Reviewing depot injection efficacy in the treatment of schizophrenia

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1 CONTINUING PROFESSIONAL CPDDEVELOPMENT 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, Date of submission: April ; date of acceptance: January 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 Review All articles are subject to external double-blind peer review and checked for plagiarism using automated software. Revalidation Prepare for revalidation: read this CPD article, answer the questionnaire and write a reflective account. Online For related articles visit the archive and search using the keywords above. To write a CPD article: please gwen.clarke@rcni.com Guidelines on writing for publication are available at: journals.rcni.com/r/author-guidelines. 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). 50 april 13 :: vol 30 no 33 :: 2016 NURSING STANDARD

2 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 D 2 receptors in the four main dopaminergic pathways in the brain (Stahl 2013) (Box 1, Figure 1). Blocking dopamine D 2 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 D 2 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 D 2 receptors, but they also have effects on other receptors such as serotonin receptors (5-HT 2A ) (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 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, D 2 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 PETER LAMB Mesocortical pathway Frontal cortex Nucleus accumbens Hypothalamus Tuberoinfundibular pathway Basal ganglia Mesolimbic pathway Corpus callosum Thalamus Spinal cord Nigrostriatal pathway Cerebellum Substantia nigra Ventral tegmental area NURSING STANDARD april 13 :: vol 30 no 33 ::

3 CPD mental health 1 Depot injection for the treatment of schizophrenia has several potential side effects. Read the information in Box 1 and examine the dopaminergic pathways in Figure 1. Think of a patient medication plan you are prescribing and write down the mechanism of action of the drugs you plan to use and their potential side effects. Check the side effects by looking up the particular depot injection in the BNF. 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 antipsychotic treatment as the primary outcome measure of effectiveness (Lieberman et al 2005). A first generation antipsychotic, perphenazine, was compared with second generation antipsychotics such as olanzapine, quetiapine and risperidone. The results showed that, over 18 months, 74% of patients discontinued their treatment from the start of the trial. Overall, olanzapine had the lowest discontinuation rate at 64% although patients had significant side effects such as weight gain. Perphenazine showed similar efficacy compared with quetiapine, risperidone and ziprasidone, second generation antipsychotics included in the trial (Lieberman et al 2005). Apart from the consideration of clozapine for the treatment of patients who fail to respond to antipsychotics, the CATIE and CUtLASS trials suggested that first generation 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 52 april 13 :: vol 30 no 33 :: 2016 NURSING STANDARD

4 (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 Movement Scale (Guy 1976) Extrapyramidal Symptom Rating Scale (Chouinard and Margolese 2005) Simpson-Angus Scale (Simpson and Angus 1970) 12-item scale using a five-point scoring system to identify tardive dyskinesia Rating scale that examines dyskinesia, parkinsonism, dystonia and akathisia 10-item rating scale using a five-point scale to detect parkinsonian symptoms High score = high severity High score = high severity Low score = low severity NURSING STANDARD april 13 :: vol 30 no 33 ::

