The Maudsley Prescribing Guidelines — Study Notes

Pneumonia (antipsychotic-associated)

Pages 204–205 · Table 1.47 · Box 1.2

Background — evidence of association

• 2018 meta-analysis (14 observational studies, n = 206,899): antipsychotic use associated with a near doubling of pneumonia incidence vs no use. No difference between FGAs and SGAs, and no increase in fatality rate.
• Later analysis of US FDA spontaneous reports: relatively greater incidence with clozapine, olanzapine and antipsychotic polypharmacy (compared with haloperidol).
• 2024 20-year observational study in Finland (n = 61,889): increased risk of hospitalisation with pneumonia on antipsychotic monotherapy vs no antipsychotic use.

Is it causal? (disputed)

• One study of >8,000 people looked at incidence before and after starting various antipsychotics: no change overall or for any individual antipsychotic.
• A case–control study found duration of antipsychotic use was just one of three factors linked to increased risk (the others: severity of illness and comorbidity index).
• Schizophrenia itself seems to give a higher risk of complications (e.g. intensive care admission) in people with pneumonia, although neither diagnosis nor age appears to modify the effect of antipsychotic use on pneumonia.
• Risk of antipsychotic-associated pneumonia is increased both in patients with Alzheimer's disease and in those without.

* Not found in one study. ** Lithium seems to have a protective effect.

Which antipsychotics?

• Risk seems most pronounced with antipsychotics with high anticholinergic effects — notably clozapine and high-dose olanzapine or quetiapine — and is probably dose dependent.
• Clozapine is most often associated, with an estimated incidence of up to 30% (although TRS itself increases pneumonia risk by two-thirds).
• In two studies, clozapine re-exposure was associated with a greater risk of recurrent pneumonia than the baseline risk with initial clozapine treatment.
• Aripiprazole (and probably other dopamine partial agonists) seems to have a lower risk than pure dopamine antagonists.
• Amisulpride (a dopamine antagonist with minimal anticholinergic activity) was not linked to pneumonia in another study.

Mechanisms

Studies rarely distinguish between forms of pneumonia, but cases of antipsychotic-induced aspiration, infective (viral and bacterial) and hypersensitivity pneumonia have been documented. The mechanism is not known but is probably multifactorial.

Management

• Assume an increased risk of pneumonia for all patients taking any antipsychotic (but especially clozapine) for any period.
• Monitor all patients very carefully for signs of chest infection and start effective treatment promptly.
• Consider COVID-19, influenza and pneumococcal vaccines, although there is no direct evidence of benefit for pneumonia prevention in this specific group.
• Clozapine patients: proactively monitor and treat hypersalivation.
• Pneumonia is likely to increase clozapine levels, so close monitoring is required.
• Slower-than-usual clozapine titration may prevent cases of hypersensitivity pneumonia.
• Extra vigilance when re-exposing patients with a history of clozapine-induced pneumonia.
• Consider early referral to general medical services where there is any doubt about the severity or type of chest infection.