# 69 - Antipsychotic depotslong acting injections

# Antipsychotic depots/long-acting injections

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The Maudsley® Prescribing Guidelines in Psychiatry
CHAPTER 1
Antipsychotic depots/long-­acting injections
Long-­acting injectable preparations of antipsychotic medication are commonly prescribed in clinical practice, especially in the UK, Australasia and the EU. Real-­world, 
observational studies of patients with schizophrenia have confirmed that continued 
treatment with such medication is associated with fewer relapses and readmissions to 
hospital compared with oral antipsychotic treatment,1–5 although there are confounding factors in such studies, such as indication bias.
A 2020 Cochrane systematic review of RCTs comparing antipsychotic maintenance 
treatment with placebo for people with schizophrenia found that LAI antipsychotic 
medications (in particular, LAI haloperidol and LAI fluphenazine) were more effective 
than oral antipsychotic medications.6 However, the authors noted that only head-­to-­
head comparisons of LAI and oral antipsychotic medications can determine whether 
the former are more effective. The findings of such RCTs have generally failed to show 
the superiority of LAI antipsychotic medications that is apparent in real-­world studies,7–9 and it has been postulated that this is partly related to study design and methodology issues.2 Specifically, double-­blind RCTs are generally relatively short term and the 
study samples will tend to be biased towards patients with rather less severe illness, 
fewer comorbid conditions and better adherence to medication.10,11 Nevertheless, a 
2021 systematic review and meta-­analysis of RCTs, observational cohort studies and 
pre–post (mirror-­image) studies comparing LAIs with oral antipsychotic medications 
found that LAIs were associated with a lower risk of hospitalisation or relapse, across 
all the study designs.12 There are also hints from meta-­analyses of relevant RCTs that 
some adverse effects are less frequent with LAIs than with their oral counterparts.8,13
While it is generally accepted that treatment with LAI antipsychotic medication reduces 
the risk of relapse, the findings of studies of all designs suggest that treatment with LAIs 
does not confer complete protection against relapse.14 In clinical practice, relapse is strongly 
linked to delayed or missed doses of LAIs. Two UK studies showed that patients receiving 
10 doses a year (or fewer) of monthly paliperidone palmitate were at a substantially higher 
risk of relapse than those receiving 11 or 12 doses.15,16 Very long-­acting injections given 
consistently on time may offer better protection against relapse.17–19
LAI antipsychotic medication is recommended for all patients, but especially where a 
patient has expressed a preference for such a formulation because of its convenience or 
where avoidance of covert non-­adherence is considered a clinical priority.10,20,21 While 
LAI medication does not ensure adherence, it does ensure clinical awareness of adherence, unlike the use of oral medication. Thus, failure to adhere, which may be a sign of 
relapse or a potential cause, will be signalled by delayed attendance for, or refusal of, an 
injection, allowing the clinical team to intervene promptly. Another advantage for LAI 
antipsychotic medication is that its use may help clarify whether an unsatisfactory therapeutic response to antipsychotic medication is because of adherence problems or treatment resistance. Patients with an apparently refractory illness may simply be 
non-­adherent to their oral medication, sometimes completely so.22 Further, an LAI 
antipsychotic regimen provides the opportunity for regular scrutiny of a patient’s mental state and adverse effects.23
The proportion of patients with schizophrenia prescribed LAI antipsychotic medications varies between and across countries, suggesting that the use of such medication is influenced by factors beyond the extent of poor adherence. Greater