The United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) has announced new antidepressant safety measures for all patients, following a review prompted by concerns from patients and families. The changes require clearer suicide-risk information for patients of all ages, which is currently limited to children and young adults. For the first time, the measures also recognize Post-SSRI Sexual Dysfunction (PSSD) from certain antidepressants, which can continue even after the drugs are stopped.
Citizens Commission on Human Rights International (CCHR), a 57-year mental health industry watchdog, points out that the MHRA has once again acted before the U.S. Food and Drug Administration (FDA). CCHR calls on the FDA to issue equivalent warnings. The group's push highlights a long-standing gap in U.S. labeling that could leave millions of Americans without the full safety information now available in the UK and Europe.
The MHRA's action follows a history of regulatory divergence. In December 2003, the MHRA was the first to issue warnings that SSRI antidepressants increased suicide and self-harm risk in young people, brought to their attention by Dr. David Healy, professor of psychiatry at Bangor University in the UK. The FDA had relevant data for decades. A 1985 memo from the manufacturer of the SSRI antidepressant fluoxetine reported a suicide rate for the drug 5.6 times higher than for the older tricyclic antidepressants. In 1991, CCHR helped secure an FDA Psychopharmacologic Drugs Advisory Committee hearing into antidepressants causing suicidal ideation and violent behavior; the panel, many with conflicts of interest with pharmaceutical companies, negated the risks.
In October 2004, almost a year after the MHRA's warning, the FDA added a black-box warning for suicidal ideation in those 18 and younger, later extended to age 24. This left the implication that the risk ends on a person's 25th birthday. Dr. Healy, also an expert psychopharmacologist, warned in 2009 that antidepressants pose a risk of suicide in all age groups, citing elevated relative risks for completed suicide in ages 18–64 based on FDA trial data.
In 2018, Healy and colleagues also raised concerns about antidepressant-induced sexual dysfunction that can persist after stopping the drugs. Healy was among 22 international experts who petitioned the FDA to require prominent warnings that these drugs can reduce genital sensitivity—sometimes within 30 minutes of the first dose—with effects that may last for years or indefinitely after discontinuation. The FDA has not issued class-wide labeling to match the petition.
The MHRA is adding Post SSRI Sexual Dysfunction to patient information leaflets for the antidepressants citalopram, escitalopram, duloxetine, fluvoxamine, fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, and nortriptyline. Symptoms include genital numbness, loss of libido, erectile dysfunction, and difficulty reaching orgasm. In the U.S., psychiatrist Josef Witt-Doerring, a former FDA medical officer, reported that many taking antidepressants may experience emotional numbing, loss of sexual sensation, and detachment from pleasure—effects that can persist indefinitely. Harvard's Dr. Joseph Glenmullen warned in Prozac Backlash that SSRIs caused sexual dysfunction in up to 60% of users.
Other regulators have acted. In 2019, the European Medicines Agency adopted product information updates to warn that SSRIs and SNRIs may cause long-lasting sexual dysfunction that may continue despite discontinuation of treatment. In 2021, Health Canada completed a safety review and also announced updates to the labeling and product safety information to reflect the risk. In the UK, healthcare professionals must now discuss suicide risk and persistent sexual dysfunction when starting antidepressants, changing doses, or reviewing treatment. UK health chiefs announced that patient information leaflets will be updated to make the risks more prominent, through the use of boxed warnings.
Patients need clear and accessible information about the benefits and risks of medicines so they can make informed decisions, Dr. Alison Cave, chief safety officer at the MHRA, said. The IQVia Total Patient Tracker Database for 2020 revealed 45,204,771 Americans were taking antidepressants, including 2,154,118 in the 0-17 age group. CCHR urges the FDA to align U.S. labeling and patient information with the MHRA's updated measures. Clear, prominent warnings on suicide risk for all ages and on persistent sexual dysfunction would give American patients and families the same information already being provided in the UK and Europe. Until the FDA acts, millions of people taking these drugs are at risk, without the full safety disclosures now required elsewhere.
