Independent Prescribing in Psychiatric Care

The following case study and critical analysis concerns a recent independent prescribing episode which took place during an inpatient admission to a psychiatric hospital in England. Independent prescribing is defined as “prescribing by a pracitioner (e.g. doctor, dentist, nurse, pharmacist) responsible and accountable for the assessment of patients with undiagnosed and diagnosed conditions and for decisions about the clinical management required, including prescribing” (Department of Health (DH), 2006 p2)

The Neighbour consultation model (Neighbour, R (1987) was utilised during assessment. It was chosen due to its ease of use. Also, the guiding principles, and steps, of the prescribing pyramid were followed in order to ensure safe and appropriate actions were undertaken. (National Prescribing Centre (NPC), 1999). The patient concerned is a 44 year old man, who will be referred to as Dave, with a long term confirmed diagnosis of Schizophrenia of the paranoid type under Section F20.0 of the International Classification of Disease 11 (World Health Organization (WHO), 2018). Dave is a pseudonym which will be used in order to protect the patients anonimity, as required by the Nursing and Midwifery Councils code of practice (NMC), 2018).

Dave was admitted to hospital 24 hours previously, having agreed to an informal admission under the following circumstances. Dave was found wandering in his local area many hours after taking his dog for a walk. He had been reported missing by his wife, and in the interim, had been seen by chance, securing his dog to a tree, and leaving him behind, by a passing police patrol car. Dave's wife had confirmed that going missing, and leaving

his dog, were both very out of character for Dave. His vague, slightly distressed, and perplexed presentation had given the officers cause for concern, so he was taken, with his agreement, to the nearest Accident and Emergency Department, where following an assessment by Mental Health Liaision clinicians he agreed to an admission for further assessment. The reasons for this were that Dave, with the support of his wife, explained that he had recently been first on the scene when his friend and neighbour had suffered a fatal cardiac arrest. Dave had initiated CPR, and had been highly distressed following the subsequent death. The assessing clinicians felt that Dave might be at risk of a significant relapse of his condition which been well maintained with Clozapine for some four years. Their notes report Dave's responses being considerably delayed, which they believed to have been attributed to Dave making considerable efforts to mask the fact that he was hearing voices.

Dave was able to confirm that there was no suicidal ideation present, but was less clear about an increase of intrusive internal voices. Dave reported not having slept properly since witnessing his friends death, some three weeks previously, and his wife reported a significant decrease in appetite. It was confirmed, by Dave, his wife, and the remaining contents of a dossette box brought to the hospital by Dave's wife that there had been no missed doses of Clozapine. Dave agreed to be seen for this consultation by an inpatient multi-disiplinary team of four, including the responsible inpatient Consultant Psychiatrist. There had been an opportunity to view extensive historic clinical notes prior to the assessment. These revealed that Dave had responded very well to Clozapine, having been prescribed it following its consideration due to all of the necessary criteria having been reached. They also showed that Dave has been consistently concordant and colaborative with all aspects of his care, for a period of years.

A nationwide Swedish study found that Clozapine, followed by long acting injectable antipsychotic medications (Tilhonen et al, 2017) to be the treatments with the highest rates of relapse prevention in scizophrenia. Dave has a long term community Consultant Psychiatrist and a Care Co-ordinator.

Dave attends his local Clozapine Monitoring Clinic, as required, for regular monitoring of his blood, the results are then provided to the Clozapine Patient Monitoring Service, who in turn authorise the release of the next Clozapine prescription if safe to do so. Dave has been sucessfully maintained on a Clozapine total daily dose of 525 mg, prescribed to be administered at 200 mg in the morning and 325 mg at night. In tablet form Clozapine is available in 100 mg and 25 mg tablets. The prescribed daily amount has been regularly reviewed, and has remained unchanged for the past 18 months. No other medications currently prescribed. Dave is a long term 10 to15 cigarettes a day smoker, which is clinically significant in relation to Clozapine. He does not drink alcohol or take illicit drugs.

Clozapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration (National Institute of Clinical Excellence (NICE), 2017) Therefore, following deliberation of the appropriate stratergy the continuation of the current treatment presented as the only appropriate choice, provided that the assessment confirmed the diagnosis, Dave's blood results did not prevent continuation, and his agreement was given at consultation.

