National Recovery Month Special - Ultram(Tramadol): Not As Safe As Some Believe

This month is National Recovery Month, a national observance held every September by the Substance Abuse and Mental Health Services Administration (SAMHSA) to promote and support new evidence-based treatment and recovery practices, the emergence of a strong and proud recovery community, and the dedication of service providers and community members across the nation who make recovery in all its forms possible. Recovery month is in its 32nd year and celebrates the gains made by those in recovery from addictions. And to observe this month, our September blogs will feature information on substances of abuse that affect our seniors whether it be a substance use disorder, dangers of mixing medications or contributing to cognitive issues or falls.

"Substance use disorders among our seniors have nearly doubled since 2006, affecting almost 6 million older adults," said Attorney RJ Connelly III. "The reality is that seniors with a substance use problem face many more risks than younger people due to cognitive impairments, medication interactions, nutritional concerns, poor social supports, and the risk of falls. Misusing or abusing substances is also linked to increased mortality rates and higher costs of healthcare."

Americans continue to have a stereotypical view of substance abuse and addiction. It happens to the “other family” -- not ours. Many believe it is a problem of the “lower class”, those lacking education, the young, the homeless, and even minorities. These are stereotypes and stereotypes die hard because, in most cases, they are the refuge of those who are neck-deep in denial. In truth, addiction and abuse can be found in every family, every culture, every economic class, and, as we will discuss in our September blogs, at any age. In this week's blog, we will look at Tramadol (Ultram), which was once thought to be a pain reliever with little downside.

What is Tramadol (Ultram)

Tramadol was first introduced in the United States in 1995 under the brand name Ultram and was initially marketed as a safer non-controlled analgesic with less potential for abuse than traditional opioids. Tramadol (Ultram) quickly became the second most commonly prescribed narcotic-type analgesic, ranking behind only hydrocodone with acetaminophen products.

Ultram (Tramadol) fits into a group of drugs called opiate agonists and is prescribed to treat moderate to severe pain by changing the way the body sensed pain by binding with its opiate receptors. Although chemically similar to morphine, it provides relief but is only about one-tenth as potent. Physicians embraced the marketing strategy that Ultram (Tramadol) was much safer than the traditional narcotic pain relievers, however, we are now aware that this medication is not without its risks.

Narcotics and Opioids - The Same Thing?

Let’s take a moment here to discuss the difference between narcotics and opioids, something many readers of our blog have asked about. The difference is subtle and usually comes down to a legal definition. A narcotic is sometimes mistakenly used to refer to illicit drugs such as heroin (used for a "high"), but legally and medically, a narcotic is any drug that relieves pain. But for all intents and purposes, narcotics are the same thing as opiates and opioids.

Drugs like hydrocodone and oxycodone can be described as prescription narcotics or opioids. Heroin is also considered a narcotic because it acts on the same receptors in the brain and causes the same effects as prescription opioids. Narcotics, opiates, and opioids are all drugs that reduce the intensity of pain signals reaching the brain. They all affect certain areas of the brain that control emotion, which is how they’re able to reduce pain sensations. The only difference between opiates and opioids is that opiates are naturally derived, while opioids are man-made.

So, once again, narcotics are any drugs that relieve pain, opiates are considered narcotics and are made naturally (such as the poppy), and opioids are also narcotics, but they are derived synthetically. Now back to our discussion on Tramadol.

Over-Prescribing the Drug

By 2002, the patent on Ultram expired and the Food and Drug Administration (FDA) approved a generic version of Ultram, called Tramadol which is now manufactured by multiple drug companies. It was after the generic version of the drug became available and much less expensive when it began to be prescribed at higher rates that the problems began to surface.

Tramadol implication in overdose deaths in seniors

In 2010, the FDA received information from a study that Tramadol was not to be prescribed for those individuals who presented with suicidal behaviors, had addiction histories, or were depressed or emotionally unstable. By 2011, reports were pouring into researchers that Tramadol was linked to over 20,000 emergency room visits around the country. In Florida alone, where a high number of elderly individuals were taking the medication, there were 380 overdose deaths reported.

As reports like this continued to rise, it was apparent that changes needed to be made regarding the prescribing of Tramadol. In 2014, the Drug Enforcement Administration (DEA) stepped in and classified Tramadol as a controlled substance and thus subject to much stricter controls.

