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Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 143-145

Association of headache, anxiety, and depression with the treatment of levetiracetam for epilepsy

1 Department of Pharmacology, Batterjee Medical College, Jeddah, Kingdom of Saudi Arabia
2 Department of Neurology, Jeddah National Hospital, Jeddah, Kingdom of Saudi Arabia
3 Department of Microbiology, Batterjee Medical College, Jeddah, Kingdom of Saudi Arabia
4 Department of Clinical Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia
5 Department of Musculoskeletal and Sports Injury Rehabilitation, Batterjee Medical College, Jeddah, Kingdom of Saudi Arabia

Date of Submission21-Oct-2020
Date of Acceptance09-Jul-2021
Date of Web Publication16-Aug-2021

Correspondence Address:
Mohammad Jaffar Mantargi
Department of Pharmacology, Batterjee Medical College, North – Obhur, Jeddah 21442
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjhs.sjhs_234_20

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The current case report bears the details of the adverse drug reactions (ADRs) associated after the administration of the levetiracetam for the management of newly diagnosed epilepsy in a female patient aged 37 years. Datum related to the patient, medications and observed ADRs were noted after getting the consent from the patient during which she has explained her experiences after the beginning of the consumption of the said drug. The Naranjo's scale and World Health Organisation, Uppsala Monitoring Centre scales analysis for the assessment of the correctness of the ADR paved for the certainty of the side effect. Drug regimen modification was initiated by the neurologist after the complaints of uneasiness from the patient after which she was identified to be complying with the other medication. Therefore, it can be said that if any patient on antiepileptic medications experiences discomfort, must bring those issues in light as there is always other options available for the management of the epilepsy without delay.

Keywords: Adverse drug reactions, epilepsy, levetiracetam, Naranjo's scale, WHO UMC scale

How to cite this article:
Mantargi MJ, Kondanath S, Ikram N, Vigneshwaran E, Awais M, Thattarauthodiyil U. Association of headache, anxiety, and depression with the treatment of levetiracetam for epilepsy. Saudi J Health Sci 2021;10:143-5

How to cite this URL:
Mantargi MJ, Kondanath S, Ikram N, Vigneshwaran E, Awais M, Thattarauthodiyil U. Association of headache, anxiety, and depression with the treatment of levetiracetam for epilepsy. Saudi J Health Sci [serial online] 2021 [cited 2021 Nov 30];10:143-5. Available from: https://www.saudijhealthsci.org/text.asp?2021/10/2/143/323874

  Introduction Top

Epilepsy is a neurological electrical imbalance which proceeds with the excess propagation of impulses between the neurons in the brain which paves a path for the unprovoked convulsions and seizures if the prior is waved undetected or mismanaged. Majority of the cases are idiopathic, whereas the incidence and prevalence of the same may point toward the genetic factors, infections such as meningitis, head trauma such as car accidents, brain tumors, stroke, poisons such as lead (Pb), frequent hypoglycemia, drug overdose and many to follow, which results in the development of partial/focal seizures or generalized seizures.[1],[2]

In current times, the disorder is very well understood at the ground level whereas at the advanced level it projects few challenges in determining the etiology and pathophysiology for determining the line of treatment.[1],[2],[3]

With the dedication of many researchers, physicians, and neurologists, wide varieties of medications have been developed to counter the challenges posed by the disorder at different stages which includes Phenytoin and its analogs, Carbamazepine, Barbiturates, Benzodiazepines, Valproic acid, and its salt, Ethosuximide, Vigabatrin, Lamotrigine, Famotrigine, Felbamate, Gabapentine, Tiagabine, Levetiracetam, Pregabaline, and Topiramate with the main plan to control the excitatory neurotransmitters including aspartate and glutamate, or to control the functioning of voltage-gated ion channels including Na + or Ca2+, simultaneously increasing the activity of inhibitory neurotransmitters, including GABA.[1],[2],[3]

In the case of newly epilepsy diagnosed patients, it is clinically prevalent that the management starts with Levetiracetam, Lamotrigine, Topiramate, Gabapentin, and Vigabatrin. Which can be changed to the first line of choice agents including Carbamazepine, Phenytoin, Barbiturates, Valproates, and Diazepam (Especially in case of Status Epilepticus).[1],[2],[3]

It is revealed through the review of literature that the above-mentioned agent possesses the potential chances of developing the adverse drug reactions (ADRs) and drug interactions and one such unintended effect noticed due to the use of Levetiracetam is explained here forth.

