Side effects of topiramate is driving me insane, some advice would be appreciated

Topiramate is an anticonvulsant medication used for a variety of disease states. Initially, the United States Food and Drug Administration (FDA) approved topiramate for the treatment of partial and complex epilepsy; however, its use has also been expanded to other labeled and off-labeled indications. Topiramate use for migraine prophylaxis is supported by extensive evidence; 1 however, broadened prescription of topiramate has brought an increased awareness of its side-effect profile, which includes several neurocognitive and psychiatric side effects. During initial studies of topiramate, several cases of neurocognitive and neuropsychiatrie adverse events were reported. Some of these side effects include somnolence, nervousness, psychomotor slowing, anorexia, confusion, difficulty in memory, agitation, aggression, emotional lability, apathy, and depersonalization. 2 Here, we report the case of a 21-year-old woman who developed episodes of dissociation while receiving topiramate for migraine headache. To the best of our knowledge, this is the first reported case of topiramate-induced dissociative disorder.

Topiramate-induced Dissociative Disorder

1 Dr. Sarwar is with the Department of Psychiatry and Dr. McGinnis is Associate Professor of Psychiatry—Both from the University of Toledo, in Toledo, Ohio.

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Ronald A McGinnis , MD

1 Dr. Sarwar is with the Department of Psychiatry and Dr. McGinnis is Associate Professor of Psychiatry—Both from the University of Toledo, in Toledo, Ohio.

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1 Dr. Sarwar is with the Department of Psychiatry and Dr. McGinnis is Associate Professor of Psychiatry—Both from the University of Toledo, in Toledo, Ohio.

ADDRESS FOR CORRESPONDENCE: Sajjad R. Sarwar, MD, Dept. of Psychiatry, MS #1193, Health Science Campus, University of Toledo, 3000 Arlington Ave., Toledo, OH 43614; Phone: 419-215-2447; Fax: 419-383-5695; E-mail: [email protected]

FUNDING: No funding was received for the preparation of this article.

FINANCIAL DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

PMCID: PMC3173756 PMID: 21922065

Abstract

Topiramate is associated with various psychiatric and neurocognitive side effects. We report a case of a 21-year-old woman who was prescribed topiramate for the treatment of migraine headaches by her neurologist. She developed episodes of dissociation while receiving topiramate. These episodes increased when the dose of medicine was increased. The frequency of these episodes decreased as the medicine dose was tapered down, and these episodes eventually stopped after the medicine was discontinued. There was no recurrence of symptoms during the 23-week follow-up period.

Keywords: Topiramate, dissociative disorder

Introduction

Topiramate is an anticonvulsant medication used for a variety of disease states. Initially, the United States Food and Drug Administration (FDA) approved topiramate for the treatment of partial and complex epilepsy; however, its use has also been expanded to other labeled and off-labeled indications. Topiramate use for migraine prophylaxis is supported by extensive evidence; 1 however, broadened prescription of topiramate has brought an increased awareness of its side-effect profile, which includes several neurocognitive and psychiatric side effects. During initial studies of topiramate, several cases of neurocognitive and neuropsychiatrie adverse events were reported. Some of these side effects include somnolence, nervousness, psychomotor slowing, anorexia, confusion, difficulty in memory, agitation, aggression, emotional lability, apathy, and depersonalization. 2 Here, we report the case of a 21-year-old woman who developed episodes of dissociation while receiving topiramate for migraine headache. To the best of our knowledge, this is the first reported case of topiramate-induced dissociative disorder.

Case Report

Our patient was a 21-year-old woman with a known diagnosis of neurocardiogenic syncope and chronic migraine. She was referred to us by her cardiologist, when during a follow-up visit for a neurocardiogenic syncope, she began talking like a baby. She did not remember any part of the episode and could not give details of the incident. She mentioned that she had been having these episodes since May 2010.

