Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN
Written By: Phillippe Greenough
Article Updated: 01/24/2021
Number of References: 37 Sources
Tramadol is an opioid painkiller, and while fairly weak compared to morphine and heroin can still produce very unpleasant or even painful withdrawal symptoms. It also has additional interactions that can cause very strong psychological withdrawal symptoms. Here, we will look at the way tramadol works, the specific symptoms of tramadol withdrawal, the timeline involved, and some effective treatments.
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The symptoms of tramadol withdrawal will include the physical symptoms of withdrawal from other opioids, although there may be more psychological unrest than with other opioids. Even though tramadol may not be as potent as many other opioids, the additional interactions with serotonin and norepinephrine systems can cause more intense psychological symptoms and these may persist for longer as well.
Tramadol has an intermediate half-life of around 6 hours in healthy adults and combined with its fairly weak μ-opioid receptor interactions, the physical withdrawal symptoms may not reach severe levels. Withdrawal symptoms often begin within 8 to 10 hours of the last drug use and will escalate, stabilize, then resolve over about 7 days. This first week will exhibit the worst of the physical symptoms, and the psychological symptoms can be quite severe during this time as well.
Tramadol withdrawal symptoms are not usually dangerous themselves, but if someone has a pre-existing health condition they may be at an increased risk for dangerous complications. People who have co-occurring heart health issues or diabetes are at an increased risk for cardiac arrest, although this is very rare, and diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome (HHNS), respectively. Additionally, older people who use tramadol and who are suffering from osteoarthritis are at an increased risk of potentially fatal outcomes, although the mechanism for this is unclear. This may be due to either tramadol use or tramadol withdrawal and further research is needed to discern the exact causes, risks, and some possible preventative measures.
A general overview of the tramadol withdrawal timeline may look something like this:
Within half a day from the last tramadol use, withdrawal symptoms will begin to appear. The first symptoms are usually sweating, increased anxiety, and minor chills. Over the next 24 hours, these symptoms will intensify and are often joined by hot flashes, a very runny nose, stomach pains, cravings for tramadol, restlessness, fatigue, and tremors. The second day frequently exhibits pains in the muscles, joints, and bones, alongside other symptoms such as increased heart rate, elevated blood pressure, insomnia, loss of appetite, vomiting, diarrhea, and allodynia. These symptoms will often worsen over the first three or four days before reaching a plateau. They may remain at a fairly stable level for a day or two before beginning a resolution over the next few days. A common timeline for the worst of the physical symptoms is between five to seven days, depending on someone’s use habits.
Some symptoms that may be experienced during the first week of tramadol withdrawal may include:
The beginning of the second week often proves much better than the beginning of the first week. The physical symptoms are usually well on their way to total resolution by now, with the exception of sweating and diarrhea. The psychological symptoms, while usually staying fairly stable during the first few weeks, may be more pronounced during this time as the physical symptoms are no longer as distracting. This may make it seem like they have gotten worse, as someone is more acutely aware of the mental discomfort during the second week. Insomnia may still be present as well, although it is often much improved. Once appetite begins to return to normal and someone begins eating more food and more regularly, this can also go a long way towards improving someone’s subjective experience of tramadol withdrawal symptoms.
Some symptoms that may be expected during the second week of tramadol withdrawal can include:
By the third week, the physical symptoms are usually totally resolved. Insomnia may still be somewhat problematic, although this is usually more psychological in nature rather than physical. Depression, anxiety, and cravings are frequently still present at fairly high levels and mood swings may be expected as well. As the memory of withdrawal fades over time, it is not uncommon for someone to reminisce and think about tramadol use fondly. This time is very critical, as most opioid relapses happen during, or shortly after acute withdrawal. By the fourth week of tramadol withdrawal, often the only remaining symptoms are psychological in nature. Sleep has usually returned to normal, and appetite levels or stomach issues are often resolved by now. Depression, cravings, and anxiety are almost certainly still present and may be for some time still.
If someone has not already entered treatment after detox, it is highly recommended that they do so now. The risk of relapse is real, and the cravings for tramadol can come and go. It is not uncommon to experience no cravings for weeks or months, only to have them appear suddenly and strongly. Continued care and treatment can provide the tools needed to deal with the cravings and other psychological symptoms in a healthy, sober way.
While the post-acute symptoms of tramadol withdrawal may be strictly psychological, they can still pose dangers and challenges to someone’s continued recovery. Additionally, the sometimes profound depression that can arise during withdrawal can lead to suicidal thoughts, and unfortunately, suicide attempts. While these risks are indirect, they can result in very unfortunate outcomes and should not be taken lightly. Finally, these symptoms can be quite long-lasting, oftentimes persisting for months or even years in some cases.
