A 45-year-old woman presents with increasing tremor in her arms and a new tremor in her legs. These have been present for the past 3 weeks. She was in a motor vehicle accident 6 weeks ago and sustained a neck injury as well as increased fear, anxiety, and insomnia since the accident. Her exam shows a postural tremor which is mild. Current medications: sertraline, zolpidem, tramadol, and naproxen.
Which medication is the most likely cause of the tremors? A) Sertraline B) Zolpidem C) Tramadol D) Naproxen
The likely cause of her tremor is sertraline, a selective serotonin reuptake inhibitor (SSRI). It is possible the patient has serotonin syndrome with the combination of sertraline and tramadol. Tremors are almost always present with serotonin syndrome. SSRIs can cause tremors separate from serotonin syndrome. The tremor is usually postural and resolves with discontinuation of the medication. In one case series of fluoxetine-induced tremor, it lasted for months after discontinuation.
Hyponatremia
Another important, underappreciated side effect of SSRIs is hyponatremia. SSRI use is more common in patients who are admitted with severe (Na < 125 mEq/L) and very severe (Na < 115 mEq/L) hyponatremia. A meta-analysis of 39 studies looking at antidepressant exposure risk and development of hyponatremia found the highest risk being in patients exposed to serotonin-norepinephrine reuptake inhibitors (7.44%) and SSRIs (5.59%); mirtazapine was much less likely to be associated with hyponatremia (1%). Hyponatremia due to SSRIs is elevated in elderly patients and women. Simultaneous use of diuretics and angiotensin converting enzyme inhibitors further increases the risk of hyponatremia in patients who use SSRIs.
Yawning
Yawning is an interesting side effect of SSRIs. In a case report by Sinha and colleagues, a patient developed frequent yawning (5 times every 15 minutes) when her escitalopram dose was increased from 5 mg to 15 mg. Roncero et al described a case of yawning in a patient on escitalopram that resolved when the dose of escitalopram was reduced. In a review of drug-induced yawning, SSRIs as a class were most frequently involved, and sertraline, fluoxetine, and paroxetine were implicated.
Bleeding Risk
SSRIs have been linked to increased bleeding risk, especially upper gastrointestinal hemorrhage. Laporte and colleagues showed an association of SSRI use and risk of bleeding in a meta-analysis of 42 observational studies, with an odds ratio of 1.41 (95% CI, 1.27-1.57; P <.0001). The risk of upper gastrointestinal bleeding is further increased if patients are also taking NSAIDs according to a recent meta-analysis with an odds ratio of 1.49 in patients taking SSRIs and NSAIDS compared to patients taking NSAIDs alone. Make sure to think about patients’ bleeding risks when starting SSRIs.
Pearls: Yawning and tremors are common issues in primary care — consider SSRIs as a possible cause. Look at the medication list in patients with severe hyponatremia and consider SSRIs as a possible cause. Make sure to think about patients’ bleeding risks when starting SSRIs.
COMMENTARY
How Much Do You Know About SSRI Side Effects?
DISCLOSURES
| April 10, 2025How Much Do You Know About SSRI Side Effects?
A 45-year-old woman presents with increasing tremor in her arms and a new tremor in her legs. These have been present for the past 3 weeks. She was in a motor vehicle accident 6 weeks ago and sustained a neck injury as well as increased fear, anxiety, and insomnia since the accident. Her exam shows a postural tremor which is mild. Current medications: sertraline, zolpidem, tramadol, and naproxen.
Which medication is the most likely cause of the tremors?
A) Sertraline
B) Zolpidem
C) Tramadol
D) Naproxen
The likely cause of her tremor is sertraline, a selective serotonin reuptake inhibitor (SSRI). It is possible the patient has serotonin syndrome with the combination of sertraline and tramadol. Tremors are almost always present with serotonin syndrome. SSRIs can cause tremors separate from serotonin syndrome. The tremor is usually postural and resolves with discontinuation of the medication. In one case series of fluoxetine-induced tremor, it lasted for months after discontinuation.
Hyponatremia
Another important, underappreciated side effect of SSRIs is hyponatremia. SSRI use is more common in patients who are admitted with severe (Na < 125 mEq/L) and very severe (Na < 115 mEq/L) hyponatremia. A meta-analysis of 39 studies looking at antidepressant exposure risk and development of hyponatremia found the highest risk being in patients exposed to serotonin-norepinephrine reuptake inhibitors (7.44%) and SSRIs (5.59%); mirtazapine was much less likely to be associated with hyponatremia (1%). Hyponatremia due to SSRIs is elevated in elderly patients and women. Simultaneous use of diuretics and angiotensin converting enzyme inhibitors further increases the risk of hyponatremia in patients who use SSRIs.
Yawning
Yawning is an interesting side effect of SSRIs. In a case report by Sinha and colleagues, a patient developed frequent yawning (5 times every 15 minutes) when her escitalopram dose was increased from 5 mg to 15 mg. Roncero et al described a case of yawning in a patient on escitalopram that resolved when the dose of escitalopram was reduced. In a review of drug-induced yawning, SSRIs as a class were most frequently involved, and sertraline, fluoxetine, and paroxetine were implicated.
Bleeding Risk
SSRIs have been linked to increased bleeding risk, especially upper gastrointestinal hemorrhage. Laporte and colleagues showed an association of SSRI use and risk of bleeding in a meta-analysis of 42 observational studies, with an odds ratio of 1.41 (95% CI, 1.27-1.57; P <.0001). The risk of upper gastrointestinal bleeding is further increased if patients are also taking NSAIDs according to a recent meta-analysis with an odds ratio of 1.49 in patients taking SSRIs and NSAIDS compared to patients taking NSAIDs alone. Make sure to think about patients’ bleeding risks when starting SSRIs.
Pearls: Yawning and tremors are common issues in primary care — consider SSRIs as a possible cause. Look at the medication list in patients with severe hyponatremia and consider SSRIs as a possible cause. Make sure to think about patients’ bleeding risks when starting SSRIs.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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