What are the potential side effects of Tramadol (opioid analgesic)?

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From the Guidelines

Tramadol can cause several side effects, including common effects like dizziness, headache, and nausea, as well as more serious effects like seizures and serotonin syndrome, and its use should be approached with caution, especially in patients with certain medical histories or taking specific medications, as noted in the most recent guidelines 1.

Common Side Effects

  • Dizziness
  • Headache
  • Drowsiness
  • Nausea
  • Vomiting
  • Constipation
  • Sweating
  • Dry mouth These side effects are well-documented in various studies, including a Cochrane review that concluded limited evidence supports the use of tramadol for cancer pain treatment and that it is likely not as effective as morphine in this setting 1.

Serious Side Effects

  • Seizures
  • Serotonin syndrome (confusion, rapid heart rate, fever, muscle stiffness)
  • Slowed or difficult breathing
  • Allergic reactions (rash, itching, swelling) These serious side effects highlight the need for careful patient selection and monitoring when prescribing tramadol, as emphasized in guidelines that recommend avoiding tramadol in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications due to the risk of serotonin syndrome 1.

Special Considerations

Patients with a history of seizures, head injury, metabolic disorders, or those taking certain medications like antidepressants should use tramadol with caution due to an increased risk of adverse effects 1. The medication's potential for psychological dependence and physical withdrawal symptoms when stopped abruptly, as well as its risk of addiction, particularly with prolonged use or higher doses, must also be considered 1.

Dosage Recommendations

The NCCN panel recommends a maximum daily dose of 400 mg for immediate-release formulations (100 mg 4 times a day) or 300 mg/day for extended-release formulations for adults with normal hepatic and renal function, with lower doses recommended for older adults and those with hepatic and/or renal dysfunction to reduce the risk of seizures 1.

From the FDA Drug Label

Tramadol products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a cause of drug-related deaths. Patients should be cautioned about the concomitant use of tramadol products and alcohol because of potentially serious CNS additive effects of these agents Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS depressant drugs. Serious potential consequences of overdosage with tramadol hydrochloride (tramadol hydrochloride) tablets are central nervous system depression, respiratory depression and death. Withdrawal symptoms may occur if tramadol hydrochloride is discontinued abruptly Reported symptoms have included anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations.

The potential side effects of Tramadol include:

  • Central Nervous System Depression: caused by excessive doses or combination with other CNS depressants
  • Respiratory Depression: a serious potential consequence of overdosage
  • Death: may occur as a consequence of accidental ingestion of excessive quantities
  • Withdrawal Symptoms: may occur if tramadol is discontinued abruptly, including anxiety, sweating, insomnia, and others 2
  • Abuse and Addiction: tramadol has mu-opioid agonist activity and can be abused, with risks of addiction and dependence 2

From the Research

Potential Side Effects of Tramadol

Tramadol, an opioid analgesic, has several potential side effects associated with its use. Some of the common side effects include:

  • Dizziness
  • Nausea
  • Dry mouth
  • Sedation
  • Seizures
  • Serotonin syndrome

Serious Adverse Effects

More serious adverse effects of tramadol include:

  • Serotonin syndrome, which can occur due to tramadol's serotonin and norepinephrine reuptake inhibitory effects 3
  • Seizures, which can be caused by tramadol's inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors 4
  • Neurobehavioral deficits, which can result from long-term utilization of tramadol 4

Risk Factors for Adverse Effects

Certain risk factors can increase the likelihood of adverse effects when taking tramadol, including:

  • Medical comorbidities
  • Use or abuse of supratherapeutic doses of tramadol
  • Concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors 3
  • Coadministration of antidepressants, which can increase the risk of seizures and serotonin syndrome 5

Management of Adverse Effects

Adverse effects of tramadol can be managed by:

  • Administering benzodiazepines
  • Providing supportive care
  • Discontinuing tramadol and other contributing agents 3
  • Administering cyproheptadine in moderate to severe cases of serotonin syndrome 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures.

The American journal of medicine, 2018

Research

Tramadol: seizures, serotonin syndrome, and coadministered antidepressants.

Psychiatry (Edgmont (Pa. : Township)), 2009

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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