5 CPD mental health 2 Supporting patients to make decisions and choices is an important part of effective care planning. In your clinical practice, use the six areas summarised in Table 2 as an aide memoire to structure a meaningful exchange of information with a patient. Write a reflective account about what it felt like to use this style. Pay attention to how the patient responded to being asked about their choices and the advantages and disadvantages of this approach. BOX 2 patients maintained outpatient status (Uchida et al 2013). This finding questions the efficacy of depot injection over a longer time period. Patients place more importance on whether they think medication is efficacious as opposed to other factors, such as side effects (Kikkert et al 2006). It is therefore important to provide patients with information about the efficacy of a particular medication and to have an honest appraisal process in place to evaluate all treatment options. Nurse prescribers should support the patient to make choices about the treatment they would prefer (Table 2). It is important that nurses explore collaboratively what motivates the patient to take medication. To do this, nurse prescribers and mental health nurses require knowledge about why a particular medication works, and its range of side effects (Gray et al 2009b). It is important for nurse prescribers and other healthcare professionals to engage collaboratively with the patient and to discuss the evidence base that supports the use of each medication. Simple questions could be used during the first patient consultation (Doran 2013); for example, I believe that some medication could be helpful to you in feeling better. How do you feel about that? followed by what are the main two problems that you would like medication to help with? The patient can be given the opportunity to discuss how they want to take their medication, in particular the choice between a daily routine of taking oral medication versus an injection formulation and the dosing Advantages and disadvantages of depot injection Advantages Improved bioavailability of the drug. Less potential for misuse or overdose. Administration of the drug facilitates regular contact with the nursing team. Prescriber knows the exact amount of the drug prescribed and administered. Assists patients who have difficulty remembering to take a daily dose of oral medication. Disadvantages Potential effect on the therapeutic relationship between the patient and healthcare professional. Potential needle injection site problems such as pain, irritation and abscess formation. Potential for delayed or prolonged side effects. Slow dose titration required. Patients may experience lack of control over their treatment plan. Association of stigma. Requirement to travel to the clinic to receive the medication or to receive home visits. (Adapted from Burton 2010, Stevens and Rodin 2011, Brissos et al 2014) intervals involved. Patients should also be given information about potential side effects and how these can be managed. Patients may view depot injection as invasive, particularly since it can cause tissue damage at the injection site. Some patients experience pain, with most pain felt five minutes after administration (Phillips and Dillon 2009). Brissos et al (2014) provided a critical appraisal of depot injections and the advantages and disadvantages of their use compared with oral medication. This information must be articulated to patients to ensure that they are informed about their treatment options and can exercise choice. Some of the advantages and disadvantages of the use of depot injection listed in Box 2, and referred to in this article, can be used as a basis for discussion with the patient. Nurses can practice a shared decision-making framework. Topics for patient choice (Table 2) have been shaped around the role of depot injection in the treatment of schizophrenia, and can facilitate a culture of shared decision making. Important factors for shared decision making are knowledge exchange and the use of advanced treatment directives (Gray et al 2009b). In an examination of how patients exercised their choice with regards to medication, patients who are supported to access information from different sources to make their decisions informed service users were favoured (Gale et al 2012). Complete time out activity 2 Depot injection Patients and nurse prescribers have various drug options to choose from. Eight drugs are licensed for the treatment of schizophrenia in the UK via depot injection. The BNF (2015) provides clear indications and dosing schedules for each of the medications discussed in this article and should be referred to when one of these medications is prescribed. Fluphenazine decanoate, haloperidol, zuclopenthixol decanoate and flupentixol decanoate are classed as first generation antipsychotics. Risperidone, olanzapine embonate, paliperidone and aripiprazole are classed as second generation antipsychotics (BNF 2015). Fluphenazine decanoate Fluphenazine enanthate was the first depot injection to be manufactured in 1966, followed 18 months later by fluphenazine decanoate (Johnson 2009). Fluphenazine decanoate belongs in the phenothiazine group (BNF 54 april 13 :: vol 30 no 33 :: 2016 NURSING STANDARD

6 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 Frequency of administration Location of medication administration Site of administration Advance treatment directives 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. Administration of depot injection could be weekly, two to four weekly, or at set or flexible intervals (British National Formulary (BNF) 2015). Patients can choose to receive a depot injection at home, at a GP clinic or a community mental health clinic. Some depot injections are licensed for different muscle sites (BNF 2015). Patients can make treatment decisions when they are well for implementation if they become ill. 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. 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. Patients may prefer to attend a medication clinic to receive the depot injection so that they can discuss their physical health needs with a community nurse. If a patient is considering a depot injection, discussing the administration site with them could assist them to choose which medication they would prefer. Advance treatment directives can be offered 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 monitoring requirements All medication is associated with side effects and 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. NURSING STANDARD april 13 :: vol 30 no 33 ::