  Case Report Top

A 37-year-old Indian woman presented at the neurology outpatient clinic with the complaints of confusion, whole body pain, disorientation, weakness, lethargy, agitation, discomfort, uneasiness, lack of interest, slurred speech, missing words during speech, lack of understanding, visual disturbances, and loss of taste. She had a fit 24 h before reporting at the clinic. The fit started with a loud scream after which she fell on the ground with uncontrollable movement of the limbs accompanied with drooling. The fit lasted 3 min. On examination, there was a deep tongue and cheek bite. Although the patient could not recall the fits incident. She was not suffering from any other disease or any gynecological problem in the past. There was no family history of epilepsy. She was a housewife, having two kids, and recently shifted to Saudi Arabia for 4 years to join her husband working in a private firm. She is having a busy happy life without any psychosocial problems away from her motherland.

The patient underwent computerized tomography scan of the brain, chest X-ray, and hematological tests which were normal. At the emergency department, she was administered phenytoin in dextrose normal saline stat and the patient was discharged without any home medications.

On follow-up neurologist prescribed magnetic resonance imaging scan of the brain, Electroencephalograph, and blood test for electrolytes. The results were normal and the patient was advised levetiracetam - 500 mg twice daily dose and suggested to revisit after a month.

After about a month of treatment, the patient experienced two episodes of fits over a period of 5 h starting from 11:00 pm in the night till 4:00 am in the morning. The patient was given a dose of sedative/anxiolytic “midazolam” intravenously stat in the emergency and discharged with 1,000 mg of levetiracetam twice daily, and counselled to report to the outpatient department after a month.

The patient had started to suffer from serious mood swings after increasing the dose of the drug, which included restlessness, agitation, depression, sad mood with feeling to cry, rejection by others, loss of sleep, migraine-like severe headache. On reporting to the neurologist after a month levetiracetam was replaced with 500 mg of valproic acid and sodium valproate, multivitamin for 30 days, and an antidepressant (mirtazapine) for 10 days. The patient was advised for a follow-up after 1 month again.

  Discussion Top

The objective of the antiepileptic medications is to control the onset of seizures in new onset epileptic patients. However, almost 70%–80% of new-onset epileptic fits can be controlled to the fullest with the currently available agents, but approximately 50% of the patients with these drugs may suffer from ADRs.[1],[2],[3]

The simultaneous administration of alternate medications including Ayurveda, Homeopathy, Unani, Chinese, and Herbal (Complementary and Alternate Medicine) must be avoided as it may interfere with the pharmacokinetic and pharmacodynamic parameters of antiepileptic medications. Previously published manuscripts have revealed that the drugs of alternate medications related to Ayurveda, Homeopathy, Unani, Chinese, and Herbal may cause serious ADRs.[4]

Levetiracetam monotherapy has proved to be as good as carbamazepine or valproic acid for patients with new-onset epilepsy (generalized seizures). Asians specifically are highly susceptible for developing ADRs against carbamazepine, lamotrigine, or phenytoin and in comparison, levetiracetam is considered devoid of any specific or intense ADRs.[1],[2],[3] Whereas, in the present case scenario, the patient on levetiracetam expressed severe headache, anxiety, and depression soon after the beginning of the treatment with the said drug. According to the WHO UMC ADR scale, it was identified as certain ADR. According to Naranjo's scale, it was identified as probable ADR.[5],[6]

