What is Bupropion Toxicity?
Bupropion hydrochloride is a type of antidepressant medication that has been around since 1985. It’s approved by the FDA to treat major depressive disorder (a severe form of depression), seasonal affective disorder (a type of depression that’s related to changes in seasons), and to help people quit smoking. It’s also used for other issues like sexual problems caused by other antidepressants, generalized anxiety disorder, ADHD, and bipolar disorder, even though these are not its main uses.
There are different versions of Bupropion: some that you take and their effects are immediate, some that release the medication slowly, and some that work for extended periods.
There can be side effects like dry mouth, constipation, headache, nausea, feeling restless, difficulty sleeping, and weight loss. In 1986, Bupropion was temporarily removed from the market because it caused seizures in some people with bulimia, a serious eating disorder. It was returned in 1989 at lower doses. Now, people with a history of seizures or certain eating disorders, or who are withdrawing from alcohol or certain drugs, should not take Bupropion. The risk of seizures can increase depending on the dose, with a 0.1% risk at daily doses below 300 mg and a 0.4% risk at doses up to 450 mg daily.
Taking too much Bupropion can cause serious issues, often including seizures, increased heart rate, and restlessness. The extended version of Bupropion can cause seizures up to 24 hours after taking it. Overdosing can also result in more dangerous conditions like prolonged seizures, life-threatening heart rhythm problems, and shock caused by heart failure.
What Causes Bupropion Toxicity?
Bupropion is a type of medication known as an aminoketone, which works by blocking the re-absorption of certain chemicals (specifically, norepinephrine and dopamine) in the brain. If someone accidentally takes too much of this medication, they might experience seizures, including a type of severe seizure called status epilepticus, but doctors aren’t exactly sure why this happens.
This medication can also cause some problems with the heart. Symptoms might include delays in the electrical signals that control the heartbeat, leading to wider gaps between heartbeats (shown as widened QRS and QT intervals on an electrocardiogram). It could also cause an irregular heart rhythm (dysrhythmia), or even a sudden drop in blood pressure and poor blood flow to the body’s tissues due to heart failure (cardiogenic shock).
Interestingly, the delays in cardiac electrical signals are not related to the passage of sodium ions in and out of heart cells, which is usually the cause of these types of delays. Instead, bupropion affects structures known as myocardial gap junctions, which help to coordinate the beating of the heart by facilitating communication between adjacent heart cells.
Risk Factors and Frequency for Bupropion Toxicity
Antidepressants are often linked to cases of overdose, especially since they’re used by people dealing with depression. There have also been reports of people intentionally misusing Bupropion, an antidepressant, because its structure is similar to amphetamines and synthetic cathinones. Some even misuse it by snorting it.
In 2020, the American Association of Poison Control Centers recorded 16,926 cases of Bupropion overdoses. Roughly half of these (8,668 cases) were single exposures, and sadly, eight of them resulted in death.
Signs and Symptoms of Bupropion Toxicity
If you think someone might have been exposed to a harmful substance or overdose, it’s important to gather a detailed history and conduct a physical exam. You should try to figure out when and how much of the substance the person took, and whether they ingested any other substances. Understanding the reasoning behind the overdose can also be important. It’s also a good idea to review their medication history to see if they’re at risk of seizures or cardiovascular collapse from any drug interactions.
The symptoms observed in cases of overdose can vary widely. Common symptoms include a fast heart rate (tachycardia), seizures, and agitation. The chance of having a seizure can range from 17% to 47%, based on past studies. Some other symptoms that may be noted are high blood pressure, delirium, excessive reflex actions, clonus (involuntary muscle contractions), depression of the central nervous system, numbness, and abnormal muscle postures (dystonia).
- When and how much of the substance was consumed
- Were any other substances ingested
- The reason behind the potential overdose
- Prior medication history
- Tachycardia -fast heart rate
- Seizures
- Agitation
- Hypertension – high blood pressure
- Delirium
- Hyperreflexia – excessive reflex actions
- Clonus – involuntary muscle contractions
- Central nervous system depression
- Numbness
- Dystonia – abnormal muscle postures
Testing for Bupropion Toxicity
If you’ve arrived at the hospital due to an overdose, the medical team has certain priorities they take care of to ensure your safety. They’ll initially check your airway to ensure you’re breathing properly and your heart is circulating blood as it should. Following this, they will usually establish intravenous access, meaning they’ll insert a thin tube into your vein. This will allow the team to supply necessary medicine or fluids directly into your bloodstream.
Along with this, the team will continuously keep track of your heart’s performance and also check your vital signs frequently. These vitally important checks help doctors monitor your overall health constantly and pick up any changes or signs of improvement or worsening condition.
There’s also a check called a 12-lead ECG, which is a simple test that helps the doctors assess the health of your heart’s electrical activity. This can help determine if there are any abnormal electrical pathways in your heart which may affect how it’s functioning.
On another note, your doctors will carry out tests to check the levels of acetaminophen and salicylate in your blood as they are often consumed too much (co-ingestants). This can aid your medical team in identifying what substance was used for the overdose and to formulate a strategic treatment plan.
In case you are experiencing seizures or have altered mental state, your blood glucose will be checked quickly using a point-of-care device. However, keep in mind that routine tests or measurements for bupropion and hydroxybupropion (other substances that could be associated with overdoses) in your bloodstream are not generally available or recommended.
