Can someone experience restlessness after several months of being on Zoloft (sertraline)?

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From the Guidelines

Yes, someone can experience restlessness after several months of being on Zoloft (sertraline). This symptom, sometimes called akathisia or psychomotor agitation, can develop even after a period of stable medication use, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. Restlessness on Zoloft may manifest as an inability to sit still, pacing, fidgeting, or a persistent feeling of inner tension. If you're experiencing this side effect, don't stop taking Zoloft abruptly, but consult your healthcare provider promptly. They might adjust your dosage (typically 50-200 mg daily), switch you to a different antidepressant, or add a medication to manage this side effect.

Some key points to consider when managing restlessness on Zoloft include:

  • The potential for behavioral activation/agitation, which may occur early in SSRI treatment, with dose increases, or with concomitant administration of drugs that inhibit the metabolism of SSRIs 1
  • The importance of slow up-titration and close monitoring, particularly in younger children, to minimize the risk of dose-related behavioral activation/agitation 1
  • The need for education and awareness about the potential side effects of SSRIs, including restlessness, to ensure prompt recognition and management 1

Temporary coping strategies while waiting to see your doctor include:

  • Regular exercise
  • Relaxation techniques
  • Maintaining a consistent sleep schedule It's essential to work closely with your healthcare provider to manage restlessness and other potential side effects of Zoloft, as they can help you develop a personalized plan to minimize symptoms and optimize treatment outcomes.

From the FDA Drug Label

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: ... feeling agitated, restless, angry or irritable Stopping sertraline too quickly may cause serious symptoms including: ... feeling restless

Restlessness can be a symptom that occurs during treatment with sertraline or when stopping the medication too quickly. The FDA drug label does not specify a time frame for when restlessness can occur, but it does mention that it can happen, especially when the dose is changed or when stopping the medication. Therefore, it is possible for someone to experience restlessness after several months of being on Zoloft 2.

From the Research

Restlessness and Zoloft

  • Restlessness can be a symptom associated with the use of antidepressants, including Zoloft (sertraline) 3.
  • A systematic review of 18 studies found that the onset or exacerbation of restless legs syndrome and an increase in periodic limb movements are uncommon after starting an antidepressant, including SSRIs like Zoloft 3.
  • However, the review noted that sertraline, along with other SSRIs like fluoxetine, may increase periodic limb movements, although these are unlikely to be clinically significant 3.
  • Another study discussed the benefits and risks of long-term SSRI use, including the potential for tachyphylaxis and discontinuation syndrome, but did not specifically address restlessness as a side effect 4.
  • There is limited evidence on the specific effects of Zoloft on restlessness, but SSRIs are generally considered to be well-tolerated and safe for long-term use 4, 5.

Long-term Use of Zoloft

  • Long-term use of SSRIs like Zoloft can increase the risk of tachyphylaxis and discontinuation syndrome 4.
  • Patients on long-term SSRI therapy should be periodically monitored to reassess the risk-benefit ratio of remaining on the medication 4.
  • The decision to continue or discontinue Zoloft should be an active one, involving both the patient and prescriber, and should be revisited periodically 4.

Zoloft and Restless Legs Syndrome

  • There is limited evidence on the specific relationship between Zoloft and restless legs syndrome, but one study suggested that SSRIs like sertraline may increase periodic limb movements, which can be a symptom of restless legs syndrome 3.
  • However, the study noted that these increases are unlikely to be clinically significant 3.
  • Further research is needed to fully understand the relationship between Zoloft and restless legs syndrome 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Selective Serotonin Reuptake Inhibitors: How Long Is Long Enough?

Journal of psychiatric practice, 2021

Research

Selective Serotonin Reuptake Inhibitors.

Handbook of experimental pharmacology, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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