Fluoxetine Syndrome Blog

Wondering why you cannot tolerate antidepressants? SSRIs can cause Serotonin Syndrome

Many people diagnosed with depression cannot tolerate antidepressants even at low doses. Sometimes medications have the potential to do more harm than good – if your body cannot tolerate them. To treat the symptoms of depression, patients often try different medications to no avail; nothing seems to work. In the worst-case scenario, a serious adverse reaction to antidepressants such as SSRIs can include a potentially fatal condition known as ‘Serotonin Syndrome’.

What is an SSRI?

SSRI is an acronym for ‘Selective Serotonin Reuptake Inhibitor’, which is a class of drugs for the treatment of mental health conditions that includes some of the most commonly prescribed antidepressants. SSRIs are used to treat depression, anxiety disorders and other conditions such as Obsessive-Compulsive Disorder (OCD).

Serotonin is one of the important chemical messengers of brain cells; it regulates mood, emotion, social behaviour, sleep, memory, learning and other functions. It is thought that people who suffer from depression have lower levels of serotonin in the brain. Since SSRIs work by blocking the re-absorption of serotonin, more of it remains available for cells to use, causing the level of serotonin in the brain to increase over time. Symptoms are relieved once an appropriate level of serotonin is achieved. This is why it takes several weeks before patients and their doctors can know whether or not a treatment plan is working.

Some patients cannot tolerate even the first few doses of SSRIs.

What is Serotonin Syndrome?

When treated with SSRIs, people who cannot tolerate these drugs are at risk for the serious drug reaction called Serotonin Syndrome. The symptoms include:

  • rapid heart rate
  • agitation / restlessness / panic attacks
  • shivering
  • twitching muscles
  • loss of muscle coordination
  • heavy sweating
  • high fever
  • seizures

There can be a range in the severity of symptoms. In the case of mild symptoms, the side effects are usually alleviated once the medication is stopped. Some patients, however, experience severe symptoms which can be fatal if left untreated.

What causes SSRI intolerance?

The answer is in your genes.

Not all patients experiencing mood swings or depression have abnormally low levels of serotonin in the brain. Even though they have normally functioning liver enzymes that metabolize SSRIs properly, they are still unable to tolerate these medicines, even at low concentrations, and can experience side effects within a few hours of getting the first doses. People who experience such symptoms frequently carry a mutation in one of the genes that makes proteins involved in the clearance of serotonin from the body, which results in accumulated high levels of serotonin.

An excess of serotonin is commonly found in patients with bipolar disorder and other inherited mental health conditions which have anxiety and depression as part of the initial clinical presentation. The trouble for these people begins when they start taking an SSRI or other medication that further elevates serotonin levels.

What should you do if you are currently taking an SSRI, but it is not working and you are concerned about adverse side effects?

  • Talk to your doctor, pharmacist or other trusted healthcare provider. Describe your side effects in detail, as well as your family history of mental illness.
  • If Serotonin Syndrome is suspected, the recommendation would be to discontinue SSRIs and start a different type of antidepressant that does not have an effect on serotonin.
  • Request a genetic test (Genome Sequencing) to find out if you have a genetic predisposition to bipolar disorder and depression due to disruption in serotonin clearance.

What else should you consider?

People who experience adverse side effects after taking SSRIs for a few days may be at risk for SSRI intolerance and Serotonin Syndrome due to their body’s reduced drug metabolism. When one of the liver enzymes (CYP2D6, CYP2C19) involved in processing SSRIs and other medications is not working properly, the level of drug increases in the blood, which leads to significant side effects.

Only one-third of patients respond to the first line of treatment with antidepressants. The ultimate goal of Pharmacogenetics is to improve treatment outcomes by predicting a patient’s response to specific drugs – before they are prescribed. This approach allows us to move away from the traditional “trial method” of prescribing medicines and shift towards a more evidence-based, personalized approach.

A Pharmacogenetic (PGx) Test, such as Pillcheck™, can help you know in advance whether or not you are at risk for adverse side effects or may not benefit from specific medications due to inherited altered drug metabolism. However, patients with serotonin imbalance cannot tolerate SSRIs even though their liver enzymes are functioning normally. Without performing genome sequencing, a PGx Test alone will provide limited information for the SSRI-intolerant patient.

Knowing your drug metabolic profile can significantly reduce time to remission, decrease the risk of adverse side effects, improve drug efficacy and lead to overall better treatment outcomes. Knowing how your body will react to a medication such as an SSRI before you take it can make all the difference to your health and well-being.

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Learn more about role of pharmacogenetics in mental health here