Switching from Brand‐Name to Generic Psychotropic Medications: A Literature Review

Abstract

Generic medications do not undergo the rigorous approval process required of original medications. Their effectiveness and safety is expected to be equal to that of their more expensive counterparts. However, several case reports and studies describe clinical deterioration and decreased tolerability with generic substitution. Pubmed was searched from January 1, 1974 to March 1, 2010. The MeSH term "generic, drugs" was combined with "anticonvulsants," "mood stabilizers," "lithium," "antidepressants," "antipsychotics," "anxiolytics," and "benzodiazepines." Additional articles were obtained by searching the bibliographies of relevant references. Articles in English, French, or Spanish were considered if they discussed clinical equivalence of generic and brand-name medications, generic substitution, or issues about effectiveness, tolerability, compliance, or economics encountered with generics. Clinical deterioration, adverse effects, and changes in pharmacokinetics are described with generic substitution of several anticonvulsants/mood stabilizers (carbamazepine, valproate, lamotrigine, gabapentin, topiramate, lithium), antidepressants (amitriptyline, nortriptyline, desipramine, fluoxetine, paroxetine, citalopram, sertraline, venlafaxine, mirtazapine, bupropion), antipsychotics (risperidone, clozapine), and anxiolytics (clonazepam, alprazolam). Generics do not always lead to the anticipated monetary savings and also raise compliance issues. Although the review is limited by publication bias and heterogeneity of the studies in the literature, we believe there is enough concern to advise generic switching on an individual basis with close monitoring throughout the transition. Health professionals should be aware of the stakes around generic substitution especially when health economics promote universal use of generics.

Metabolism of Bupropion by Carbonyl Reductases in Liver and Intestine

“…Currently, over 11 million prescriptions annually of bupropion have been issued to more than 40 million patients (Reese et al, 2008;Desmarais et al, 2011). Bupropion hydrochloride (HCl) extended release (ER) tablets, which is marketed as Wellbutrin XL by Biovail, has many generic manufacturers, such as Teva Pharmaceutical Industries/Impax Laboratories, Mylan, Actavis, and Par Pharmaceuticals, which use a current bioequivalence (BE) standard based on C max and AUC.…”

Bioequivalence and therapeutic equivalence of psychotropic drugs

“…Similar reports have been filed with regards to substituting the branded olanzapine and risperidone with generic formulations [18][19][20]. A review of literature regarding the therapeutic differences between the reference psychotropic drugs and their generic counterparts was published in the prestigious journal ''CNS Neuroscience and Therapeutics'' [21]. The paper summarized all cases published in PubMed in 1974-2010.…”

“…Przegląd piśmiennictwa dotyczącego różnic terapeutycznych pomiędzy psychotropowymi lekami referencyjnymi i ich odpowiednikami opublikowano w 2011 roku w prestiżo-wym czasopiśmie ,,CNS Neuroscience and Therapeutics'' [21]. …”

A health economic perspective on generic therapeutic substitution

“…A systematic review of studies comparing adverse events in antiepileptic drugs found no difference in the odds of uncontrolled seizures for patients on generics relative to patients on branded medications when randomised controlled trials were considered, but found increasing drug and service utilisation in patients on generics when observational studies were assessed 13. In a study of neurology, psychiatry and transplantation medicine, there were significant differences between generics and branded therapies,14 while in a literature review of psychotropics, the authors cautioned that there was sufficient evidence to warrant switching to generics on an individual basis with close monitoring during the transition period 15. In drugs with a narrow therapeutic index—such as tacrolimus and ciclosporin in transplant medicine—it has been advocated that small changes in exposure could result in increased toxicity or reduced immunosuppression that requires careful monitoring and supervision by a transplant specialist 16.…”