CPD CONTINUING
PROFESSIONAL
DEVELOPMENT
Reviewing depot injection efficacy
in the treatment of schizophrenia
NS839 Jones A, Jones M (2016) Reviewing depot injection efficacy in the treatment of schizophrenia.
Nursing Standard. 30, 33, 50-59. Date of submission: April 11 2015; date of acceptance: January 14 2016.
Abstract
Schizophrenia is a severe and enduring mental health disorder. Treatment
includes antipsychotic medication and psychological interventions.
Medication can be administered as a depot injection; these treatments
reduce the risk of relapse in some people with schizophrenia who have
difficulties adhering to oral medication regimens. This article outlines the
types of depot and medications that are available for the treatment of
schizophrenia, and discusses the evidence base supporting their efficacy.
The role of antipsychotic medication as part of a treatment plan should be
reinforced by enabling patients to make an informed choice about which
medication best supports their health and wellbeing.
Authors
Adrian Jones Clinical academic lead, Betsi Cadwaladr University Health
Board, Mold, North Wales.
Martin Jones Associate professor, associate dean research and director,
Department of Rural Health, University of South Australia, Whyalla,
Australia.
Correspondence to: Adrian.Jones3@wales.nhs.uk
Keywords
adherence, antipsychotic medication, antipsychotics, depot,
depot injection, long-acting medication, medicines management, mental
health, nurse prescriber, schizophrenia
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50  april 13 :: vol 30 no 33 :: 2016 NURSING STANDARD
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Aims and intended learning outcomes
The aim of this article is to raise awareness
of the types of antipsychotic depot and
medication available for the treatment of
schizophrenia. After reading this article and
completing the time out activities you should
be able to:
 Describe the mechanism of action of
antipsychotic medication for the treatment
of schizophrenia.
 List the types of depot injection and
medication licensed for the treatment of
schizophrenia.
 Critically appraise the evidence base
supporting the use of depot injection in the
treatment of schizophrenia.
 Discuss the importance of patient choice in
medicines management.
 Discuss the importance of information
exchange, side effects monitoring and
patient engagement.
Introduction
Schizophrenia is a severe mental health
disorder that affects around seven to eight
individuals per 1,000 over their lifetime
(Saha et al 2005). Schizophrenia is one of a
group of disorders that fall into the category
of psychosis. It is a disorder in which the person
has positive symptoms such as hallucinations
or delusions, negative symptoms such as
social withdrawal and emotional blunting, or
both (National Institute for Health and Care
Excellence (NICE) 2014).
The disorder can lead to problems in
psychosocial functioning, which can affect the
family and carer burden (Naber et al 2015).
Antipsychotic medication is the mainstay of
treatment for patients with schizophrenia,
alongside social and psychological techniques
used to manage the disorder (NICE 2014).
12/04/2016 09:41
 This article provides a review of depot
antipsychotic medication for use by nurse
prescribers and nurses who support people who
are prescribed antipsychotic medication.
A framework that can be used to support
patients to make an informed choice about
which medication best supports their health and
wellbeing is also discussed. Other social and
psychological treatments are important, but it is
not within the scope of this article to discuss these.
Antipsychotic medication
For patients who present with a first episode
of psychosis or require long-term maintenance
