Psychiatric Adverse Effects from Levetiracetam Linked to Certain Factors

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Researchers aimed to identify risk factors associated with a psychiatric event following a first prescription for levetiracetam.
The following article is part of conference coverage from the American Epilepsy Society’s Annual Meeting in New Orleans, LA. The Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.

NEW ORLEANS — Levetiracetam is more likely to induce psychiatric adverse effects in individuals with epilepsy who use recreational drugs, have a history of depression, are female, and experience more social deprivation. This research was recently presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30–December 4, 2018, in New Orleans.

Individual risk factors were identified using a literature review with an adapted Delphi method, after which incident epilepsy cases were isolated within the Health Improvement Network database between 2000 and 2012. Those who received a first-time levetiracetam prescription were assigned a 2-year follow-up period.

The prediction model was obtained through use of logistic regression, with sensitivity analyses performed on those with no history of psychiatric adverse events in order to discern the model’s predictive power. Brier score was employed to assess model calibration and discrimination.

This study included incident cases of epilepsy in 9595 individuals. Levetiracetam was administered to 14% (n=1173) of participants, all of whom were taking it for the first time. Within 2 years, 14% (n=165) of these individuals taking levetiracetam experienced a psychiatric adverse effect. Independent correlations were found between psychiatric adverse effects and recreational drug use (odds ratio [OR] 2.02; P =.008), depression (OR 2.20; P <.001), anxiety (OR 1.74; P =.015), social deprivation (OR 1.15; P =.028) and being female (OR 1.41; P =.050).

These factors were incorporated into a final prediction model that stood up well to k=5 fold cross-validation (area under the receiver operating characteristic curve [AUC]=0.68; 95% CI, 0.58-0.79).

The probability of incurring a psychiatric adverse effect with no risk factors was 8%; for 1 risk factor, it was 11% to 17%; for 2 risk factors, it was 17% to 31%; for 3 risk factors, it was 30% to 42%; and for all risk factors, it was 49%. Those without a history of depression or anxiety (61%; n=710) showed greater risk for a psychiatric adverse effect with greater age, female sex, use of recreational drugs, larger number of antiepileptic drugs in use, and higher dose of levetiracetam. This model also held up to a k=5 fold cross-validation (AUC=0.74; 95% CI, 0.58-0.90) for generalizability.

The study researchers concluded that “depression and recreational drug use appear to confer the highest risk for those with a history of psychiatric signs or symptoms. There was also a graded risk according to the number of risk factors present. For those without a history of psychiatric signs or symptoms, increasing age, female sex, levetiracetam dose, and [antiepileptic drug] polytherapy were all associated with increased risk.”

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Josephson CB, Engbers JDT, Jette N, et al. Prediction tools for psychiatric adverse effects following levetiracetam prescription. Presented at: AES 2018; November 30-December 4, 2018; New Orleans, LA. Poster 2.274.