General Warnings

Drugs That Cause REM Sleep Behavior Disorder

REM (Rapid Eye Movement) sleep is a stage of sleep characterized by vivid dreaming and rapid eye movements. It is one of the five stages of sleep that humans experience during a typical sleep cycle. During REM sleep, the brain is highly active and the body is in a state of muscle paralysis. This is thought to be a protective mechanism to prevent the body from acting out the often-vivid dreams that occur during this stage of sleep. REM sleep is important for the consolidation of memories and learning, as well as emotional regulation.

The duration of REM sleep varies throughout the night, with longer periods occurring later in the sleep cycle. On average, adults spend about 20-25% of their sleep time in REM sleep. However, REM sleep patterns can be influenced by a variety of factors, such as age, sleep disorders, medications, and substance use.

Disruptions to REM sleep can have negative effects on overall health and well-being. For example, REM sleep deprivation has been linked to problems with memory, concentration, mood, and immune function.

What is Rem Sleep Behavior Disorder?

REM sleep behavior disorder (RBD) is a sleep disorder in which a person physically acts out their dreams during REM sleep. Normally, during REM sleep, the body is in a state of muscle paralysis to prevent the person from physically acting out their dreams. However, in people with RBD, this muscle paralysis does not occur, allowing them to physically act out their dreams.

RBD is a type of parasomnia, which is a category of sleep disorders that involve abnormal behaviors or movements during sleep. The symptoms of RBD can range from mild, such as talking or moving limbs, to more severe, such as shouting, punching, or kicking. RBD can be dangerous for the person with the disorder and their bed partner, as injuries can occur during episodes.

RBD is often associated with other neurological conditions, such as Parkinson’s disease, multiple system atrophy, and Lewy body dementia. However, it can also occur in people without any underlying neurological conditions. RBD is diagnosed through a combination of clinical evaluation, sleep studies, and monitoring of muscle activity during sleep.

Can drugs cause REM sleep behavior disorder (RBD)?

Yes, certain drugs have been associated with the development of REM sleep behavior disorder (RBD). Medications that affect the levels of neurotransmitters in the brain, particularly those that increase dopamine activity, have been linked to the development of RBD.

List of Drugs That Cause REM Sleep Behavior Disorder

Here is a list of some of the drugs that have been associated with REM sleep behavior disorder (RBD):

1.      Tricyclic antidepressants: Tricyclic antidepressants (TCAs) are a class of medications that have been associated with an increased risk of REM sleep behavior disorder (RBD). TCAs work by increasing the levels of certain neurotransmitters in the brain, including serotonin and norepinephrine, which can disrupt the normal regulation of REM sleep.

Studies have shown that TCAs can increase the frequency and severity of RBD episodes in some individuals. For example, a study published in the Journal of Sleep Research found that 13 out of 18 patients with RBD who were taking TCAs experienced a reduction in RBD symptoms after discontinuing the medication.

The risk of developing RBD while taking TCAs may depend on the specific medication and the dose used. For example, a study published in the Journal of Clinical Psychopharmacology found that amitriptyline, a commonly prescribed TCA, was associated with an increased risk of RBD compared to nortriptyline, another TCA. Some examples of tricyclic antidepressants that can cause REM sleep behavior disorder include amitriptyline, nortriptyline, imipramine, clomipramine, doxepin, trimipramine, desipramine, and protriptyline.

2.      Selective serotonin reuptake inhibitors (SSRIs): Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed class of antidepressant medications that work by increasing the levels of serotonin in the brain. While they are generally considered safe and effective, some studies have suggested that they may increase the risk of developing REM sleep behavior disorder (RBD) in certain individuals.

One study published in the journal Sleep Medicine found that individuals who took SSRIs were more likely to experience RBD than those who did not take these medications. However, the study also noted that the risk was relatively low and that SSRIs did not appear to be a major contributor to the development of RBD.

It is important to note that not all individuals who take SSRIs will develop RBD, and the risk appears to be relatively small. However, if you are taking an SSRI and are experiencing symptoms of RBD, it is important to speak with your healthcare provider to determine the best course of action. Examples of SSRIs that have been associated with RBD include fluoxetine, sertraline, and citalopram.

