The patient is a 51-year-old man of Somali origin with a diagnosis of treatment resistant schizoaffective disorder, who first came to the UK in 1990. He was referred to psychiatric services in 2001 at the age of 31. For the 8-year period following this, he had a number of psychiatric admissions due to frequent relapses in his mental state. It was not until 2010, when he was started on clozapine together with lithium during an admission, that he experienced good clinical response.
Unfortunately, later in the year 2010, the patient travelled abroad and ran out of medication, resulting in relapse. He was admitted to hospital under Section 3 of the Mental Health Act (MHA) upon return to Britain. This section allows for a person to be admitted to hospital for treatment if their mental disorder is of a nature and/or degree that requires treatment in hospital. In addition, it must be necessary for their health, their safety or for the protection of other people that they receive treatment in hospital. He has been hospitalised almost continuously since then. Up until 2017, when he was referred to our unit, he had been managed in various psychiatric in-patient settings. He was trialled on clozapine on two further occasions but discontinued each time in the context of poor compliance with oral treatment and blood monitoring. Treatment with clozapine showed good response and relative stability in his mental state, as compared with rapid and severe deterioration seen with discontinuation. When unwell and severely psychotic he presented as highly distressed, with high risk towards himself in the form of suicide attempts and self-neglect, and towards others through verbal threats and episodes of violence in response to his psychotic experiences.
During the brief periods when he received clozapine treatment (in total, less than 12 months), he developed cardiac symptoms. In 2012, he had episodes of tachycardia and chest pain and a partial right bundle branch block (RBBB) was noted on his electrocardiogram (ECG). Due to non-attendance at cardiology appointments, he was discharged from cardiology follow up. In 2015, he had persistent tachycardia on clozapine and attended accident and emergency (A&E) after he developed palpitations, chest pain and shortness of breath, with evidence of a soft systolic murmur on examination. In 2016, RBBB was again noted on an ECG, but his consistent refusal to attend cardiology investigations and clinics hampered any further assessment of this. Cardiology advice given at the time was to limit clozapine dose to a maximum of 150 mg daily in the absence of further investigation, preventing the attainment of therapeutic levels. He discontinued treatment shortly after.
In the intervening periods of clozapine discontinuation, multiple other treatment approaches were trialled with inadequate response. The medications trialled included zuclopentixol decanoate depot, risperidone long-acting injection, haloperidol decanoate depot, aripiprazole depot and eventually oral olanzapine before referral and transfer in June 2017 to our unit, a locked rehabilitation ward, with an aim to re-challenge with clozapine alongside investigation of his cardiac function. At the time of transfer, he was taking olanzapine 20 mg, semi-sodium valproate 1.5 g and regular benzodiazepine, clonazepam, for agitation. Other medications prescribed included vitamin D, aspirin and lansoprazole. His medical history at this point included an old non-healed fractured left humerus, clozapine-induced constipation, and a fully treated pulmonary tuberculosis (TB).
On transfer in June 2017, RBBB on ECG and a systolic murmur on examination were present, though, in his severely unstable mental state, he continued to refuse cardiology investigations and appointments. Cardiology advice was sought, which did not object to clozapine rechallenge, but advised to monitor ECG and troponins during treatment.
The patient was eventually re-commenced on clozapine in January 2018, and titrated to 300 mg daily using an oral/intramuscular titration regimen. In the third week of clozapine titration at a dose of 350 mg daily, he experienced persistent cough and was feeling generally unwell. Bloods showed normal troponin and a mildly raised C-reactive protein (CRP). ECG showed T-wave inversion, borderline prolonged PR interval and a QTc of 440 msec. He was treated for suspected pneumonia with antibiotics and clozapine treatment continued. Following considerable improvement in mental state, the team were able to take him for an echocardiography in June 2018, which demonstrated moderate-to-severely reduced left ventricular function, with an ejection fraction of 37%. He was given a diagnosis of left ventricular heart failure by cardiologists at King's College Hospital, and commenced on ramipril and bisoprolol. At the time of this diagnosis, the decision was made with cardiology to maintain treatment with clozapine at a dose of 300 mg daily as it had been highly beneficial to his mental state.
Further advice was sought in October 2018 regarding a potential increase in clozapine as the patient remained unwell. His clozapine level was 0.24 mg/l, which is below the recommended range of 0.35-0.5 mg/l according to the Maudsley prescribing guidelines. However, cardiology advised against dose increases without an improvement in cardiac function. Both ramipril and bisoprolol were gradually titrated upwards to 10 mg daily with close monitoring of blood pressure, heart rate and renal function, particularly in the context of co-prescription with lithium. Eplerenone 25 mg was added to heart failure treatment in November 2018; however, this was discontinued following worsening renal function and an increase in lithium levels.
A repeat echocardiogram in November 2018 showed that the patient's cardiac function had improved with treatment using ramipril and bisoprolol, and his left ventricular function was within normal limits, with an ejection fraction of 56%. The subsequent advice from the cardiology team was that, in light of the improved ejection fraction, it would be safe to continue clozapine and that further increases could be done alongside ECG and troponin measurements.