Switching medication products during the treatment of psychiatric illness

Abstract

Background. The common practice of switching between branded (reference) medications and their corresponding generic products, between generic products, or even from a generic product to a branded medication during the treatment of central nervous system (CNS) disorders may compromise efficacy and/or tolerability. Methods. We assessed the published literature from March 1, 2010 through June 30, 2017 via PubMed using the MeSH term 'generics, drugs' alone and in combination with class-specific terms (e.g., 'anticonvulsants', 'mood stabilisers'), for studies detailing outcomes following product switches. Results. Although some studies comparing the initiation of reference versus generic drugs suggest equivalence between products, several studies detailing a switch between reference and generic products describe reductions in efficacy, reduced medication adherence and persistence, and increased overall health care resource utilization and costs associated with generic substitution. Conclusion. When product switches are considered, they should only proceed with the full knowledge of both patient and provider.

Switching among branded and generic medication products during ongoing treatment of psychiatric illness

“…The variation in study outcomes is consistent with the understanding that generic products may be associated with higher or lower exposures compared with the reference product, and while lower exposure can reduce drug efficacy, higher exposure might compromise tolerability. The studies suggest that, on average, generic products generally may be therapeutically equivalent to their reference counterparts at initiation of treatment 12…”

“…For some drugs, batch-to-batch variability in product pharmacokinetics might be great enough that bio-inequivalence could occur between batches of the same product,20 potentially due to differences in excipients such as fillers, colourings or coatings. In addition, there is likely a cumulative effect of variability throughout the lifecycle of both generic and reference products as batch sizes are increased, manufacturing sites are added or changed, and additional formulations are produced 12 15. Finally, two generic products may differ even more from one another than they do from the reference product: one generic product might be associated with lower exposure compared with the reference and the second with higher exposure (figure 1), and as variability increases over the reference product’s lifecycle, differences between successive generic products may grow with increasing time between their introduction.…”

“…Neither survey included comparisons between generic products. It is possible, therefore, for switches, particularly from one generic product to another, to result in clinically significant increases or decreases in plasma drug levels, with potential effects on efficacy or safety 12. In a single study that assessed bioequivalence among four generic products with the same reference, using adjusted indirect comparisons, each pair demonstrated bioequivalence based on AUC but exceeded the acceptance range in 2 of 6 comparisons for C max 23.…”

“…or (3) Does any switch (ie, from reference to generic, from generic to reference or from generic to generic) affect patient outcomes? Findings from a recent review by Blier et al of studies of psychotropic medications that addressed these questions are summarised in table 1 12…”

“…Agencies tasked with generic drug approval expect that generic products demonstrating bioequivalence with their reference product will have no clinically important efficacy or safety differences from the reference 9 10. Nonetheless, a substantial proportion of patients and physicians queried in one study thought that generic products may be less safe and effective compared with the reference product,11 reflecting the larger question of whether bioequivalence reliably translates to therapeutic equivalence,12 and more specifically, whether the efficacy and safety of a psychotropic medication will remain consistent through planned or unplanned switches between reference and generic products or between different generic products.…”