Long-term use of tramadol can lead to physical dependence and addiction, seizures, serotonin syndrome, changes in hormone levels and heart problems. The body gets used to the drug, and withdrawal is possible if you stop suddenly. If you want to quit, do it under clinical guidance via a medical detox.
Tramadol is an opioid pain reliever available by prescription only. It has been classified as a Schedule IV controlled substance in 2014, a federal category for drugs with known potential for abuse. In 2025, 26.2 million tramadol prescriptions were dispensed in the U.S. [1].
How Tramadol Affects the Body
Tramadol works in two ways. First, your liver changes tramadol into a more powerful chemical form, called M1, that binds to opioid receptors. These receptors are found on nerve cells, and when M1 attaches to them, they reduce the pain signals sent to the brain. M1 is up to six times as potent in relieving pain as tramadol itself [2].
Secondly, tramadol keeps more serotonin and norepinephrine moving in the brain. These are chemical messengers that impact mood, alertness, and pain. This action increases pain relief — but also the risk of seizures and serotonin syndrome [1].
Common Side Effects of Tramadol
The most frequent side effects of tramadol are:
- Nausea and vomiting
- Headache and dizziness
- Constipation
- Itchiness
These tend to occur early, not after months of consistent use [2]. A review of 19 clinical trials found nausea, dizziness, constipation, and sleepiness all occurred more often with tramadol than with placebo (a pill with no medicine in it). For every seven people taking tramadol, one more person had nausea [3].
Long-Term Side Effects of Tramadol
Some of the problems with long-term use of tramadol will not show for weeks or months, as the body becomes dependent on the drug.
Addiction, Dependence, and Tolerance
Tolerance means you need a bigger dose of tramadol to get the same pain relief as before. Physical dependence happens when the body gets used to the presence of the drug in order to function. Dependence is the reason why if you suddenly stop or reduce the dose dramatically you will experience withdrawal symptoms. Prolonged opioid use can lead to both developing tolerance and dependence, and these can develop in a few days to weeks [4].
Addiction, or opioid use disorder (OUD), is something else. It means losing control of use and continuing to use in spite of the negative consequences. People without a history of OUD have developed it while taking tramadol [2].
A history of alcohol or drug problems increases the risk of addiction. In 2024, approximately 0.4% of people age 12 or older in the U.S. used tramadol in a way that was not prescribed. In that year, 16.2% of 7.6 million people misusing prescription opioids misused tramadol products [1][4]. Learn more on our prescription drug addiction page.
Risk of Seizure
A seizure is a surge of electrical activity in the brain that can cause shaking, staring spells, or loss of consciousness. Seizures have been reported in patients taking tramadol in therapeutic and higher doses [4]. The risk is also increased if tramadol is taken with:
- Selective serotonin reuptake inhibitor (SSRI) antidepressants
- Tricyclic antidepressants
- The muscle relaxer cyclobenzaprine
- Other opiates
- Older class of antidepressants called monoamine oxidase (MAO) inhibitors
- Psychotic drugs
The risk of having a seizure is increased if you have previously had a seizure or have a head injury or epilepsy. Alcohol or drug withdrawal increases the risk as well. In a U.S. study of nearly 97,000 people with seizures, tramadol users had a 41% greater risk than codeine users of seizures serious enough to require a hospital visit [4][5].
Serotonin Syndrome
Serotonin syndrome is a build up of serotonin in the body. It can be fatal in extreme cases. The recommended dose of tramadol is sufficient to qualify for serotonin syndrome. It is most likely to occur when tramadol is taken in combination with other drugs that increase serotonin: SSRIs, tricyclic antidepressants, triptans used to treat migraine, antidepressants such as mirtazapine and trazodone, the muscle relaxant cyclobenzaprine, MAO inhibitors, and other medications [4].
Combination of medications
Common symptoms from the combination of pain medications such as tramadol and depression medications are agitation or hallucinations, fast heart rate, blood pressure extremes, high temperature, hyperactive reflexes, stiff muscles, nausea and vomiting or diarrhea.
