This week, Mad in America explores four new articles around the negative effects of selective serotonin reuptake inhibitors (SSRIs). The first article finds that SSRIs triple the risk of sexual dysfunction. The second is a discussion about long-term antidepressant use and withdrawal. The third links SSRIs to increased risk of gastrointestinal bleeding. The fourth finds that service users often report not being informed about the possible negative effects of SSRIs.
SSRIs Triple the Risk of Sexual Dysfunction
A new study published in the European Journal of Clinical Pharmacology confirms many previous findings that SSRIs can cause sexual dysfunction. The study, led by Sarah Dagostin Ferraz from the Universidade do Extremo Sul Catarinense in Brazil, also reports a link between SSRIs and reduced sexual desire, but this association did not reach statistical significance.
The authors performed a review and meta-analysis of randomized controlled trials (RCTs) that evaluated sexual dysfunction as an outcome measure. Included RCTs examined adults with a depression diagnosis that were not taking antidepressants at baseline, and were randomly placed in either an SSRI or placebo group. RCTs that examined pregnant or lactating women and people with schizophrenia, bipolar, or substance abuse diagnoses in addition to depression were excluded. In total, the authors included data from 6 RCTs in their meta-analysis.
SSRI use was linked to a more than tripled risk (3.28 times more likely) of orgasmic dysfunction compared to placebo. The evidence base for this finding was rated as having high certainty. These drugs were also linked to a 21% increased risk of significantly reduced sexual satisfaction. The evidence for this finding was rated at moderate certainty. Participants taking SSRIs were 40% more likely to report decreased sexual desire, but this finding did not reach statistical significance.
This research had three main limitations. Some included studies may have had methodological or reporting biases. Included studies used different measures of sexual dysfunction. These studies generally had short follow-up periods.
Prolonged Antidepressant Use and Escalating Withdrawal Risks
In a new article published in the Australian Prescriber, Katherine Wallis of the University of Queensland in Australia identifies several risk factors linked to prolonged withdrawal when trying to quit these drugs, including longer duration of use and higher doses.
Service users are often prescribed these drugs on a long-term basis. According to NHANES data, in the US, a quarter of those taking antidepressants remain on the drugs for more than 10 years—despite the risks of long-term adverse effects. In Australia, clinical guidelines recommend deprescribing after at least one year of stability. However, the average duration of antidepressant use is four years.
Stopping or reducing antidepressants can cause withdrawal symptoms ranging from mild to severe, including anxiety, fatigue, impaired concentration, akathisia, and suicidality. Studies have found that moderate to severe withdrawal occurs for up to 80% of those trying to stop the drugs, 40% may have symptoms lasting more than two years, and 25% are unable to stop taking antidepressants altogether.
Wallis notes that withdrawal can typically be differentiated from a return of symptoms by examining how soon after dose reduction or discontinuation negative effects start, and how quickly they resolve after restarting the previous dose. Symptoms that appear within one to two days after stopping or reducing antidepressants, and disappear quickly when restarting, are likely related to withdrawal. Symptoms that take longer to return after dose reduction, and longer to resolve after restarting, are more likely related to relapse.
Wallis identifies several factors that make withdrawal more likely and more severe. Longer duration of taking these drugs, and higher doses, are both linked to more likely and more severe withdrawal. Children, adolescents, and service users taking antidepressants for withdrawal are more likely to experience withdrawal. Specific antidepressants are also more likely to trigger withdrawal symptoms, including paroxetine (Paxil), venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq), and mirtazapine (Remeron).
According to Wallis, slow tapering is the best way to avoid withdrawal symptoms when reducing or stopping antidepressants. For most service users, Wallis writes, a schedule of reducing the dose by 25% to 50% every two to four weeks can be effective. For service users that have struggled with withdrawal symptoms in the past, or those at high risk for severe withdrawal, an extremely slow taper is more likely to limit withdrawal symptoms. Service users should allow at least two weeks between each dose reduction. If moderate to severe withdrawal symptoms occur, the dose should be reverted until the symptoms subside. Wallis recommends that people reducing or stopping antidepressants maintain “a healthy lifestyle including sleep hygiene, physical activity, social support and minimising alcohol. ”
SSRIs Linked to Increased Risk of Gastrointestinal Bleeding
A new study published in The International Journal of Medical Science and Health Research finds that SSRIs are linked to an increased risk of both upper and lower gastrointestinal (GI) bleeding. This research, led by Sabrina Dwi Elvira from Hang Tuah University in Indonesia, also reports that the combination of SSRIs and NSAIDs significantly increase GI bleeding risk.
