Reversible cerebral vasoconstriction clusters within days of starting triptans, SSRIs and related drugs

Design

Case-non-case disproportionality study in the WHO pharmacovigilance database (VigiBase, extract June 2025)

Population

735 CNS vasculitis cases and 1,553 reversible cerebral vasoconstriction syndrome cases

Primary outcome

Drugs disproportionately reported with each syndrome; time to onset

Effect

Teprotumumab with RCVS: 6 cases, adjusted ROR 60.17 (95% CI 18.66 to 194.05); female sex adjusted ROR 2.57 (95% CI 2.23 to 2.97)

A case-non-case study in the WHO pharmacovigilance database identified 735 cases of CNS vasculitis and 1,553 cases of reversible cerebral vasoconstriction syndrome (RCVS). It used adjusted reporting odds ratios and examined time to onset, dechallenge and fatality.

CNS vasculitis was mainly associated with the immune checkpoint inhibitors pembrolizumab and nivolumab and with propylthiouracil, at a median of about 36 days after starting. RCVS was mainly associated with serotonergic and vasoactive drugs: triptans, ergot derivatives, SSRIs and cannabis, with a much shorter median onset of about 9 days. The strongest RCVS signal was a new association with teprotumumab (6 cases; adjusted ROR 60.17, 95% CI 18.66 to 194.05). Female sex was independently associated with RCVS (adjusted ROR 2.57, 95% CI 2.23 to 2.97).

These are spontaneous reports. They show disproportionate reporting, not risk, and the teprotumumab signal rests on six cases. Most people taking triptans or SSRIs will never have RCVS. The practical value is recognition: sudden severe headache soon after starting or increasing one of these drugs is a reason to review the medicine and arrange urgent assessment.

• Treat a sudden, severe 'thunderclap' headache soon after starting a triptan, ergot, SSRI or cannabis as an emergency needing assessment.
• Ask about recent medicines, including over-the-counter and recreational drugs, in new severe headache.
• Review the suspected drug with the treating team; do not restart it without advice.
• In patients on immune checkpoint inhibitors, consider vasculitis in new neurological symptoms.
• Report suspected cases to your pharmacovigilance centre.

Why it matters

It separates two drug-induced neurovascular syndromes by timing, which helps in deciding what to suspect and when.

Don't overread it

These are spontaneous reports, which show reporting patterns rather than risk, and the teprotumumab signal comes from six cases.

The statistics, in plain English

A reporting odds ratio of 60 means the drug appeared in RCVS reports far more often than expected among all reports. With only six cases the interval (18.66 to 194.05) is very wide, and it cannot be turned into a risk because the number of people exposed is not known.

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