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What is Tramadol? Is it a Safe Alternative to Opioids?


What is Tramadol?

Tramadol is a conventional powerful centrally acting analgesic drug with stable medication effects on opioid systems such as μ-opioid receptors and non-opioid systems such as 5-Hydroxytryptamine and Noradrenaline reuptake inhibition.

Tramadol is a prominent pain relieving drug with antidepressant effects like venlafaxine (venlafaxine is a drug used to treat depression and certain anxiety disorders).

Tramadol is similarly related to the chemical structure of all dual action antidepressants, like venlafaxine. Thus, tramadol and venlafaxine both liberate monoamines (such as serotonin or norepinephrine) in neural transmission, leading to the tramadol effects on mood.

Antidepressant effects for tramadol have been noticed in clinical trials in combination with or without other antidepressants. And currently researches and clinical trials are still going in terms of drug-drug interaction when tramadol is used in conjunction with serotonergic antidepressants. But a recent analysis has clearly concluded that “precaution is necessary” if tramadol is prescribed to the patients of antidepressants with clear contraindications for the use of tramadol in patients taking Mono-Amine Oxidase inhibitors, was reported to cause serotonin syndrome even in the absence of collateral use of antidepressants. Hypomania was reported in patients with psychiatric history of anxiety when tramadol was prescribed for them. However, it is rare to notice such a mood-elevating effect in patients who have no previous psychiatric medication history.

History of Tramadol

Tramadol was a new approach in anesthetic or you can say pain-relieving medication, and In 1977 before releasing it into the market many researches and clinical trials were done for 15 years. Tramadol was first manufactured in Germany in 1962. The United States was not accepting the use of this drug, but it was finally approved by the United States Food and Drug Administration (FDA) in 1995. But at that time, the drug was not used in controlled form and that time it was considered a safe drug. And with time, more and more research and clinical trials showed that the drug has some short term and some long term side effects and also have drug drug interaction. Since it was the only opioid available in the market and however, the medication was easy to get, so its abuse became common day by day. The total number of prescriptions per year in the United States in 2013 was estimated to be more than 44 million, making tramadol one of the most prescribed opioids This classification was based on Tramadol’s approved medical uses, its potential for abuse, and its potential for causing dependence and addiction as compared to other Schedule IV controlled substances. Tramadol is approved and licensed for use in children over 1 to 3 years of age in Europe, depending on the country’s tramadol was used for moderate to severe supraspinal pain management. In the United States, tramadol is only approved for children older than 17 years of age.

Why Should I use Tramadol?

Tramadol is an effective short-term treatment for those suffering from moderate to severe pain. Tramadol Citra 100mg is also a good option for those who want to avoid trying drugs such as Oxycontin, Percocet, or Norco and who do not want to become addicted to drug addiction. This medicine might have some of the side effects and warnings but when used correctly, for pain from an injury, or any other cause, that is not relieved over the time by non opioid drugs, then let Tramadol bring some relief to your pain.

But it should not be specially used for chronic pain and for a long period of time because there might be a chance of developing dependency on the medicine.and the extended-release form should be used for chronic pain and the medication should not be suddenly stopped if used for a long period of time it might lead to withdrawal symptoms such as sweating, nausea, or anxiety. Researches are still going about the use of Tramadol in pregnancy so talk to your doctor about whether it is safe for you or not.

Is it a safe alternative to opioids?

The German pharmacists concluded that the drug is less prone to be used than other opioids. People move to higher doses then to snorting or shooting up as they build up tolerance and no longer feel the same effect at the same dose.

One recent survey says that nasty side effects become more pronounced  for tramadol for a long period of time because after consuming it is absorbed passed through the liver to get the full effect users do not transition to snoring or injecting.

Tramadol has its own risk to consume because the dual mechanism of action consisting of binding to the opioid receptors in the brain and inhibiting norepinephrine and serotonin reabsorption, cause an unpredictable rate of metabolism in different people which lead to different rate of effectiveness and toxicity to the patients.

Dual mechanisms of action have risks associated, like atypical reaction as compared to other opioids as risk for opioid medication and selective serotonin reabsorption inhibitor are incurred after tramadol use.

The  tramadol drug contains a synthetic opioid which is metabolized into an opioid in the body and acts on the centers of the brain, just like other opioids. Consuming the drug, especially at higher doses and for longer periods of time than a doctor recommends, can lead to dependence. Therefore tramadol is an opioid and is addictive and addiction occurs when consumed in daily life and can produce significant and behavioral changes and when Tramadol is used for a long time, it can become habit-forming, causing mental and physical dependence, which in turn, cause withdrawal symptoms and make it difficult to stop taking it and some of symptoms of addiction include uncontrollable cravings and inability to control negative thought on personal relationships or finances.