The patient’s boyfriend, who witnessed her behavior during several episodes and had told her about them, was also interviewed after obtaining consent of information. He also reported episode incidence since May 2010. According to him, the patient’s episodes were happening 1 to 2 times per week and were usually precipitated by stress. During an episode, the patient spoke like a child. The boyfriend also observed that episodes occurred when the patient was scared or soon after they had an argument. He reported that during an episode, he would leave her alone until she improved, which would take 2 to 24 hours. He reported that she had no memories of these episodes or events happening around that time. He said that he never discussed these events with a doctor because he thought that it was normal immature behavior. He also mentioned the patient began taking topiramate in May 2010. Her neurologist prescribed the drug as a treatment for migraine headaches. According to her boyfriend, the prescribed dose of topiramate was initially 100mg twice daily and was then gradually increased to 100mg in the morning and 150mg at bedtime. As the dosage increased, so did the frequency of the episodes. He reported that the maximum frequency was up to four episodes per week. The patient was on 250 mg per day until January 2011. Her neurologist decreased the dose and eventually discontinued the medication on February 6, 2011 because it was no longer alleviating her migraine headaches. According to her boyfriend, since February 6, 2011, the patient only experienced one episode of talking like a child within a 24-hour period after the medicine was discontinued. Since then, she has not had an episode.

The patient’s father was also interviewed to find out if the patient had any similar episodes in the past. According to him, the patient had no previous history of any similar episodes or any other psychiatric condition. The patient was also screened for the past experience of trauma, but no such history was reported. Neurological workup including magnetic resonance imaging, electroencephalogram, and full laboratory evaluation revealed no abnormalities. A full psychiatric evaluation revealed no other axis I or II diagnoses. The patient was followed up regularly by telephone every four weeks to inquire about relapse of any similar episodes. At the time of publication of this manuscript, it was 23 weeks since the patient had an episode of speaking like a baby. She denied any episode occurrences since topiramate was discontinued during those 23 weeks.

Discussion

Topiramate has been known to cause various neurocognitive symptoms including confusion and psychomotor slowing language problems, particularly word-finding difficulties. 2 Initial clinical studies of topiramate showed one case of depersonalization on low doses and two cases on the higher doses. 8

In our case study, there are several factors that point to the conclusion that the symptoms were caused by topiramate. First, the patient had no previous psychiatric history, no previous exposure to trauma, and no premorbid personality disorder. Second, the symptoms started soon after the initiation of topiramate therapy and the frequency of episodes increased with the dose increase of topiramate. Third, the number of episodes decreased as the dose of topiramate was reduced, and symptoms disappeared after the medication was discontinued and have not recurred for an additional 23 weeks during the follow-up period.

The exact mechanism behind these symptoms is not known; however, a potential explanation comes from the effect of topiramate on serotonin levels. Recent studies have found that a significant increase in mean plasma serotonin levels was observed with respect to the basal levels in patients taking topiramate compared to those of a control group. 7 It is also described that serotonergic hallucinogens, such as lysergic acid diethylamide, mescaline, and dimethyltryptamine, also produce dissociative symptoms via their stimulation of 5-HT2 receptors. 3 , 4 Furthermore, serotonergic systems heighten sensory processing via the 5-HT2 receptor. Some suggest that dissociation may result from excessive serotonergic activation at the thalamic level, resulting in interference of sensory transmission. 5 Others suggest that hippocampal overstimulation is responsible for dissociative phenomena. 6 The symptoms in this patient may have been caused by an increase in serotonergic activity at thalamic or hippocampal sites, leading to dissociative symptoms.

Conclusion

Despite topiramate’s ability to alleviate migraine and epilepsy symptoms, side effects are common. Some of them may be unusual. The prescribing physician should be aware that it may induce rare adverse effects such as dissociation and should encourage patients to report these side effects even if they initially appear awkward to them. More research is needed to find the mechanism behind these side effects.

References

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Side effects of topiramate is driving me insane, some advice would be appreciated.

I was recently diagnoised with Intracranial Hypertension after having headaches for way over two years to a point where I litrally couldn’t lift my head off of my pillow on a morning. I was in absolute agony. But I got to a point where it just became a normal thing. I was investigated under neurology around two years ago, and they passed it off as normal headaches after a CT scan came back normal.