7 CPD mental health 3 Using the BNF, identify a medication plan you are currently working to. Note the mechanism of action of the antipsychotic medication, how to start the dose, how to titrate off the dose, and the main potential side effects. Discuss this new learning with your mental health pharmacist or psychiatrist to embed your learning. Reflect on how your practice has changed in light of this knowledge. 4 Investigate the extent to which local protocols for practice in the administration and monitoring of antipsychotic medication reflect patient choice, and empower the patient to make informed decisions. Make contact with your local mental health pharmacist so you can be part of protocol review groups for antipsychotic medication and prescribing guidelines. Use this experience to further your knowledge and contribution to supporting patient choice and patient safety. 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 thioxanthene group (BNF 2015). Peak drug concentration occurs seven days after injection and takes nine weeks to achieve a steady state (Taylor et al 2015). In terms of mental state and behaviour, no difference was found between flupentixol and other depot injections or oral antipsychotics (Mahapatra et al 2014). Low doses appear to be equally protective against relapse as high doses (Mahapatra et al 2014). Risperidone Risperidone is a powder that is reconstituted with a liquid to form biodegradeable microspheres. The route of administration is deep intramuscular injection into either the deltoid or gluteal muscle (BNF 2015). When the drug is injected, the microspheres degrade, giving the drug its unique steady-state profile. Risperidone is potently antagonistic at D 2 receptors and antagonistic at 5-HT 2A, alpha 1 adrenoreceptors receptors and histamine-1 receptors (BNF 2015). The drug reaches peak concentration after 35 days and takes eight weeks to reach a steady state (Taylor et al 2015). Drug tolerance can be assessed by initially prescribing oral risperidone; the oral dose can be used as a guide for the depot dose. The BNF (2015) provides guidance for continuing oral prescription of risperidone for four to six weeks after the first depot injection. Olanzapine embonate Olanzapine embonate is a D 1, D 2, D 4, 5-HT 2A, histamine-1 and muscarinic receptor antagonist (BNF 2015). The drug is reconstituted and administered into the gluteal muscle only by deep intramuscular injection. It reaches peak concentration in two to three days and achieves a steady state after eight weeks (Taylor et al 2015). The BNF (2015) outlines the dosing regimens that are aligned with the daily oral dose of olanzapine. 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). 56 april 13 :: vol 30 no 33 :: 2016 NURSING STANDARD

8 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 D 2 agonist, has weak 5-HT 1A partial agonism and 5-HT 2A 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). It is important that movement disorder side effects of antipsychotics are assessed as part of routine practice. The assessment of potential or actual risk of neurological or metabolic side effects of antipsychotics should also guide the choice of depot injection made by the patient and prescribed by the nurse. Patients value the opportunity to discuss medication as part of their care package, particularly if they are concerned about side effects and how these might affect their social functioning. This discussion can enhance the depth of the relationship with the nurse prescriber. Complete time out activities 4 and 5 Conclusion This article provided information and evidence on the main types of depot injection used in the UK for the treatment of patients with schizophrenia. Levels of evidence, side effect profiles and, importantly, a framework for patient choice were discussed. Nurse prescribers, in consultation with patients, should weigh up all these factors when prescribing depot injection for schizophrenia. Depot injection is, and continues to be, a worthwhile treatment option for people diagnosed with schizophrenia NS Complete time out activity 6 5 Read the guidance on the administration of oil-based depot and other antipsychotic injections to adults (Feetam and White 2014). Familiarise yourself with the best practice points on preparation for intramuscular administration and standard operating procedures for administration techniques. Write a reflective account on your current practice, making reference to guidance and protocols in relation to administration of depot injections and antipsychotic medication. 6 Now that you have completed the article, you might like to write a reflective account as part of your revalidation. Guidelines to help you are on page 62. References Adams CE, Fenton MK, Quraushi S, David AS (2001) Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. British Journal of Psychiatry. 179, 4, Berwaerts J, Liu Y, Gopal S et al (2015) Efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia: a randomised clinical trial. JAMA Psychiatry. 72, 8, Besenius C, Clark-Carter D, Nolan P (2010) Health professionals attitudes to depot injection antipsychotic medication: a systematic review. Journal of NURSING STANDARD april 13 :: vol 30 no 33 ::

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