Tramadol (Ultram) alternatives: What can I take instead of tramadol?

Compare tramadol alternatives | Belbuca | Cymbalta | Naproxen | Celebrex | Voltaren gel | Natural alternatives | How to switch meds

We have all experienced pain at some point and can therefore understand that the scale of pain ranges from a manageable ache to uncomfortable to, frankly, excruciating. Management of pain is fundamental to optimizing the quality of life. Pharmacologic approaches to pain management are a pillar of many treatment plans. Still, widespread and uncontrolled prescribing in the 1990s triggered the first wave of an epidemic in the misuse and overdoses of specific types of analgesic medications known as opioids.  Between 1999-2020, more than 564,000 people died from an overdose involving any opioid medication, including both prescription and illicit opioids. The Centers for Disease Control and Prevention (CDC) have committed to fighting the opioid overdose epidemic in many ways, including by aiding providers, healthcare systems, and payers with data, tools, and evidence-based guidance to support improved opioid prescribing and patient safety. 

It is critical to establish an accurate understanding of the type of pain experienced to be able to consider non-opioid options like over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs) such as Motrin (ibuprofen), which are at least as effective as opioids, like tramadol.

As part of this assistance, the CDC recently updated its Clinical Practice Guideline for Prescribing Opioids for Pain, which includes five guiding principles for implementing the recommendations. One of these guiding principles consists of an appropriate assessment of the type of pain and treatment of pain—whether opioids are part of the treatment regimen. This is important since pain management requires a multimodal and multidisciplinary approach, including optimizing physical and mental health. Non-drug measures, such as exercise, ice, heat, massage, and weight loss, should be emphasized in managing any type of pain, as appropriate. 

Tramadol is a synthetic codeine analog that acts, at least in part, through weak agonist activity at mu opioid receptors. It is also a weak serotonin/norepinephrine reuptake inhibitor (SNRI). It is associated with less histamine release than other opiates, which presents as a pseudoallergy, so it is a recommended alternative to opiates should this reaction of itching, flushing, and sweating occur. Tramadol has been available in the United States since 1995, but not until 2014 did it become a schedule IV controlled substance by the Food and Drug Administration (FDA) based on data suggesting abuse potential similar to other schedule IV opioids available at that time. 

Severe acute pain is defined as pain experienced for less than one month and maybe most appropriate for short courses of opioids like tramadol. In contrast, subacute pain has been present for one to three months, and chronic pain is pain experienced for more than three months. For subacute and chronic pain, reliance on opioids for pain management becomes less desirable given their side effect profile. For these types of pain, opiates should only be initiated if the expected benefits of improved pain and function are expected to outweigh some of the side effects and risks of long-term use, such as dependence. It’s important to note that the CDC’s recommendations do not apply to pain related to sickle cell disease, cancer, or patients receiving palliative or end-of-life care. Other types of pain also exist, including nerve pain, which may be best managed by additional classes of medications.

Tramadol is a synthetic codeine analog that acts, at least in part, through weak agonist activity at mu opioid receptors. It is also a weak serotonin/norepinephrine reuptake inhibitor (SNRI). It is associated with less histamine release than other opiates, which presents as a pseudoallergy, so it is a recommended alternative to opiates should this reaction of itching, flushing, and sweating occur. Tramadol has been available in the United States since 1995, but not until 2014 did it become a schedule IV controlled substance by the Food and Drug Administration (FDA) based on data suggesting abuse potential similar to other schedule IV opioids available at that time. 

What can I take in place of tramadol?

Tramadol is currently available under the brand names ConZip and Qdolo; the brand Ultram has since been discontinued. It serves as an alternative to a stronger opioid analgesic. Still, it can produce subjective effects similar to those of morphine or oxycodone at supratherapeutic doses above the maximum total daily dose of 400 mg. In patients with impaired renal function, dose reductions should be employed. In addition to typical side effects seen with opioids, such as sedation and respiratory depression, the side effects of tramadol also include seizures and low blood sugar, among others. Being a weak SNRI, people taking multiple agents with similar mechanisms of action are at risk of developing serotonin syndrome, which can be life-threatening. Ultimately, as a controlled substance, tramadol poses risks of abuse, diversion, dependence, and withdrawal. For these reasons, pain relief may be sought with alternative painkillers like tramadol.

Other options are available to manage pain that either does not improve with tramadol, if side effects like drowsiness and constipation become intolerable, or if drug interactions pose problems. Alternative prescription medications include other opioid analgesics, NSAIDs or acetaminophen, and antidepressant SNRIs. These options may be more suitable for certain individuals.

Other alternatives to tramadol

• Zohydro ER (extended-release hydrocodone bitartrate)
• Hysingla ER (extended-release hydrocodone bitartrate)
• Apadaz (benzhydrocodone/acetaminophen)
• Olinvyk (oliceridine)
• Toradol (ketorolac)
• Lodine (etodolac)
• Meclofenamate
• Relafen DS (nabumetone)
• Nucynta (tapentadol)

Top 5 tramadol alternatives

The following are some of the most common alternatives to tramadol.

1. Belbuca (buprenorphine)

Belbuca is a buccal film of the active ingredient, buprenorphine, that is approved for chronic pain. The mechanism of action of buprenorphine differs from that of tramadol in that it is both a partial agonist at mu opioid receptors and an antagonist at kappa opioid receptors. Given the partial agonist activity, there may be less abuse potential than with full agonists—as dose increases, subjective effects like euphoria, which often drives abuse, plateau. This is also beneficial as it allows for a wider safety margin; certain effects, like respiratory depression, also plateau despite increasing doses. 

