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Fentanyl and Monoamine Oxidase Inhibitors

Serotonin Toxicity And Severe Serotonin Toxicity | Turning Point of Tampa

Writing about fentanyl and monoamine oxidase inhibitors is a difficult subject, with a lot of very clinical and medically heavy terms. Nevertheless, it is important to explain the potential consequences of using them in combination.

Both illicit and pharmaceutical grade fentanyl are considered synthetic opioids and carry a high risk for an adverse fentanyl reaction. Regular users of fentanyl frequently suffer from negative outcomes such as addiction, dependence and/or death by overdose.

Mixing Fentanyl and Monoamine Oxidase Inhibitors

In Vitro Receptor Assays And Human Cloned Receptor Assays Have Been Studied | Turning Point of Tampa

Mixing fentanyl and monoamine oxidase inhibitors can cause drug interactions that, in certain circumstances, are possibly life threatening. Since fentanyl and monoamine oxidase inhibitors are medications that will increase the levels of serotonin in a person’s body – it is imperative in self-medication management and patient management – to be aware that taking selective serotonin reuptake inhibitors or MAOI drugs with fentanyl, has the potential for harmful side effects.

Cardiac Surgery and Cancer

Pharmaceutical grade fentanyl is generally prescribed by a physician. It is administered in a controlled medical setting to such patients that suffer severe post operative pain from cardiac surgery, coronary artery surgery, cancer and many other medical procedures. If taken as prescribed, it is efficacious in the control of post-surgical pain.

Drug Interactions

Illicit fentanyl, also called fentanyl analogues, are most often used in the manufacture of counterfeit opioid pills such as oxycontin and morphine, because it makes them more potent. Because of the lack of accurate pharmacological data, illegal fentanyl has been involved in most fatal drug interactions in the recent past. In fact, fentanyl was responsible for more deaths in 2021 than auto accidents or Covid.

Again, because there are no guarantees in the quality of the drug or of the drug’s potency, illicit or illegal fentanyl users are in extreme danger when taking anything that might contain even slight traces of the substance. Less than 2 grams, which is the weight of a small thumbtack, can be fatal.

Phamacokinetic and Pharmacodynamic Interactions

When one drug interacts with another at the level of metabolism, absorption or excretion – it is referred to as a pharmacokinetic drug interaction. When this interaction takes place within the body, unpredictable results follow. This interaction is the main reason it is so dangerous to combine serotonergic agents like Lexapro or Citalopram with fentanyl, or any other opioids -synthetic or otherwise.

Synergistic drug interactions at the level of receptor sites are also dangerous and unpredictable, especially when fentanyl is involved. A strengthening or potentiating effect between two drugs is referred to as a pharmacodynamic interaction.

Severe Serotonin Toxicity

Another hazard that can have devastating effects is when two different particular drugs exceed the expectation of the combined effect of each drug independently. It is for this reason that aspirin and ibuprofen should not be taken together, as it can cause bleeding of the stomach lining.

However, when fentanyl is ingested in combination with an antidepressant, a build up of too much serotonin in the brain can be the result.

Serotonergic Opioids

The terms serotonergic drugs and narcotic analgesics refers to fentanyl as well as other drugs such as methadone, meperidine and tramadol or oxycodone and codeine. These substances have enough serious side effects and adverse reactions by themselves. However, there are even more potentially serious side effects these substances can initiate when used in combination with antidepressants like a monoamine oxidase inhibitor.

Pharmacological grade or fentanyl analogues, or any other opioid analgesics, should never be mixed with particularly large doses of any antidepressant drug. If you or someone you know is taking an MOA inhibitor or a serotonin reuptake inhibitor, they need to be made aware that dangerous and life-threatening adverse side effects can occur, especially due to the unpredictable and serious nature of opioid analogues.

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors were an early iteration of a class of antidepressant drugs that were originally developed in the 1950’s to treat depression, anxiety and panic disorder. monoamine oxidase inhibitors are effective but have taken a backseat to another class of antidepressant drugs that are somewhat safer and have fewer side effects.

Use of monoamine oxidase inhibitors typically requires some diet restrictions and avoiding certain other medications. Also, MAO inhibitors can cause dangerously high blood pressure when taken with certain foods or medications.

MAO Inhibitors are a Good Option for Some

In spite of its limitations, MAO inhibitors are still a good option for some people. In certain cases, they relieve depression when other treatments have failed.

However, care should be taken to avoid another hazard in combining any antidepressant with an opioid, or opioid analogue. The use of these or any other serotonergic opioids with a serotonin regulator type drug can precipitate serotonin syndrome. This condition is explained further, later in this article.

How Monoamine Oxidase Inhibitors Work

Antidepressants such as monoamine oxidase inhibitors ease depression by affecting the chemical messengers in the brain that are used by brain cells to communicate. Like most antidepressants, MOAI’s work by effecting changes in brain chemistry that cause depression, anxiety and other negative psychological conditions.

An enzyme known as monoamine oxidase can strip the neurotransmitters – norepinephrine, serotonin and dopamine – of their effectiveness. MAOI drugs work by halting this action and prevent this process from happening. This enables more of these neurotransmitters to be available in the brain, which can then effect positive changes in both brain cells and neurotransmitter connections.

Selective Serotonin Reuptake Inhibitors

Another class of antidepressants called serotonin reuptake inhibitors, also known as serotonergic drugs, were first developed in the 1970’s to treat several conditions such as depression, general anxiety disorder, compulsive-obsessive disorder and social anxiety.

Due to the risk of serious adverse effects, and even death, it is generally recommended that the use of serotonin reuptake inhibitors (SSRIs) should be avoided if used in combination with an MAO inhibitor, because there is a high risk of precipitate serotonin toxicity or serotonin syndrome occurring.