therapy, administration of antipsychotic
medication alongside the delivery of
psychological interventions is the recommended
treatment option (NICE 2014). Depot
injections are widely used to treat the symptoms
of schizophrenia. Non-adherence to medication
regimens is a major challenge in the treatment
of schizophrenia (Brissos et al 2014).
First generation antipsychotic drugs
antagonise or block dopamine D2 receptors in
the four main dopaminergic pathways in the
brain (Stahl 2013) (Box 1, Figure 1). Blocking
dopamine D2 receptors in the mesolimbic
pathway produces the desired effect on the
positive symptoms of schizophrenia, but
blockade of the other three dopaminergic
pathways (Box 1) has the potential to lead
to side effects. For example, blockade of
D2 receptors in the nigrostriatal pathway
can cause extrapyramidal side effects such
as pseudoparkinsonism (Chadwick and
Bressington 2009).
Second generation antipsychotic drugs, such
as risperidone, exert their effect by blocking
D2 receptors, but they also have effects on
other receptors such as serotonin receptors
(5-HT2A) (British National Formulary (BNF)
2015). Stahl (2013) provided an example of
how the serotonergic effect of a particular drug
is connected to the moderation of dopamine
release in the mesocortical pathway, where
dopamine should be released thus improving the
cognitive symptoms of schizophrenia. Second
generation antipsychotic medication has an
effect on a range of receptors and offers a distinct
clinical and side-effect profile (BNF 2015).
Complete time out activity 1
Oral medication versus depot injection
There is a range of first and second generation
oral medication and depot injections that
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can be used to treat the symptoms of
schizophrenia. The efficacy and effectiveness
of all types of antipsychotic medication has
been debated following publication of the Cost
Utility of the Latest Antipsychotic Drugs in
Schizophrenia Study (CUtLASS) in the UK
(Jones et al 2006, Lewis et al 2006) and the
Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) study in the United
States (US) (Lieberman et al 2005).
BOX 1
Dopaminergic pathways in schizophrenia
Nigrostriatal pathway (projects from the substantia nigra to the basal
ganglia): dopamine blockade results in various movement disorders collectively
called extrapyramidal side effects. In tardive dyskinesia, for example, D2
receptors are upregulated (their numbers increase) to overcome chronic
blockade of the receptors.
Mesolimbic pathway (projects from the midbrain ventral tegmental area
to the nucleus accumbens): psychosis results from excessive dopamine
transmission in the mesolimbic pathway. Dopamine receptor blockade leads to
control of positive symptoms.
Tuberoinfundibular pathway (projects from the hypothalamus to the anterior
pituitary gland): blockade of dopamine receptors in the tuberoinfundibular
pathway leads to hyperprolactinaemia caused by increased release of prolactin,
resulting in milk production, breast tissue development and sexual dysfunction.
Mesocortical pathway (projects from the midbrain ventral tegmental area to
the prefrontal cortex): dopamine blockade exacerbates low concentrations of
dopamine in the mesocortical pathway in patients with schizophrenia, leading
to cognitive impairment and negative symptoms.
(Adapted from Gray et al 2009a, Stahl 2013)
FIGURE 1
Brain and spinal cord showing pathways involved in schizophrenia
Basal ganglia Corpus callosum
Mesocortical Thalamus
pathway
Nigrostriatal
pathway
Frontal
cortex
Nucleus
accumbens
Hypothalamus
Cerebellum
Tuberoinfundibular
Substantia nigra
pathway
Mesolimbic Ventral tegmental area
pathway
PETER LAMB
Spinal cord
 