On assessment Dave had capacity to understand and give consent to his treatment. Dave was asked about suicidal ideation, and whether he he felt able to keep himself safe on the ward. This was to enable the MDT to consider a safe, but least restrictive, level of nursing observations. Dave confirmed that he was not experienceing thoughts of suicide. Dave was asked to briefly outline the events that led to his admission. Dave gave non-verbal clues that he would not be able to discuss details of the main incident of truama.Therefore, it was acknowledged, and verbalised to Dave that it would not be necessary to do so. He then confirmed his continued agreement to his inpatient admission, with his diagnosis, and his Clozapine treatment plan. He confimed that he has no known allergies, and that he does not use any over the counter or other unprescribed medications, including herbal preparations. Dave was informed that his physical health examination, including vital signs and ECG, had produced results within the normal ranges, and that the results of the blood sample given on admission would be available the following day, and would be communicated both to him, and to the CPMS.

Dave was asked if he had previously been given full information regarding the potentially serious side effects of Clozapine, whether he was aware of the reasons for the regular blood sampling, and whether he understood the importance of reporting any signs flu like symptoms or signs of infection. Dave confirmed that he was fully aware. He was asked whether he was experiencing any constipation, and whether he knew the potentially serious implications of ignoring any inability to pass regular motions. Dave confirmed that he understood he must seek immediate medical advice in the event, but had never suffered constipation. Dave was weighed during his physical examination, and was found to have a healthy weight of 79.6kg to a height ratio of 180cm, giving a BMI of 24.5(National Health Service, (NHS), 2018) Dave said that he felt this is because he likes to walk his dog. A GASS-C (Hynes, 2015) which is an assessment tool used to monitor levels of side effects for Clozapine, was used as it has been found to provide a way to reliably and systematicaly monitor side effects. Dave achieved a very low score, denoting a low level of unpleasant and/or potentially serious, side effects.

Dave was asked if he was aware that cigarette smoke reduces the levels of Clozapine in blood, and that therefore should he stop smoking it would be likely that he would require a reduction in his Clozapine dose. He was further informed that failure to reduce the dose could lead to toxicity. It was stressed that this should not dissuade Dave from choosing to stop smoking, and that support in doing so would be provided should he want it. The health benefits of giving up smoking were emphasised, in line with the responsibility to provide brief interventions and opportunistic health promotion (NICE, 2006) However, Dave made it clear that he had no intention of giving up smoking at that time.

Dave was informed how often he would be seen for review (NPC,1999) during his admission, and that the pre-admission treatment plan, including the current prescription of Clozapine, at the current dose, would be continued, and was likely to be continued unchanged on discharge. He was asked if he agreed with this plan. Agreement was confirmed. It was explained to Dave that he was welcome to have his wife accompany him to future reviews on the ward. In line with recommendations for involving carers, (NICE, 2017) he was assured that his wife would be kept up to date with his treatment plan, should he still wish for this to continue. Dave confirmed that he did not want this to change. He was asked whether he had any questions or concerns in any regard, and whether he understood the proposed arrangements. Dave confirmed that he understood and had no concerns.

Dave gave the impression of a man who had good insight into his mental health condition, and how to keep himself well. However, having experienced an unavoidable trauma he had come into hospital as a result of this, and no other reason. Dave was unable to say why he had been

wandering alone for so long. He appeared sleep deprived, and perhaps suffering from the effects of his recent distressing experience. However, it was possible to confirm the long term diagnosis, and that treatment with Clozapine should continue unless blood counts prevented it. It was communicated to Dave that the admission was likely to be fairly short in duration, and would involve the opportunity to recover from his ordeal, and safeguard against anything that may have been missed which could have led to his uncharacteristic behaviour. He was asked whether he had any questions to ask. Dave confirmed that he was in agreement, and that he had no questions at that time. He was thanked for his input and the information he had provided, and the consultation was concluded.

