Drs. Cohen and Loonen have written a thoughtful and timely paper of high clinical relevance on the clinical challenges of switching between immediate and extended release drugs . In this context, they also touch upon similar issues regarding the switch from original to generic drugs, their discussion of which I will attempt to expand in the following.
As many original branded drugs have lost patent protection, clinicians worldwide are under exceeding pressure by healthcare payers to switch patients to less expensive, purportedly bioequivalent, generics. It is widely taken for granted that generic medications which fulfill bioequivalence criteria to original products as stipulated by both the European Medical Agency and the Food and Drug Administration , are basically interchangeable with the original drugs in clinical practice. Drs. Cohen and Loonen point to some of the difficulties of doing this, using mainly the example of epilepsy. In addition to their arguments, it should also be noted that the American Epilepsy Society recommends that a generic drug should not be substituted for a brand name antiepileptic without the approval of the patient and the prescribing physician .
When extending these considerations to the field of psychiatry, clinicians have long realized that switching between original and generic compounds may lead to both efficacy and tolerability problems in individual patients. This has been documented for antipsychotics such as clozapine , as well as for antidepressants/anxiolytics like citalopram . Pharmacokinetic studies of clozapine  and venlafaxine  have demonstrated considerable plasma level differences between original and generic products, thus providing support for the clinical findings.
Regarding pharmacokinetics, one needs to realize that what is necessary to obtain regulatory approval for a generic antipsychotic or antidepressant usually consists of comparable bioavailability data from 30 to 40 healthy volunteers . Clearly, this does not allow to account for potential influences of disease stage, ethnicity, age, or gender. It is also a well-known fact that even within homogeneous groups of patients, large interindividual efficacy and safety/tolerability variations are apparent. Next to that, although generic drugs have to contain the same active ingredients as their original counterparts, different inactive expedients may influence dissolution and time of onset of action.
The authors also correctly underscore switching problems in relation to adherence behaviour. As compliance is a challenge in managing chronically ill patients over the long term, the influence of patient preferences and intake habits must not be underestimated. Switching patients from branded drugs, they have gotten used to, to generics or even from one generic to another can potentially undermine the delicate attitude balance toward a specific medication. Moreover, a nocebo-effect  can complicate the treatment process, as a consequence of which patients may experience tolerability problems that again jeopardize compliance behavior. As adherence problems represent a key risk factor for relapse, which leads to substantial suffering and healthcare cost, clinicians need to carefully balance this risk against the savings on drug costs when switching patients to generics.
The arguments briefly reviewed above should not be misunderstood as an attempt to discourage the widespread use of generic psychotropic medications. Yet, they underscore the importance to judiciously reflect on benefit-risk ratios, especially when considering a switch from original to generic drugs or from one generic to another in patients who are chronically ill and on stable medication regimens. Unfortunately, there is a dearth of sound clinical evidence to guide clinicians in this process, but the necessity of providing relevant information to patients when considering a switch, as well as intensified clinical observation along the switching process makes much intuitive sense even in the absence of controlled trials.