second episode, he walked to a nearby college hostel. There he stood apparently staring into space. The duration of this is uncertain as he is amnesic for the event. Hostelmates who went for a walk at 2 AM found him standing unresponsive and naked. He was assumed to be a thief and assaulted. During the assault, he regained awareness and started screaming for them to stop. The beating was aborted only by the arrival of another hostelmate, who recognized him on coming down after hearing the commotion. He also reported that on waking from sleep, he is only partially aware of his actions and reports feeling a dream like state in which he does the same thing repetitively. He talks irrelevantly during these episodes and regains awareness only after an hour. He denied any history of excessive daytime sleepiness, cataplexy, episodes of paralysis on waking, hypnogogic or hypnopompic hallucinations. There was no history of poor nocturnal sleep or family history of sleep disorders. He denied any prior history of somnambulism. He was not taking any other medications. After 4 weeks of topiramate he came back to us for follow up, greatly distressed though his migraines were better. A 24 hour video EEG and polysomnography were carried out to rule out any epileptic or sleep disorders. He did not undergo any memory or IQ testing. The medication was stopped and he was followed up for a period of 6 months during which no further episodes were reported, however his migraines returned at their earlier frequency. The patient refused a rechallenge with topiramate and was put back on Flunarizine and Valproate.

Topiramate has been shown to have a wide variety of effects on the CNS. TPM has been associated with decline in fluency, attention, concentration, processing speed, language skills, perception and working memory in epileptic patients on medication. Verbal deficits appearing shortly after initiating TPM and disappearing variably after drug withdrawal have also been reported.⁵ Other side effects noticed have been fatigue, impaired concentration and `abnormal thinking'.² The effects on sleep architecture have not yet been studied with TPM as with other antiepileptics. Carbamazepine, phenytoin and phenobarbitone have been seen to increase slow wave sleep. Gabapentin and lamotrigine increase REM sleep.⁶ It is well known that highly complex emotional and motor behaviours such as occur during sleep walking and confusional arousals can arise from the brainstem and primitive neural structures without involvement of higher neural structures like the cortex. During sleep such activity may be generated without control by the cortex. Drugs may produce this dissociation by manipulation of cholinergic/glutaminergic neurotransmitter systems.⁷ Presumably TPM interferes with sleep architecture and induces a sleep state dissociation leading to the above clinical manifestations.

In this case the temporal relationship of the introduction of TPM and the onset of somnambulism and automatic behaviour as well as the remission with discontinuation of the drug suggests the causative role of TPM. On the adverse drug reaction probability scale described by Naranjo et al, this report scores 7 making it probable that topiramate caused this particular side effect.⁸ This report presents a yet undescribed side effect of TPM. Further clinical studies looking at sleep architecture in patients on TPM may help clarify the effect of TPM on sleep and behaviour.

REFERENCES

1. Genton P, Biraben A. [Use of topiramate in clinical practice (part 2). Multicentric retrospective evaluation of its safety]. Rev Neurol (Paris) 2000;156:1120_5.

2. Ashkenazi A, Silberstein SD. The evolving management of migraine. Curr Opin Neurol 2003;16:341-5.

3. Diener HC. Pharmacological approaches to migraine. J Neural Transm Suppl 2003;64: 35-63.

4. Ben-Menachem E, Henriksen O, Dam M, Mikkelsen M, Schmidt D, Reid S, et al. Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia 1996;37:539-43.

5. Ojemann LM, Ojemann GA, Dodrill CB et al. Language Disturbances as Side Effects of Topiramate and Zonisamide Therapy. Epilepsy Behav 2001;2:579-84.

6. Foldvary-Schaefer N. Sleep complaints and epilepsy: The role of seizures, antiepileptic drugs and sleep disorders. J Clin Neurophysiol 2002;19:514-21. Review.

7. Mahowald MW, Schenk CH. Parasomnias: sleepwalking and the law. Sleep Med Rev 2000;4:321-39.

8. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.

Copyright 2003 - Indian Journal of Medical Sciences.