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 CPD mental health
The CUtLASS comprised two pragmatic
randomised controlled trials of effectiveness
and cost utility. The first trial compared
first generation (typical) antipsychotics with
second generation (atypical) antipsychotics
(Jones et al 2006). The second trial compared
clozapine, a second generation antipsychotic,
with other second generation antipsychotics
(Lewis et al 2006). Jones et al (2006) reported
no disadvantage in quality of life scores or
symptoms after one year of treatment in patients
who received a first generation antipsychotic,
such as sulpiride and trifluoperazine, compared
with those receiving second generation
antipsychotics, such as olanzapine. In addition,
trial participants did not express a clear
preference for either class of treatment, first
generation or second generation.
The CUtLASS 2 trial was designed to examine
the effect of clozapine on quality of life and
symptoms in patients who showed a suboptimal
response to more than two antipsychotics (Lewis
et al 2006). In effect, this trial was looking at
patients who had a form of schizophrenia that
was resistant to treatment. The comparator drug
was another second generation antipsychotic,
such as risperidone, olanzapine or quetiapine.
The results showed no difference in quality of
life between the treatment groups, but there
was improved symptom control in patients
treated with clozapine compared with patients
who received a different second generation
antipsychotic. Patients in the clozapine treatment
arm of the study also experienced fewer
extrapyramidal side effects (Lewis et al 2006).
The CATIE trial examined the relative
effectiveness of a range of second generation oral
antipsychotics and used rate of discontinuation of
1 Depot injection antipsychotic treatment as the primary outcome
for the treatment of measure of effectiveness (Lieberman et al 2005).
schizophrenia has several A first generation antipsychotic, perphenazine,
potential side effects. was compared with second generation
Read the information in antipsychotics such as olanzapine, quetiapine
Box 1 and examine the and risperidone. The results showed that, over
dopaminergic pathways 18 months, 74% of patients discontinued their
in Figure 1. Think of a treatment from the start of the trial. Overall,
patient medication plan olanzapine had the lowest discontinuation rate
you are prescribing at 64% although patients had significant side
and write down the effects such as weight gain. Perphenazine showed
mechanism of action of similar efficacy compared with quetiapine,
the drugs you plan to use risperidone and ziprasidone, second generation
and their potential side antipsychotics included in the trial (Lieberman
effects. Check the side et al 2005).
effects by looking up the Apart from the consideration of clozapine for
particular depot injection the treatment of patients who fail to respond
in the BNF. to antipsychotics, the CATIE and CUtLASS
trials suggested that first generation
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antipsychotics remain a viable treatment
option for people with schizophrenia in terms
of efficacy and quality of life, provided they
are prescribed appropriately (Lewis and
Lieberman 2008).
The effects of oral antipsychotics with
depot injections have been compared in a
number of systematic reviews and critical
appraisals. Side effect profiles were found to
be substantially different in a comparison of
15 antipsychotics, including first and second
generation, but differences in efficacy, although
robust, were small in a meta-analysis of 212
eligible trials (Leucht et al 2013). This led the
authors to challenge the simple classification
of antipsychotics as either first generation or
second generation, and to conclude that the
choice of antipsychotics should be adapted to
the needs of the patient.
Depot injection conferred significant
benefits in reducing relapse rates compared
with oral formulations in another systematic
review (Leucht et al 2011). Similarly, Castillo
and Stroup (2015) concluded that there was
little difference in the effectiveness between
the various depot injection available but
identified, from the clinician’s perspective,
the factors of patient choice, baseline health
factors and consideration of the particular side
effect profiles of the individual formulations.
Depot injection should be considered for
patients who have difficulty adhering to oral
medication regimens (Castillo and Stroup
2015). NICE (2014) recommended that depot
