Schizophrenia case studies: putting theory into practice

This article considers how patients with schizophrenia should be managed when their condition or treatment changes.

Olanzapine 5mg tablet pack

Treatments for schizophrenia are typically recommended by a mental health specialist; however, it is important that pharmacists recognise their role in the management and monitoring of this condition. In ‘Schizophrenia: recognition and management’, advice was provided that would help with identifying symptoms of the condition, and determining and monitoring treatment. In this article, hospital and community pharmacy-based case studies provide further context for the management of patients with schizophrenia who have concurrent conditions or factors that could impact their treatment.

Case study 1: A man who suddenly stops smoking

A man aged 35 years* has been admitted to a ward following a serious injury. He has been taking olanzapine 20mg at night for the past three years to treat his schizophrenia, without any problems, and does not take any other medicines. He smokes 25–30 cigarettes per day, but, because of his injury, he is unable to go outside and has opted to be started on nicotine replacement therapy (NRT) in the form of a patch.

When speaking to him about his medicines, he appears very drowsy and is barely able to speak. After checking his notes, it is found that the nurses are withholding his morphine because he appears over-sedated. The doctor asks the pharmacist if any of the patient’s prescribed therapies could be causing these symptoms.

What could be the cause?

Smoking is known to increase the metabolism of several antipsychotics, including olanzapine, haloperidol and clozapine. This increase is linked to a chemical found in cigarettes, but not nicotine itself. Tobacco smoke contains aromatic hydrocarbons that are inducers of CYP1A2, which are involved in the metabolism of several medicines[1],[2],[3]
. Therefore, smoking cessation and starting NRT leads to a reduction in clearance of the patient’s olanzapine, leading to increased plasma levels of the antipsychotic olanzapine and potentially more adverse effects — sedation in this case.

Patients who want to stop, or who inadvertently stop, smoking while taking antipsychotics should be monitored for signs of increased adverse effects (e.g. extrapyramidal side effects, weight gain or confusion). Patients who take clozapine and who wish to stop smoking should be referred to their mental health team for review as clozapine levels can increase significantly when smoking is stopped[3],[4]
.

For this patient, olanzapine is reduced to 15mg at night; consequently, he seems much brighter and more responsive. After a period on the ward, he has successfully been treated for his injury and is ready to go home. The doctor has asked for him to be supplied with olanzapine 15mg for discharge along with his NRT.

What should be considered prior to discharge?

It is important to discuss with the patient why his dose was changed during his stay in hospital and to ask whether he intends to start smoking again or to continue with his NRT. Explain to him that if he wants to begin, or is at risk of, smoking again, his olanzapine levels may be impacted and he may be at risk of becoming unwell. It is necessary to warn him of the risk to his current therapy and to speak to his pharmacist or mental health team if he does decide to start smoking again. In addition, this should be used as an opportunity to reinforce the general risks of smoking to the patient and to encourage him to remain smoke-free.

It is also important to speak to the patient’s community team (e.g. doctors, nurses), who specialise in caring for patients with mental health disorders, about why the olanzapine dose was reduced during his stay, so that they can then monitor him in case he does begin smoking again.

Case 2: A woman with constipation

A woman aged 40 years* presents at the pharmacy. The pharmacist recognises her as she often comes in to collect medicine for her family. They are aware that she has a history of schizophrenia and that she was started on clozapine three months ago. She receives this from her mental health team on a weekly basis.

She has visited the pharmacy to discuss constipation that she is experiencing. She has noticed that since she was started on clozapine, her bowel movements have become less frequent. She is concerned as she is currently only able to go to the toilet about once per week. She explains that she feels uncomfortable and sick, and although she has been trying to change her diet to include more fibre, it does not seem to be helping. The patient asks for advice on a suitable laxative.

What needs to be considered?

Constipation is a very common side effect of clozapine. However, it has the potential to become serious and, in rare cases, even fatal[5],[6],[7],[8]
. While minor constipation can be managed using over-the-counter medicines (e.g. stimulant laxatives, such as senna, are normally recommended first-line with stool softeners, such as docusate, or osmotic laxatives, such as lactulose, as an alternative choice), severe constipation should be checked by a doctor to ensure there is no serious bowel obstruction as this can lead to paralytic ileus, which can be fatal[9]
. Symptoms indicative of severe constipation include: no improvement or bowel movement following laxative use, fever, stomach pain, vomiting, loss of appetite and/or diarrhoea, which can be a sign of faecal impaction overflow.

As the patient has been experiencing this for some time and is only opening her bowels once per week, as well as having other symptoms (i.e. feeling uncomfortable and sick), she should be advised to see her GP as soon as possible.

The patient returns to the pharmacy again a few weeks later to collect a prescription for a member of their family and thanks the pharmacist for their advice. The patient was prescribed a laxative that has led to resolution of symptoms and she explains that she is feeling much better. Although she has a repeat prescription for lactulose 15ml twice per day, she says she is not sure whether she needs to continue to take it as she feels better.

What advice should be provided?

As she has already had an episode of constipation, despite dietary changes, it would be best for the patient to continue with the lactulose at the same dose (i.e. 15ml twice daily), to prevent the problem occurring again. Explain to the patient that as constipation is a common side effect of clozapine, it is reasonable for her to take laxatives before she gets constipation to prevent complications.

Pharmacists should encourage any patient who has previously had constipation to continue taking prescribed laxatives and explain why this is important. Pharmacists should also continue to ask patients about their bowel habits to help pick up any constipation that may be returning. Where pharmacists identify patients who have had problems with constipation prior to starting clozapine, they can recommend the use of a prophylactic laxative such as lactulose.