Some of the most common post-acute symptoms of tramadol withdrawal include:
These symptoms may be most intense in the days, weeks, and months immediately after ceasing tramadol use and usually dissipate over time. While the physical symptoms are due to downregulation, the prolonged post-acute symptoms are due to the neurological remodeling that occurs after downregulation has begun. While these symptoms may not seem severe, they can pose a serious hurdle to someone’s continued sobriety. Aside from depression and anxiety promoting isolationist behaviors, the cravings for tramadol can sometimes grow more intense over the first few months. As the memory of the pain and discomfort of withdrawal fades, the idea of a return to tramadol use may seem more and more attractive. If someone has not done so already, it is highly recommended that they seek out treatment and care as soon as possible as having support, care, and direction during this time can be crucial.
The intensity of tramadol withdrawal, while on average less intense than withdrawal from other opioids, shows some variability between individuals. While the factors that contribute the most are directly related to tramadol use habits, other factors that can play a role include genetics, age, and underlying health issues. Depending on these factors, both the intensity and the duration of tramadol withdrawal can be affected. While some people may recover quite quickly and fully, others may experience persistent symptoms that may last for years in some cases.
Some of the factors that can greatly contribute to the intensity and the duration of tramadol withdrawal symptoms include:
The largest contributors to the intensity and duration of the symptoms of tramadol withdrawal are related to someone specific tramadol use habits. The more tramadol someone uses, the more downregulation occurs in the brain. The more downregulation occurs, the worse the symptoms will be when someone stops using tramadol. After downregulation begins a further process of neurological remodeling can occur. The longer someone uses tramadol, the more complete this process of downregulation becomes, therefore the longer symptoms will persist after someone stops using tramadol.
Different from most other opioids, tramadol exhibits some significant metabolic differences between people. This has to do with liver function in general, which can be affected by age or disease, and specific genetics, which can alter the way certain metabolic enzymes are expressed in the liver. As far as general liver function is concerned, tramadol is often metabolized slower by the elderly or people who have impaired liver function. This can result in a slower onset of tramadol withdrawal symptoms and subsequently a longer withdrawal period. That also means, however, that the symptoms of withdrawal will likely not be as severe. Someone’s genetic background can have a significant impact on the speed of tramadol metabolism. Specifically, people who have mutations to CYP 2D6 liver enzymes will metabolize tramadol much slower than the general population. This can also lead to a longer, although typically less intense withdrawal period.
The existence of co-occurring mental health disorders can contribute to both the intensity and the duration of tramadol withdrawal symptoms, although this contribution is very indirect. Since depression and anxiety are such common symptoms of tramadol withdrawal, if someone were to have a pre-existing mental health condition involving one of these symptoms, they may experience heightened versions during withdrawal. Finally, these psychological symptoms may linger for longer if someone had an issue with depression or anxiety before tramadol use.
Tramadol is an opioid painkiller similar to morphine, although it is much weaker. Aside from interactions with the opioid system, it also directly produces effects in the serotonin and norepinephrine neurotransmitter systems which is unique among opioids. Serotonin is a mood elevator, regulator, and aids digestive function while norepinephrine is responsible for attention, learning, and affects emotional states. As far as it’s opioid interactions are concerned, tramadol is roughly 5 to 10 times weaker than morphine milligram-per-milligram depending on the route of administration. The opioid interactions, while frequently being weaker than with other opioids, are amplified by the effects produced in serotonin and norepinephrine systems.
When someone uses tramadol, it will weakly bind with the μ-opioid receptor while also acting as a reuptake inhibitor of serotonin and norepinephrine. This acts to increase levels of serotonin and norepinephrine in between neurons, leading to stronger signaling produced in these symptoms. The opioid stimulation combined with the increased signaling in these other neurotransmitter systems can combine to produce a greater analgesic effect than would be achieved through μ-opioid stimulation alone.
Using tramadol for an extended period, usually just a few weeks of daily use, the brain will begin to adapt to its presence. The chronic stimulation to μ-opioid receptors will cause the brain to reduce the sensitivity of these receptors in an attempt to maintain balance through a process called downregulation. This will also occur with serotonin and norepinephrine systems, as continued reuptake inhibition leads to elevated signaling in these systems. After downregulation has begun, a further and more comprehensive process known as neurological remodeling will begin. Remodeling is the process of enacting structural changes that will allow the brain to operate more efficiently in a μ-opioid, serotonin, and norepinephrine downregulated environment. While downregulation may happen fairly quickly, remodeling is a slow process that often takes months to produce noticeable changes.
While the symptoms of tramadol withdrawal are rarely fatal, they are almost always extremely uncomfortable. Entering a tramadol detox center can help reduce the discomfort and the risks of withdrawal through medications and medical monitoring. Furthermore, they can provide behavioral and clinical therapy to help someone find relief from the psychological symptoms and develop new, healthy ways to cope with tramadol withdrawal and life after detox. Entering one of these facilities can also provide connections and resources for continuing recovery and care after detox has been completed. This can make the difference between someone achieving a healthy and long-lasting recovery or relapsing back into tramadol use.Tramadol Detox Centers
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