injection should be offered ‘where avoiding
covert non-adherence (either intentional or
unintentional) to antipsychotic medication is
a clinical priority within the treatment plan’
or when a preference is expressed by the
patient for this type of treatment after an
acute episode.
Movement-related side effects
If patients are to be prescribed depot
antipsychotics as the treatment of choice for
schizophrenia, nurses should ensure that they
are able to identify movement-related side
effects, such as dystonia and akathisia, as well as
long-term side effects, such as tardive dyskinesia.
Examples of rating scales to assess these
movement disorders are provided in Table 1.
The development of metabolic disorders
has been associated with the use of second
generation antipsychotics, although the
causal effect is not clear (De Hert et al 2012).
Metabolic disorders include weight gain,
and impaired glucose and lipid regulation
12/04/2016 09:41
 (De Hert et al 2012). Recognition of these
disorders, and their treatment, require training
and a biological understanding of what causes
these side effects. Nurse prescribers may wish
to consider using tools such as the Health
Improvement Profile (Hardy et al 2015) to
measure the presence of these conditions at
baseline and during ongoing monitoring.
Patient choice
Nurse prescribers, and all mental health
nurses who support patients in taking their
medication, should advocate in relation to
patient choice. Improvements are required
in supporting patient choice. Morrison et al
(2015) found that Australian case managers
had insufficient knowledge about the side
effects of antipsychotic medication and used
persuasion to address medication adherence.
Prescribing decisions should be informed
by patient choice, and several factors should
be evaluated before a decision can be made,
for example, previous response to treatment
including side effects, what symptoms the
patient is experiencing and the presence of any
comorbidities (NICE 2014). Two important
choices for the patient relate to which body site
they would like the depot injection administered
and whether the injection is administered at
home or in the clinic setting (NICE 2014).
Depot injection has several advantages and
disadvantages that should be discussed with
patients (Box 2).
Oral formulations may not be appropriate
for patients who forget to take their medication
regularly, for patients who have difficulty
swallowing, or for those who dislike the taste
of the medication. Other patients may prefer
to have a depot injection because it avoids the
daily routine of taking medication, or they
may prefer to have less contact with mental
health services.
When depot injections were first introduced in
the UK, psychiatrists were sceptical about their
ability to maintain a treatment effect (Johnson
2009). Psychiatrists viewed depot injection
as ‘old fashioned’ and ‘stigmatising’, which
influenced their prescribing decisions (Patel et
al 2003). However, patients were positive about
being prescribed depot injections (Waddell and
Taylor 2009).
Patients value the opportunity to discuss
their medication with a nurse, and the depot
clinic affords them this opportunity (Phillips
and McCann 2007). There is a lack of research
investigating the attitudes of healthcare
professionals to depot injection, and the role of
nurse prescribers (Besenius et al 2010). Nurses
have not always been positive about their role
in medicines management. Gray (2015) argued
in support of reframing discussions with
patients about medicines management away
from a negative coercive approach to one that is
essentially caring in nature.
Non-adherence to antipsychotic treatment
leads to increased risk of relapse and
hospital admissions (Nosé et al 2003). A low
discontinuation rate (18%) of treatment with
depot haloperidol was reported in
a systematic review of eight clinical trials
involving 371 patients with schizophrenia
(Quraishi et al 1999). This suggests that
the relapse rate might be lower with depot
preparations. However, nurse prescribers
should evaluate this finding carefully because
both old and new trials have methodological
flaws (Quraishi et al 1999).
Little difference between depot injections
in terms of relapse prevention, efficacy or
tolerability was found in an examination of the
efficacy and side effect profile of first generation
depot injection (Adams et al 2001). In a study
in which patients with schizophrenia were
prescribed a first generation depot injection
over a ten-year follow-up period, only 18.9% of

