However, in 2008 she developed neutropenia from clozapine leading to its discontinuation. This resulted in a major relapse warranting hospital admission. She then had trials of medications which included amisulpride 1200 mg/day, olanzapine up to 30 mg/day (above BNF maximum) and aripriprazole 30 mg/day, all of which failed to control her symptoms. The team had to finally rechallenge her with clozapine with limited further options. She immediately developed red results due to neutropenia and clozapine #Bcr-Abl inhibitor keyword# was completely stopped. She was then initiated with risperidone at 8 mg/day, which produced minimal response and severe extrapyramidal side

effects, necessitating discontinuation. She quickly relapsed and was eventually readmitted as Inhibitors,research,lifescience,medical an inpatient, exhibiting severe incongruous laughter, agitation, hostility, verbal aggression, delusions of persecution and control, somatic passivity and auditory hallucinations. As quetiapine had not been considered previously, it was initiated with Inhibitors,research,lifescience,medical the dose increased up to 750 mg daily. At the 750 mg dose, it was noted that only her behavioural symptoms had responded. She became less agitated and more amenable. However, her delusions and hallucinations persisted. At this stage a trial of a high dose of over 750 mg/day (above BNF limit) was considered as she had failed to respond adequately to various combinations

as listed above. When the dose of quetiapine reached 1000 mg daily, noticeable improvement was produced in her delusions Inhibitors,research,lifescience,medical and hallucinations. She reported feeling ‘much improved’. The dose was eventually increased up to 1400 mg daily with close monitoring. This dose was well tolerated. The only side-effect reported was that of sedation, which improved by switching her from the once-daily modified release formulation of 1400 mg/day to the standard formulation of quetiapine Inhibitors,research,lifescience,medical administered in divided doses of 400 mg (morning)

and 1000 mg (night). She eventually reported herself to be ‘very much improved’ and ‘back to her normal self’. She was successfully discharged from inpatient care back into the community. Discussion Clozapine and quetiapine ever have some pharmacological similarities, which include the quick dissociation from D2 receptors. This shared property may explain the efficacy of high-dose quetiapine in the above two cases which have previously only responded to clozapine. Kapur and Seeman have discussed this property in their neuroimaging study on antipsychotic drugs’ fast dissociation from D2 receptors [Kapur and Seeman, 2001]. Interestingly, in both of our patients, doses of quetiapine up to 800 mg/day only had an effect on reducing their behavioural symptoms, but their delusions persisted. It was only when the doses went up to 1000 mg/day that significant benefits were gained for the psychotic symptoms.