Abstract
A submission for formal licensing of a medicine and its therapeutic indications is largely a decision dictated by financial considerations. The licensing process is costly and so a manufacturer must anticipate generating sufficient profit to cover at least this outlay and more besides. In the modern world of short effective patent length and long-winded regulatory approval, it is inevitable that some useful drugs are never licensed, or more commonly, licensed for only a fraction of their potential indications. Bupropion is a case in point: an effective antidepressant that is licensed in many countries only as an aid to smoking cessation. In this issue, Derek Tracy’s team present a systematic review of bupropion, undoubtedly the most comprehensive ever conducted, and conclude that bupropion is a very effective antidepressant, both alone and as an adjunct, but is without typical antidepressant adverse effects such as weight gain and sexual dysfunction. Long out of patent, bupropion seems destined to remain unlicensed in depression despite its obvious clinical utility.
Bupropion, unusually, is a dopamine reuptake inhibitor which, one assumes, enhances dopaminergic transmission. Dopamine antagonism, on the other hand, is an action of all currently licensed antipsychotics. D2 blockade remains the most likely mode of action for antipsychotics but recent discoveries suggest a much more complex picture, as Kjell Fuxe and others describe in this issue. D2 receptors take many forms, have many functions and are widely but unevenly distributed in the brain. As the authors describe, these qualities lead to complex interactions with glutamate, GABA, serotonin, glycogen synthase kinase-3 and adenosine (via the A2A receptor) systems and signal new research avenues for non-D2 antipsychotic drugs. This is already exemplified by the development of pimavanserin, a 5HT2 inverse agonist and the first antipsychotic without direct dopaminergic effects.
Also in this issue, Matthew Cordiner and colleagues report on outcomes associated with a peculiar practice: that of prescribing both oral and depot antipsychotics at the same time. This phenomenon is completely without evidential support, or indeed logical consistency, but it remains stubbornly prevalent. As the authors of this paper note, its popularity may well be predicated on the efficacy of this peculiar type of polypharmacy: they showed that the practice was seen in around 40% of patients and was associated with lower discontinuation rates than monotherapy. No adverse consequences of polypharmacy were detected.
In a fascinating report, Simon Chu examines the result of forced switching of anticholinergic medication for clozapine patients with hypersalivation. A shortage of hyoscine caused patients to change treatment or stop altogether. Those that switched to pirenzepine or atropine reported an improvement in their excess salivation whereas those receiving no replacement reported no change. Drug shortages may be a good thing, it seems.
This issue also includes four intriguing case reports. Musa Umar and colleagues describe the use of high dose (600 mg) pyridoxine in the successful treatment of widespread and severe tardive dyskinesia. A useful review of the relevant literature accompanies the case report. Swapanjit Sarma and colleagues describe the case of a woman whose clozapine was abruptly stopped because of constipation. Within five days she had become severely psychotic, assaultative and exhibited oculogyric crisis and severe and painful dystonia. Jessica Meisner and colleagues describe a fatality that occurred as a result of the use of hallucinogenic plant alkaloid ibogaine in opiate withdrawal. Finally, Roberto Averna and colleagues report on the successful use of 5 mg daily of aripiprazole in the successful treatment of disruptive mood dysregulation disorder in an 11-year-old boy.