antidepressants: safety measures for all patients to improve communication of the risk of suicidal thoughts and behaviours and persistent sexual dysfunction

MHRA Drug Safety Update regarding new safety measures to enhance communication between prescribers and patients taking any antidepressant class (1):

• mandates clear, proactive discussions at initiation, dose titration, or routine clinical review regarding two key risk domains: suicidal thoughts/behaviours and persistent sexual dysfunction
  • the term "post selective serotonin reuptake inhibitor (SSRI) sexual dysfunction" ("PSSD") will be added to Patient Information Leaflets (PILs) for antidepressants associated with a risk of persistent sexual dysfunction
  • explicit inclusion of "PSSD" in product information aims to better reflect patient experiences and raise awareness among prescribers and patients
• introduces a mandatory Patient Safety Leaflet (ancillary leaflet) to be distributed by prescribers and pharmacists starting in 2027 to support informed consent and risk-benefit discussions

Advice for Healthcare Professionals

• discuss with patients when starting or changing the dose of an antidepressant or at their next review, the risk of suicidal thoughts and behaviours
  • advise patients to seek urgent medical attention if they experience new or worsening feelings of suicidal intent in relation to starting an antidepressant, especially early in treatment or following dose changes
• discuss with patients when starting or changing the dose of an antidepressant, or at their next review, that there is evidence that some antidepressants are associated with a risk of sexual dysfunction and that symptoms may continue after stopping treatment with certain antidepressants. Some patients refer to this as “PSSD”
• follow the relevant NICE guidance and monitor your patients regularly after starting treatment with an antidepressant
• give your patient the safety (ancillary) leaflet when it becomes available in 2027 to support your risks and benefits discussions
• report suspected adverse reactions associated with antidepressants on a Yellow Card

Clinical Context and Risk Factors

• suicidal thoughts and behaviours:
  • highest vulnerability occurs during initial treatment initiation, brand or formulation switching, and dose titration upward or downward
  • patients, families, and carers must be alerted to early warning signs (such as agitation, akathisia, worsening anxiety, or sudden mood shifts) and provided with clear emergency contact pathways
• persistent sexual dysfunction (PSSD):
  • sexual dysfunction (e.g., erectile dysfunction, anorgasmia, loss of libido, genital anaesthesia) is a recognized side effect during active treatment across several antidepressant classes
  • while the term "PSSD" specifically incorporates "SSRI" (post selective serotonin reuptake inhibitor sexual dysfunction), persistent post-withdrawal sexual dysfunction is also reported with serotonin-norepinephrine reuptake inhibitors (SNRIs) and other serotonergic agents; prescribers must explicitly inform patients that in a subset of individuals, sexual symptoms may persist even after complete withdrawal and discontinuation of the antidepressant
• routine monitoring and reporting:
  • close clinical review must be maintained in accordance with NICE depression and anxiety guidelines
  • clinicians are encouraged to use the MHRA Yellow Card scheme to report any suspected cases of persistent post-withdrawal sexual dysfunction or severe psychiatric adverse effects

Reference:

1. Medicines and Healthcare products Regulatory Agency (MHRA). Antidepressants: new safety measures for all patients to improve communication of the risk of suicidal thoughts and behaviours and persistent sexual dysfunction. Drug Safety Update. Published October 2026.