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There are some medications that may help to manage the withdrawal symptoms of Tramadol. However, some of these medications are recommended to avoid when consuming  Tramadol, but they are effective in controlling some of the withdrawal symptoms.

  • Benzodiazepines is a medication that can help to manage the symptoms of withdrawal, especially if the primary symptom of withdrawal is anxiety or restlessness.
  • Buprenorphine is a synthetic medication that acts on the opioid receptors of the brain, blocking the effects of Tramadol to bind to these receptors
  • Naloxone is another opioid antagonist often used to counteract opioid withdrawal or overdose symptoms.
  • Methadone is yet another opioid antagonist which binds to the opioid receptors for a longer time at a lower intensity than opioids.
  • Clonidine and Moxonidine are drugs that have been found to be effective in treating opioid withdrawal symptoms but that are usually used to control high blood pressure.

Side effects

Some of the uncommon side effects are;

  • Hypoglycemia 
  • Weakness, 
  • Fainting or lightheadedness, 
  • Anxiety, 
  • Heart palpitations, 
  • Excessive hunger, 


  • Tramadol toxicity: Tramadol is passed through the liver and excreted from the body through the kidneys so people who have kidney or liver disease may not be able to process and may build up toxic levels.
  • Seizures: who have never had seizures may be at risk of having seizures while on medication.
  • Ultra-rapid metabolism: it happens when Tramadol is metabolized in the body too quickly, resulting in stronger side effects, including shortening or slowed or stopped breathing and children are especially prone to this health risk.
  • Breathing problems: People who already have lung conditions may experience more difficulty breathing when using Tramadol or those who have asthma or lung disease, or who are over the age of 75, are at higher risk for breathing problems.


Withdrawal Symptoms

Tramadol works differently than other opioids by not only activating opioid receptors in the brain but also by blocking neurotransmitters like serotonin and norepinephrine from being reabsorbed back into the brain which makes it difficult to stop taking it.

Generally, opioid withdrawal symptoms usually occur within about 12 hours of the last dose and tramadol withdrawal symptoms may seem similar to the flu;


Early opioid withdrawal symptoms occur within a few hours of the last dose, such as;

  • Anxiety
  • Restlessness
  • Agitation
  • Racing heart rate
  • Hypertension
  • Fast breathing
  • Runny nose
  • Sweating
  • Tearing up
  • Yawning
  • Muscle and body aches
  • Trouble sleeping and/or insomnia

Delayed opioid withdrawal symptoms occur such as;

  • Loss of appetite
  • Pupil dilation
  • Difficulties concentrating or thinking clearly
  • Irritability
  • Drug cravings
  • Chills and goosebumps
  • Stomach pain and cramping
  • Diarrhea
  • Vomiting

Choice of Alternative opioids

  • Paracetamol and ibuprofen cannot be considered as effective alternatives because of their insufficient efficacy to treat moderate to severe pain. 
  • Among the other opioids, oxycodone and hydrocodone are two opioid prodrugs but the impact is now well established.
  • Other oral alternatives for tramadol and codeine are scarce.
  • Buprenorphine is a partial μ-opioid receptor agonist, which differs from other opioids because of its “bell shaped” analgesic dose–response curve in animals and a potential ceiling effect limited by its partial agonist activity for Pharmacodynamics effects.
  • Morphine has demonstrated efficacy and safety when used appropriately in nociceptive pain management in children


  • we would recommend adapting tramadol prescription to the patient’s pharmacogenetic profile and this is unfortunately not yet the case, and we thus recommend distinguishing the acute and the chronic nociceptive pain management settings.
  • In case of chronic and perception or sensation of pain or in situations where tramadol prescription can be planned in advance such as elective surgery, we strongly recommend that phenotyping/genotyping are considered according to the guidelines based on genotype/phenotype for tramadol should be implemented, as codeine.
  • Tramadol, the current alternative to codeine for children and their diseases may not be as safe as initially thought for the same reasons as codeine.
  • We advise starting at low doses (1 mg/kg/dose; three to four times daily) and adjusting the dosing according to tolerance and observed efficacy and at the end phase of medication, tramadol should be continued at the minimal effective dose depending on the tolerance and efficacy.
  • For the outpatient, we would recommend morphine as a first-line therapy in all tramadol with unknown status.
  • We further recommend contraindication to prefer morphine than tramadol in the following situations like immediate discharge after a surgical intervention or at risk factors for respiratory depression or at sleep apnoea syndrome or in obesity or after ENT surgery.
  • Tramadol should be given with caution like all opioids in children when initiating a treatment, its use may be pursued in the majority of the pediatric population for the treatment of moderate to severe pain.

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