TABLE 1
Rating scales to identify and assess movement disorders in patients who received
antipsychotic medication
Scale Description Rating
Abnormal Involuntary 12-item scale using a five-point scoring High score = high severity
Movement Scale (Guy 1976) system to identify tardive dyskinesia

Extrapyramidal Symptom
Rating Scale (Chouinard
and Margolese 2005)
Simpson-Angus Scale
(Simpson and Angus 1970)
Rating scale that examines dyskinesia, High score = high severity
parkinsonism, dystonia and akathisia
10-item rating scale using a five-point Low score = low severity
scale to detect parkinsonian symptoms

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 CPD mental health

patients maintained outpatient status (Uchida intervals involved. Patients should also be
et al 2013). This finding questions the efficacy of given information about potential side effects
depot injection over a longer time period. and how these can be managed.
Patients place more importance on whether Patients may view depot injection as invasive,
they think medication is efficacious as opposed particularly since it can cause tissue damage
to other factors, such as side effects (Kikkert et at the injection site. Some patients experience
al 2006). It is therefore important to provide pain, with most pain felt five minutes after
patients with information about the efficacy administration (Phillips and Dillon 2009).
of a particular medication and to have an Brissos et al (2014) provided a critical
honest appraisal process in place to evaluate all appraisal of depot injections and the advantages
treatment options. Nurse prescribers should and disadvantages of their use compared with
support the patient to make choices about the oral medication. This information must be
2 Supporting patients treatment they would prefer (Table 2). articulated to patients to ensure that they are
to make decisions and It is important that nurses explore informed about their treatment options and can
choices is an important collaboratively what motivates the patient to exercise choice. Some of the advantages and
part of effective care take medication. To do this, nurse prescribers disadvantages of the use of depot injection listed
planning. In your clinical and mental health nurses require knowledge in Box 2, and referred to in this article, can be
practice, use the six about why a particular medication works, and used as a basis for discussion with the patient.
areas summarised its range of side effects (Gray et al 2009b). Nurses can practice a shared decision-making
in Table 2 as an aide It is important for nurse prescribers and framework. Topics for patient choice (Table 2)
memoire to structure other healthcare professionals to engage have been shaped around the role of depot
a meaningful exchange collaboratively with the patient and to discuss injection in the treatment of schizophrenia,
of information with the evidence base that supports the use of each and can facilitate a culture of shared decision
a patient. Write a medication. Simple questions could be used making. Important factors for shared decision
reflective account during the first patient consultation (Doran making are knowledge exchange and the
about what it felt 2013); for example, ‘I believe that some use of advanced treatment directives (Gray
like to use this style. medication could be helpful to you in feeling et al 2009b). In an examination of how
Pay attention to how better. How do you feel about that?’ followed patients exercised their choice with regards
the patient responded by ‘what are the main two problems that you to medication, patients who are supported to
to being asked about would like medication to help with?’ access information from different sources to
their choices and The patient can be given the opportunity make their decisions – ‘informed service users’ –
the advantages and to discuss how they want to take their were favoured (Gale et al 2012).
disadvantages of this medication, in particular the choice between Complete time out activity 2
approach. a daily routine of taking oral medication
versus an injection formulation and the dosing
Depot injection
BOX 2 Patients and nurse prescribers have various
Advantages and disadvantages of depot injection drug options to choose from. Eight drugs are
licensed for the treatment of schizophrenia in
Advantages the UK via depot injection. The BNF (2015)
Improved bioavailability of the drug. provides clear indications and dosing schedules
Less potential for misuse or overdose.
for each of the medications discussed in this
Administration of the drug facilitates regular contact with the nursing team.
Prescriber knows the exact amount of the drug prescribed and administered.
article and should be referred to when one of
Assists patients who have difficulty remembering to take a daily dose of these medications is prescribed. Fluphenazine
oral medication. decanoate, haloperidol, zuclopenthixol
decanoate and flupentixol decanoate are classed
Disadvantages
Potential effect on the therapeutic relationship between the patient and
as first generation antipsychotics. Risperidone,
healthcare professional. olanzapine embonate, paliperidone and
Potential needle injection site problems such as pain, irritation and abscess aripiprazole are classed as second generation
formation. antipsychotics (BNF 2015).
Potential for delayed or prolonged side effects.
Slow dose titration required. Fluphenazine decanoate
Patients may experience lack of control over their treatment plan. Fluphenazine enanthate was the first depot
Association of stigma. injection to be manufactured in 1966, followed
Requirement to travel to the clinic to receive the medication or to receive 18 months later by fluphenazine decanoate
home visits.
(Johnson 2009). Fluphenazine decanoate
(Adapted from Burton 2010, Stevens and Rodin 2011, Brissos et al 2014)
belongs in the phenothiazine group (BNF

