This week Mad in America examines three studies related to adverse effects of antidepressants. The first study finds that antidepressant use is linked to suicidal behavior and self-injury in people with a bipolar disorder diagnosis. The second finds that antidepressant increase the risk of irregular heartbeat and sudden death in people taking antipsychotics. The third finds that people taking antidepressants commonly report negative effects such as insomnia, weight gain, anxiety, and sexual dysfunction.

Antidepressant Use Linked to Self-Injury and Suicidal Behavior

A new article published in Psychiatry Research finds that antidepressant use in people with a bipolar disorder diagnosis was linked to increased suicidal thoughts and behaviors. This study, led by Yutong Deng from Peking University Sixth Hospital in Beijing, China, additionally finds that antidepressant use was linked to increased risk of self-injury.

The goal of this study was to examine the link between antidepressant use and suicidal thoughts, suicidal behaviors, and non-suicidal self-injury in people with a bipolar disorder diagnosis. The authors used data from 575 patients diagnosed with bipolar disorder from 15 medical centers in China. The authors tracked antidepressant use and changes in suicidal thoughts, behaviors, and self-injury.

Antidepressant use was linked to a 90% higher risk of worsening non-suicidal self-injury, 70% increased odds of suicidal thoughts, and an 80% increase odds of suicidal behavior such as suicide attempts and taking concrete steps towards a suicide attempt.

The authors also conducted several subgroup analyses. They suggested the possibility that antidepressants were worse for those with mania than depressive symptoms, that those with low household income had worse effects, and that lithium may have a protective effect. Yet their own conclusion is that “the observed subgroup differences did not reach statistical significance on interaction testing and should be regarded as hypothesis-generating.” Generally, when a measure does not achieve statistical significance, it is considered to have failed to show an effect.

This research had three key limitations. The study’s design means that the results can only speak to associations, not causes. The authors cannot definitively say that antidepressants caused suicidal and self-harm behaviors, only that they are linked. Patients and service users that were prescribed antidepressants may have had more severe symptoms at baseline, possibly biasing the results towards worse outcomes. This research was conducted within China, limiting generalizability ot other populations.

Antidepressants Linked to Increased Risk of Irregular Heartbeat and Sudden Death in People Taking Antipsychotics

A new study published in JAMA Open finds that antidepressant use is linked to increased risk of irregular heartbeat and sudden death in people taking antipsychotics. This study, led by Hsiu-Ting Chien from National Taiwan University, also finds that citalopram (Celexa) and escitalopram (Lexapro and Cipralex) were associated with the highest risk of adverse outcomes.

The goal of this research was to investigate whether SSRIs taken with antipsychotics increased the risk of irregular heartbeat or sudden death compared to antipsychotics alone. The authors used data collected from health insurance databases in the US (MarketScan) and Taiwan (National Health Insurance Research Database).

In order to be included in the current study, patients and service users had to be adults taking an antipsychotic for a psychotic disorder diagnosis with no history of irregular heartbeat or SSRI use. During each week of the study, patients and service users were classified as either initiating an SSRI or not. The authors followed participants for up to one year to identify irregular heartbeat and sudden death. In total, the authors used data from 498,898 patients and service users, including 307,818 from the US and 191,080 from Taiwan.

In US patients, taking an SSRI alongside an antipsychotic was linked to a 51% increase in the risk of irregular heartbeat or sudden death. This risk was significantly higher in Taiwanese patients, with SSRI use in addition to an antipsychotic associated with a 232% increased risk of irregular heartbeat or sudden death. In the US cohort, this increased risk was only linked to SSRIs known to cause dangerous irregular heartbeats (citalopram and escitalopram), with these drugs associated with a 120% increase in the risk of irregular heartbeat or sudden death. In the Taiwanese cohort, both the SSRIs known to cause dangerous irregular heartbeat and those with conditional risks for irregular heartbeat were linked to higher risk of irregular heartbeat and sudden death.