How Ultram(Tramadol) Affected Addiction Treatment

As a licensed addictions clinician and clinical trainer in the Commonwealth of Massachusetts for over 30 years before my retirement, I had my own experiences with providers who were quite liberal in prescribing the drug to older adults despite long histories of drug addiction before it was reclassified as a controlled substance.

Providers would nearly always assure me that my concerns about Tramadol were “not valid”, stating that it was “not a narcotic” implying that it carried no major abuse potential. In fact, many considered this medication to be as safe as over-the-counter pain relievers.

This belief made Tramadol a particularly dangerous drug — because it was, as later discovered, a highly addictive substance that was prone to abuse. Those in treatment for addiction would make one phone call and a script for the drug arrived with multiple refills. But because other more powerful opiates and opioids were available on the street for a price not that much different than Tramadol, users opted for the more powerful substance. But then things began to change.

As the so-called opioid epidemic began to hit mainstream media followed by the crackdown on the number of prescriptions being written for pain medications, the Tramadol issue started coming to light.

Those we saw in outpatient treatment were referred to our clinic because they were taken off oxycodone or hydrocodone and put on Tramadol due to the scrutiny providers were receiving around the prescribing of the powerful narcotics. Many of them suffered from severe arthritis, spinal stenosis, or other painful conditions and Tramadol just did not work. So, they took more than the prescribed amount seeking pain relief, unfortunately, they developed a tolerance to the medication and had some rather severe withdrawal issues. This change also affected seniors.

Seniors and Ultram/Tramadol

As we discussed many times in the previous blogs, seniors are more susceptible to the adverse effects of medications for a number of reasons and it is essential for medical providers to recognize that there is a Tramadol-associated risk with this group. In fact, a recent study of Emergency Room visits regarding Tramadol found over one-third involved patients 65 and older. And Tramadol presents another major problem, a condition called serotonin syndrome, that we will discuss in a bit.

In seniors, Tramadol can cause central nervous system (CNS) depression leading to breathing problems and death. The causes of this CNS depression appear to be the result of using more Tramadol than prescribed to address out-of-control pain or due to interactions with other medications and alcohol use. Seniors who have been prescribed other medications that depress the CNS like sedatives, tranquilizers, muscle relaxants, antidepressants should be evaluated thoroughly before adding Tramadol to their medication list.

Tramadol has also been associated with seizures in seniors over the age of 65 with nearly 25% of new seizure activity in this group being attributed to the use of this medication. Research seems to indicate that this increase is the result of changes in the brain caused by co-morbid conditions such as stroke, heart disease, Alzheimer's disease, and brain tumors.

In seniors with existing renal disease or diabetes, according to one study, Tramadol has been associated with hypoglycemia, although in a small number of cases those without the risk factors also developed hypoglycemia. Compared with codeine, Tramadol use was associated with a 52% increased risk of hospitalization and appeared to be at the greatest risk of hospitalization due to hypoglycemia during the first 30 days of initiating Tramadol use.

We know Tramadol’s action on the opiate receptors of the body, but it also has a very unique feature that can also contribute to dependence in its users. This drug exerts some of its effects through actions on serotonergic and noradrenergic neurotransmission, which increases brain levels of the neurotransmitters serotonin and norepinephrine. These changes are similar to those induced by antidepressant drugs like venlafaxine (Effexor).

What does this mean? Not only does Tramadol affect pain levels through its narcotic action, but it also acts as a mood elevator, affecting the pleasure centers of the brain. Yes, addiction is a major concern but there is also another -- its effects on serotonin can lead to a potentially deadly condition called serotonin syndrome.

Anti-Depressants and Ultram(Tramadol)

In 2019, a study was released from University Hospitals that found Ultram(Tramadol) had the ability to interact with common antidepressants, not only making it less effective for pain but also increased the likelihood that users could become addicted since it took upwards of three times more of this medication to control breakthrough pain.

The method of research included a review of 152 patients who received care at the University Hospitals and were on Tramadol for at least 24 hours. And according to Derek Frost, a pharmacist at University Hospital and the study’s lead author, “As we looked at the secondary analysis, it ended up being four times as much over their entire hospital stay.”

The anti-depressants affected by Tramadol are Prozac (fluoxetine), Paxil (paroxetine), and Wellbutrin (bupropion). Other anti-depressant medications such as Zoloft, Celexa, and Lexapro did not appear to inhibit the pain-blocking effects of Tramadol.