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 2015) and may have two peak concentration
levels – the first peak within a few hours after
injection and a second peak eight to 12 days
later – and takes eight weeks to achieve a steady
state (Taylor et al 2015).
No significant difference in relapse rates
between this depot injection and oral
antipsychotics was found, with significantly
more people relapsing in the placebo group
(Maayan et al 2015). There appears to be less
risk of the development of movement disorders
with fluphenazine depot compared with oral
medication (Maayan et al 2015).
Haloperidol decanoate
Haloperidol decanoate is a butyrophenone
(BNF 2015). The drug reaches its peak
concentration in seven days and reaches a
steady state in 14 weeks (Taylor et al 2015).
In a systematic review no differences were
reported between haloperidol depot and the
oral formulation in terms of efficacy (Quraishi
et al 1999). In addition, no differences in terms
of mental state, side effects and relapse rates
were found between depot haloperidol and
other depot injections (Quraishi et al 1999).
Zuclopenthixol decanoate
Zuclopenthixol decanoate is a different type
of compound and belongs in the thioxanthene
group (BNF 2015). Zuclopenthioxol is
long acting compared with the short-acting
acetate compound. The drug reaches peak
concentration in four to seven days and
takes 12 weeks to reach a steady state
(Taylor et al 2015).

TABLE 2
Topics to assist patient choice in the treatment for schizophrenia
Issue Description Rationale

Drug formulation There are several drug formulations available, such
as tablets, liquids, and depot or orodispersible
formulations, for the range of medication prescribed
for the treatment of schizophrenia.
Some patients prefer a particular formulation to
help them remember to take their medication.
Patients who live on their own might not have
family members to prompt them with adherence
and might therefore prefer a depot injection.

Frequency of Administration of depot injection could be weekly,
administration two to four weekly, or at set or flexible intervals
(British National Formulary (BNF) 2015).
Nurses can assist patients to consider
frequency of administration by identifying that
some depot injections have fixed administration
periods whereas others are flexible. The nurse
should always refer to the latest edition of the
BNF to provide accurate information.

Location of medication Patients can choose to receive a depot injection at Patients may prefer to attend a medication
administration home, at a GP clinic or a community mental health clinic to receive the depot injection so that they
clinic. can discuss their physical health needs with a
community nurse.

Site of administration Some depot injections are licensed for different If a patient is considering a depot injection,
muscle sites (BNF 2015). discussing the administration site with them
could assist them to choose which medication
they would prefer.

Advance treatment Patients can make treatment decisions when they Advance treatment directives can be offered
directives are well for implementation if they become ill. and enable the patient to exercise choice when
making their treatment decisions.

Societal views Stigma associated with being mentally ill. The patient may choose to receive medication
in a GP clinic on a monthly basis to avoid
perceptions of stigma associated with attending
a mental health clinic.

Side effects and All medication is associated with side effects and
monitoring requirements these should be explained to patients. Patients should
be offered information about side effects that they
can access when they are at home, such as leaflets
and websites.
Patients should be given information about how
side effects can be monitored and the range
of interventions that can be offered. This can
assist patients to make informed choices about
the type of medication they wish to take.

