EEG response to brand-name and generic clozapine. Report of four cases

Aims: The interchangeability of a generic and the brand-name drug is based on the criterion of essential similarity which requires that the generic drug has the same amount and type of active principle, the same route of administration, and the same pharmacokinetic as the original drug, as demonstrated by a bioequivalence study. However, bioequivalence is not necessarily the same as drug effectiveness and tolerability. Objective: To report EEG changes in 4 patients with schizophrenia (aged 24–60 years, one female) who were switched between branded and generic clozapine (Leponex, Novartis AG, Switzerland vs. Klozapol, Anpharm S.A., Poland). Methods: EEG recordings were performed before and two weeks after switch from branded to generic clozapine (n=1), from generic to branded clozapine (n=2) and during the switch in both directions in one patient. Two raters blind to drug status analyzed the EEG visually. Additionally, the quantitative analysis (qEEG) with FFT was performed. Results: In three patients EEG was worsened during administration of generic clozapine. It corresponded to increase in delta and theta power and slowing of alpha rhythm in qEEG. One patient showed minimal EEG improvement during treatment with generic clozapine, that corresponded to decrease in delta power. Conclusions: These data raise the question if the present essential-similarity requirement is sufficient. We argue it should also include more rigorous analyses e.g. the EEG response for clozapine.