Abstract
Brexpiprazole is a dopamine, D2 partial agonist newly licensed in the United States. Like its forerunner aripiprazole, brexpiprazole attaches to postsynaptic D2 receptors, blocking the effect of endogenous dopamine but at the same time stimulating the receptors. As Saibal Das and colleagues explain in this issue, the extent of this intrinsic (agonist) activity determines the efficacy and tolerability of D2 partial agonists. With too much intrinsic activity (such as the now abandoned bifeprunox), efficacy is impaired, and nausea and insomnia are common. With too little, D2 antagonist activity predominates, and hyperprolactinaemia and extrapyramidal symptoms are the result. Brexpiprazole has somewhat less intrinsic activity than aripiprazole but does not have actions of pure antagonists. In trials, brexpiprazole showed efficacy in both schizophrenia and depression. It also seems to be well tolerated, with few reports of insomnia or nausea and only a slight increase in the incidence of akathisia in one study. Early signs are that brexpiprazole is at least as well tolerated as placebo, a first for an ‘antipsychotic’ drug and perhaps the beginning of a new area in the treatment of schizophrenia.
In another report in this issue, Matthew Cordiner and coworkers examine outcomes with old and new long-acting antipsychotics. Their findings are rather surprising: both risperidone and zuclopenthixol depots out-performed paliperidone palmitate depot, and by some distance. No obvious explanations present themselves, but the fact that prescribers had little or no experience of using paliperidone at the time of the study is likely to have had some negative influence on outcomes. Iloperidone was also once developed as a long-acting injection but never marketed as such. It sees limited use in its oral form in countries where it is licensed. Dawn Ionescu and colleagues describe their small crossover trial of iloperidone for anger and irritability in patients with depression. No effect was seen, in contrast with iloperidone’s known antihostility effects in psychotic disorders.
Two papers in this issue address aspects of the use of clozapine. Memduha Aydin and coworkers describe three cases in which clozapine was continued despite low neutrophil counts. All three were helped by low-dose lithium, which increased white cell counts in each case. These observations accord with previous reports that lithium can produce useful increases in white cell counts in people on clozapine who have neutropenic episodes coincidental to clozapine treatment. Robert Lozano and colleagues report on their preliminary finding of an increased prevalence of selective immunoglobulin M deficiency in people receiving clozapine. Such deficiency often leads to infection and atopy, conditions frequently seen in people receiving clozapine.
Two further reports complete this issue, each relating to the treatment of older patients. From Denmark, Pernille Jul Østergaard and fellow researchers outline their findings of analgesic use in old-age psychiatry. More than half of the patients studied were taking analgesics on admission. By discharge, this number had not changed significantly but fewer than a quarter had any clear record as to why the analgesics had been prescribed. Many patients were taking NSAIDs or opiates, both groups of drugs having important adverse effects in older people. Lastly, Daniel Kamp and others describe a case of hypothermia resulting from the use of risperidone and pipamperone. This is not the first description of this adverse effect but it certainly adds to the theory that hypothermia results from 5HT2 receptor antagonism. It is worth reflecting on the fact that without this adverse effect being recognized, the world today would be a very different place: long before chlorpromazine was known to be antipsychotic it was used to induce hypothermia and used in surgical procedures specifically for this purpose.