The authors note that while SSRIs were linked to increased risk of dangerous, irregular heartbeat and sudden death, these adverse outcomes were rare. In the US, the frequency of these adverse outcomes was 0.074% for SSRI initiators. In Taiwan, the frequency was 0.187%. This translates to roughly 1 event per 1,354 patients in the US and 1 event per 536 patients in Taiwan.

This study had several limitations. The study’s design means the results can only speak to links between SSRI use, irregular heartbeat, and sudden death rather than definitely saying that SSRIs cause these adverse outcomes. The data used in the current work came from insurance claims databases. This means the authors did not have data on factors that could have influenced the findings, such as symptom severity, lifestyle, medication adherence, additional clinical risk factors, etc. There were significant differences between the US and Taiwanese cohorts, possibly due to patient characteristics, prescribing practices, or genetics. The data came form the US and Taiwan, limiting generalizability to other populations.

Antidepressants Linked to Negative Effects Such as Weight Gain, Insomnia, Anxiety, and Sexual Dysfunction

A new study published in Depression and Anxiety finds that people taking antidepressants commonly experience negative effects such as insomnia, weight gain, anxiety, and sexual dysfunction. This research. led by Gashaw Sisay Chanie from the University of Gondar in Ethiopia, also reports adverse effects were more likely in certain groups, including women, those with low income, and limited physical activity.

The goal of this research was to examine the frequency of adverse effects from antidepressants, which adverse effects were most common, and factors that were linked to these negative effects. The authors used data from 422 patients in the Amhara regional state of Ethiopia. To be included in the study, participants had to be adults with a depressive disorder diagnosis taking antidepressants. Participants responded to structured questionnaires about demographic information, clinical history, antidepressant use, and adverse effects of antidepressants.

In total, 82.9% of participants reported at least one adverse effect of antidepressants. The most commonly reported negative effects were weight gain (64%), nausea and vomiting (51%), dry mouth (49%), and headache (41%). More than one-third of participants reported tremor, drowsiness, and insomnia. More than 20% reported loss of appetite, problems with urination, anxiety, and sexual dysfunction. Around 10% reported constipation.

Women were 3.5 times more likely to report adverse effects of antidepressants compared to men. Participants with low income (4.53 times more likely) and low levels of physical activity (4.52) were also significantly more likely to report negative effects.

This research had three main limitations. The study’s design means the authors can only report on links between antidepressants and negative effects. The self-report nature of the data means it is susceptible to misremembering and providing socially desirable rather than accurate responses. The participants all came from a specific region in Ethiopia, limiting generalizability to other populations.

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Chanie, G. S., Geremew, G. W., Beyna, A. T., Fenta Misker, M., Ayele, H. S., Teshager, A. W., Takele, G. M., Bizuneh, G. K., Azanaw, J., Belachew, E. A., & Simegn, W. (2026). Patients reported adverse effects of antidepressants among depressive disorder and associated risk factors: A multicenter cross‐sectional study. Depression and Anxiety, 2026(1). (Link)

Chien, H.-T., Lin, S.-W., Kung, T.-J., Wang, C.-C., Dong, Y.-H., Hwang, T.-J., Lin, F.-J., & Toh, S. (2026). Ventricular arrhythmia and sudden death risk with concomitant antipsychotic and SSRI use. JAMA Network Open, 9(4). (Link)

Deng, Y., Xu, N., Huang, J., Hu, X., Huang, S., Cui, Z., Li, Y., Wang, L., Zhang, Y., Sun, P., Su, Z., Yao, Z., An, C., Jia, Y., Wang, Z., Rong, H., Lin, K., He, Z., Hu, S., … Yu, X. (2026). Antidepressant use and worsening of non-suicidal self-injury and suicidality in bipolar disorder: A multicenter retrospective cohort study. Psychiatry Research, 364, 117301. (Link)