Is generic lamotrigine as good
Summary: my conclusion here could change quickly; but as of October 2008, I'm not too worried. However, some evidence suggests that generic lamotrigine is not quite equivalent. And my apologies: somewhere I wrote it would get cheap soon, but apparently the current generic manufacturer has exclusive rights all the way through 2009. Cheaper after that.
A series of articles have been published on this issue now. All these data must be interpreteted against a background of concern, amongst both patients and doctors, that generics will not be as effective as the original trade-name medicationHaskins (no one seems to expect that the generic will be more effective). In other words, there is a degree of expectation that the generic won’t work. That means suggestive cases -- e.g. when seizures occur after a switch to generic lamotrigine -- are more likely to be remembered and reported than cases in which the generic worked as well as the trade-name version.
One of the first major articles on this
issue may include such a bias.Makus
The authors conducted a survey
looking for doctors who’d had patients do poorly on generic lamotrigine. Five
percent of the doctors who responded (which was only 24% of those who received
the survey) reported problems with the generic. In other words, 95% of those who
responded had not seen a problem. Overall, of 544 doctors to whom the survey was sent, 6 physicians provided data on 8
patients who experienced adverse reactions on a brand-to-generic switch.
However, interestingly, seizure control was regained in all but 1 case on a
switch back to the branded drug.
One of the ways investigators have tried to compensate for observation bias is to compare rates of return to trade name switching amongst different medications. Another Canadian teamAndermann found that switch-back-to-generic rates were 20% for clobazam (akin to clonazepam/Klonopin); 20% for valproate/Depakene (which is akin but not identical to the divalproex/Depakote pair); and 13% for lamotrigine/lithium. By contrast, another study found higher rates of switch back overall: 28% for lamotrigine, versus between 21% to 44% for other anti-seizure medications.LeLorier.1 One could interpret these data as suggesting that lamotrigine is no worse than other medications in terms of the generic working less well than the tradename version. If anything, it might be a little better than average.
However, another way to avoid
observational bias would simply be to look at actual blood levels of medications
before and after a switch to generic. Such a study was just published two months
ago (August 2008), and indeed showed that in 21 out of 26 cases, blood levels
were lower on the generic compound.Berg
Finally, after all that we come to a frequently referenced article..LeLorier.2 This is one of several articles published by this team, using the same statistical method. Their focus in this article was on the health care system costs of switching to generic. Interestingly, by their analysis, the money saved on generic lamotrigine was eclipsed in the slightly increased cost of care overall.
How to interpret all this? Here's mine. Whereas neurologists use lamotrigine to control seizures, psychiatrists use it to control mood stability. For mood, lamotrigine seems to exhibit a "dose -response relationship": in other words, the higher the dose, the better the symptom control. Whereas the difference between 50 mg and 200 can be substantial, the difference between 250 mg and 300 is often quite subtle. So if there really is a lower blood level with the generic, the consequences in terms of symptom control may not be very profound -- in psychiatry. In neurology, that could be quite different, because a slight difference in blood level could mean the difference between not having seizures, and having one -- where a single seizure can have terrible consequences. In other words, control of epilepsy may be much more sensitive to the absolute drug level than control of mood symptoms. That's good news for psychiatry. Mind you, this is my speculation.
Moreover, if a patient has started on a generic from the beginning, and gets good symptom control, the whole issue is moot. So it won't be long, if the generic continues to work as well as it has so far for me, before this whole issue is less concerning. Nevertheless, based on the 2008 article by Berg and colleagues above, I’ll be figuring that my patient might be losing a bit of her prior blood level when switching to generic lamotrigine. Occasionally that might even mean I will move the dose up a little when I switch, although I have not done that yet.