What is Selective Serotonin Reuptake Inhibitor Toxicity?
Selective serotonin reuptake inhibitors (SSRIs) are a type of medicine often used to treat depression. They can also be prescribed for conditions like anxiety, obsessive-compulsive disorder, panic disorders, and eating disorders. SSRIs are generally safer than older types of antidepressants, like monoamine oxidase inhibitors and tricyclic antidepressants, which can have more severe side effects.
All SSRIs work in a similar way – they enhance the action of serotonin, a chemical in the brain that helps regulate mood. Even though they’re safer to use than older antidepressants, SSRIs can still have effects on the heart, particularly at high doses. For example, certain SSRIs, like citalopram and escitalopram, are known to prolong the QTc interval, which is a measurement on an electrocardiogram (ECG) that reflects how long it takes for your heart muscles to recharge between beats. There have also been reports of other heart-related side effects, like irregular heartbeat and slower heart rate, linked to fluoxetine, another SSRI.
Although side effects from SSRIs can vary widely and are often unclear, common ones include low sodium levels in the blood (hyponatremia), sexual dysfunction (anorgasmia), drowsiness or stimulation, and stomach irritation. Seizures have been reported but are uncommon. SSRIs may also reduce the ability of blood platelets to stick together and form a clot, a process that is critical for preventing bleeding.
Symptoms of side effects from SSRIs can be different for each person, and some experts suggest using the term “serotonin toxicity” instead of “serotonin syndrome”. This shift in terminology emphasizes that this condition is a range of symptoms, not just a single entity. For people with mild symptoms, having relief from a mental health condition might outweigh these potential side effects.
What Causes Selective Serotonin Reuptake Inhibitor Toxicity?
Serotonin toxicity, a serious reaction to a type of medication known as SSRI, can occur due to accidental or intentional overdose, a new medication being introduced into the body, an increased dosage, or the combination of two medications that both increase serotonin activity. In fact, the most serious cases usually occur when different drugs are combined, and they each increase serotonin levels through separate methods. An example of this would be combining a monoamine oxidase inhibitor and a serotonin reuptake inhibitor.
Many different kinds of medication can affect serotonin levels in various ways. Aside from SSRIs, medications such as ondansetron, methadone, clomipramine, amitriptyline, dextromethorphan, fentanyl, meperidine, tramadol, trazodone, venlafaxine, and pentazocine can increase serotonin by blocking its reuptake. This means they prevent the body from absorbing serotonin, which causes increased levels. Other medications like linezolid, methylene blue, St. John’s wort, or monoamine oxidase inhibitors (like phenelzine, selegiline, and isocarboxazid) increase serotonin levels by stopping or slowing down the metabolism of serotonin. MDMA and mirtazapine enhance serotonin release. Tryptophan is a building block for serotonin. Cocaine increases serotonin synthesis. Buspirone, fentanyl, dihydroergotamine, lithium, LSD, metoclopramide and triptans stimulate serotonin receptors.
There’s ongoing research about the safety of opioids when used with SSRIs. While some studies show that synthetic opioids can inhibit the serotonin transporter (a protein that helps control serotonin levels), there have been cases where drugs like fentanyl and oxycodone, which don’t typically affect the serotonin transporter, have been linked to cases of serotonin toxicity.
Risk Factors and Frequency for Selective Serotonin Reuptake Inhibitor Toxicity
In 2016, the American Association of Poison Control Centers noticed over 50,000 cases of overdoses related to SSRIs (a type of medication). Unfortunately, 102 of those cases resulted in death. However, in almost all of these cases, other substances were involved along with the SSRI. According to the report, Sertraline and Fluoxetine were the most frequently used SSRIs. One research study also found that about 14% of the 469 SSRI overdoses resulted in serotonin toxicity, a dangerous reaction to too much of the medicine.
Signs and Symptoms of Selective Serotonin Reuptake Inhibitor Toxicity
Serotonin toxicity is a condition that’s identified based on specific symptoms. Initially, criteria set by Sternbach were used, which looked for symptoms such as muscle overexcitement, automatic nervous system stimulation, and altered consciousness levels. Muscle symptoms were often more notable in the lower parts of the body. The presence of continuous, spontaneous muscle spasms served as an indicator of serotonin toxicity. However, since the Sternbach criteria were somewhat vague, the Hunt serotonin toxicity criteria were developed. Symptoms of serotonin toxicity as per Hunt criteria include:
- Continuous, spontaneous muscle spasms
- Triggered muscle spasms with either restlessness or excessive sweating
- Eye spasms with either restlessness or excessive sweating
- Tremors and exaggerated reflexes
- Eye spasms, muscle stiffness, and high body temperature (>38 C)
Besides looking for these signs and symptoms, it’s crucial to obtain a history of exposure to serotonin or a suspected overdose for diagnosing serotonin toxicity.
