How Drugs Interfere With Rem Sleep

Sleep is a complex and pervasive cognitive state that is affected by medications in many different ways. There are more than 90 recognised sleep disorders, each with clear diagnostic criteria. Sleep disorders can be divided into three large groups: those producing insomnia, those causing daytime sleepiness, and those disrupting sleep.

Many medications affect sleep stages and can cause sleep disorders or exacerbate the effect of chronic illnesses on sleep. Benzodiazepines, for example, are frequently used to treat insomnia, but there may be a withdrawal syndrome with rapid eye movement (REM) rebound. Other drugs that can interfere with REM sleep include antidepressants, antipsychotics, anti-seizure medications, and asthma or allergy medicines.

Benzodiazepines and non-benzodiazepines

Benzodiazepines are commonly used to treat insomnia. They are rapid eye movement (REM) sleep suppressant medications, and withdrawal often results in episodes of increased REM sleep (REM sleep rebound). Benzodiazepines suppress REM sleep and reduce stages 3 and 4 sleep while increasing stage 2 sleep.

Benzodiazepines are gamma-aminobutyric acid (GABA) neuroreceptor agonists. They act by enhancing the inhibitory effects of the GABA neurotransmitter on neuronal excitability, resulting in increased neuronal permeability to chloride ions. This shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

The benzodiazepines approved by the US Food and Drug Administration (FDA) as hypnotics include flurazepam, temazepam, quazepam, estazolam, and triazolam. Temazepam is useful for treating initial and middle insomnia as it has an intermediate rate of absorption and duration of action. It also has no active metabolites, reducing the risk of cognitive impairment and grogginess the following day. Triazolam is often chosen as a short-term adjunct to behavioural therapy for helping patients fall asleep, while estazolam and quazepam are used for sleep-maintenance insomnia. Flurazepam is frequently chosen as a short-term treatment for insomnia.

Non-benzodiazepine hypnotics such as zolpidem and zaleplon are newer benzodiazepine-like agents with fewer side effects and good efficacy. Zolpidem has a rapid onset of action (20-30 minutes) and is, therefore, a good drug for sleep induction. It decreases sleep latency and increases sleep duration. Zaleplon has a shorter onset of action, achieving peak serum concentrations within 1 hour of administration, which may account for the lower incidence of daytime grogginess and reduced withdrawal rebound insomnia.

While benzodiazepines are effective in treating insomnia, they should be prescribed with caution and professional judgement. Patients should be closely monitored for possible long-term side effects.

Selective serotonin reuptake inhibitors

SSRIs work by increasing serotonin levels in the brain, which can have a calming effect and improve mood. However, serotonin also plays a role in regulating sleep, and altering its levels can disrupt sleep patterns. SSRIs have been shown to suppress REM sleep, which is thought to be important for brain function and memory consolidation. This suppression of REM sleep by SSRIs can lead to increased REM sleep latency, meaning it takes longer to enter this stage of sleep. It can also result in a complete lack of REM sleep, which has been associated with poorer quality of life scores and an increased risk of mental health issues, insomnia, and Parkinson's disease.

Additionally, the stimulating effect of SSRIs can cause insomnia in some individuals. This is particularly true for the antidepressant medication Wellbutrin (bupropion), which can be very stimulating and disrupt sleep. To mitigate these sleep disturbances, it is recommended that SSRIs be taken in the morning rather than at night. If sleep problems persist, it is important to consult a doctor, as abruptly stopping or changing the dosage of SSRIs can have adverse effects.

While SSRIs can interfere with REM sleep, they do not activate the REM sleep homeostat. This means that even with the pharmacological inhibition of REM sleep by SSRIs, the REM sleep homeostat remains active and can compensate for the sleep deficit. This suggests that the brain can still maintain the necessary levels of central nervous system activity during sleep, despite the reduction in REM sleep caused by SSRIs.

Opioid pain relievers

Opioids can also affect rapid eye movement (REM) sleep, which is the stage of sleep when you tend to have vivid dreams. REM sleep is important for memory retention and strengthening your immune system. Opioids block access to REM sleep and the deeper, more restorative stages of non-REM sleep.

Disrupting the sleep cycle can have negative short-term and long-term consequences. It can lead to excessive daytime sleepiness and a chronic feeling of fatigue. Disrupted sleep can also increase symptoms of chronic pain, perpetuating a cycle of increased pain, opioid use, and sleep problems.

Some common opioid pain relievers include:

• Fentanyl (Duragesic)
• Morphine (Avinza)
• Hydrocodone (Norco)
• Oxycodone (OxyContin)
• Oxymorphone (Opana)
• Tramadol (Ultram)

Alpha-blockers

In addition, alpha-blockers have been found to be effective in treating nightmares and sleep disruptions caused by post-traumatic stress disorder (PTSD). Prazosin, a type of alpha-blocker, has been shown to be effective in treating PTSD-induced nightmares by blocking the effects of norepinephrine.

However, it is important to note that alpha-blockers may have side effects, including low blood pressure, sexual dysfunction, and reflex tachycardia (fast heartbeat). They can also interact with other medications, such as alcohol, citrus juices, or erectile dysfunction drugs. Therefore, it is essential to consult a healthcare provider before taking alpha-blockers to weigh the benefits against the potential risks.

Stimulants

Some common stimulants that can interfere with REM sleep include amphetamine-dextroamphetamine (Adderall), methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and lisdexamfetamine (Vyvanse). These drugs are often prescribed to treat ADHD, but they can also be used to treat other conditions such as narcolepsy and chronic fatigue syndrome.

The effects of stimulants on sleep can be mitigated by adjusting the dose or timing of the medication. Non-stimulant medications such as atomoxetine (Strattera), clonidine (Kapvay), and guanfacine (Intuniv) may also be effective alternatives, depending on the condition being treated.

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