Clinical experience has shown considerable potential benefits from long-term continuous medication for chronic or relapsing forms of schizophrenia. These benefits have not always been realised.

To review the research literature in order to understand the problems of long-term medication and use of antipsychotic oral medication and long-acting injections (LAIs), and to place these in an historical context.

Review of literature.

Research showed that the potential success of LAI therapy depends on the quality of the follow-up service.

Following the advent of second-generation oral antipsychotics confidence in the use of LAIs has eroded and that mistakes made in LAI use during the past century may be repeated.

Depot antipsychotics are widely used in clinical practice. Long-acting formulations of second-generation antipsychotics are now being developed and introduced.

To review the pharmacology, pharmacokinetics and adverse effect profiles of currently available antipsychotic long-acting injections (LAIs).

The psychopharmacological properties of first- and second-generation antipsychotic LAIs are reviewed using data available up to October 2008.

First-generation antipsychotic (FGA) LAIs are associated with a high rate of acute and chronic movement disorders. Risperidone LAI is better tolerated in this respect, but is associated with hyperprolactinaemia and weight gain. Olanzapine LAI causes weight gain and other metabolic effects but appears not to be associated with an important incidence of movement disorders.

Dosing of LAIs is complicated by delayed release of drug, changes in plasma levels without change in dose, and by the lack of data establishing clear dose requirements. All LAIs offer the prospect of assured adherence (although patients may still default on treatment) but their use is complicated by adverse effects, complex pharmacokinetics and confusion over dose–response relationships.

Antipsychotic long-acting injections (LAIs) are often used in an attempt to improve medication adherence in people with schizophrenia.

To compare first-generation antipsychotic long-acting injections (FGA–LAIs) with first- and second-generation oral antipsychotics in terms of clinical outcome.

Systematic literature review.

A meta-analysis of randomised controlled trials (RCTs) showed no difference in relapse or tolerability between oral antipsychotics and FGA–LAIs but global improvement was twice as likely with FGA–LAIs. Four prospective observational studies were identified; two studies reported lower discontinuation rates for FGA–LAIs compared with oral medication and two found that outcome was either no different or better with oral antipsychotics. Mirror-image studies consistently showed reduced in-patient days and admissions following a switch from oral antipsychotics to FGA–LAIs.

The results are variable and inconclusive. Some evidence suggests that FGA–LAIs may improve outcome compared with oral antipsychotics. Methodological issues may partly explain the variable results. Selective recruitment in RCTs and lack of randomisation in observational studies are biases against LAIs, whereas regression to the mean in mirror-image studies favours LAIs. In terms of future research, a long-term pragmatic RCT of an FGA–LAI against an oral antipsychotic, in patients with problematic adherence, would be of value.

Second-generation antipsychotics (SGAs) represent an advance in the long-term management of schizophrenia.

To review the available evidence concerning SGA long-acting injections (LAIs).

A systematic review of the literature was conducted using PubMed.

Risperidone long-acting injection was the first licensed SGA–LAI compound and is effective in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. Olanzapine pamoate has recently been approved in Europe. In terms of efficacy, at injection intervals of up to 4 weeks it appears comparable to oral olanzapine, although the potential for ‘post-injection syndrome’ (delirium) calls for additional safety considerations. Paliperidone palmitate is currently under review with the licensing authorities. It also affords the potential advantage of monthly dosing.

More long-term comparisons of SGA–LAIs with oral SGAs as well as with first-generation antipsychotic LAIs are needed. These studies should include cost-effectiveness data.

Data from the USA, Australia and Europe suggest that the proportion of patients with schizophrenia prescribed an antipsychotic long-acting injection (LAI) varies from around a quarter to a third. Use of LAIs has been associated with male gender and younger age.

To characterise the use of LAIs in people with schizophrenia in three clinical settings in the UK.

The study used audit data from quality improvement programmes conducted by the Prescribing Observatory for Mental Health.

Long-acting injections were found to be prescribed for between a quarter and a third of patients, depending on the clinical setting. Flupentixol, risperidone and zuclopenthixol were most commonly prescribed and were combined with an oral antipsychotic in half of cases, frequently constituting high-dose prescribing. The use of LAIs was not consistently associated with age, gender or ethnicity.

Antipsychotic LAIs are commonly prescribed. We did not replicate previous findings with respect to demographic variables associated with their use.

The attitudes of staff and patients have been demonstrated to influence the acceptance of long-acting injections (LAIs) or depot antipsychotics.

To examine the attitudes of patients and staff to LAIs.

A systematic review was carried out. Studies included contained quantitative data for attitudes of patients or staff to LAIs.

Twelve studies published subsequent to the systematic review reported in 2001 were identified. Five studies conveyed an overall positive attitude. The most positive attitudes among patients were seen in those already prescribed an LAI. Positive attitudes of staff correlated closely with the extent of their knowledge of LAIs.

Long-acting injections continue to have an image problem, arguably perpetuated by manufacturers of oral second-generation antipsychotic drugs, and exacerbated by the predominant use of these medications as a ‘last resort’ often for the most stigmatised individuals. The introduction of better-tolerated LAIs and better education of both staff and patients may encourage individuals to re-examine their attitudes.

A patient-centred approach to care, focusing on recovery, demands a reconsideration of how choices are made about treatment, how this affects medication adherence, and the role of long-acting antipsychotics (LAIs) in this process.

To explore the role of the mental health professional (particularly nurses) in helping patients manage their medication, with a specific focus of the use and administration of LAIs.

A pragmatic review of the literature.

Patients (by experience) and mental health professionals (by training and clinical practice) are experts in the care and treatment of psychosis. When patients and clinicians make a joint decision both are more likely to adhere to the treatment plan. In this paper we consider good practice in the administration of LAIs that focuses on where and when they should be given and administration techniques. Skills for talking with patients about their medication that include exchanging information, monitoring the effects of medication and making advance choices about treatment in the event of a crisis are also discussed.

Mental health professionals require a range of competences to help patients manage their medication effectively.

The community treatment order (CTO) is the legal framework by which people in the community are compelled to accept treatment. Both antipsychotic long-acting injections (LAIs) and CTOs are used to address treatment non-adherence.

To investigate the relationship between CTOs and LAI use in patients with schizophrenia.

Prescribing, demographic and CTO data were collected for patients from four community mental health clinics in Melbourne, Australia, in 1998 and 2002.

Against a background of increasing use of oral second-generation antipsychotic (SGA) medication and decreasing use of LAIs, the rates of CTO implementation doubled from 13% to 26% of patients with schizophrenia between 1998 and 2002. Proportionally more patients with a CTO are prescribed LAIs rather than oral SGAs.

The relationship between receiving an LAI and being subject to a CTO is significant, and reflects the consideration given to enhancing adherence in a community mental health setting.

Long-acting injections (LAIs) of antipsychotic drugs were developed over 40 years ago in an attempt to improve the long-term treatment of schizophrenia.

To review existing guidelines concerning antipsychotic use generally, and LAIs in particular, and how patients might be identified as potential candidates for LAI treatment.

Literature review.

Currently several first-generation and one second-generation antipsychotic LAIs are available, with others under development. Although the use of LAIs is widespread around the world, patterns of use vary widely. Important considerations regarding the use of LAIs include the indications for long-term pharmacotherapy in schizophrenia in general, the indications for LAIs, the risks associated with LAIs, the need to update guidelines and the issue of cost.

The use of these injections in first-episode psychosis and treatment-refractory schizophrenia is not currently a focus of recommendations, but should be considered. Long-acting injections remain an underutilised option in many countries despite frequent non-adherence with oral medication and subsequent relapse.