Case 3: A mother is concerned for her son who is talking to someone who is not there

A woman has been visiting the pharmacy for the past 3 months to collect a prescription for her son, aged 17 years*. In the past, the patient has collected his own medicine. Today the patient has presented with his mother; he looks dishevelled, preoccupied and does not speak to anyone in the pharmacy.

His mother beckons you to the side and expresses her concern for her son, explaining that she often hears him talking to someone who is not there. She adds that he is spending a lot of time in his room by himself and has accused her of tampering with his things. She is not sure what she should do and asks for advice.

What action can the pharmacist take?

It is important to reassure the mother that there is help available to review her son and identify if there are any problems that he is experiencing, but explain it is difficult to say at this point what he may be experiencing. Schizophrenia is a psychotic illness which has several symptoms that are classified as positive (e.g. hallucinations and delusions), negative (e.g. social withdrawal, self-neglect) and cognitive (e.g. poor memory and attention).

Many patients who go on to be diagnosed with schizophrenia will experience a prodromal period before schizophrenia is diagnosed. This may be a period where negative symptoms dominate and patients may become isolated and withdrawn. These symptoms can be confused with depression, particularly in younger people, though depression and anxiety disorders themselves may be prominent and treatment for these may also be needed. In this case, the patient’s mother is describing potential psychotic symptoms and it would be best for her son to be assessed. She should be encouraged to take her son to the GP for an assessment; however, if she is unable to do so, she can talk to the GP herself. It is usually the role of the doctor to refer patients for an assessment and to ensure that any other medical problems are assessed. 

Three months later, the patient comes into the pharmacy and seems to be much more like his usual self, having been started on an antipsychotic. He collects his prescription for risperidone and mentions that he is very worried about his weight, which has increased since he started taking the newly prescribed tablets. Although he does not keep track of his weight, he has noticed a physical change and that some of his clothes no longer fit him.

What advice can the pharmacist provide?

Weight gain is common with many antipsychotics[10]
. Risperidone is usually associated with a moderate chance of weight gain, which can occur early on in treatment[6],[11],[12]
. As such, the National Institute for Health and Care Excellence recommends weekly monitoring of weight initially[13]
. As well as weight gain, risperidone can be associated with an increased risk of diabetes and dyslipidaemia, which must also be monitored[6],[11],[12]
. For example, the lipid profile and glucose should be assessed at 12 weeks, 6 months and then annually[12]
.

The pharmacist should encourage the patient to attend any appointments for monitoring, which may be provided by his GP or mental health team, and to speak to his mental health team about his weight gain. If he agrees, the pharmacist could inform the patient’s mental health team of his weight gain and concerns on his behalf. It is important to tackle weight gain early on in treatment, as weight loss can be difficult to achieve, even if the medicine is changed.

The pharmacist should provide the patient with advice on healthy eating (e.g. eating a balanced diet with at least five fruit and vegetables per day) and exercising regularly (e.g. doing at least 150 minutes of moderate-intensity activity or 75 minutes of vigorous-intensity activity per week), and direct him to locally available services. The pharmacist can record the adverse effect on the patient’s medical record, which will help flag this in the future and thus help other pharmacists to intervene should he be prescribed risperidone again.

*All case studies are fictional.

About the author

Nicola Greenhalgh is lead pharmacist, Mental Health Services, North East London NHS Foundation Trust

References

[1] Chiu CC, Lu ML, Huang MC & Chen KP. Heavy smoking, reduced olanzapine levels, and treatment effects: a case report. Ther Drug Monit 2004;26(5):579–581. doi: 10.1097/00007691-200410000-00018

[2] de Leon J. Psychopharmacology: atypical antipsychotic dosing: the effect of smoking and caffeine.Psychiatr Serv 2004;55(5):491–493. doi: 10.1176/appi.ps.55.5.491

[3] Mayerova M, Ustohal L, Jarkovsky J et al. Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations. Neuropsychiatr Dis Treat 2018;14:1535–1543. doi: 10.2147/NDT.S163839

[4] Ashir M & Petterson L. Smoking bans and clozapine levels. Adv Psychiatr Treat 2008;14(5):398–399. doi: 10.1192/apt.14.5.398b

[5] Young CR, Bowers MB & Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull 1998;24(3):381–390. doi: 10.1093/oxfordjournals.schbul.a033333

[6] Taylor D, Barnes TRE & Young AH. The Maudsley Prescribing Guidelines in Psychiatry. 13th edn. London: Wiley Blackwell; 2018

[7] Oke V, Schmidt F, Bhattarai B et al. Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis — a case report. Int Med Case Rep J 2015;8:189–192. doi: 10.2147/IMCRJ.S86716

[8] Hibbard KR, Propst A, Frank DE & Wyse J. Fatalities associated with clozapine-related constipation and bowel obstruction: a literature review and two case reports.Psychosomatics 2009;50(4):416–419. doi: 10.1176/appi.psy.50.4.416

[9] Medicines and Healthcare products Regulatory Agency. Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus. 2020. Available from: https://www.gov.uk/drug-safety-update/clozapine-reminder-of-potentially-fatal-risk-of-intestinal-obstruction-faecal-impaction-and-paralytic-ileus (accessed April 2020)

[10] Leucht S, Cipriani A, Spineli L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382(9896):951–962. doi: 10.1016/S0140-6736(13)60733-3

[11] Bazire S. Psychotropic Drug Directory. Norwich: Lloyd-Reinhold Communications LLP; 2018

[12] Cooper SJ & Reynolds GP. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. J Psychopharmacol 2016;30(8):717–748. doi: 10.1177/0269881116645254

[13] National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. Clinical guideline [CG178]. 2014. Available from: https://www.nice.org.uk/guidance/cg178 (accessed April 2020)

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Citation
The Pharmaceutical Journal, Schizophrenia case studies: putting theory into practice;Online:DOI:10.1211/PJ.2020.20207857

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