Treatment Options for Bupropion Toxicity
If you accidentally consume too much of a drug called bupropion, the first line of treatment is to provide support and care. There isn’t a direct antidote to reverse the overdose. Doctors might also consult with poison control centers or toxicology experts, especially for serious cases where important body functions are affected. If you reach the hospital quickly after taking a large amount of the drug, activated charcoal may be given to help remove the excess drug from your body. Overdoses that happen by accident usually don’t cause serious health problems, but there have been cases where people have seizures even after a small overdose.
If you have a seizure, the first choice of treatment are medications called benzodiazepines. These are a type of drug that can help control seizures. If benzodiazepines don’t work, then doctors might use something called barbiturates. Doctors usually avoid using other anti-seizure medications because they might interact with the drug that caused the overdose in the first place. In the event of life-threatening heart rhythm problems—the kind where your heart isn’t beating properly—doctors typically follow advanced cardiac life support guidelines which might also include other treatments depending on your condition. Sometimes, the overdose can cause an irregularity to show up on your heart rhythm test. In such cases, sodium bicarbonate, which is a form of baking soda, might be used. Unfortunately, the sodium bicarbonate might not always work in cases of a bupropion overdose.
If your heart isn’t pumping blood effectively due to the drug overdose— a condition called cardiogenic shock—vasopressors, a group of medicines that constrict blood vessels, might be used. In severe and life-threatening poisonous situations such as continued seizures or hemodynamic instability (where there isn’t enough blood flow), the administration of a special fat-based solution called intravenous lipid emulsion (ILE) may be used. However, this solution isn’t usually recommended during a type of cardiac arrest where there is no heartbeat but there is electrical activity because it might interfere with other treatments.
ILE has been seen, in some cases, to quickly improve the heart’s ability to pump blood and the amount of blood that is pumped out in each heartbeat after an overdose. While ILE is usually used as a last resort, these cases may suggest that starting its usage sooner could be beneficial. Advanced life support techniques like veno-arterial extracorporeal membrane oxygenation (VA ECMO) may be included in the treatment of cases where the heart isn’t pumping enough blood or during cardiopulmonary arrest—a condition when your heart stops beating and your lungs stop working.
Patients who have seizures, heart-related instability, life-threatening heart rhythms, and severe changes in mental condition should be monitored in an intensive care unit. If an overdose of a long-acting form of bupropion happens (even due to an issue in the prescribed amount), the patient should be observed for 24 hours because of the risk of delayed onset seizures. A patient is ready to be discharged once their symptoms have subsided.
What else can Bupropion Toxicity be?
Whenever someone swallows a harmful substance, it’s important for medical professionals to evaluate the situation and consider the possibility of multiple substances being ingested at once. Bupropion, a common medication, can cause a variety of reactions similar to those caused by other drugs or substances. These include conditions known as sympathomimetic, anticholinergic, and serotonin syndromes. Therefore, medical professionals should always consider these potential syndromes when dealing with Bupropion ingestion.
What to expect with Bupropion Toxicity
Taking too much bupropion, a type of antidepressant, luckily doesn’t often result in death. To put it in perspective, in 2020, there were only eight deaths reported to US poison centers out of nearly 17,000 cases involving bupropion.
Taking a closer look at specific side effects, a study of over 1,000 people who took too much bupropion found that half experienced an elevated heartbeat (also known as tachycardia), nearly a quarter showed changes in their electrocardiogram (an ECG is a test that measures the electrical activity of the heartbeat), and about one in six had seizures.
Interestingly, the study showed that taking benzodiazepines (a class of drugs commonly used for treating anxiety and insomnia) along with bupropion was associated with a lower chance of experiencing seizures. However, it’s not yet clear whether giving bupropion overdose patients benzodiazepines as a preventive measure is a good idea.
In a separate study of over 400 patients, those showing a heart rate of 120 beats per minute or more (or 20 beats per minute above what’s normal for their age in the case of children), were almost seven times more likely to have a seizure. Having an altered mental status (a broad term meaning any impairment in cognitive function) also increased the risk of having a seizure.
It’s important to know that none of the patients who ended up having seizures showed no symptoms when they first entered the emergency department.
In comparing bupropion to another type of antidepressant – SSRIs (selective serotonin reuptake inhibitors), a study of over 30,000 adolescent overdoses showed that overdosing on bupropion posed a higher risk. This included a risk of death (although it was still quite low at 0.23% compared to 0%), a higher risk of seizures (27% compared to 8.5% for SSRIs), and more severe outcomes like the need for CPR, the need for a tube to be inserted down the throat to aid with breathing (intubation), the need for drugs to raise blood pressure (vasopressors), and treatment with benzodiazepine. Thus, it’s clear that overdosing on bupropion can potentially be more dangerous than overdosing on SSRIs for adolescents.
Possible Complications When Diagnosed with Bupropion Toxicity
Severe complications can occur, though they are not limited to the following:
- Continuous seizures (status epilepticus)
- Severe changes in behavior or consciousness that can cause a loss of protection to the airway
- Heart failure resulting from problems in the heart (cardiogenic shock)
- Severe irregular heartbeats that can be life-threatening (dysrhythmias)
Preventing Bupropion Toxicity
People who are taking antidepressant medication have a higher risk of trying to harm themselves by taking too much medication. For this reason, it’s very important that doctors regularly check in with their patients to ensure they are not having thoughts of suicide. It’s also a good idea for patients to store their medications in a safe place where children can’t easily reach them. Patients should also know to call their local poison control center if they are worried that they might have accidentally taken too much of their medication.
