Comparative potential for generating spontaneous signals for abuse and dependence among drugs used for attention...

The comparative liability for abuse and dependence of drugs used for attention deficit hyperactivity disorder (ADHD) has been poorly explored so far.

To evaluate the relative potential of medications used for ADHD for generating spontaneous reports of abuse and dependence in international pharmacovigilance data.

A disproportionality analysis was conducted using data recorded in VigiBase®, the World Health Organisation global database of individual case safety reports (ICSRs). ICSRs recorded between 1 January 2002 and 30 June 2023, referring to paediatric and adult subjects with known sex and aged ≥ 15 years and involving suspect drugs used for ADHD, were included. Reporting odds ratios (RORs) for 'Drug abuse and dependence', along with their 95% confidence intervals (CIs), were calculated using methylphenidate as the reference drug and with adjustment for age, sex, seriousness, reporter qualification and continent of reporting. Several sensitivity analyses were performed.

Among the 55 219 ICSRs included, 2633 were reports of drug abuse and dependence. The proportion of drug abuse and dependence reports was significantly lower for all studied drugs than for methylphenidate, except for lisdexamfetamine (ROR: 1.06, 95% CI 0.91-1.24). Sensitivity analyses yielded results comparable to the primary analysis, but with a slightly higher ROR for lisdexamfetamine when excluding US data (ROR: 1.26, 95% CI 1.03-1.54).

Methylphenidate and lisdexamfetamine emerged as the two drugs with the highest likelihood of safety reports related to abuse and dependence. These findings challenge previous statements suggesting that the abuse potential of lisdexamfetamine was lower than that of other psychostimulant drugs used for ADHD and advocate for further pharmacoepidemiological studies in this field.