Antipsychotic Long-acting Injections
Martin Livingston
Edited by Peter Haddad, Tim Lambert, John Lauriello Oxford University Press, 2010, £32.95, pb, 282 pp. ISBN: 9780199586042

This book could quite easily be subtitled ‘back to basics’, detailing as it does how to use effectively a form of treatment that many psychiatrists and members of multidisciplinary teams might consider outmoded. What has caused us to reappraise the value of delivering antipsychotic medication by a long-acting parenteral route? The past decade has been a sobering period for psychopharmacology. The STAR*D studies have revealed how ineffective our current antidepressants are, with only 34% of a representative clinical population recovering with the first-choice drug, in this case citalopram. Treatment of the psychoses has been bedevilled by what has turned out to be spurious claims of superiority of the newer drugs. There was a bullish start to the new antipsychotic era in the 1990s, with the emergence of new compounds labelled atypical on the grounds they were much better tolerated, specifically with regard to movement disorder side-effects. The cause was trumpeted by the drug industry and taken up by a grateful psychiatry community eager to have new and better medications for schizophrenia and the other psychoses. Carefully carried out meta-analyses have since brought us back down to earth. Superiority in avoiding movement disorder may well be a function of trials which involved comparisons with high-dose haloperidol. The newer drugs are not without risks, such as advancing the onset of cardiac disease and diabetes in a patient population already disabled by their mental illness. Meta-analyses have also revealed that any claims of superiority in terms of efficacy of the newer antipsychotics against positive symptoms, negative symptoms and cognitive functioning appear difficult to justify, although there may be minor differences between the drugs in terms of efficacy in these symptom areas.

This is the background which has obliged us to return to some fundamental issues in drug treatment of patients with mental disorders. How many of our patients are actually taking the drugs we prescribe for them? The CATIE study, quoted in the preface to the book, showed that by the 18-month stage in this well-run US treatment trial, 74% of patients were not taking their antipsychotic medication; the study also failed to show superiority of four newer antipsychotics v. an older drug, perphenazine. Attention now focuses on how to improve treatment adherence, especially in the psychoses, and there is an upsurge of interest in the role of long-acting injections. The advantage of this approach to treatment delivery is of course that covert non-adherence is eliminated when patients receive their medication by long-acting injection.

This multi-author book is therefore timely and should go some way towards eliminating the prejudice against using long-acting injections which has been evident especially in the USA. The authors even go so far as to advocate the possibility of using long-acting injections in first-onset cases, on the basis that prevention of relapse is a key factor in improving outcome. The book contains information about initiating treatment with these injections.

There are several technologies used in formulating the means whereby the sustained release of the injected antipsychotic drug is achieved. There are three options: oil-based in ‘conventional’ long-acting antipsychotic injections such as flupenthixol decanoate; microsphere-based as in risperidone; and crystal-based in the latest compound, paliperidone pamoate. The differing pharmacokinetic characteristics of these delivery vehicles determine the time taken for the drug to reach steady state. Knowledge of this parameter provides invaluable guidance to the clinician on when to withdraw any oral antipsychotic supplements. All too often treatment is abandoned prematurely due to ignorance of this sort of information in clinical practice.

There are chapters in the book on adherence, adverse effects, an international perspective on use, and guidance on how to improve the uptake of long-acting medication in psychosis. There is discussion of the rather neglected area of injection technique, a topic which often seems remote to doctors but not so for patients, who frequently complain of pain and discomfort at the injection site and this is a common reason for requesting discontinuation. A chapter also discusses how to encourage greater uptake of long-acting injectable preparations by patients - not always the easiest sell for the psychiatrist or community psychiatric nurse. As the cover states, the emphasis is on schizophrenia but the use of long-acting antipsychotics in bipolar disorder is also discussed. Prescribing long-acting injections in this indication is bound to increase as trials of antipsychotics in this disorder multiply. Pharmaceutical companies in this age of financial stringency are obliged to look into every possible application of the drugs in their ‘back list’. A fortnightly or even longer antipsychotic injection may be beneficial especially to patients with multiple manic presentations and a track record of non-adherence.

The book is not a particularly easy read. Some of the chapters contain over-detailed, dense with data analyses of the key papers. Summarising tables and figures in graph form would facilitate assimilation of the information by the reader and permit a more readable, less daunting text. The importance of this book, as the authors point out, is that the use of long-acting injections, especially of the first-generation drugs, will not be too familiar to younger psychiatrists and pharmacists as well as to psychiatric nurses. The messages contained in this worthy book should also be of interest to pharmaceutical representatives, lest hype replaces more thoughtful consideration of the merits of new antipsychotic compounds. There is still a place in modern psychiatric practice for long-acting formulations where adherence is an issue. There is no harm therefore in reminding ourselves that a fundamental principle of medical treatment is to ensure, where possible, that the patient takes the treatment. This book should do much to allow the sustained absorption of that very basic clinical message.