Weekly Research Digest: Psych Drugs Linked to Poor Heart Health and Gastrointestinal Bleeding

This week Mad in America examines studies related to adverse events associated with antipsychotics and antidepressants, including two studies that found increased risk of irregular heartbeat for both classes of drugs, one that found poor heart health indicators associated with antipsychotics, and another that links antidepressants to gastrointestinal bleeding.

Cardiometabolic Adverse Effects of Long-Term Antipsychotic Treatment In Children and Adolescents with Non-Psychotic Disorders: A Systematic Review of Available Evidence

A new study published in European Child & Adolescent Psychiatry finds that long-term use of antipsychotics in children and adolescents without psychotic disorders is linked to several adverse heart health outcomes including weight gain, high blood sugar, high cholesterol, and metabolic syndrome. The current work, led by Ramya Padmavathy Radha Krishnan from the University of Sydney in Australia, also found evidence that antipsychotics may be linked to high blood pressure, but this finding was not consistent across examined studies.

The goal of this study was to examine existing evidence around the link between antipsychotic use in children and adolescents without a psychosis diagnosis and adverse effects related to heart health. The authors used a meta-analysis design, examining clinical trials and observational studies that looked at children and adolescents without a psychosis related diagnosis that were given antipsychotic drugs. In order to be included in the current analysis, studies had to be published in English and the duration of antipsychotic use had to be at least 12 months.

Studies were classified as showing an increase of the adverse outcome, a decrease, or no change/inconclusive. The authors did not consider the strength of the observed associations or whether or not they were statistically significant. In total, the authors investigated 15 observational studies including 114,141 subjects. The majority of subjects were male (83.4%). No clinical trials that fit the inclusion criteria were identified. Included studies examined 12 different antipsychotics, with risperidone being the most common.

Twelve of 15 included studies examined weight gain as an adverse effect of antipsychostics. Eleven of these 12 studies (91.7%) found that subjects gained weight after using antipsychotics. Risperidone and aripiprazole were both linked to significant weight gain while quetiapine and ziprasidone were associated with smaller increases.

Six of 15 studies examined hyperglycaemia. All six studies reported increased hyperglycaemia after antipsychotic use. All investigated antipsychotics were linked to this increase. Six studies also investigated high cholesterol, with four of six finding decreased good cholesterol and increased bad cholesterol after antipsychotic use. Four studies looked at high blood pressure, with just one finding a link between increased blood pressure and aripiprazole. Two studies examined the presence of metabolic syndrome, both finding an increase in at least one criteria for metabolic syndrome linked to risperidone.

The authors point to several limitations in the current work. There were few studies and no clinical trials that met their inclusion criteria. Differing methods between the studies made comparisons difficult. While most of the included studies reported positive associations, the authors believe there may be unpublished studies that reported no associations.

Risk of Gastrointestinal Bleeding by Specific SSRIs And SNRIs: A Systematic Review and Meta-Analysis

A new study published in the British Journal of Clinical Pharmacology finds that SSRI and SNRI antidepressant use is linked to increased risk of gastrointestinal bleeding (GIB). This research, led by Ainhoa Gomez-Lumbreras from the University of Utah, reports that venlafaxine, often sold as Effexor, was associated with the largest increased risk.

The aim of this study was to examine the risk of GIB linked to specific SSRI and SNRI antidepressants. The authors used a systematic review and meta-analysis to achieve this aim. They searched for articles that investigated GIB in connection to six SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) and two SNRIs (venlafaxine and duloxetine). To be included in the current work, studies had to examine GIB risk around specific drugs and include a measure of that risk. Case reports, and case series were excluded. Twenty studies were included in the current review and meta-analysis.

The authors report “all antidepressants significantly increase the risk of GIB as compared to no antidepressant treatment or placebo.” The SNRI venlaflaxine (Effexor) was linked to the highest increased risk of GIB. People using this SNRI were 50% more likely to experience GIB. The SSRI paroxetine (Paxil) showed the lowest increased risk at 30%.

The other investigated drugs increased GIB risk as follows:

• Citalopram (Celexa) – 38% increased risk of GIB
• Fluoxetine (Prozac)) – 38%
• Escitalopram (Lexapro) – 37%
• Sertraline (Zoloft) – 34%
• Fluvoxamine (Luvox) – 33%
• Duloxetine (Cymbalta) – 32%

This analysis had several limitations. Most (85%) of the included studies were observational. The included studies used varying definitions of exposure to antidepressants and GIB, limiting validity of the findings. Data on dosage was not available so the authors could not determine GIB risk based on dose taken. Only SSRIs and SNRIs were included, meaning many antidepressants were not evaluated. Most of the included studies were from western countries, a few came from Taiwan, and one from Brazil. This limits generalizability to other populations in low- and middle-income countries.

Exploring the Link Between Antipsychotic and Antidepressant Use and Severe Qt Prolongation: Impacts on Ventricular Arrhythmias and Sudden Cardiac Death

A new study published in Heart Rhythm finds that antipsychotics, such as thioridazine and haloperidol, were associated with significantly increased odds of severe QT prolongation, a condition that often leads to heart arrhythmia. The current work, led by Chun-Li Wang of Chang Gung University in Taiwan, finds a similar link between severe QT prolongation and the antidepressant escitalopram, commonly sold as Lexapro.