I work in an opticians and realised that dizziness, migranes, light-headedness were becoming regular things as well as my vision becoming a real problem in my left eye when one of the optomertrists recommended they check up on my vision and realised I had a field defect and papilledema on my left optic nerve. He gave me an urgent referral to neurology.

The neurologist was convinced I had no problems, even after me telling him where the referral had come from, he still said he didn’t know who had referred me and why. But said because it had been investigated before, to put it to rest he would send me for a lumbar puncture. He also said he would eat his hat if I had a problem.

I had my lumbar puncture and it came back that my CSF pressure was 37, and that it needs treating. I am now under opthalmology, and on medication. But I am not taking very well to the medication at all. At first the doctors put me on acetazolamide, and that put me in A&E. So they adviced me against that. Then my neurologist suggested Topiramate. The effects weren’t bad at first. My GP recommended that I stay off work the first week as I’m not just on one floor and with some of the side effects, I may be a bit disorientated. It’s now been 4 weeks and I am stll not back at work. I’ve lost nearly a stone in the last week from vomiting which my GP said will just be the dose (how quick they’ve upped it), I have no appetite, I just feel so dizzy and unsteady all the time and the tingling in my hands and feet are driving me crackers!! I just feel like I’m complaining constantly. I also find simple tasks like adding numbers up or just trying to remember simple things are becoming a problem. Has anyone else had an experience like this? I don’t know anyone on this medication and don’t want to keep bothering my GP.

0 likes, 16 replies

16 Replies

Dumdum laurajane2508

Posted 9 years ago

Hi, I can understand your symtoms and concerns as it happened to me. Firstly spend some time looking on the American sites to see that just how toxic this drug is seen to be over there. It is known as Topamax and searching under that will also bring you masses of information. Here they appear to disregard all this and seem to be happily prescribing it without considering the long term issues. The American Federal Drug Agency also has information on this drug that has some amazing statistics in it. Read the side effects in the box and then circle every one that you are affected with. it will be a lot. I took the drug as part of a pain management issue. We told them at the time I had previous history with Gabapentin and Pregabalin (epileptic drugs) as well but they declined to listen. I started the drug at the end of December 2012 and it was in January that I started the most horrendous and ongoing experience ever. I took 11 tablets. Seven once a day and then it was doubled to two a day. On day seven I stopped myself driving as I was dizzy and disorientated. On day eight I fell badly. I could not see properly and had the tingling. Apparantly I was walking around holding on the the wall to keep balance and walking like I had Parkinsons. I was white as a sheet and it was when a friend who was a medical professional came in that a halt was called. My GP was contacted and they were stopped immediately. That weekend was awful, in bed and in retrospect all the symptoms of a stroke and I knew then what I know now I would have presented myself at Casualty as being concerned I had a strike. I went down from a size 16/18 to a 12 in three weeks (in America they trialled it as an endocrine drug but gave up because of the side effects although the weight loss was amazing for the obese patients. My eyes dropped by two points and I went into distance glasses. I was and am and remain word blind and that is after months in Speech Therapy (Aphaisia and Word Blind is a common issue on the American sites. I also remain uncoindinated with eye to hand and my text messages are not readable but cause a lot of humour. I cannot raise my left arm fully and my hearing has dropped in my left ear. My neuropathic pain stopped dead and did not come back for about ten months. I battled hard to get help. First MRI brain was normal but not done at the time. First neurologist told me she did not get my problem and thought that it was a fair swap pain for speech. She went to the drug company on my behalf and saw us a couple of months later. In front of her was a large pile of information from the drug company and she showed me two sheets on recovery rates in five year old from the speech issues I was having. I was not particulary polite at that time and asked to look at the other information the drug company had supplied and she stated that the drug company had catargorically said she could not share anything else with me. . says it all but at that stage I did not have the energy to deal with it. Battled hard with Pain Consultant and went into Speech Therapy. Manages to control the stutter but it did nothing for the word blindness, Battled harder and evenually got a referral to National Neurological Hospital UCH. Originally picked up by voice specialist but quickly referred into Neuro as vocal cords not working as expected. Have now had another MRI brain, Pet Scan Brain, Pet CT Scan, Lumbar Puncture and very long appointment in NeuroPysch. Problem is they now seem to think the drug has kicked off a hidden degenerative disease and seem hesitant to link the drug as being responsible. But talking to more junior staff and research fellows the drug is known to be a nightmare. Apparantly hundreds of people are left word blind by it. I now have a days dementia screening to go through and then we will talk to the Prof again at the end of the month and hopefully some decision can be made. My husband (a healh professional) says I do not have dementia and It is just that I cannot say what I want to say. I know it was the drug by the sequence of events and time scale. I know the drug company is keeping some thing quiet. I ask each Consultant I come across if they have shares in the company! My plan is to use the media to let the world know what has happened to me. You are where I was. The reason the drug is built up slowly is because it is so toxic. You need to stop it now. If you can circle your side effects on the drug information leaflet and you have loads (which you will have) then it must be a valid reason to stop. Ask for a referral into a specialist unit as well. UCH have been brilliant. Never doubted me once compared with local unit. Try to find a meditation group that teaches self healing meditation. Mummyemw