Some minor indications of this condition can include vomiting, sleepiness, enlarged pupils, or excessive sweating. Severe symptoms can include a decreased consciousness level, changes in the electrocardiogram (ECG), and seizures, especially with overdoses more than 75 times the usual dose. The impact of excessive serotonin varies as its receptors are most concentrated in the muscle cells, automatic nervous system, and the digestive system, which explains the diversity of symptoms shown.
Testing for Selective Serotonin Reuptake Inhibitor Toxicity
If a patient is suspected to have serotonin toxicity, which is a type of poisoning, their initial treatment would typically resemble that of any other case of overdose or altered mental health. The processes involved include setting up an intravenous drip for administering fluids and medications, starting heart rate monitoring, stabilizing vital body functions such as heart rate and breathing, and hydrating the patient with fluids if needed.
Diagnosing serotonin toxicity isn’t solely based on observable symptoms, but also involves ruling out other potential causes of the altered mental state. This means that even though there’s no specific lab test to confirm serotonin toxicity, it’s still vital to run comprehensive tests to essentially cross out other possible causes of the patient’s symptoms.
Treatment Options for Selective Serotonin Reuptake Inhibitor Toxicity
Nelson and his team have suggested guidelines for managing an overdose of SSRI (antidepressant) medication at home. They propose that patients who are only showing minor symptoms and have taken less than five times their own usual dose or less than five times the typical starting dose in a patient new to SSRI, may be observed at home. However, this should only be done while in direct communication with a regional poison control center.
The main approach to treating an SSRI overdose is supportive, meaning the focus is on managing symptoms rather than directly counteracting the medication. This often involves stopping all medication that increases serotonin levels, and using a class of medication called benzodiazepines to manage agitation (or restlessness). Medications like Droperidol and haloperidol should not be used to manage this restlessness because they can stop sweating, leading to a dangerous rise in body temperature.
In some severe cases, there may be symptoms like high-grade fever, muscular rigidity (stiffness), and increased muscle tone. These patients may need endotracheal intubation and ventilatory support, which means a tube is inserted into their windpipe to help them breathe.
Extreme muscle stiffness can lead to dangerous rises in body temperature and even death. So, patients with these severe symptoms should be cooled down quickly. If the benzodiazepines don’t successfully control muscle spasms or the body temperature rises above 41.1°C, a procedure involving intubation and temporary paralysis can be considered. In cases that don’t respond to this supportive approach, drugs like cyproheptadine or chlorpromazine, which have effects against serotonin, might be offered, though it’s unclear if these drugs can change the patient’s outcome. Cyproheptadine can only be given via a tube that enters through the nose or mouth because there’s no version that’s given intravenously (via injection).
However, medications like acetaminophen, NSAIDs, or aspirin aren’t used to control body temperature in these situations, as the issue isn’t a change in the set temperature of the body.
What else can Selective Serotonin Reuptake Inhibitor Toxicity be?
It’s crucial to understand that serotonin toxicity is different from a condition known as the neuroleptic malignant syndrome (NMS). NMS typically develops slowly and can cause symptoms like slowed movements, and strong, constant muscle stiffness, among other symptoms. This condition can last for weeks, which makes it much longer than serotonin toxicity. Serotonin toxicity usually goes away within 24 hours once treatments involving serotonin are stopped.
What to expect with Selective Serotonin Reuptake Inhibitor Toxicity
The outlook for patients who have overdosed on SSRIs (a type of antidepressant) is generally positive, and they are expected to fully recover. In one study, a typical stay in the hospital for this type of overdose was around 15.3 hours. If the overdose is a mild case, the patient can be monitored in the emergency department for about 6 hours before they can be safely sent home.
The duration of the symptoms can be affected by the specific type of SSRI that was taken — for instance, it generally takes about 4 to 6 days for the body to get rid of half the amount of fluoxetine, an SSRI, which is longer than other similar drugs.
Patients with severe symptoms should be transferred to the intensive care unit where they can be closely monitored and properly treated.
