A common side effect of antidepressants could be a surprising warning sign

A new study suggests that for people treating depression with common medications, the frequency of their yawning might track with how well they are healing. Published in the Journal of Psychiatric Research, the findings indicate that while these drugs often increase yawning overall, persistent or worsening yawning could signal that the treatment is not effectively reducing depressive symptoms. This offers clinicians a potential physical marker to help distinguish between medication side effects and the lingering symptoms of the disorder itself.

Selective serotonin reuptake inhibitors, or SSRIs, are the most prescribed medications for treating depression. While they are generally considered safe, they come with a range of physical side effects that can affect a patient’s quality of life. One of the stranger and less understood reactions is excessive yawning. This is not the yawning of boredom or simple tiredness but a distinct physiological response to the medication.

The link between yawning and brain chemical activity is well established in animal models. Neurotransmitters like serotonin, dopamine, and acetylcholine play a role in triggering this reflex. However, few researchers have tracked this phenomenon systematically over time in a clinical psychiatric setting. Most existing information comes from isolated case reports rather than structured observation.

To bridge this gap, a team of researchers from the University of Health Sciences in Istanbul, Türkiye, designed a prospective study. Lead author Yusuf Ezel Yıldırım, a psychiatrist at the Bakirkoy Prof. Dr. Mazhar Osman Training and Research Hospital for Psychiatric, Neurologic and Neurosurgical Diseases, sought to understand if this yawning was merely a nuisance or if it held clinical meaning. The team wanted to see if the frequency of yawning correlated with the severity of a patient’s depression or their quality of sleep.

The researchers recruited 150 adults aged 18 to 65 who were diagnosed with major depressive disorder. A key requirement for participation was that none of these patients had taken SSRIs before the study began. This exclusion ensured that any changes observed could be attributed to the new medication regimen rather than past usage. The participants were prescribed standard SSRI treatments such as sertraline, escitalopram, or fluoxetine.

Free daily newsletter

Before taking their first dose, patients completed several detailed questionnaires. These surveys measured the severity of their depression using the Beck Depression Inventory and the intensity of their insomnia using the Insomnia Severity Index. The team also used a scale specifically designed to rate the frequency and disruptiveness of yawning. This custom assessment asked patients to rank their yawning from nonexistent to a level that severely impacted daily activities.

One month after starting treatment, the researchers followed up with the participants to assess their progress. Of the original group, 110 patients completed this second phase of the study. The researchers compared the new scores against the baseline data gathered four weeks earlier. They looked for patterns connecting the physical side effects to the psychological outcomes.

The results showed a clear general trend regarding the physical reaction to the drugs. The severity of yawning increased for the group as a whole after starting the medication. The number of patients reporting “excessive yawning” that frequently disrupted their lives jumped from roughly 5 percent to over 15 percent. This confirmed that the medication was indeed driving the physical behavior in a substantial portion of the group.

However, the data revealed a more nuanced relationship when the researchers looked at individual treatment outcomes. At the start of the study, patients with higher depression scores tended to report more yawning. This connection persisted even after accounting for age and other factors. It suggests that the act of yawning is biologically linked to the depressive state itself, not just the drugs.

The most distinct finding emerged when the team divided the patients into two groups based on how well the medicine worked. One group consisted of “responders,” defined as those whose depression scores dropped by at least half. The other group was “non-responders,” whose condition did not improve as markedly.

Among the patients who responded well to the treatment, yawning severity decreased slightly or stayed the same. In contrast, the non-responders experienced a sharp rise in yawning severity. The statistical analysis showed that this increase was not a random occurrence. It implies that if a patient continues to yawn excessively or if the yawning worsens markedly, it might indicate that the depression is not lifting.

The study also examined whether sleep issues played a role in this phenomenon. While insomnia scores generally improved for everyone, the changes in yawning happened independently of how well the patients slept. The yawning was more closely tied to other physical side effects like nausea, sweating, or dry mouth. This points to a reaction in the autonomic nervous system rather than simple fatigue or drowsiness.

This distinction is important because yawning is often misinterpreted in clinical practice. When a patient on antidepressants reports constant yawning, doctors often assume the patient is sedated or lethargic. This can lead to the mistaken belief that the patient is experiencing “asthenia,” a state of physical weakness and lack of energy.

If a clinician misinterprets this yawning as a sign of worsening depression or fatigue, they might increase the medication dosage. Based on the study’s findings, increasing the dose in a non-responding patient who is already yawning excessively might not address the root issue. The yawning may be a red flag that the current treatment path is ineffective for that specific individual.

Despite these insights, the study has limitations that affect how the results should be interpreted. The follow-up period lasted only one month. It remains unclear if the yawning persists, worsens, or resolves over a longer timeframe such as six months or a year. Additionally, the data relied entirely on patients reporting their own symptoms, which can introduce bias.

Future research needs to include objective measures of yawning to verify self-reports. Longer studies could track the trajectory of this symptom over extended periods to see if the body eventually adapts. The researchers also note that cultural factors can influence how people perceive and report bodily functions, which may affect data collection in different regions.

For doctors, the immediate takeaway is practical and applicable to daily monitoring. Persistent yawning should not be automatically dismissed as a sign of tiredness or boredom. Instead, it might serve as a subtle biological signal that the current treatment plan requires adjustment. By paying attention to this overlooked symptom, psychiatrists may be able to identify patients who are not responding to treatment much earlier.

The study, “Prevalence of SSRI-Related yawning and relationship with clinical features in patients with major depressive disorder: A prospective study,” was authored by Yusuf Ezel Yıldırım, Eray Yurtseven, Pınar Çetinay Aydın, and Mehmet Güven Günver.