These symptoms can occur within a few hours to days after taking tramadol, and in some cases, hours or even days later [4]. In the case of individuals with chronic pain, many of them are on long-term prescription of antidepressants. Therefore, don’t forget to inform your prescriber about all other medications you are taking.
Hormones and Blood Sugar Levels
For extended periods of time, long-term use of opioid pain relievers, including tramadol, can alter hormones that are produced by the body as well as blood sugar levels, causing [4]:
- Adrenal insufficiency (Addison’s disease). Long-term use of opioids affects the adrenal glands on top of the kidneys that produce the stress hormone, cortisol. Insufficient cortisol is reported in more than half of patients who have used opioids for a month or longer. It can cause nausea and vomiting, loss of appetite, feeling weak, tired and dizzy, and low blood pressure.
- Low sex hormones. Opioids taken for long periods of time have been associated with androgen deficiency which causes low levels of male sex hormones such as testosterone.
- Hypoglycemia (low blood sugar). This can become severe enough to require a hospital stay. Hypoglycemia was seen mostly in older patients, those with diabetes, and people with kidney disease [4].
Slowed Breathing and Interaction With Tranquilizers
Tramadol can slow breathing, as can other opioids, a problem called respiratory depression. Tramadol is also very dangerous to combine with alcohol, benzodiazepines such as alprazolam (Xanax), sleeping pills, or other sedatives. These combinations can result in extreme drowsiness, coma or death [4].
Opioids can also cause central sleep apnea, which happens when the brain stops sending signals to the body to breathe during sleep for short periods of time. The risk is dose dependent [2].
Pain Relief Vs Risk Over Time
Tramadol’s reputation as a gentler, safer opioid is questioned in a 2025 review of adults with chronic pain. Tramadol reduced pain by less than 1 point on a 0-10 pain scale compared to a placebo. In contrast, it doubled the risk of serious adverse events like heart failure [3]. Clinical guidance recommends a review of the risks and benefits of continuing tramadol prescription every 3 months [2].
Symptoms of Tramadol Withdrawal
People who have a physical dependence on tramadol can experience withdrawal symptoms if they suddenly stop using the drug, or if they reduce the amount they are taking too quickly. The following are reported withdrawal symptoms:
- Irritability, anxiety, and restlessness
- Watery eyes, runny nose, yawning, and sweating
- Back pain and joint pain, muscle aches, chills
- Stomach cramps, nausea, vomiting, and diarrhea
- Difficulty sleeping and loss of appetite
- Higher heart rate, breathing rate, and blood pressure
A less common form of tramadol withdrawal does not resemble typical opioid withdrawal and includes symptoms such as hallucinations, paranoia, intense anxiety or panic attacks, confusion or feeling numb/fuzzy in hands and feet [1].
In this type of withdrawal, individuals also risk relapse and experiencing severe withdrawal symptoms such as hallucinations, extreme anxiety, and suicide. The FDA has issued a warning about the potential for serious harm to dependent patients who are discontinued from tramadol too quickly [4].
How to Safely Taper Off Tramadol
Tapering down your dose in small steps over time (under the supervision of a doctor) is the safest way to come off tramadol. This tapering schedule will depend on your dose, the length of time you have been taking tramadol and for what reason, as well as your overall physical and mental health. Typically a supervised taper is scheduled in the following way: [4][6].
Gradual reduction. The dose is reduced by no more than 10% to 25% of the total daily dose, allowing several weeks to pass between each decrease in dose, typically every 2 to 4 weeks. CDC recommends that patients who have taken opioids for a year or longer decrease their dose by about 10% a month or slower. A safe and complete tapering could take months to years to complete.
Flexible pacing. Your tapering schedule can be paused if severe withdrawal symptoms appear. In some cases, you may even need to return to the dose you were taking before. Any changes are your doctor’s decision.
