To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.

To investigate the impact of this temporary policy change on clinical and safety outcomes.

All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.

Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.

There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

‘Rebound’ or ‘withdrawal’ symptoms are frequently observed after a sudden discontinuation of clozapine. We describe a patient with treatment-resistant schizoaffective disorder who developed agranulocytosis on clozapine but was successfully switched to treatment with olanzapine with no deterioration in her condition. We put forward three possible theories which may have accounted for the lack of rebound symptoms in this patient: the pharmacological profile of olanzapine, the anticholinergic effects of hyoscine hydrobromide, and the possibility that this patient may not be treatment-resistant and so have a reduced risk of rebound psychosis due to displaying a different pathophysiology.

None.

To provide additional data concerning the safety, effectiveness and local prescribing trends of clozapine in elderly patients.

Retrospective observational case-series analysis.

Data were collected from the medical files of 167 patients prescribed clozapine.

All patients prescribed clozapine in the last 15 years by the psychogeriatric service in Christchurch, New Zealand. The subjects were mostly aged over 65; however, patients under 65 are also accepted into the service on a case by case basis if they have an age-related health condition.

Twenty-five (15.0%) patients had their clozapine stopped due to a significant adverse reaction, including eleven who developed significant neutropenia. Seventy-four (44.3%) of the patients had no recorded side effects at all. Sixty-five (38.9%) of our elderly patients died while taking clozapine, though none of these deaths was felt to be related to clozapine use. Several patients safely initiated clozapine in either their own home or a nursing home without requiring hospital admission. Only two patients ceased clozapine due to ineffectiveness, and one hundred, forty-two (86.1%) of the patients had positive comments in their medical record regarding the benefits of clozapine for their particular case.

We found clozapine could be used safely and effectively in our patient group, for a wider range of indications and at lower doses than younger patients. Data collection regarding cause of death in elderly patients who were ever prescribed clozapine was problematic, and more research into this area is required.

Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.

A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.

Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.

The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.