What are the risks of extra pyramidal symptoms when using Zoloft (sertraline)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 19, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Zoloft (sertraline) has a low risk of causing extrapyramidal symptoms (EPS) compared to other psychiatric medications. The provided evidence does not specifically discuss the risk of EPS with Zoloft, but it does mention that SSRIs, including sertraline, can have various side effects, such as dizziness, fatigue, and sensory disturbances, which may be related to EPS 1. However, these symptoms are not explicitly described as EPS.

When considering the risk of EPS with Zoloft, it is essential to note that SSRIs are generally associated with a lower risk of EPS compared to other psychiatric medications, such as antipsychotics 1. The mechanism behind SSRI-induced EPS likely involves serotonin's indirect effects on dopamine pathways in the brain, as serotonin can inhibit dopamine release in certain brain regions.

Some key points to consider when prescribing Zoloft include:

  • Starting with a low dose and gradually increasing it to minimize the risk of adverse effects 1
  • Monitoring patients for symptoms, especially in the first 24 to 48 hours after dosage changes 1
  • Being cautious when prescribing Zoloft to patients with pre-existing movement disorders or those taking other medications that affect dopamine 1
  • Considering dosage reduction or discontinuation if EPS develops while taking Zoloft 1

Overall, while the evidence does not provide a clear estimate of the risk of EPS with Zoloft, the available data suggest that SSRIs, including sertraline, are relatively safe regarding movement disorders 1. Therefore, Zoloft can be considered a relatively safe choice among antidepressants when EPS is a concern.

From the FDA Drug Label

The safety profile observed with sertraline treatment in patients with major depressive disorder, OCD, panic disorder, PTSD, PMDD and social anxiety disorder is similar ... extrapyramidal symptoms, Laboratory Tests ... In man, asymptomatic elevations in serum transaminases (SGOT [or AST] and SGPT [or ALT]) have been reported infrequently (approximately 0. 8%) in association with sertraline hydrochloride administration.

The risk of extrapyramidal symptoms when using Zoloft (sertraline) is noted in the drug label, but no further details are provided regarding the frequency or severity of these symptoms 2.

From the Research

Risks of Extra Pyramidal Symptoms with Zoloft (Sertraline)

The use of Zoloft (sertraline) has been associated with extra pyramidal symptoms (EPS), although the exact risk is not well-established. Some studies suggest that sertraline, like other selective serotonin re-uptake inhibitors (SSRIs), may cause significant extrapyramidal side-effects 3.

Evidence of EPS with Sertraline

  • A review of the literature identified thirteen published cases of sertraline-induced EPS, with several cases confounded by concomitant medications 3.
  • A case report presented a patient who developed EPS associated with sertraline, with daily ratings obtained using the Abnormal Involuntary Movement Scale 3.
  • Another study reported a case of a child who developed extrapyramidal symptoms while on a combination of risperidone, methylphenidate, sertraline, tropisetron, and ketorolac, which resolved with the administration of benztropine, an anticholinergic drug 4.

Mechanism of EPS with Sertraline

The exact mechanism of EPS with sertraline is not well-understood, but it is thought to occur through an interaction between serotonergic and dopaminergic pathways 3.

Comparison with Other Medications

  • Extrapyramidal symptoms are a well-known side effect of antipsychotic medications, but can also be caused by non-antipsychotic agents, including some antidepressants, lithium, and antiemetics 5.
  • A case report of a patient who developed EPS with aripiprazole, an atypical antipsychotic, highlights the importance of slow titration to minimize the risk of EPS 6.

Pharmacologic Profile of Sertraline

  • Sertraline is a highly specific, potent inhibitor of serotonin reuptake, with no clinically significant effects on norepinephrine and dopamine uptake 7.
  • Its pharmacologic profile permits once-daily dosing, with a wide safety margin and minimal side effects, including nausea, diarrhea, and sexual dysfunction 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Extrapyramidal adverse effects associated with sertraline.

Progress in neuro-psychopharmacology & biological psychiatry, 1998

Research

Drug-induced extrapyramidal reactions.

Journal of paediatrics and child health, 2002

Research

A case of Aripiprazole and extra pyramidal side effects.

Journal of psychopharmacology (Oxford, England), 2006

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.