CongreveCottage Dumdum

Posted 9 years ago

I echo your sentiments completely. My only regret is that I didn’t have the wonderful weight loss apart from losing some weight over a three year period when I was too ill to eat anything other than a bit of yoghurt! I want my life back, I’m still not word perfect after 18 months off it and I fear my sight will never be normal again.

laurajane2508 Dumdum

Posted 9 years ago

Thank you for your reply, I just feel on my own. I don’t know anyone on this medication so can’t really ask how they found it etc. I am going to visit my GP again tomorrow but find it frustrating because they seem as though they are very limited. I understand it is a specialist area with it being IIH and everything, but if why not let me keep in contact with my neurologist then? Because at the minute I’m between the two! GP won’t do anything without speaking to neurologist, so I’m just being discussed between the two. I just want to get back to work and everything but I am not really in a fit state at the moment.

LeaLea4 Dumdum

Posted 8 years ago

LeaLea4 CongreveCottage

Posted 8 years ago

I didn’t get the awesome loss of weight blessing either. I gained 38lbs in 3 months because all in that time frame I had a full Hysterectomy, started on the new meds all basically not needed in the type given or period! One, a Beta Blocker, Two, an anxiety med, and Three, the Topamax! Not sure witch med med made me gain weight but it definitely wasn’t the surgery because I lost 20lbs with immediately! Anyway, for me it would have nice to have at least two plus sides to Topamax as it is controlling my migraines! However, I’m now learning all of my new and really bad Neuro problems may be because of this med and I’m getting off this med NOW.

Dumdum LeaLea4

Posted 8 years ago

It might be controlling your migraines but . I am about to go back up to National Neurological Centre next week for my annual review. They are concerned enough to want to keep me for ten years and all based on the taking of eleven tablets. I remain word blind and struggle with reading and writing etc. The permnent tiredness is a nightmare, and at the end of the day with having concentrated hard to concentrate on communication we are down to hand signals indoors rather than talking The fact that the drug company witheld information from me via the first consultant makes me think it is a potential time bomb waiting to go off,

morgulon Dumdum

Posted 8 years ago

Wow you guys are scaring me. I have been taking topamax 50mg 2x a day for about 2 months now for migraines. My hands and feet are a little numb I am losing weight and the migraines are gone. I am experiencing a little difficulty finding words but its not that bad. I am taking a online math class and doing well. I will have family and friends keep a eye on me so I don’t start to lose it now that I know what to look for. I am sorry you guys are having such trouble with this drug.

betsy70690 LeaLea4

Posted 8 years ago

Memory impairment is common. Some people once off didn’t realize how much it had effected their mind. Some people jokingly, or not, call it dope-a-max for that reason. That was my experience as well.