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Tramadol vs. Hydrocodone: 6 Differences to Consider

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Key takeaways:

  • Tramadol (ConZip, Qdolo) and hydrocodone (Hysingla ER) are opioid medications. They’re both controlled substances that can lead to dependence, misuse, and overdose. But when comparing tramadol versus hydrocodone, tramadol is less likely to be misused.
  • Tramadol and hydrocodone both block pain signals by attaching to opioid receptors (binding sites). But tramadol also affects brain chemicals called serotonin and norepinephrine. This is thought to contribute to its pain-relief effects.
  • Common opioid side effects include dizziness, tiredness, and nausea. Tramadol may be more likely than hydrocodone to cause severe side effects, such as serotonin syndrome and seizures. But the risk is low with both medications.
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Tramadol (ConZip, Qdolo) and hydrocodone (Hysingla ER) are opioid medications. They’re used to treat pain that isn’t relieved by nonopioid medications.

When comparing tramadol versus hydrocodone, they have several similarities. For example, both medications come with risks of misuse and overdose. This is especially true if they’re used for long periods of time or at high doses. But there are also several differences between these opioid medications. We’ll cover six distinctions below.

1. Tramadol and hydrocodone are both opioids, but they work differently

Tramadol and hydrocodone are both opioid medications (commonly called narcotics). All opioids work by activating opioid receptors (binding sites). These receptors are all over the body, including your brain, spinal cord, and stomach.

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  • Opioid side effects: Along with other opioids, tramadol and hydrocodone have side effects and risks to consider.
  • Avoid alcohol with opioids: Combining opioids and alcohol has potentially severe risks, including an increased chance of overdose.
  • Can you manage pain without opioids? Yes, other options exist besides opioids, and they’re often less risky.

By activating opioid receptors, opioids slow down or block pain signals from reaching your brain. So even if your body is hurting — after an injury, for example — you shouldn’t feel pain as strongly if you’re taking tramadol or hydrocodone.

But tramadol also works in another way. Tramadol increases the activity of two chemicals in the body: serotonin and norepinephrine. It’s thought that increasing the levels of these chemicals can lower the intensity of your pain. Hydrocodone isn’t known for having a major effect on these chemicals.

Another difference between tramadol and hydrocodone is that tramadol is a synthetic opioid. This means it’s derived from lab-made materials. Hydrocodone is a semisynthetic opioid. It’s derived from a naturally occurring opiate (codeine).

2. Tramadol and hydrocodone are both controlled substances. But they’re in different schedules

Tramadol and hydrocodone are controlled substances. This means they’re more likely to cause dependence and misuse than other medications. They also have restrictions on how they’re prescribed and refilled.

Dependence and misuse can lead to opioid use disorder (OUD). This medical condition occurs when someone takes opioids despite significant consequences. OUD is more likely if you take your opioid differently from how it’s prescribed. This includes taking a larger amount or taking it for longer than what’s recommended. Misuse is also more likely if you or someone in your family has a history of substance use disorder.

Hydrocodone is a Schedule 2 controlled substance. Tramadol is a Schedule 4 controlled substance. Schedule 4 controlled substances are less likely to cause dependence or misuse than substances in Schedule 1, 2, or 3.

Research supports this. Tramadol is less likely to be misused than hydrocodone and other Schedule 2 opioids, such as oxycodone (Roxicodone, Oxycontin). Still, tramadol carries a risk of dependence and misuse. Some research shows that people are more likely to continue taking tramadol long term compared with other short-acting opioids.

If you or someone you know struggles with substance use, help is available. Call the Substance Abuse and Mental Health Services Administration’s National Helpline at 1-800-662-4357 to learn about resources in your area.

3. Tramadol and hydrocodone come in different forms

Tramadol and hydrocodone are both oral medications. Tramadol is available in immediate-release and extended-release forms. Hydrocodone is available only in ER form (unless it’s part of a combination product that contains another nonopioid medication).

Tramadol is available as an:

Tramadol IR and ER tramadol tablets, and the tramadol / acetaminophen combination tablet, are available as generic medications. All other tramadol forms are brand-name only.

Hydrocodone medications are available as an:

All hydrocodone medications come in a generic form. Some hydrocodone products are FDA approved to treat cough only. One example is hydrocodone / homatropine tablet and liquid (Hycodan).

4. Tramadol and hydrocodone have different dosages

Tramadol IR tablets and liquid can be taken every 4 to 6 hours in most cases. So can combination hydrocodone / acetaminophen medications. Tramadol IR and hydrocodone / acetaminophen work quickly, but they don’t last long in the body.

Tramadol ER tablets and capsules are taken once a day. Their pain-relief effects last about 24 hours. But they don’t work as quickly as tramadol IR.

Hydrocodone ER tablets and capsules are also taken once daily. Like tramadol ER, they may take a few hours to work, but their effects should last about a day.

If you need pain relief for a short time or you are new to opioids, tramadol IR or a hydrocodone combination product may be a better option than long-acting opioids like hydrocodone ER or tramadol ER. But if you have chronic pain and need lasting pain relief, long-acting options may be best.

5. Tramadol and hydrocodone have common side effects, but there may be differences

All opioids have some common risks. So tramadol side effects and hydrocodone side effects are similar, including:

  • Drowsiness
  • Dizziness
  • Nausea and vomiting
  • Constipation
  • Itchiness

Most side effects are mild and improve as your body gets used to the medication. But constipation may last for as long as you take your opioid. This may require treatment in some cases.