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 CPD mental health
Zuclopenthixol is successful in preventing
relapse and requires less anticholinergic
medication compared with other depot
injections for the treatment of schizophrenia
and other severe mental illness (da Silva Freire
Coutinho et al 1999). Zuclopenthixol depot
causes sedation so it may be the preferred
choice of treatment for symptoms of agitation,
although the prescriber should be aware
that the drug might worsen symptoms of
psychomotor retardation (Levi 2007).
Flupentixol decanoate
Flupentixol decanoate also belongs in the
3 Using the BNF,
thioxanthene group (BNF 2015). Peak drug
identify a medication
concentration occurs seven days after injection
plan you are currently
and takes nine weeks to achieve a steady state
working to. Note the
(Taylor et al 2015).
mechanism of action
In terms of mental state and behaviour, no
of the antipsychotic
difference was found between flupentixol and
medication, how to start
other depot injections or oral antipsychotics
the dose, how to titrate
(Mahapatra et al 2014). Low doses appear to
off the dose, and the
be equally protective against relapse as high
main potential side
doses (Mahapatra et al 2014).
effects. Discuss
this new learning
Risperidone
with your mental
Risperidone is a powder that is reconstituted
health pharmacist or
with a liquid to form biodegradeable
psychiatrist to embed
microspheres. The route of administration is
your learning. Reflect on
deep intramuscular injection into either the
how your practice has
deltoid or gluteal muscle (BNF 2015).
changed in light of this
When the drug is injected, the microspheres
knowledge.
degrade, giving the drug its unique steady-state
profile. Risperidone is potently antagonistic at
4 Investigate the D2 receptors and antagonistic at 5-HT2A, alpha1
extent to which local adrenoreceptors receptors and histamine-1
protocols for practice receptors (BNF 2015).
in the administration The drug reaches peak concentration after
and monitoring of 35 days and takes eight weeks to reach a steady
antipsychotic medication state (Taylor et al 2015). Drug tolerance can be
reflect patient choice, assessed by initially prescribing oral risperidone;
and empower the patient the oral dose can be used as a guide for the depot
to make informed dose. The BNF (2015) provides guidance for
decisions. Make contact continuing oral prescription of risperidone for
with your local mental four to six weeks after the first depot injection.
health pharmacist
so you can be part of Olanzapine embonate
protocol review groups Olanzapine embonate is a D1, D2, D4,
for antipsychotic 5-HT2A, histamine-1 and muscarinic
medication and receptor antagonist (BNF 2015). The drug
prescribing guidelines. is reconstituted and administered into the
Use this experience to gluteal muscle only by deep intramuscular
further your knowledge injection. It reaches peak concentration in
and contribution to two to three days and achieves a steady state
supporting patient after eight weeks (Taylor et al 2015). The BNF
choice and patient safety. (2015) outlines the dosing regimens that are
aligned with the daily oral dose of olanzapine.
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NS_1790.indd 56
Drug trials have examined whether
switching patients receiving oral olanzapine
treatment who are stable to olanzapine
administered by depot injection leads to any
deterioration in symptoms. In a study in which
patients were randomised to receive one of four
dose regimens of olanzapine (300mg every two
weeks, 405mg every four weeks, 150mg every
two weeks, or 45mg every four weeks), there
was no significant difference in drug efficacy
between patients receiving oral olanzapine
and those receiving the depot formulation
(Kane et al 2010).
Patients and nurse prescribers should
be aware of the risk of post-injection delirium/
sedation syndrome when using this drug
(Sadock et al 2015). This syndrome was
noted in 0.07% of injections, with symptoms
occurring either immediately or up to three
to five hours after injection (Detke et al
2010). Healthcare organisations should have
protocols in place to safely manage this risk;
for example, ensuring that the patient remains
in the healthcare setting for a minimum of
three hours after each injection for monitoring
(BNF 2015). Post-injection delirium/sedation
syndrome has not been observed following
depot injections of other antipsychotics
(Lindenmayer 2010).
Paliperidone
Paliperidone, a metabolite of risperidone,
is a second generation antipsychotic that
may be administered monthly as a depot
(Sadock et al 2015). The drug takes 13 days
to reach peak concentration and 20 weeks
to reach a steady state (Taylor et al 2015).
After initial dose titration, the patient can be
offered administration by deep intramuscular
injection either via the deltoid or gluteal
muscle (BNF 2015). The gluteal muscle site
was slightly better tolerated by patients in one
study, although patient preference varied by
geographic location, with patients from the
US expressing a preference for the deltoid site
(Hough et al 2009). Patients who are prescribed
this medication can be offered a choice of
