Background: Recently, there is a surge in the number of reports on levetiracetam associated mental and behavioural abnormalities.

Objective: We aimed to systematically review descriptive studies on mental and behavioural abnormalities related to levetiracetam.

Methodology: Our study was registered in International prospective register of systematic reviews [CRD42021245388]. MEDLINE/PubMed, Scopus, and Cochrane Library databases were searched from inception to May 2021 without any restrictions. We also performed a bibliographic search of included articles to identify additional studies. Only descriptive studies on levetiracetam associated mental and behavioural abnormalities were included for this review. Quality assessment of the included studies was assessed using tool developed by Murad et al.

Results: Data from 37 out of 2578 studies consisting a total of 42 patients (19 male and 23 female) aged between 5 and 66 years were included in the review. They received levetiracetam dose between 500 to 3500 mg per day. Mental or behavioural abnormalities included psychosis, anxiety, depression, hypomania, seizures, confusion, behavioural challenges, catatonia, mania obsessive-compulsive behaviour, irritability, suicidality, alcohol abuse, delirium, hallucinations, schizophrenia, and hypersexuality which were reported from included studies. Dose reduction or modification, treatment substitution, immediate or eventual treatment cessation was made with levetiracetam therapy, and alternatives were used to treat the ongoing condition of the patient. Methodological quality of included studies were graded as moderate (n=19;51.3%) and good (n=18;48.7%). Four studies (n=4;10.8%) explained on dechallenge and rechallenge phenomenon. Bias on selection, ascertainment and reporting were low among included studies.

Conclusion: Clinicians should be aware of the possible mental and behavioural abnormalities due to levetiracetam with their practice in clinical settings. Dose reduction or modification, treatment substitution, immediate or eventual treatment cessation seems to be effective in the management of levetiracetam associated mental and behavioural abnormalities.