Abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users: A Phase I randomized controlled trial

Abstract Rationale Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. Methods In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2 mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥ 7 days between each treatment: ESL (800 mg, 1600 mg, 2000 mg, and 2400 mg); ALP (1.5 mg and 3.0 mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine–Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24 h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task—Revised tests. Principal results Peak scores for Drug-Liking VAS (maximum effect [E max ]) were significantly higher for both ALP doses than for PBO (p  max was significantly lower for all ESL doses than both ALP doses (p  max for ESL 800 mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p = 0.19). At the three higher ESL doses (1600 mg and the supratherapeutic doses of 2000 mg and 2400 mg), Drug-Liking VAS E max was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3–13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p  Conclusion This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-‘liking’ at higher doses, the magnitude of these effects was small.