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

Abstract

Switches between branded (reference) medications and the corresponding generic medications or between two different corresponding generic medications occur commonly during the treatment of central nervous system disorders. Prescribing a generic product in place of a reference product can reduce patient and pharmacy costs. But there can be implications. Planned or unplanned switches from one product to another during ongoing treatment may introduce variability in drug exposure which could in turn compromise efficacy and/or tolerability. Studies comparing the initiation of reference versus generic products do not provide clear evidence of the superiority of reference or generic products generally, whereas several studies examining a switch between reference and generic products suggest that reductions in efficacy or medication adherence and persistence may be associated with generic substitution. Clinicians should work with patients to facilitate a consistent supply of reference or generic drug product that provides stable exposure to avoid clinical deterioration or poor tolerability.

Decrease in Antidepressant Efficacy After Change in Generic Formulation

“…Instead most BE studies are performed on a small number (12–36) of young, healthy volunteers who are predominantly male and White. These research participants are not representative of the patients who will eventually take the medication 14 . Moreover, current regulations do not require BE studies comparing different generic versions, so variability in the dose of the active pharmaceutical ingredient (API) can be greater between these formulations than between each generic and the brand-name drug 11 …”

“…These research participants are not representative of the patients who will eventually take the medication. 14 Moreover, current regulations do not require BE studies comparing different generic versions, so variability in the dose of the active pharmaceutical ingredient (API) can be greater between these formulations than between each generic and the brand-name drug. 11 In addition, active ingredients make up a very small proportion of what is contained in most medications.…”

“…Increasing batch sizes or changes in manufacturing sites can occasionally introduce variability in the amount of the API, despite manufacturing requirements 3 . This variability can increase over the lifecycle of a medication creating further disparities in efficacy between branded and generic versions 14 …”

“…3 This variability can increase over the lifecycle of a medication creating further disparities in efficacy between branded and generic versions. 14 In some US states and in many parts of the world, pharmacies can change generic formulations of a particular drug at any time and without prior notification to patients or their prescribers. 20 Clinicians are usually unaware when these substitutions occur and may not take the changes into account when determining a patient's response to a specific antidepressant medication.…”

Understanding authorized generics—A review of the published clinical data

“…The PK for these 2 hypothetical generics would result in very different drug exposures. 16 Results from one review that included antiepileptics, antipsychotics, antidepressants, benzodiazepines and psychostimulants concluded that changes in PK resulting from a switch from a branded to a generic psychotropic medication are generally unlikely, but possible in some patients. It was also noted that switches among generics may result in PK changes exceeding ±20 % in instances where each generic differs from the reference drug in opposing directions.…”