In England, there are several medicines that are generally prescribed by mental health trusts on an ongoing basis, most notably clozapine and long-acting antipsychotic injections. Consequently, there is a risk that these medications may not be documented on GPs’ clinical systems, which if missed can result in:
- Drug interactions between clozapine and other medicines (e.g. co-trimoxazole, carbamazepine, chloramphenicol) not being alerted through GP clinical decision-making software. In addition, patients presenting with physical health concerns, such as constipation, may not be considered as experiencing side effects from clozapine;
- Healthcare professionals in secondary care, particularly those in acute services (who often rely on Summary Care Records [SCR] to complete medicines reconciliation), accessing incomplete medication records that could lead to omission of clozapine and unnecessary deterioration of a patient’s mental health.
Although clozapine-induced agranulocytosis is often the foremost safety concern, there is increasing concern regarding clozapine-induced constipation. In 2017, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a drug safety alert on the gastrointestinal adverse effects of clozapine. The alert stated that healthcare professionals should:
- Advise patients to report constipation immediately;
- Actively treat any constipation that occurs;
- Exercise particular care in certain patient groups.
Following a series of incidents within Hertfordshire Partnership University NHS Foundation Trust (HPFT), the author was concerned about the lack of records of clozapine treatment on the GP clinical system. A short study was therefore undertaken in November 2019, with the support of local commissioners, to identify the frequency of recording of clozapine on GP clinical systems and the frequency of patients presenting with symptoms of constipation to the GP.
Clozapine service users under the care of HPFT, and selected GPs, were identified via the clozapine monitoring database and electronic patient records.
A data collection form was developed by the author, which required a member of the GP surgery to review GP clinical patient notes for each identified patient and ascertain whether:
1. There was a clear record that the patient was being treated with clozapine in the medication history section of the GP clinical system;
2. Clozapine treatment was documented in the SCR;
3. It was clearly documented that the patient receives a supply of clozapine from the local mental health trust;
4. There were any prescriptions issued for laxatives in the previous six months;
5. The patient was documented as suffering from constipation in the previous three years and whether this was attributed to clozapine.
The data collection tool was sent to each patient’s GP practice and returned via email.
A total of 199 patients were identified as being treated with clozapine by HPFT and being under the specified clinical commissioning group. Ten patients were excluded from the study, as it was not possible to identify their GP from hospital records. Data collection forms were sent to 49 GP surgeries that encompassed the 189 patients. In total, 35 GP surgeries responded and data collection forms were returned for 160 patients (85% response rate). Each GP surgery had a mean of 4 patients taking clozapine and the range was between 1 and 19 patients. In total, four surgeries had ten or more patients taking clozapine.
Some 54% (n=86) of records clearly showed that the patient was taking clozapine (and that it was prescribed by HPFT), and 51% (n=82) had clozapine on their SCR. One-quarter (n=40) of patients were taking a laxative and 28% (n=45) had complained of constipation in a consultation in the last three years. Of these 45 patients, clozapine was attributed in 29% (n=13) of cases.
Only 54% of patients having clozapine recorded clearly in GP records is in line with a similar audit completed by Parker et al. in London in 2010, in which 45% of patients did not have clear documentation in GP records that they were prescribed clozapine, as well as with a Prescribing Observatory for Mental Health (POMH-UK) audit in 2020, which indicated that 58% of patients (n=3,902) on clozapine nationally had the drug recorded on their SCR[3,4].
As part of the audit, GP surgeries were instructed how to record clearly and asked to confirm when this had been completed. This was done for all 160 patients, and now at least 80% of the original 199 identified patients who are being treated with clozapine have accurate GP records and SCR.
The implications for medication safety are extremely significant. GP records and SCRs are used by the wider healthcare team and need to be accurate for the safety of the patient.
Only 25% of patients were prescribed a laxative, which we can use as a proxy for the presence of constipation. This number is lower than that in a study by Bailey et al., which showed that 34–36% of patients had a laxative prescribed, and much lower than the prevalence of clozapine-induced constipation, which is thought to be 35–60%[5,6].
However, constipation is not always associated with patients’ clozapine use and is only attributed in 29% (n=13) of occasions. If GP records were clearer and awareness of this side effect was more common, then this association may be higher.
When laxatives were prescribed (n=40), most patients only required one laxative (55%); the most prescribed laxative was macrogol (30%, n=19), followed by senna (23%, n=15) and lactulose (16%, n=10).
Guidelines on the use of laxatives in clozapine are suggested in The Maudsley Prescribing Guidelines in Psychiatry and Clozapine Handbook; however, the body of evidence on which treatment to select for clozapine-induced constipation is not strong[6,7].
The 2017 MHRA alert highlighted a lack of awareness of the gastrointestinal complications associated with clozapine. The low use of laxatives in this patient group in this audit highlights similar findings. Work needs to be done locally and nationally, among healthcare professionals and patients, to address this issue and make the use of clozapine safer for those that need it.
This audit identified that there are gaps in the recording of hospital-only medications, such as clozapine, on GP clinical systems. This can impact clinical decision-making for GPs, hinder medicines reconciliation that relies on the use of SCR and have a detrimental effect on medication safety. It also highlighted that there is still work to do to raise awareness of the gastrointestinal complications associated with clozapine.
In response to these findings, a local action plan has been drawn up:
- A new trust clozapine policy has been written, with updated information for GPs and guidelines on the management of clozapine-induced constipation;
- Training sessions were offered to GPs and pharmacists in surgeries where a lack of awareness of clozapine has been identified following this work.
Sally Butterworth is the principal clinical pharmacist, Community Mental Health Services, and Chetan Shah is chief pharmacist at Hertfordshire Partnership University NHS Foundation Trust.
- 1Joint Formulary Committee. 80th ed. London: : BMJ Group and Pharmaceutical Press 2020.
- 2Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus. Medicines and Healthcare products Regulatory Agency. 2017.https://www.gov.uk/drug-safety-update/clozapine-reminder-of-potentially-fatal-risk-of-intestinal-obstruction-faecal-impaction-and-paralytic-ileus (accessed Mar 2021).
- 3Parker C, Somasunderam P. Audit of GP practice records of patients prescribed clozapine. Prog Neurol Psychiatry 2010;14:11–6. doi:10.1002/pnp.156
- 4Barnes TRE, MacCabe JH, Kane JM, et al. The physical health and side-effect monitoring of patients prescribed clozapine: data from a clinical audit conducted in UK mental health services. Therapeutic Advances in Psychopharmacology 2020;10:204512532093790. doi:10.1177/2045125320937908
- 5Bailey L, Varma S, Ahmad N, et al. Factors predicting use of laxatives in outpatients stabilized on clozapine. Therapeutic Advances in 2015;5:256–62. doi:10.1177/2045125315591917
- 6Taylor DM, Barnes TRE & Young AH . The Maudsley Prescribing Guidelines in Psychiatry . 13th ed. New Jersey: : Wiley Blackwell 2018.
- 7Bleakley S & Taylor D. Clozapine Handbook. Stratford Upon Avon: : Lloyd-Reinhold Communications LLP 2013.