Missing Warnings About ‘Persistent’ Sexual Dysfunction in Labeling of Common Antidepressants: Public Citizen Sues FDA for Failure To Act

Generally approved in the 1990s by the Food and Drug Administration (FDA), selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used by millions of Americans, mainly to treat major depression or certain other psychiatric conditions, such as anxiety and obsessive-compulsive disorder. Common examples of these drugs include fluoxetine (PROZAC) and venlafaxine (EFFEXOR XR).

Although U.S. labeling of SSRIs and SNRIs warns that sexual problems (dysfunction) can potentially occur during treatment with these drugs, such warnings are unacceptably insufficient, according to an April 2018 FDA petition submitted by an international group of clinicians and researchers.[1]

The petitioners requested the addition of boxed warnings — the most prominent warnings that the FDA can require — in the labels of these drugs to indicate that serious sexual dysfunction can emerge during treatment and remain afterwards or emerge or worsen when these drugs are stopped.

The petitioners also requested that the FDA require the issuance of a Dear Health Care Provider letter to inform clinicians who prescribe SSRIs and SNRIs of persistent sexual dysfunction risks. They also asked the FDA to develop a medication guide and communication plan to make patients aware of these risks.

Although the petition was filed six years ago, as of August 2024 the FDA had not responded to it. Therefore, in May 2024 Public Citizen sued the FDA due to this harmful delay.

As shown in the Table below, Public Citizen’s Health Research Group has designated almost all SSRIs as Limited Use because they have a boxed warning about their increased risk of suicidal thoughts and behaviors in children, adolescents and young adults.[2] SSRIs are associated with other serious adverse effects, including seizures, abnormal bleeding and a rare but potentially fatal condition called serotonin syndrome.

Likewise, we have designated SNRIs as either Limited Use or Do Not Use depending on whether they are associated with more adverse effects than alternative medications.

Table: SNRIs and SSRIs Available in the United States[3]

†A brand-name combination drug that contains another active ingredient
*Designated as Limited Use by Public Citizen’s Health Research Group
**Designated as Do Not Use by Public Citizen’s Health Research Group
Note: Unless noted otherwise, the Health Research Group’s designations are the same for brand-name drugs and their generic versions.

The 2018 FDA petition

Current U.S. labeling of SSRIs and SNRIs acknowledges that these drugs can cause symptoms of sexual dysfunction in males (including decreased sex drive [libido] and ejaculation or erection problems) and females (including decreased sex drive or orgasm problems [known as anorgasmia]).[4] A commonly held assumption among clinicians is that these symptoms typically subside after the drug is stopped because, except for a vague mention regarding fluoxetine, the labeling of these drugs does not indicate that such symptoms can persist.

To support the concerns about the persistence of impaired sexual function related to all SSRIs and SNRIs, the petitioners discussed evidence demonstrating that symptoms of sexual dysfunction can linger for years or even indefinitely after these drugs are discontinued. They also discussed that in some cases, such effects only emerge or worsen when the drugs are stopped and that such problems can occur after only a brief exposure to these drugs.

For example, sexual dysfunction persisted after treatment discontinuation among 21% of 1,475 SSRI users who submitted voluntary adverse drug reaction reports through early January 2018 to the U.K. government. Likewise, out of 300 case reports of lasting drug-induced sexual dysfunction from several countries received by some of the petitioners, 41 pertained to SSRI or SNRI users whose symptoms only appeared or worsened substantially when these drugs were stopped.[5] Additionally, a systematic review of animal studies showed considerable and enduring effects on sexual behavior after exposure to an SSRI early in life.[6]

The petitioners highlighted two types of persistent sexual dysfunction that are not reflected in the labeling of SSRIs and SNRIs. The first, called post-SSRI sexual dysfunction, is characterized by genital anesthesia (numbing) and pleasureless orgasm. The second condition, called persistent genital arousal disorder, is characterized by a relentless and uncontrollable feeling of arousal in the genitals without any feeling of sexual desire. Both conditions make it “difficult or impossible to engage in normal intimate relationships,” according to the petitioners.

Public Citizen lawsuit

International drug regulators acted on similar petitions. In 2019 and 2021, respectively, the European Medicines Agency and Health Canada revised the labeling of SSRIs and SNRIs to warn that there have been reports of long-lasting sexual dysfunction with symptoms persisting after discontinuation of these drugs.[7],[8]

In contrast, the FDA has not responded to the 2018 petition. Therefore, in May 2024, Public Citizen sued the FDA for its inaction.[9] In this lawsuit, Public Citizen represented Dr. Antonei B. Csoka, one of the scientists who submitted the petition.

The lawsuit alleges that the FDA has behaved unlawfully by failing to act on the petition and asks the Court to compel the FDA to issue a decision on the petition. “The FDA needs to act in a timely way to inform the public about the risks associated with use of these drugs,” said Michael Kirkpatrick, an attorney with Public Citizen’s Litigation Group and lead counsel on the case.

What You Can Do

If you have a mental health condition, try behavioral therapy. SSRIs and SNRIs should be reserved for severe cases.

If you are currently using an SSRI, SNRI or another antidepressant, do not decrease your dose or stop taking that drug without consulting your clinician.

If you are experiencing symptoms of sexual dysfunction and are currently using or have used SSRIs or SNRIs in the past, do not be shy to discuss your condition with your clinician.

Call your clinician or seek emergency medical help, as appropriate, if you are taking an SSRI or SNRI and develop signs and symptoms of serotonin syndrome, such as confusion, high fever, elevated blood pressure, rapid heartbeat or muscle rigidity.
 

References

[1] Healy D, Bahrick AS, Ben-Sheetrit J, et al. Citizen petition: Sexual side effects of SSRIs and SNRIs. Int J Risk Saf Med. 2018;29(3-4):135-147.

[2] Drug profile for SSRIs. Last reviewed April 30, 2024. https://www.worstpills.org/monographs/view/53. Accessed August 5, 2024.

[3] Food and Drug Administration. Depression medicines. September 2019. https://www.fda.gov/media/132665/download. Accessed August 5, 2024.

[4] Eli Lilly and Company. Label: fluoxetine (PROZAC). August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018936%20s112lbl.pdf. Accessed August 5, 2024.

[5] Healy D, Le Noury J, Mangin D. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases. Int J Risk Saf Med. 2018;29(3-4):125-134.

[6] Simonsen AL, Danborg PB, Gøtzsche PC. Persistent sexual dysfunction after early exposure to SSRIs: Systematic review of animal studies. Int J Risk Saf Med. 2016;28(1):1-12.

[7] European Medicines Agency, Pharmacovigilance Risk Assessment Committee (PRAC). PRAC recommendations on signals. June 11, 2019. https://www.ema.europa.eu/en/documents/other/new-product-information-wording-extracts-prac-recommendations-signals-adopted-13-16-may-2019-prac_en.pdf. Accessed August 5, 2024.

[8] Health Canada. Summary safety review - selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) - assessing the potential risk of sexual dysfunction despite treatment discontinuation. August 5, 2021. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR00254. Accessed August 5, 2024.

[9] Public Citizen. Press release: FDA sued over inaction on citizen petition. May 20, 2024. https://www.citizen.org/news/fda-sued-over-inaction-on-citizen-petition/. Accessed August 5, 2024.