Abstract
The editorial [1] and lead paper [2] in the December 2009 issue of this Journal both rightly champion lithium as an effective mood stabilizer; indeed, perhaps the only agent truly warranting that term based on level 1 (systematic review of all clinical trials) evidence. However, both articles note lithium lacks a ‘commercial champion’ [2] and is under-prescribed as ‘agents that had stronger commercial backing soon eclipsed it’ [1]. Mahli, Adams and Berk describe ways in which sponsored clinical trials can bias against lithium in favour of sponsored medications [2]. Mahli and Gershon note that even though lithium has ‘endured competition’ from antidepressants and anticonvulsants it is currently ‘the atypical antipsychotics that form the charge, with their eager migration into the lucrative mood stabilizer arena’ [1].
Beyond these articles’ excellent review of the role of lithium in pharmacotherapy, they raise the wider issue of trust in the pharmacotherapy evidence base in the medical literature. This has become a highly contentious topic in recent years [3,4]. For example Turner et al. found that for 74 Food and drug administration (FDA) registered studies of 12 antidepressants, publication and other bias led the medical literature to present 48 of the 51 (94%) published trials as positive for the antidepressants in question, whilst the FDA analysis including unpublished trials and accounting for other bias concluded only 38 of the 74 (51%) trials were positive [5].
Internal industry documents have come to light in litigation against the pharmaceutical industry that reveal the extent to which industry champions newly patented drugs in the medical literature, CME and advertising. This is unsurprising from a commercial perspective. In psychiatry the atypical antipsychotics as a class currently have longest patent life. From a commercial perspective they are medications in search of illnesses. Internal industry documents do indeed confirm the eagerness with which some companies are trying to position their atypical antipsychotics in the ‘lucrative mood stabilizer arena’. For example, internal documents from Eli-Lilly in 1997 concerning its antipsychotic olanzapine (Zyprexa), included a slide entitled ‘Bipolar vision of product evolution’ that stated: ‘To be a leader in the bipolar market, Zyprexa will need to be viewed as a true mood stabilizer’ (italics in the original) and described needing to have efficacy in mania, depression and maintenance phases as well as off-label promotion for sub-syndromal ‘complicated mood’. This was despite the documents also indicating the company did not have the data to support this aim [6].
It is thus vital for a trustworthy medical literature that there be transparency and greater separation of medication trials, journals and Continuing Medical Education (CME) from industry sponsorship. Medications need to be ‘championed’ on a true evidence base, not on marketing based information. In the meantime commercial realities mean that the medical profession itself will have to strive hard to champion off-patent medications that warrant a reminder to prescribers. Therefore thanks are due to Mahli et al. for championing an old, off-patent, yet beneficial medication.