3.      Serotonin-norepinephrine reuptake inhibitors (SNRIs): Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of drugs commonly used to treat depression, anxiety, and other psychiatric disorders. Like SSRIs and tricyclic antidepressants, SNRIs can also cause REM sleep behavior disorder (RBD) as a potential side effect. The exact mechanism by which SNRIs cause RBD is not fully understood, but it is believed to be related to their effect on the levels of certain neurotransmitters in the brain, particularly serotonin and norepinephrine.

Examples of SNRIs that have been reported to cause RBD include venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq). In some cases, the onset of RBD symptoms may occur shortly after starting treatment with an SNRI, while in other cases it may not develop until months or even years after starting treatment. It is important to note that not everyone who takes an SNRI will experience RBD as a side effect, and the risk may be influenced by individual factors such as age, gender, and overall health status.

4.      Monoamine oxidase inhibitors (MAOIs): Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs that can also cause REM sleep behavior disorder (RBD). These drugs work by inhibiting the activity of the enzyme monoamine oxidase, which is responsible for breaking down neurotransmitters such as serotonin and norepinephrine in the brain. By increasing the levels of these neurotransmitters, MAOIs can improve mood and alleviate symptoms of depression. However, they can also disrupt normal REM sleep and cause RBD. Examples of MAOIs that have been associated with RBD include phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan). RBD has been reported as a rare side effect of these drugs, and it is thought to be related to their effects on serotonin and norepinephrine levels in the brain.

5.      Antipsychotic medications: Antipsychotic medications are a class of drugs used to treat various mental health conditions, such as schizophrenia, bipolar disorder, and depression. They work by blocking the activity of dopamine, a neurotransmitter that plays a role in regulating mood, behavior, and cognition. Antipsychotics can also affect the levels of other neurotransmitters, such as serotonin and norepinephrine.

Some antipsychotic medications have been associated with REM sleep behavior disorder (RBD). RBD is a sleep disorder in which a person acts out their dreams, often with violent or aggressive behaviors, during the REM stage of sleep. This can cause injury to the person or their sleep partner.

The exact mechanism by which antipsychotics cause RBD is not fully understood, but it is thought to be related to their effects on dopamine and other neurotransmitters. Antipsychotics that have been linked to RBD include clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.

6.      Anti-seizure medications: There is limited research on the relationship between anti-seizure medications and REM sleep behavior disorder (RBD). However, some studies suggest that certain anti-seizure medications may increase the risk of RBD. For example, a case report published in the Journal of Clinical Sleep Medicine described a patient with epilepsy who developed RBD after starting treatment with lamotrigine, an anti-seizure medication.

Another study published in the Journal of Clinical Neurology found that patients with epilepsy who were taking a combination of valproic acid and lamotrigine had a higher risk of developing RBD compared to those who were taking other anti-seizure medications. Examples of anti-seizure medications that can cause REM sleep behavior disorder include carbamazepine (Tegretol), phenytoin (Dilantin), and valproic acid (Depakene).

7.      Parkinson’s disease medications: Parkinson’s disease (PD) medications can also cause REM sleep behavior disorder (RBD). RBD is more common in patients with PD and can be an early sign of the disease. The medications that can cause RBD in PD patients are levodopa and dopamine agonists. Levodopa is the most effective medication for treating the symptoms of PD, but it can cause RBD in some patients, especially at higher doses. Dopamine agonists such as pramipexole and ropinirole are also used to treat PD and have been associated with RBD, although the risk is lower than with levodopa.

8.      Benzodiazepines: Benzodiazepines are a class of medications that are commonly used as sedatives, anxiolytics, and hypnotics. These drugs enhance the activity of a neurotransmitter called gamma-aminobutyric acid (GABA), which can produce sedative effects. However, benzodiazepines have also been associated with the development of REM sleep behavior disorder (RBD).