The goal of this study was to examine rates of severe QT prolongation in people exposed to antipsychotics and antidepressants. The authors used data from electronic medical records in Taiwan to investigate this relationship. To be included in the current research, patients had to be prescribed antipsychotic or antidepressant drugs and had to have received a baseline and follow-up electrocardiogram. In total, the authors examined data from 43,526 people, 28,892 taking antipsychotics and 14,634 taking antidepressants.

Five antipsychotic drugs were linked to severe QT prolongation:

• Thioridazine – 445% increased risk
• Haloperidol – 288%
• Clothiapine – 217%
• Chlorpromazine – 201%
• Sulpiride – 152%

The antidepressants escitalopram (Lexapro) and fluoxetine (Prozac) were also linked to severe QT prolongation (89% and 54% respectively). The authors note that these risks were more substantial when multiple drugs were taken together. Severe QT prolongation was associated with an increased risk of ventricular arrhythmia (191% more likely) and sudden cardiac death (116%) in antipsychotic users, as well as a 178% increased likelihood of ventricular arrhythmias in antidepressant users.

There were several limitations to the current work. The design means the data can only speak to links, not causes. In other words, this data cannot definitively say that these drugs are causing severe QT prolongation. Data on genetic predisposition to QT prolongation and over the counter drugs was not available. These factors could have affected the results. Other data points were sometimes incomplete. The study only looked at people that had received an electrocardiogram. There is a possibility that these patients would have been higher risk than those not receiving this assessment. As the authors looked only at medical records from Taiwan, generalizability to other populations is limited.

Arrhythmic Events Pertinent with Antidepressants: A Bayesian Disproportional Analysis Mining the FDA Adverse Event Reporting System Database

A new study published in Frontiers in Psychiatry reports a link between antidepressant use and increased risk of irregular heartbeat. This study, led by Shan Cao of Sun Yat-sen University, also found a link between heart arrhythmia and the antipsychotic quetiapine, often sold as Seroquel.

The goal of the current work was to investigate the connection between commonly used antidepressants and arrhythmic events. The authors used the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to examine this link. They reviewed records related to heart arrhythmia in seven antidepressants (citalopram, escitalopram, fluoxetine, sertraline, mirtazapine, venlafaxine, and duloxetine) and one antipsychotic often used as an antidepressant (quetiapine).

Citalopram (Celexa) was linked to QT prolongation (114% more likely to be reported in FAERS), atrial fibrillation (82%), heart block (37%), and ventricular arrhythmia (55%). Escitalopram (Lexapro) was associated with QT prolongation (72%), atrial fibrillation (34%), and ventricular arrhythmia (51%). Fluoxetine (Prozac) was linked to QT prolongation (39%) and atrial fibrillation (68%). Quetiapine (Seroquel) was linked to QT prolongation (58%) and ventricular arrhythmia (139%). Sertaline (Zoloft) was associated with atrial fibrillation (32%) and mirtazapine (Remeron) was linked to heart block (40%). Duloxetine (Cymbalta) and venlafaxine (Effexor) were not linked to increased FAERS reporting rates of arrhythmic events.

The authors acknowledge several limitations to the current work. The FAERS database relies on spontaneous self reports of adverse events. This can lead to inaccurate and incomplete records. The authors did not have access to data on baseline service user characteristics, dosage, or duration of exposure to antidepressants. The current work only examined eight drugs. Drugs that are more frequently prescribed will inevitably show up more often in adverse event databases, making comparisons between drugs more difficult. Arrhythmias are likely underreported as they typically require monitoring to detect.

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Cao, S., Huang, Z., Yang, W., Yang, S., Chen, X., & Xie, X. (2025). Arrhythmic events pertinent with antidepressants: A Bayesian disproportional analysis mining the FDA Adverse Event Reporting System Database. Frontiers in Psychiatry, 16. (Link)

Gomez‐Lumbreras, A., Tawfik, A. G., Del Fiol, G., Kawamoto, K., Reese, T., Trinkley, K., Jones, A., Mitchell, J., & Malone, D. C. (2025). Risk of gastrointestinal bleeding by specific ssris and snris: A systematic review and meta‐analysis. British Journal of Clinical Pharmacology. (Link)

Radha Krishnan, R. P., Dzidowska, M., Zheng, D., Wong, Z. S.-Y., Buckley, N. A., & Raubenheimer, J. E. (2025). Cardiometabolic adverse effects of long-term antipsychotic treatment in children and adolescents with non-psychotic disorders: A systematic review of available evidence. European Child & Adolescent Psychiatry, 34(11), 3331–3343. (Link)

Wang, C.-L., Wu, V. C.-C., Wu, C.-L., & Chang, S.-H. (2025). Exploring the link between antipsychotic and antidepressant use and severe QT prolongation: Impacts on ventricular arrhythmias and sudden cardiac death. Heart Rhythm. (Link)