Clozapine is dopamine D1 , dopamine D2,, 5-HT2A, alph1 – adrenoceptor, and muscarinic – receptor antagonist (British National Formulary (BNF), 2018)

Clozapine is metabolised principally via CYP1A2 therefore clearance is increased in smokers. Smoking reduces plasma levels of clozapine by up to 50% so smokers may need higher doses. Likewise, patients who stop smoking may experience a 50% increase in plasma level so will need dose reduction (NHS, 2017)

The use of clozapine with other potentially myelotoxic agents such as carbamazepine may increase the risk and/or severity of hematologic toxicity. Clozapine alone is associated with a significant risk of agranulocytosis. Although the mechanism of clozapine-induced agranulocytosis is unknown, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression (NICE, 2017)

The dose for adults 18-59 is 12.5 mg 1-2 times a day for day 1, then 25 mg-50 mg for day 2, then increased, if tolerated, in steps of 25-50 mg daily, dose to be increased gradually over 14-21 days, increased up to 300 mg daily in divided doses, larger dose to taken at night, up to 200 mg daily may be taken as a single dose at bedtime; increased in steps of 50-100 mg 1-2 times a week if required, it is preferable to increase once a week; usual dose 200 mg-450 mg daily, max 900 mg per day. (BNF, 2018)

Blood results particularly white blood cell counts are used to monitor patients on clozapine treatment. The Clozapine Patient Monitoring Service is responsible for monitoring the WBC counts of patients who are being

prescribed Clozapine, specifically Clozaril. They report blood results in three colour bands that apply to both initial and on treatment samples as follows:

GREEN

WBC > 3.5 x 109/L neutrophils > 2.0 x 109/L

Indicates a satisfactory result that is within acceptable ranges, valid to initiate/continue clozapine treatment. For the initiation of clozapine treatment, a green result is required.

AMBER

WBC 3.0 – 3.5 x 109/L and/or neutrophils 1.5 – 2.0 x 109/L

Indicates a result that indicates that although the patient may continue clozapine treatment, extra caution must be exercised and twice weekly bloods sampling is required until count stabilises or increases. Once a green result is obtained the monitoring frequency can return to that which the patient on prior to the amber result. However, for the initiation of clozapine treatment a green result is required.

RED

WBC < 3.0 x 109/L and/or neutrophils < 1.5 x 109/L

Result is not satisfactory, not valid to initiate or to continue clozapine treatment. Clozapine treatment must stop immediately.

The intervals for monitoring blood levels are weekly for the first eighteen weeks then at least two weekly. If Clozapine continued and and blood count stable after one year then at least four weekly. This includes four weeks after any discontinuation (BNF, 2018)

Agranulocytosis is a disorder in which there is a severe acute deficiency of white blood cells (Neutropenia) by result of damage to the bone marrow. Characterized by fever, and ulceration of the mouth and throat. It can rapidly lead to death. This is the most well known adverse effect of Clozapine. In the UK the risk of death is in the region of 1 in 10,000 patients exposed (The Maudsley Prescribing Guidelines in Psychiatry, 2012) This indicates that the risk is currently well managed by the approved Clozapine monitoring systems

Clozapine has been associated with impairment of intestinal peristalsis. Potentially fatal risk of intestinal obstruction can result. It is essential that constipation is recognised and actively treated.

Fatal mycarditis and cardiomyopathy has been reported, most commonly in patients who commenced Clozapine within two months.

Perform a physical examination before starting Clozapine. Specialist examination required if there are cardiac abnormalities or history of heart disease found. Only to be started in the absence of severe heart disease, and if the benefit outweighs the risk.

Persistant tachycardia, especially in the first two months, should prompt observation for other indicators of mycarditis or cardiomyopathy.

If myocarditis or cardiomyopathy suspected clozapine should be stopped and patient evaluated urgently by cardiologist.

Discontinue permanently in clozapine-induced myocarditis or cardiomyopathy.

Blood lipids and weight measured at baseline, every three months for the first year, then yearly.

Avoid in symptomatic liver disease. Avoid in progressive liver disease. Avoid in heptatic failure. Monitor heptatic function regularly.

Fasting blood glucose level should be taken at baseline, after one month, then every 4-6 months.

Close medical supervision should be provided during initiation due to a risk of collapse because of hypotension or convulsions.

On planned withdrawal reduce dose over1-2 weeks to avoid rebound psychosis. If abrupt withdrawal is necessary observe the patient carefully.