Similarly, a wide variety of cases pertaining to the ADRss of levetiracetam have been published earlier. Rafael et al. have identified the development of severe anemia, leucopenia, and thrombocytopenia after initiation of the therapy with the said drug.[7] Furthermore, Alberto et al. in their meta-analysis of levetiracetam has clearly explained the development of somnolences, dizziness, fatigue, depression, irritability, and insomnia (Neuropsychiatric disturbances) to the optimum effect which is dose independent[8] some of the reactions are also seen in infusion-related cases.[9]

As the patient was switched from levetiracetam to valproic acid and valproate a decrease in agitation, anxiety, depression, and headache was noticed which disappeared within a few days of the start of treatment with valproic acid. Even this change can be taken up with the pharmacist also as the research shows even pharmacist can help through advising the patient in a rational direction following with the reporting of ADR if any.[10]

Hence, with this report it may be concluded that the change of medication in cases of epilepsy is preferred if the patient feels side effects with the medication, furthermore the patient should not wait for the next appointment once he/she feels the side effects.

A randomized control trial or a meta-analysis of the previously published case reports or case series could be designed including a higher number of patients suffering with the similar conditions to develop a proper understanding of the adverse reactions to levetiracetam.

If any kind of changes experienced by the patient either at the start of therapy or during the treatment including confusion, whole body pain, disorientation, weakness, lethargy, agitation, discomfort, uneasiness, lack of interest, agitation, slurred speech, missing words during speech, lack of understanding, visual disturbances, and loss of taste must be reported to the caregivers and physician as soon as possible.

Alternate medications related to Ayurveda, Homeopathy, Unani, Chinese, and Herbal (Complementary and Alternate Medicine) must be avoided to prevent ADR.

ADR reporting must be made mandatory for all health-care professionals for the upliftment of the health care in a better way.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


We would like to thank our participants for being so expressive, calm, and composed during the time of the study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Dieter S, Steven CS. Drug treatment of epilepsy in adults. BMJ 2014;348:g2546.  Back to cited text no. 1
Swaroop HS, Ananya C, Nithin K, Jayashankar CA, Satish Babu HV, Srinivas BN. Levetiracetam: A review of its use in the treatment of epilepsy. Int J Med Biomed Res 2013;2:166-72.  Back to cited text no. 2
Srujana MP, Vigneshwaran E, Kumar GS, Jyoshna K, Jaffar Sadiq MM. Assessment of quality of life in children with epilepsy in rural settings of South India: A cross sectional study. Chrismed J Health Res 2017;4:110-6.  Back to cited text no. 3
  [Full text]  
Jaffar SM, Chandrasekhar KB, Padmanabha RY, Bushra S. Assessment of nigella sativa induced adverse drug reactions. Indian J Pharm Prac 2013;6:34-7.  Back to cited text no. 4
Pawar V, Krishna SN, Narayana G, Sadiq J, Thomas D. A possible case of filgrastim induced death. Indian J Pharm Prac 2012;5:79-80.  Back to cited text no. 5
Sajida S, Jaffar S M, Balaji K, Narayana G. A possible case of complete loss of vision after intra ocular administration of bevacizumab: Case report. Indian J Pharm Prac 2013;6:1-2.  Back to cited text no. 6
García Carretero R, Romero Brugera M, Olid-Velilla M, Salamanca-Ramirez I. Pancytopenia associated with levetiracetam in an epileptic woman. BMJ Case Rep 2016. doi: 10.1136/bcr-2016- 217407.  Back to cited text no. 7
Verrotti A, Prezioso G, Di Sabatino F, Franco V, Chiarelli F, Zaccara G. The adverse event profile of levetiracetam: A meta-analysis on children and adults. Seizure 2015;31:49-55.  Back to cited text no. 8
Sreelalitha N, Vigneshwaran E, Narayana G, Reddy YP, Reddy MR. Identification and assessment of the infusion related reactions of medications. Indian J Pharm Prac 2012;5:38-43.  Back to cited text no. 9
Vigneshwaran E, Harichandana V, Sadiq MM, Alavudeen SS, Khan NA, Ahmed T. Knowledge, attitude and practice of community pharmacists towards adverse drug reactions reporting. J Young Pharm 2020;12:75-80.  Back to cited text no. 10


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