The goal of this research was to examine the link between SSRI use and GI bleeding. The authors conducted a review of RCTs and controlled observational studies with adult patients exposed to SSRIs that reported GI bleeding as am outcome. In total, the authors used data from 23 studies. This included 20 controlled observational studies and 3 RCTs.
SSRI exposure was linked to between 22% and tripled risk of upper GI bleeding. The overall combined increased risk of upper GI bleeding was 67%. SSRIs were also linked to a nearly tripled risk (2.96 times more likely) of lower GI bleeding. The combination of SSRIs and NSAIDs was linked to a more than quadrupled risk (4.25) of GI bleeding. Adding aspirin to SSRIs and NSAIDs astronomically increased the risk of GI bleeding (28 times more likely). The authors note that proton pump inhibitors prescribed alongside SSRIs significantly reduced the increased risk of upper GI bleeding.
This research had two main limitations. Most of the included studies were observational. This means the results cannot definitively say that SSRIs cause GI bleeding. Studies used varying definitions of “current” and “past” SSRI exposure. This limited the author’s ability to perform subgroup analyses.
Service Users Report Receiving Inadequate Information About SSRI Risks
A new peer-reviewed report published by the Inner Compass Research Institute finds that service users often report not being told about possible negative effects of SSRIs. This research, led by Nicolas Badre from the University of San Diego, reports that many service users said they would have been less likely to start SSRIs if they had been told about all the possible negative effects.
The goal of this study was to examine which SSRI negative effects patients could recall being told about and assess whether service users felt adequately informed. The authors recruited 1,260 US adults that had been prescribed SSRIs to participate in an online survey about SSRI negative effects they could recall clinicians discussing with them and what negative effects they would have liked to be informed about before starting SSRIs.
Less than 1% (0.6%) of participants reported being informed about all 11 possible negative effects covered in the survey. Just 11.2% said they had been informed about all the possible negative effects they would have wanted to know about. Forty-three-point-nine percent of participants reported that knowing about all the possible negative effects of SSRIs would have made them less likely to take these drugs.
This study had four main limitations. The participants self-reported what negative effects they could recall receiving information about. These responses could have been biased due to misremembering. Participants volunteered for this research through online survey platforms. This means the population is not representative of all people taking SSRIs in the US. Only US adults were included in this study, limiting generalizability to other populations. The list of 11 possible negative effects of SSRIs used in the current work was incomplete and notably did not include weight gain and akathisia. Inclusion of additional negative effects could have affected the results.
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Badre, N., Cohen, D., Geier, E. (2026). Are You Adequately Informed?: A Survey of Patient Recall and Preferences Concerning SSRI Side Effect Information. Inner Compass Research Institute. (Link)
Dagostin Ferraz, S., Kuyunga, L., Rech, P., Rodrigues Uggioni, M. L., Rodrigues Candido, A. C., Dagostin, V. S., Silva, F. R., Colonetti, T., Grande, A. J., & da Rosa, M. I. (2026). Sexual dysfunction associated with selective serotonin reuptake inhibitors in adults with depression: A systematic review and meta-analysis. European Journal of Clinical Pharmacology, 82(3). (Link)
Elvira, S. D., Fortuna, Y. D. R., Silvianingrum, R., & Sukma, A. A. M. (2026). The impact of selective serotonin reuptake inhibitor (SSRI) antidepressants on the risk of gastrointestinal bleeding : A systematic review of randomized controlled trials and controlled observational studies. The International Journal of Medical Science and Health Research, 48(5), 66–134. (Link)
Wallis, K. A. (2026). Stopping antidepressants: When and how. Australian Prescriber, 49(3), 99–103. (Link)
