Patient 1 is a 68-year-old married white British male with a diagnosis of TRS. He first presented with psychosis to psychiatric services in 1965 at age 17. Over the next four decades he was treated with a number of antipsychotic agents including sulpride, aripiprazole, haloperidol and olanzapine; all were at up to maximal British National Formulary recommended doses and a minimum of 12 weeks' duration with compliance assured during inpatient episodes; he experienced a number of relapses over time. He did not achieve remission and was started on clozapine in 2002 (dose 400 mg daily). Following that, he was functional and relatively stable for 11 years, aside from some minor residual psychotic and anxiety symptoms.
His medical history at this time included ischaemic heart disease (IHD), cardiomyopathy with an ejection fraction of 35%, congestive heart failure (NYHA II) and bilateral pedal oedema. In 2014, following a decline in his cardiac function, his maintenance clozapine dose was reduced from 350 mg to 300 mg daily. Unfortunately, this was followed by a severe psychotic relapse characterized by prominent thought disorder, paranoid delusions, self-neglect and increasingly aggressive and challenging behaviour. His clozapine dose was increased back to 350 mg but his mental state continued to deteriorate and due to violence and aggression he was transferred to a psychiatric intensive care unit in March 2015.
In August 2016 he was admitted to the National Psychosis Unit, having been an inpatient for over 2 years. His symptoms at this time included persistent persecutory delusional beliefs, obsessive-compulsive traits, anxiety, mood lability, prominent difficulties in concentration and memory and irritability with outbursts of aggression. Psychotropic medication on admission included lurasidone 111 mg (which he had been treated with for over 1 year), sertraline 100 mg and diazepam 6 mg daily. On admission, he scored 115 on the PANSS total score and 29/30 on the Mini Mental State Exam (MMSE). An MRI brain scan was within normal limits; blood tests on admission were mostly within normal limits, except for a raised urea of 13.9 mmol/L (3.3-6.7) and an increased prolactin level of 894 mIU/L (100-410), attributed to lurasidone. The pharmacotherapeutic approaches considered included a trial of high-dose olanzapine, switching from sertraline to vortioxetine because of the added benefit in attention and cognitive flexibility, or adding either memantine or donepezil as adjuncts to aid cognition.
In August 2016 it was decided to increase his lurasidone dose to 148 mg daily. Sertraline was switched to adjunct vortioxetine 10 mg, which was gradually titrated to 20 mg over the next couple of weeks. By September 2016 there was noticeable improvement in symptoms, and by December 2016 he was in remission, scoring 44 on the PANSS total score. Pregabalin 25 mg BD was prescribed as an anxiolytic after stabilization on lurasidone and vortioxetine, and benzodiazepines were down-titrated and stopped. He was successfully discharged home in January 2017. Psychotropic medication on discharge included lurasidone 148 mg, vortioxetine 20 mg and pregabalin 25 mg BD. He described his wellbeing as 9 out of 10, compared to having been 1 out of 10 at admission. The family described his change as 'miraculous, and that he had not been so well, even while being treated with clozapine'. Subsequent follow up confirmed a sustained functional and symptomatic recovery.