What medications cause serotonin syndrome?

Certain medications or drug interactions cause excessive serotonin levels in the brain, resulting in serotonin syndrome.

Serotonin syndrome can be life threatening due to the potential for severe neurological, cardiovascular, and metabolic disruptions, leading to various health complications.

What is serotonin syndrome?

Serotonin syndrome is a serious medical condition that occurs when serotonin accumulates in your brain past a certain level.

Serotonin is a hormone and a neurotransmitter (brain messenger) involved in complex body functions like mood, thought process, memory, and narrowing or constriction of the blood vessels (vasoconstriction).

Serotonin syndrome occurs due to excessive stimulation of serotonin receptors in your brain and central nervous system. This may happen from increased serotonin production, decreased serotonin reuptake (reabsorption), or impaired breakdown of serotonin.

The combined or single use of certain medications that affect serotonin levels may increase the risk of having this syndrome under specific conditions, particularly when not taken according to medical guidance.

Mild symptoms of serotonin syndrome may include:

• restlessness
• shivering
• diarrhea
• agitation
• excessive sweating

As the condition progresses, more severe symptoms may include:

• loss of consciousness
• seizures
• muscle rigidity
• high fever
• confusion
• irregular heartbeat

If left untreated, serotonin syndrome has serious health complications. Muscle breakdown (rhabdomyolysis), kidney damage, and the disruption of heart rhythms may lead to life threatening situations.

Severe cases of serotonin syndrome may also result in disseminated intravascular coagulation (DIC), which affects blood clotting and may cause excessive bleeding. 

Serotonin syndrome is a medical emergency that requires immediate attention. If you are experiencing symptoms related to serotonin syndrome, consider seeking medical intervention as soon as possible.

Medications most often involved in serotonin syndrome

Serotonin syndrome often occurs due to the use of higher doses or the interaction of substances that affect serotonin levels in the body (serotonergic drugs), leading to higher levels in the brain of this neurotransmitter.

Medications commonly involved in serotonin syndrome include:

• Selective serotonin reuptake inhibitors (SSRIs): Using a higher dose of SSRIs or taking more than one of these medications may lead to an unwanted increase in serotonin levels. Taking SSRIs, such as fluoxetine (Prozac), with other medications that increase serotonin levels, like monoamine oxidase inhibitors (MAOIs) or certain recreational drugs, like MDMA (Ecstasy), may trigger serotonin syndrome.
• Serotonin-norepinephrine reuptake inhibitors (SNRIs): Combining SNRIs, such as venlafaxine (Effexor), with SSRIs, MAOIs, or other SNRI medications may lead to serotonin syndrome.
• Tricyclic antidepressants: When taken in combination with other serotonergic medications, imipramine (Tofranil) may lead to serotonin syndrome. Increasing your dosage without medical supervision may also increase your risk.
• Monoamine oxidase inhibitors (MAOIs): When combined with foods or medications that contain tyramine or when used concurrently with other serotonergic drugs, MAOIs can elevate serotonin levels. Examples of MAOIs include phenelzine (Nardil).
• Triptans: Doctors prescribe these medications to treat migraine, but when taken simultaneously with other medications that increase serotonin levels, they can cause serotonin syndrome. Examples include sumatriptan (Imitrex).
• Recreational drugs: MDMA (Ecstasy) directly affects serotonin release, increasing the risk of serotonin syndrome.

If you are undergoing treatment for different conditions or are seeing different healthcare professionals, it is a good idea to let all of them know about the complete list of medications you use.

If your SNRI, SSRI, MAOI, or other medication isn’t working as expected, avoid increasing the dose yourself. Instead, discuss other options with your healthcare team.

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Medications least likely to cause serotonin syndrome

While some medications may raise your chances of serotonin syndrome, others generally carry a lower risk. These medications include:

• Mirtazapine: Mirtazapine (Remeron) is an atypical antidepressant that affects serotonin and norepinephrine levels in the brain, but its action mechanism differs from SSRIs and SNRIs. Doctors generally consider Rameron to have a lower risk of inducing serotonin syndrome.
• Amitriptyline: Amitriptyline (Elavil) is an atypical antidepressant that affects serotonin receptors. While it does modulate serotonin levels, research suggests it has a lower risk of inducing serotonin syndrome.
• Quetiapine: Using atypical antipsychotics alongside other serotonergic agents or higher doses of antipsychotics can lead to serotonin syndrome. However, quetiapine (Seroquel) may be less likely than other atypical antipsychotics to trigger serotonin syndrome.

While these medications may carry a lower risk, the potential for serotonin interactions still exists. Consult with your healthcare professional before changing doses or when taking other medications. 

How long does serotonin syndrome last?

The duration of serotonin syndrome varies based on its severity and the promptness of medical intervention. The severity of the syndrome may go from mild to severe, with symptoms ranging from temporary discomfort to life threatening situations. 

Mild cases may improve within 24–72 hours of discontinuing the medications causing it. In more severe cases, recovery could take several days to weeks, depending on the extent of the serotonin overload and the resulting complications. 

However, serotonin syndrome doesn’t resolve on its own. Therefore, seeking prompt medical attention is essential.

How to prevent serotonin syndrome

To avoid the risk of serotonin syndrome, here’s a list of things to keep in mind or discuss with a healthcare professional:

• Medication interaction: Enquire about potential interactions between your medications, especially if you’re taking multiple drugs and supplements that affect serotonin levels.
• Dosage adjustments: Ask a healthcare professional about appropriate dosages and any changes needed to minimize the risk of excessive serotonin levels. Adjusting the dose yourself without the guidance of a healthcare professional is not advisable nor is it taking leftovers from medications you have already discontinued.
• Symptom awareness: Learn the symptoms of serotonin syndrome and pay attention to any unusual changes while on serotonergic medications.

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Summary

Serotonin syndrome is a potentially life threatening condition resulting from excessive serotonin levels in the body. Common symptoms include agitation, muscle rigidity, high fever, and rapid heart rate. 

Medications like SSRIs, SNRIs, MAOIs, and recreational drugs may cause it. Treatment involves discontinuing the causative medications under medical supervision, supportive care, and, in severe cases, emergency care to manage symptoms and prevent complications.

Serotonin syndrome is a medical emergency, and prompt intervention may prevent complications.