The alternative formulation of an oral tablet might be necessary for certain patients unable to take a medication like Qdolo that is only available by the oral route. The buccal film has a delayed peak concentration of a couple of hours to achieve the pain control effect, and provides a relatively long duration of action. Belbuca is a good alternative to opioid treatment that needs to be taken around the clock, but it may come with a hefty price tag.

2. Cymbalta (duloxetine)

Cymbalta is an effective alternative pain reliever to Qdolo in the management of certain types of chronic pain, which can be categorized as neuropathic pain, inflammatory or joint-related pain, and non-inflammatory/non-neuropathic pain (e.g., fibromyalgia). Cymbalta is a non-opioid medication and is labeled as an antidepressant, more specifically a serotonin/norepinephrine reuptake inhibitor (SNRI). Today, it is approved by the Food and Drug Administration (FDA) for chronic musculoskeletal pain—like low back pain, neuropathic pain associated with diabetes mellitus, and fibromyalgia; it is also used off-label for chemotherapy-induced peripheral neuropathy. 

The pain relief associated with Cymbalta is believed to be a result of increased activity of serotonin and norepinephrine within the central nervous system (CNS), which has downstream effects by decreasing pain signals. Cymbalta is overall safe and tolerable, but its packaging does include a black box warning for increased suicidal thoughts and behavior. When initiating Cymbalta, close monitoring for the emergence of such thoughts and behaviors is important.

3. Aleve (naproxen)

Naproxen is a type of NSAID and may serve as a good alternative to opioid pain medications like tramadol in several clinical scenarios. All alternatives discussed thus far are prescription medications; naproxen is available over-the-counter. As a non-opioid, one can avoid side effects more specific to opioids, like constipation and drowsiness. 

NSAIDs like Aleve do come with their own set of potential side effects. NSAID use is associated with an increased risk of cardiovascular events’, including the development of high blood pressure. Risk factors for the development of cardiovascular events include age greater than or equal to 65, higher doses, longer duration and frequency of use, and pre-existing cardiovascular disease or the presence of other risk factors for cardiovascular disease. NSAIDs can also increase bleeding event risk, so while not an opioid, they remain a medication with some risk associated with their use.

4. Celebrex (celecoxib)

NSAID use can result in gastrointestinal (GI) ulceration and bleeding. The chance of such a serious event is small, but the consequences can be devastating. Medications within the NSAID class may have more or less of a propensity to cause these significant adverse effects, and no single NSAID is entirely free of the risk of causing stomach ulcers. NSAIDs work by inhibiting an enzyme known as COX-2; prostaglandins produced by COX-2 play a role in inflammation, pain, and fever; therefore, inhibition of this enzyme can prevent the pathways that result in these symptoms. NSAIDs also inhibit, to varying degrees, the COX-1 enzyme—especially in high doses. Prostaglandins produced by COX-1 are protective within the GI tract in that they increase mucosal blood flow, mucus production, and cell growth. 

Celebrex is unique from naproxen and other NSAIDs because it selectively inhibits COX-2, so it only interferes in the pathways associated with pain—not the pathways associated with the protection of the GI mucosa. Celebrex has been found to be associated with as much as a 20% lower risk of bleeding compared to other NSAIDs, and it may be safer than nonselective NSAIDs in patients requiring long-term use (greater than 6 months) in which opiates like tramadol become less preferred, or in patients taking other medications that may also have similar GI effects, like concurrent aspirin use.

5. Voltaren gel (diclofenac 1%)

A topical pain reliever alternative to tramadol is Voltaren gel. Voltaren is an NSAID, like naproxen or celecoxib. The topical application allows for the avoidance of some of the safety concerns observed with oral NSAIDs, but it does carry the same NSAID warnings as the oral agents regarding increased risk of gastrointestinal and cardiovascular adverse events, so should always be used at the lowest dose for the shortest duration of time possible. The gel may work as well as oral NSAIDs for arthritis pain and acute musculoskeletal pain (like sprains and strains). However, it comes with a higher risk of localized adverse events, such as rash, compared to oral NSAIDs, and it is significantly more expensive than oral options.

Natural alternatives to tramadol

The management of pain should be approached from all angles, and non-pharmacologic and more natural approaches may provide some real relief. Depending on the source of the pain, physical therapy may be one way to help manage it, especially in chronic pain after injuries or surgeries. By employing therapeutic exercise, physical therapy aims to achieve optimal neuromuscular and skeletal function. Other holistic approaches, such as acupuncture or use of aromatherapy with different essential oils like peppermint oil or lavender oil, may also provide some pain relief and are generally safe, natural options to try. Turmeric is a spice with an active component known to have anti-inflammatory properties; supplementation with turmeric may provide natural pain relief. Other natural products, such as topical capsaicin, or taking magnesium supplements, may provide additional pain relief as they reduce inflammation over time.

RELATED: 13 home remedies for pain relief

How to switch to a tramadol alternative

If discontinuation of tramadol is necessary, whether to switch to an alternative agent or because the medication is no longer warranted or causing side effects, tapering the dose under the direct supervision of a healthcare provider is critical to avoid unwanted side effects and minimize withdrawal symptoms—particularly in patients who have been on opioids long-term.

It’s important to keep in mind that patients might not realize that chronic opioid use can cause increased pain sensitivity, another reason why tapering doses slowly is very important. This is why medication changes should always be executed under direct medical advice and supervision, and it is encouraged that naloxone be offered with each opioid prescription. As of March 2023, naloxone is now available without a prescription.