Selective serotonin reuptake inhibitors and MAOI’s work by keeping the hormone serotonin in the brain at levels that help stabilize mood. Serotonin is the chemical in our bodies which is needed to help us feel positive, less anxious, happier and ready to face life.

Serotonin Transporter

The body produces serotonin naturally. It is also needed for the central nervous system, which is comprised of the brain and spinal cord, to function properly. Serotonin transporters are also involved in this process and are related to the transporters for norepinephrine and dopamine as well.

Neurons in the brain communicate by using chemical messengers like serotonin, dopamine and norepinephrine. Depression, anxiety, and the like occur when these enzymes such as norepinephrine uptake inhibiting activity are not present in sufficient quantity to be effective.

Precipitating Serotonin Toxicity

Serotonin Syndrome also known as precipitate serotonin toxicity or dose dependent serotonin toxicity or severe serotonin toxicity is the flip side of this. This severe toxicity is caused by a dangerously high level of serotonin in the brain and is a potentially life-threatening condition resulting in what is known as autonomic hyperactivity.

A different spelling of dependent and dependant when referring to serotonin toxicity

The term “dose dependent serotonin toxicity” is commonly used in the United States, where the word dependent can either be a noun or an adjective. However, when using The Queen’s English, or British terminology, the word dependant in the term “dose dependant serotonin toxicity” is a more common spelling and is still used to indicate the adjective form in British English but its use in the U.S. in this form is uncommon.

However you chose to spell it, dose dependent serotonin toxicity affects people worldwide.

Patients Experiencing Serotonin Toxicity

Patients experiencing serotonin toxicity present with a combination of neuromuscular and autonomic hyperactivity symptoms. One testing method used to diagnose severe serotonin toxicity is the Hunter Serotonin Toxicity Criteria scale, which gives valuable data quickly.

The scale only requires the patient to be suffering at least one of the following to be diagnosed:

Spontaneous involuntary muscle contractions

Tremor and overactive or overly sensitive reflexes

Muscle contractions that are triggered by the examiner

Hyperhidrosis or heavy perspiration

Involuntary eye movements


Neuromuscular and Autonomic systems

The neuromuscular system includes all the muscles of the body and the nerves and motor neurons that help make movement possible. The neuromuscular system is essential in bodily movements, control of posture, and breathing.

The autonomic system includes automatic functions of the body which includes breathing, regulation of the heart, vasomotor activity which regulates the amount of blood that gets to all areas of the body, and certain reflex actions such as coughing, sneezing, swallowing and vomiting.

Signs and Symptoms

Symptoms can occur within several hours of taking a new antidepressant drug or after increasing the dose of a drug you’re already taking, or by combining opiates with SSRI or MAOI dugs.

Symptoms of clinical toxicity or serotonin syndrome can include:

Insomnia, agitation, and restlessness

High blood pressure

Rapid heart rate or tachycardia


Loss of muscle coordination

Dilated pupils

Muscles that move involuntarily

Respiratory distress, muscle rigidity, heavy sweating, diarrhea, headache, and shivering can also be symptomatic.

When a serotonin reuptake inhibitor is taken in high doses or when combined with other substances, especially alcohol or other illicit drugs such as heroin or cocaine death can occur.

Centrally Acting Analgesics

Tramadol or Clonidine should never be taken with fentanyl or monoamine oxidase inhibitors (MAO inhibitors). Acute and chronic Tramadol use can become addictive.

The combination of MAO inhibitors and Tramadol can cause significant side effects such as anxiety, confusion and hallucinations.

Clinical reports and further research found known serotonergic opioids such as tramadol, pethidine, dextromethorphan and tapentadol increase serotonergic activity.

Addiction to Fentanyl and Monoamine Oxidase Inhibitors are Suggested

Fentanyl And Monoamine Oxidase Inhibitors | Turning Point of Tampa

It is a daily struggle for anyone when addiction has become a part of our existence. It is also common that when seeking help for addiction, co-occurring disorders such as depression, anxiety or OCD, that have been hidden behind drug use, are uncovered. The question then becomes: what options are available?

Turning Point of Tampa Welcomes Those with Co-occurring Disorders

Being able to be truthful about addiction is freeing. Turning Point of Tampa has been helping those suffering with alcoholism, drug addiction, and eating disorders find solutions for over 35 years.

Our doctors, clinicians, and counselors help individuals and families find their way back to living the life they deserve. Beginning with a medical assessment and clinical biopsychosocial, our approach guides the treatment plan to include goals to solve identified problems that have been caused by using.

If medication is needed and agreed upon together with the doctor, selective serotonin reuptake inhibitors or MAOI’s could be part of the treatment plan. However, only drugs that are non-mood altering and are non-addictive, are prescribed at Turning Point of Tampa.

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Fentanyl is an opioid used for chronic and severe pain. Precise data from patients represents that back injuries, surgeries, major trauma, cancer and nerve damage are most often the cause of such chronic pain.

Fentanyl is prescribed by dose and can also be delivered in transdermal patches. There have been instances of fatal toxic encephalitis occurring from overuse.

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Fentanyl and Alcohol

Mixing fentanyl and alcohol or other illicit drugs can include an increased risk of respiratory depression, a condition that is a major contributing cause of most fatal drug interactions.

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Fentanyl and Benzodiazepines

According to the National Institute on Drug Abuse “Every day, nearly 200 Americans die after overdosing on opioids.”

Fentanyl and benzodiazepines when taken together can affect the metabolism of an individual and can have serious and fatal consequences.

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