injection site after initial dose titration.
There was no difference in recurrence of
psychotic symptoms between patients treated
with paliperidone compared with those
receiving risperidone, therefore paliperidone
does not demonstrate advantages over
risperidone (Nussbaum and Stroup 2012). Apart
from associated side effects, no difference in
efficacy was found between paliperidone and
haloperidol (McEvoy et al 2014).
12/04/2016 09:41
 Paliperidone was associated with increased
weight gain and greater increases in serum
prolactin than haloperidol, whereas
haloperidol was associated with increased
akathisia. A trial of a novel three-month
interval dosing schedule of paliperidone
showed a positive effect on reducing relapse
rates compared with placebo (Berwaerts et al
2015). Although this dosing schedule might be
useful in areas in which it is difficult to access
suitably trained healthcare professionals on a
regular basis, it is not yet licensed in the UK.
Aripiprazole
Aripiprazole is a partial dopamine D2 agonist,
has weak 5-HT1A partial agonism and 5-HT2A
receptor antagonism (BNF 2015), and is the
first of this type of antipsychotic available as
a depot (Fleischhacker et al 2014). The depot
injection is indicated for the maintenance
treatment of schizophrenia in patients who
have been stabilised on the oral formulation of
aripiprazole only. The drug takes seven days
to reach peak concentration and 20 weeks to
reach a steady state (Taylor et al 2015).
Fleischhacker et al (2014) compared
treatment of schizophrenia using a depot
injection of 400mg per month, a depot at a
sub-therapeutic dose of 50mg per month, and
a daily oral dose of 10-30mg of aripiprazole
to assess efficacy. Using estimated impending
relapse rates as the primary outcome
measure, a depot injection of aripiprazole at
a dose of 400mg per month was reported to
be non-inferior to the oral dose (10-30mg
daily), but both these treatments were
superior to the suboptimal injection dose
(50mg per month). In a 28-week trial, patients
prescribed aripiprazole given as a depot
(400mg) had a greater clinician-rated quality
of life compared with paliperidone also given
as a depot injection, and aripiprazole was also
better tolerated (Naber et al 2015).
Complete time out activity 3
Additional considerations when
prescribing depot injections
Nurses have administered depot injections
since their development and are well placed to
explore patient preference about medication.
Nurses may train as nurse prescribers, either
as a supplementary or independent prescriber
(Jones 2009). Nurse prescribing will change
the way patients and nurses interact with
each other on various levels. For example,
when nurse prescribers discuss the choice of
medication with the patient, this can lead to
informed decision making by the patient.
Guidance on the importance of competency
in the procedure for administration of depot
injection is available (Feetam and White 2014).
It is important that procedures are followed
in the administration of depot injections to
maximise the effects of the drug.
When patients are prescribed depot injections,
it is essential that a range of clinical activities are
undertaken, including monitoring and treatment
of physical health conditions and comorbidity
associated with schizophrenia (NICE 2014). 5 Read the guidance
It is important that movement disorder side on the administration of
effects of antipsychotics are assessed as part of oil-based depot and other
routine practice. The assessment of potential antipsychotic injections
or actual risk of neurological or metabolic side to adults (Feetam
effects of antipsychotics should also guide the and White 2014).
choice of depot injection made by the patient Familiarise yourself
and prescribed by the nurse. Patients value the with the best practice
opportunity to discuss medication as part of their points on preparation
care package, particularly if they are concerned for intramuscular
about side effects and how these might affect administration and
their social functioning. This discussion can standard operating
enhance the depth of the relationship with the procedures for
nurse prescriber. administration
Complete time out activities 4 and 5 techniques. Write a
reflective account on
your current practice,
Conclusion making reference to
This article provided information and guidance and protocols in
evidence on the main types of depot injection relation to administration
used in the UK for the treatment of patients of depot injections and
with schizophrenia. Levels of evidence, side antipsychotic medication.
effect profiles and, importantly, a framework
for patient choice were discussed. Nurse 6 Now that you have
prescribers, in consultation with patients, completed the article,
should weigh up all these factors when you might like to write
prescribing depot injection for schizophrenia. a reflective account as
Depot injection is, and continues to be, a part of your revalidation.
worthwhile treatment option for people Guidelines to help you
diagnosed with schizophrenia NS are on page 62.
Complete time out activity 6

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