Opioids may also increase your sensitivity to pain (hyperalgesia) and drop your blood pressure or blood glucose (sugar) levels. And they can cause withdrawal symptoms if you stop them abruptly. Withdrawal symptoms might include sweating, anxiety, and sleep disturbances. If you’ve been taking tramadol or hydrocodone for a while, work with a healthcare professional to slowly lower your dose.

Opioids can also cause dependence, misuse, and overdose. Your risk of overdose is higher if you take too much tramadol or hydrocodone. Taking it with other substances that also affect breathing increases your risk (more on that below). Overdoses are more likely in adults age 65 and older and in people who have respiratory conditions, such as asthma.

Good to know: If you take tramadol or hydrocodone, it’s a good idea to have naloxone (Narcan, Zimhi) or nalmefene (Opvee, Zurnai) on hand. These are fast-acting medications that can reverse an opioid overdose. Nalmefene is prescription only, but naloxone nasal spray is available over the counter. You can even find it for free in some cases. After administering or receiving naloxone or nalmefene, call 911. The person having an overdose still needs emergency medical care.

Tramadol vs. hydrocodone side effects

We don’t have a lot of research directly comparing tramadol versus hydrocodone. Some research shows that tramadol may cause fewer side effects, such as nausea and vomiting. But these studies are small and looked at specific types of pain, so the results can’t be extended to the general population.

Tramadol is considered to have more anticholinergic activity than hydrocodone. Anticholinergic medications block a chemical called acetylcholine in the body. They can have a range of side effects, including dry mouth.

Tramadol is less likely to be misused than hydrocodone. But two serious side effects may be more likely with tramadol than hydrocodone:

  • Serotonin syndrome: Among opioid medications, tramadol has a high risk of serotonin syndrome. But developing serotonin syndrome, a condition with high serotonin levels, is rare. It’s usually mild, but it can be severe in some cases. Serotonin syndrome is unlikely to occur with tramadol alone. But it is more likely if tramadol is combined with other medications that increase serotonin. Hydrocodone may also cause serotonin syndrome when combined with other medications that increase serotonin. But it’s less likely than it is with tramadol.
  • Seizure risk: The risk of having a seizure, especially if you have a seizure disorder, is increased with tramadol. This is because of its effects on serotonin and norepinephrine. The risk is low overall. But it’s higher if you combine tramadol with other medications that increase your seizure risk. Although seizures are not likely, the manufacturers of hydrocodone also list them in the product information as a risk.

6. Tramadol and hydrocodone may have different drug interactions

Tramadol and hydrocodone both have potential drug interactions. Drug interactions can lead to several outcomes.

Increased risk of side effects

Drug interactions often increase your risk of side effects. These include extreme drowsiness, slowed breathing, and overdose. Therefore, it’s best to avoid combining tramadol or hydrocodone with the following:

Additionally, medications that block tramadol or hydrocodone metabolism (breakdown) can increase the risk of side effects. Medications that block hydrocodone metabolism include cimetidine (Tagamet HB) and ciprofloxacin (Cipro). Medications that block tramadol metabolism include fluoxetine (Prozac) and paroxetine (Paxil).

Tramadol may be more likely to interact with medications that increase serotonin. Antidepressants are common medications that increase serotonin. Examples of antidepressants include fluoxetine, escitalopram (Lexapro), and sertraline (Zoloft). Tramadol may also be more likely to interact with medications that increase your seizure risk. This includes bupropion (Wellbutrin SR, Wellbutrin XL). Though these interactions can also occur with hydrocodone, they’re less likely.

Make tramadol or hydrocodone less effective

Certain medications speed up hydrocodone and tramadol metabolism. This can make hydrocodone and tramadol less effective. Examples include seizure medications, such as carbamazepine (Tegretol, Carbatrol) and phenytoin (Dilantin, Phenytek).

Can you take tramadol and hydrocodone together for pain?

It’s best to avoid taking more than one opioid at a time. But some people may need a long-acting and a short-acting opioid (like those with cancer pain).

Taking multiple opioids can increase your risk of dependence, misuse, and overdose. It can also increase your risk of everyday side effects, like nausea and constipation. Some people may need more than one opioid to control pain, so it’s a good idea to see if there are other effective options for managing your chronic pain.

The bottom line

Tramadol (Conzip, Qdolo) and hydrocodone (Hysingla ER) are opioid medications. They treat pain that isn’t relieved by nonopioid medications. They’re both controlled substances that have a risk of causing dependence and misuse. But hydrocodone is more likely to lead to misuse than tramadol.

If you’re prescribed an opioid for short-term pain, immediate-release tramadol is a better option in most cases. But if you need an opioid long term, your prescriber may consider extended-release (ER) tramadol or hydrocodone ER.

When comparing tramadol versus hydrocodone, their side effects are similar. This includes drowsiness, dizziness, and constipation. Tramadol may be more likely to cause serotonin syndrome or seizures, though these risks are rare. More seriously, both medications can lead to slowed breathing and overdose. This is especially true if they’re used differently from how they’re prescribed. Combining these opioids with alcohol or benzodiazepines also increases your risk.

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