Studies have suggested that benzodiazepines can reduce muscle tone during sleep, which may contribute to the development of RBD. Benzodiazepines have also been shown to suppress REM sleep, leading to a rebound effect when the drug is discontinued, which can exacerbate RBD symptoms. Additionally, long-term use of benzodiazepines has been associated with the development of cognitive impairment and dementia, which may increase the risk of RBD. Examples of benzodiazepines that have been associated with RBD include diazepam, and lorazepam.

9.      Opioids: Opioids are a class of drugs commonly used for pain management. They work by binding to specific receptors in the brain and spinal cord to reduce the perception of pain. However, opioids have also been found to cause REM sleep behavior disorder (RBD) in some cases. Studies have shown that opioids such as codeine, oxycodone, and morphine can cause RBD by suppressing the normal inhibition of muscle tone during REM sleep.

In one study, RBD was reported in 2% of patients taking opioids for chronic pain management. Another study found that RBD occurred in 11% of patients taking opioids for cancer pain. The risk of developing RBD with opioids appears to be dose-dependent, with higher doses increasing the risk. Examples of opioids that can cause RBD include methadone, oxycodone, and fentanyl.

10.    Alcohol: While not a drug in the traditional sense, alcohol consumption has been associated with RBD. Alcohol consumption is known to affect sleep architecture and can disrupt normal REM sleep patterns. In some cases, alcohol has been implicated in causing or exacerbating REM sleep behavior disorder (RBD). Alcohol can suppress REM sleep, leading to a rebound effect when REM sleep is eventually allowed, resulting in a higher likelihood of abnormal motor behaviors during REM sleep.

Additionally, alcohol can impair inhibitory functions in the brain, leading to disinhibition of motor behaviors during REM sleep. While alcohol is not a primary cause of RBD, heavy or chronic alcohol use can contribute to the development or worsening of RBD symptoms in some individuals. It is important to note that the effects of alcohol on RBD are complex and can vary depending on a range of factors, including the timing and amount of alcohol consumption, individual susceptibility, and the presence of other medical or psychiatric conditions.

It’s important to note that not everyone who takes these medications will develop RBD, and the risk may be higher for people who have a history of the disorder or other sleep disorders. If you are taking medication and experiencing symptoms of RBD, it’s important to talk to your doctor to determine the best course of action.

It’s important to note that not everyone who takes these medications will develop RBD, and the risk may vary depending on the individual and their medical history. If you are taking a tricyclic antidepressant and are experiencing symptoms of RBD, it’s important to talk to your healthcare provider to determine the best course of action.

How to Manage Drug-induced REM Sleep Behavior Disorder

The management of drug-induced REM sleep behavior disorder (RBD) depends on the underlying cause and the severity of the symptoms. The first step in management is to identify and discontinue the offending medication, if possible. In cases where discontinuation of the medication is not an option, a reduction in dosage may be considered.

For patients with persistent or severe symptoms, pharmacological treatment with clonazepam is the most commonly used therapy. Clonazepam is a benzodiazepine that has been shown to reduce the frequency and intensity of RBD episodes. The recommended starting dose of clonazepam for RBD is 0.5mg taken orally at bedtime, with the dose gradually increased up to a maximum of 2mg/day.

Non-pharmacological approaches may also be considered in the management of drug-induced RBD. These include improving sleep hygiene, such as maintaining a regular sleep schedule, avoiding alcohol and caffeine before bedtime, and creating a comfortable sleep environment. Additionally, patients may benefit from cognitive behavioral therapy aimed at reducing anxiety and stress, which can exacerbate RBD symptoms.

It is important for patients with drug-induced RBD to be closely monitored by their healthcare provider, and to report any changes in symptoms or medication use. In some cases, the management of drug-induced RBD may require collaboration between a patient’s primary care provider, neurologist, and sleep medicine specialist.

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Dr. Oche Otorkpa PG Cert, MPH, PhD

Dr. Oche is a seasoned Public Health specialist who holds a post graduate certificate in Pharmacology and Therapeutics, an MPH, and a PhD both from Texila American University. He is a member of the International Society of Substance Use Professionals and a Fellow of the Royal Society for Public Health in the UK. He authored two books: "The Unseen Terrorist," published by AuthorHouse UK, and "The Night Before I Killed Addiction."
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