The UK Clozaril Patient Monitoring Service (CPMS, 2019) is responsible for the monitoring of all Clozapine patients who are prescribed Clozaril. All prescribers, patients and pharmacists who are prescribing, dispensing or being prescribed Clozaril must be registered with them. All Clozapine patients are issued with a unique identifying number.

During an inpatient admission, in order to obtained a further supply of Clozapine to fulfil a treatment plan, the CPMS must be informed of the patients admission to hospital. Furthermore, the patients blood sample results must be securely communicated to the CPMS, who will authorise that the registered pharmacy release the next supply of Clozapine as prescribed, if appropriate in light of the results. In circumstances where a patient would normally attend a Clozapine clinic, where they would be monitored, and where they would collect their medication, it is the responsibility of the hospital prescriber to inform the CPMS of the admission, and to temporarily register themselves, and the hospital pharmacy with the CPMS as that patients prescriber and dispensing pharmacy.

In addition, the patients Community Mental Health Team, their G.P., the usual Clozapine clinic, and associated pharmacy, and the patient and/or carer, must be informed of the arrangements. This process must be reversed on discharge of the patient. On discharge a patient can only be issued with a supply of Clozapine which corresponds with the duration of their current valid blood results. This is why proper, and clear, handover of care is vital in this circumstance. This includes very clear and notes being entered onto the patients notes, and the date of the follow up appointment at patients usual Clozapine clinic be made clear and understood to the patient themslves, and all of the other parties concerned (NICE, 2018)

In regard to consideration of cost, there is no decision to be made with a Clozapine prescription due to the unique factors which goven its prescribing, which have been fully outlined.

Upon discharge any summary should mention the recent trauma, its likely impact on the patients mental health, and recommend the exploration of whether a talking therapy might be beneficial to prevent further relapse (NICE, 2017)

Should any adverse drug effects occur prescribers should make a direct notification, to through the Yellow Card Scheme, preferably using the electronic form, to the Medicines and Healthcare products Regulatory Agency. (BNF, 2018) This is especially important in the case of Clozapine, and should be done in addition to the Clozapine specific monitoring procedures already in place.

On reflection of this episode of Independent Prescribing, it is not recommended that Clozapine if prescribed by non Consultant Psychiatrists, and not recommended that the precribing for Clozapine patients is handed over to G.P.'s, unless there are exceptional circumstances, for example, for a patient living in a very remote area. And in those circumstances there would be a close partnership agreement between the G.P. and a Consultant Psychiatrist. Therefore, in an typical indepentent prescribing episode a Registered Mental Health Nurse would not prescribe Clozapine to a patient. Also, it would appear that, in mental healthcare, a community setting may be more benefical for learning to an Indepentent Nurse Prescriber.

References

Joint Formulary Commitee (2018) BNF 76: September 2018. London: Pharmaceutical Press

The Maudsley Prescribing Guidelines in Psychiatry, Eleventh Edition. David Taylor, Carol Paton and Shitij Kapur. Published 2012 by John Wiley & Sons, Ltd.

Neighbour, R. (1987). The Inner Consultation. Oxford: Radcliffe.

Closing the Gap - priorities for essential change in mental health. (2014). Department of Health, pp.1-40.

Courtenay, M. and Griffiths, M. (2005). Independent and Supplementary Prescribing. Cambridge University Press.

Flowers, C. and Arene, T. (2019). The Clozapine Clinic: A Model of Integrated Care.

Gee, S., Taylor, D., Shergill, S., Flanagan, R. and MacCabe, J. (2017). Effects of a smoking ban on clozapine plasma concentrations in a nonsecure psychiatric unit.

Green, S., Beveridge, E., Evans, L., Trite, J., Jayacodi, S., Evered, R., Parker, C., Polledri, L., Tabb, E., Green, J., Manickam, A., Williams, J., Deere, R. and Tiplady, B. (2018). Implementing guidelines on physical health in the acute mental health setting: a quality improvement approach. International Journal of Mental Health Systems, 12(1).

Kar, N., Barreto, S. and Chandavarkar, R. (2016). Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement.

Nash M. (2013). Diagnostic overshadowing: a potential barrier to physical healthcare for mental health service users

Tungaraza, T. and Farooq, S. (2015). Clozapine prescribing in the UK: views and experience of consultant psychiatrists.