Table 2.

Aetiology and mitigation of neutropenia; clinical outcomes.

Patient number	Aetiology of previous neutropenia	Initial management of neutropenia	Outcome	Progress
1	CIN	G-CSF as required	Discharged: 54.0 months after starting clozapine	Mental state improved with clozapine. The patient had six red results during the first two months of treatment with a neutrophil nadir of 0.4 × 109/l; these episodes responded to PRN (as required) G-CSF before the strategy was switched to regular G-CSF. The patient was prescribed regular filgrastim 15 million units weekly. There were no further red results. The patient was discharged to conditions of lesser security.
2	CIN	G-CSF regular	Death: 59.1 months after starting clozapine	Mental state improved with clozapine. The patient was prescribed regular filgrastim 30 million units twice weekly. There were no reported side effects associated with G-CSF. The patient died of an unrelated myocardial infarction 59.1 months after restarting clozapine
3	CIN	G-CSF as required	Clozapine discontinued: 72.6 months after starting clozapine	Mental state improved with clozapine; psychotic symptoms were more manageable. Time nursed in LTS reduced on clozapine from 88% to 4%. The patient was transferred to a less restrictive ward environment. PRN G-CSF was available in the event of neutropenia; this was not needed. Clozapine was discontinued after 72.6 months due to poor clozapine absorption related to an inflammatory bowel condition. At the second census date, the patient remained detained in conditions of high security.
4	CIN	G-CSF regular	Clozapine discontinued: 119.6 months after starting clozapine	Mental state improved with clozapine. The patient was initially prescribed regular filgrastim 15 million units three times per week. The patient refused regular G-CSF after approximately five years. PRN (as required) G-CSF was subsequently available in the event of neutropenia; this was not needed. Splenomegaly was noted on ultrasound imaging; this continues to be monitored by haematology colleagues; no other intervention has been required. Clozapine was discontinued after 119.6 months due to patient refusal. At the second census date, the patient remained detained in conditions of high security.
5	CIN	G-CSF regular	Discharged: 28.6 months after starting clozapine	Mental state improved with clozapine. Time nursed in LTS reduced on clozapine from 87% to 6%. The patient was prescribed regular filgrastim 48 million units weekly. There were no reported adverse effects associated with G-CSF. The patient was discharged to conditions of lesser security 28.6 months after restarting clozapine.
6	Medication induced	G-CSF as required	Continues on clozapine in HSS	Mental state improved with clozapine. The patient developed neutropenia after 55 months of clozapine treatment when lamotrigine was introduced. Two doses of filgrastim 30 million units were given over three days; lamotrigine was withdrawn and clozapine continued. There has been no further neutropenia. At the second census date, the patient remained on clozapine in conditions of high security.
7	Medication induced	Watch and wait	Clozapine discontinued: 0.7 months after starting clozapine	The patient developed neutropenia on risperidone prior to clozapine use. Mental state improved with clozapine which titrated to 200 mg. However, a neutropenia of 1.3 × 109/l within the first month of treatment occurred and clozapine was withdrawn. The rechallenge had occurred in December, at the time of the neutropenia the treating psychiatrist was on leave, decision making passed to the covering psychiatrist who took a cautious approach.
8	Medication induced	Watch and wait	Discharged: 52.6 months after starting clozapine	The patient developed neutropenia on sodium valproate prior to clozapine use. Mental state improved with clozapine. There were no episodes of neutropenia following clozapine rechallenge. The patient was discharged to conditions of lesser security 52.6 months after restarting clozapine.
9	Autoimmune	G-CSF as required	Continues on clozapine in HSS	Mental state improved with clozapine. The patient was monitored using the BEN reference ranges with provision for G-CSF in the event of neutropenia; this has not been needed. As at the second census date, the patient remained on clozapine in conditions of high security.
10	BEN	Lithium	Discharged: 52.7 months after starting clozapine	Mental state improved with clozapine. The patient was initially prescribed lithium at 400 mg per day to increase neutrophil count; this was not tolerated by the patient due to sedation. G-CSF was subsequently made available in the event of a neutropenia; this was not required. The patient was discharged to conditions of lesser security 52.7 months after starting clozapine.
11	BEN	G-CSF as required	Continues on clozapine in HSS	Patient had previous exposure to clozapine prior to BEN diagnosis; clozapine was previously stopped when neutrophils fell below the non-BEN levels. Mental state improved with clozapine rechallenge. The patient was prescribed lenogastrim 263 µg if neutrophils fell below 1.0 × 109/l; this was required only once within one month of restarting clozapine when neutrophil count fell to 0.9 × 109/l. No side effects were reported due to use of G-CSF. At the second census the patient remained on clozapine in conditions of high security.
12	BEN	Watch and wait	Discharged: 48.8 months after starting clozapine	Mental state improved with clozapine. Neutropenia was initially managed by optimizing neutrophil counts with afternoon sampling and exercise. The patient rapidly developed repeated low neutrophil counts with a nadir of 0.4 × 109/l. Episodes of neutropenia were initially treated with PRN (as required) G-CSF, which was later converted to regular G-CSF. The patient was prescribed regular filgrastim 15 million units on alternate days. There were no reported adverse effects associated with G-CSF. The patient was discharged to conditions of lesser security 48.8 months after starting clozapine.
13	BEN	G-CSF regular	Discharged: 17.4 months after starting clozapine	Patient had previous exposure to clozapine prior to BEN diagnosis; clozapine was previously stopped when neutrophils fell below the non-BEN levels. Mental state improved with clozapine rechallenge. The patient was prescribed regular filgrastim 30 million units twice weekly. There were no reported adverse effects associated with G-CSF. The patient was discharged to conditions of lesser security 17.4 months after starting clozapine.
14	BEN	Lithium	Discharged: 30.5 months after starting clozapine	Mental state improved with clozapine. The patient was initially prescribed lithium at 800 mg per day to increase neutrophil count: this predated clozapine treatment. There were no reported side effects associated with lithium. There were no episodes of neutropenia. The patient was discharged to conditions of lesser security 30.5 months after starting clozapine.

BEN, benign ethnic neutropenia; CIN, clozapine-induced neutropenia; G-CSF, granulocyte-colony stimulating factor; HSS, high secure services; LTS, long-term seclusion; PRN, pro re nata.