Concerns Around Serotonin Syndrome

Serotonin is a chemical produced by our body that allows brain cells and other nervous system cells to communicate with one another. When there is too little serotonin in the brain, depression is the result. But too much serotonin can lead to excessive nerve cell activity, causing a potentially deadly collection of symptoms known as serotonin syndrome.

According to the Mayo Clinic, symptoms often begin within hours of taking any new medication that affects serotonin levels or excessively increasing the dose of one that is being used. These symptoms include confusion, agitation or restlessness, dilated pupils, severe headache, changes in blood pressure and/or temperature, nausea and/or vomiting, diarrhea, rapid heart rate, tremor, loss of muscle coordination, or twitching muscles, and irregular heartbeat.

What is concerning is that in seniors, several of these symptoms are already present due to preexisting conditions, so attention needs to be paid when starting a senior on Tramadol or increasing the dosage.

The drugs most commonly associated with serotonin syndrome and Tramadol use are the selective serotonin reuptake inhibitors (SSRIs), a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder and anxiety disorders.

Some of the most commonly prescribed SSRIs are:

  • Celexa (Citalopram)

  • Lexapro (Escitalopram)

  • Prozac (Fluoxetine)

  • Paxil (Paroxetine)

  • Zoloft (Sertraline)

  • Luvox (Fluvoxamine)

  • Viibryd (Vilazodone)

Complicating matters even further is that according to multiple reputable medical researchers, more than 85% of physicians are unfamiliar with the diagnosis or treatment of serotonin syndrome or the drugs or drug combinations that are potentially involved. Although they say that providers are more apt to spot serotonin syndrome in younger patients, it is very difficult to diagnose in seniors as many of the symptoms mimic conditions already present. The key would be having knowledge that a new medication is being used and what current drugs the senior is taking that may interact with Tramadol leading to this condition.

Other drugs that are cause for concern when used with Tramadol are:

  • Blood thinners such as Warfarin

  • Antifungals, including Ketoconazole (Nizoral)

  • Antibiotics such as Erythromycin, Linezolid, and Rifampin

  • Psychotropics used to treat schizophrenia and bipolar disorder includes Lithium-based medications

  • Other medications for psychiatric issues besides SSRIs. These include monoamine oxidase inhibitors (MAO), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants like Amitriptyline.

  • Heart medications which include Digoxin and Quinidine

  • Other narcotic pain medications

  • Medication for migraine headaches which include Almotriptan (Axert), Eletriptan (Relpax) and Frovatritan (Erova)

  • Medications for seizures include Carbamazepine (Equetro and Tegretol)

  • Muscle relaxers like Flexeril

  • Even over the counter supplements like St. John’s Wort (which can increase serotonin levels)

What Can We Do?

Seniors prescribed Tramadol, as well as their family members or caretakers, need to be counseled to be aware of symptoms of serotonin syndrome, which can be reversed if detected early. With the ongoing concerns about prescribing some of the stronger opiates and seniors experiencing the painful conditions associated with aging, it is probably a good bet that Tramadol will continue to be prescribed at high rates given the scrutiny around stronger narcotic medications. Given that, education is the key.

“With the trend towards keeping seniors in their homes and out of institutional care, it is imperative that family members and home health care providers have knowledge of the medications their loved ones or clients are prescribed, thoroughly understanding why they are using them and what side-effects or drug interactions are possible,” said Attorney Connelly.

"Further, all medications should be counted on a regular basis to ensure that they are being taken as directed, whether they be narcotics or non-narcotic medications, and this also includes over-the-counter medications, supplements, and alcohol use," Connelly continued. "Staying in the home without the constant oversight of medical professionals means that those with day to day contact with the senior are the first line of defense in keeping them safe and medication compliant."

"If you think that a loved one may be misusing or abusing prescription medications, have a talk with them and if that is unsuccessful, discuss this with the prescribing physician," said Attorney Connelly. "Don't chalk up behaviors you are seeing as just another condition of aging. There is help available and programs that specialize in providing treatment for older adults, and the good news is, most insurance plans cover treatment for in-patient addiction treatment."

If you are interested in additional information or trying to locate a treatment provider, click on the SAMHSA logo below.

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