Other aspects that your clinical team will factor in include:
- Monitoring for changes in mood, suicidal thoughts, and the use of other substances during the taper.
- A plan for managing pain and addressing mental health issues before tapering off of tramadol.
Some individuals require closer monitoring during their taper than an outpatient setting can provide. These are individuals who are taking tramadol in excess of what has been prescribed to them, combining the drug with other substances such as alcohol, or who have had a seizure while taking the drug.
Those who have become addicted to tramadol through non-prescription means will also need to address the substance use disorder itself [4]. OUD can be treated with medication. Read more about treatment for opioid addiction.
Tramadol: Your Questions Answered
Is Tramadol Addictive?
Yes. Tramadol is a controlled substance and can lead to addiction like other opioids. People who start taking it for pain and have no history of drug problems can become addicted [2]. Warning signs include taking more than prescribed, running out early, getting prescriptions from more than one doctor and craving the drug.
What Happens If You Take Tramadol for a Long Time?
If used continuously over years, tolerance, physical dependence and sometimes addiction can develop. Long term use can also lower cortisol and sex hormones. There is still a risk of seizures and serotonin syndrome, and the risk is increased if a new medicine is added that interacts with tramadol. Meanwhile, pain relief may be minimal [3][4].
How to Safely Come Off Tramadol?
Don’t reduce or quit on your own. First talk to your doctor. Your doctor can slowly taper you off, can adjust the taper if you have withdrawal symptoms, and can plan other pain control options [4]. Tell your doctor about any other medicines or supplements you take, as some of these may alter the amount of tramadol in your blood [4]. If you’ve taken more tramadol than prescribed or combined it with other substances, let your doctor know immediately.
What Is Important
- Tramadol may lead to tolerance, dependence, and addiction, even in people taking it as prescribed for pain over the long term.
- Tramadol can trigger seizures and serotonin syndrome. The risk is greater with higher doses and with many antidepressants and migraine drugs.
- A review in 2025 found tramadol had about twice the rate of serious adverse events compared with placebo.
- Do not stop taking tramadol suddenly. Taper off under a doctor’s supervision to lower the risk of withdrawal and returning pain.
Hanley Center Can Help With Tramadol Abuse
If tramadol has become difficult to manage, Hanley Center in West Palm Beach, Florida, offers residential and outpatient treatment for prescription drug addiction and opioid use. The programs are for men, women, and older adults.
Treatment includes cognitive behavioral therapy (CBT) to change thinking that leads to drug use, dialectical behavior therapy (DBT) to develop skills to manage strong emotions, eye movement desensitization and reprocessing (EMDR), a trauma therapy, and motivational interviewing to help the person find their own reasons to change.
Call (561) 841-1033 to talk about your situation and next steps.
Sources
[1] Drug Enforcement Administration. 2026, May. Tramadol (Trade Names: Ultram, Ultracet). DEA Diversion Control Division, Drug & Chemical Evaluation Section.
[2] Dhesi, M., et al. 2024, Feb. Tramadol. StatPearls. StatPearls Publishing.
[3] Barakji, J. A., et al. 2025, Oct. Tramadol Versus Placebo for Chronic Pain: A Systematic Review With Meta-Analysis and Trial Sequential Analysis. BMJ Evidence-Based Medicine, 31(3), 160-169.
[4] U.S. Food and Drug Administration. 2023, Feb. ULTRAM (Tramadol Hydrochloride) Tablets: Full Prescribing Information. Janssen Pharmaceuticals.
[5] Morrow, R. L., et al. 2019, Mar. Tramadol and the Risk of Seizure: Nested Case-Control Study of US Patients With Employer-Sponsored Health Benefits. BMJ Open, 9(3), e026705.
[6] Dowell, D., et al. 2022, Nov. CDC Clinical Practice Guideline for Prescribing Opioids for Pain, United States, 2022. MMWR Recommendations and Reports, 71(3), 1-95.
