Amitriptyline's Effect On Rem Sleep: What You Need To Know

Antidepressants are known to have complex interactions with sleep. Norepinephrine and serotonin, for example, play a role in suppressing REM sleep, while acetylcholine (Ach) is key to initiating it. Many antidepressants also affect other neurotransmitters, such as muscarinic ACh, implicated in sleep regulation. Amitriptyline is a tricyclic antidepressant that has been shown to suppress REM sleep significantly and sustainably. This effect does not appear to be an epiphenomenon of antidepressant pharmacotherapy, as the initial REM sleep suppression during treatment correlated positively with antidepressant effects after three weeks.

Amitriptyline-N-oxide and REM sleep suppression

Amitriptyline-N-oxide is a metabolite of the tricyclic antidepressant amitriptyline. Both compounds have been found to have comparable sleep-inducing effects, with amitriptyline causing more pronounced suppression of REM sleep.

The Effects of Amitriptyline and Amitriptyline-N-Oxide on Sleep

In two uncontrolled pilot trials, healthy volunteers were given either 150 mg of amitriptyline-N-oxide or 75 mg of amitriptyline. Both compounds were found to have similar sleep-inducing effects, with suppression of REM sleep being more noticeable in the group that took amitriptyline. This indicates that a single dose of amitriptyline-N-oxide has less immediate effect on the central nervous system than amitriptyline.

The Link Between REM Sleep Suppression and Antidepressant Effects

REM sleep suppression has been positively correlated with antidepressant effects. Selective REM sleep deprivation in depressed patients has been found to have a notable antidepressant effect. This suggests that the REM sleep suppression caused by amitriptyline and amitriptyline-N-oxide may be linked to their antidepressant effects.

The Impact of REM Sleep Suppression on Sleep Quality

While REM sleep suppression has been linked to antidepressant effects, it may also have a negative impact on sleep quality. This paradoxical effect warrants further investigation into the role of REM sleep in sleep quality and its interaction with antidepressant medications.

The effect of amitriptyline on healthy volunteers

Amitriptyline is a tricyclic antidepressant that has been shown to suppress REM sleep significantly and sustainably in healthy volunteers. This effect does not appear to be an epiphenomenon of antidepressant pharmacotherapy, as the initial REM sleep suppression during treatment correlated positively with the antidepressant effect after three weeks. This suggests that amitriptyline's impact on REM sleep may be a central nervous system effect rather than a mere side effect of the drug's antidepressant properties.

In a 1990 study, Riemann et al. investigated the REM-suppressing effects of amitriptyline and amitriptyline-N-oxide in healthy volunteers. They found that both compounds had comparable sleep-inducing effects, but amitriptyline tended to suppress REM sleep more than amitriptyline-N-oxide, despite the former being administered at a lower dose. This provides evidence of the immediate central nervous system effects of a single dose of amitriptyline.

Another study by Winkler et al. (2016) examined the conditioning of amitriptyline-induced REM sleep suppression in healthy participants. They paired a novel-tasting drink with amitriptyline as an unconditioned stimulus during the acquisition phase. During the evocation night, when the drink was presented alone with a placebo pill, the amitriptyline group experienced significantly more REM sleep, indicating a rebound effect that interfered with the conditioned response.

Furthermore, a 1975 study by Nakazawa et al. investigated the effects of a single 25 mg dose of amitriptyline on REM sleep in five healthy subjects. They found a significant decrease in REM sleep after administering the drug 30 minutes before an uninterrupted night's sleep. However, this was not followed by any noticeable rebound elevation of REM sleep during the subsequent two recovery nights. When the same dose was administered after partial differential REM sleep deprivation, there was a significant decrease in REM sleep followed by a rebound elevation during the following recovery night.

In summary, these studies provide evidence that amitriptyline has a REM-suppressing effect in healthy volunteers, which may be associated with rebound effects when the drug is discontinued or after periods of REM sleep deprivation. The impact of amitriptyline on REM sleep is thought to be related to its effects on neurotransmitters such as norepinephrine, serotonin, and acetylcholine, which play crucial roles in regulating sleep-wake cycles and sleep architecture.

Amitriptyline and rebound REM elevation

Amitriptyline is a tricyclic antidepressant that has been shown to significantly suppress REM sleep. This suppression of REM sleep is positively correlated with the antidepressant effect of the drug.

Several studies have investigated the rebound elevation of REM sleep following the administration of amitriptyline. One study found that a single oral dose of 25 mg of amitriptyline was followed by an inhibition of REM sleep in all subjects. However, there was no noticeable rebound elevation of REM sleep during the subsequent two recovery nights. Another study found that amitriptyline significantly reduced the time spent in REM sleep and prolonged the REM latency in depressed patients throughout the treatment period. When amitriptyline was discontinued, some patients who had shown improvement during treatment experienced a REM rebound, while those who had not improved did not show a REM rebound.

A study by Nakazawa et al. (1975) investigated the rebound phenomenon by evaluating the effects of a single 25 mg dose of amitriptyline on human REM sleep using partial differential REM sleep deprivation (PDRD). They found that while amitriptyline significantly decreased REM sleep, it was not followed by a noticeable rebound elevation during the subsequent two recovery nights. However, when PDRD was performed on the following day, a rebound elevation of REM sleep was observed during the recovery night.

These findings suggest that while amitriptyline does suppress REM sleep, the rebound elevation may depend on various factors such as individual variations, the timing of administration, and the patient's response to treatment. More research is needed to fully understand the rebound elevation of REM sleep following amitriptyline administration.

Amitriptyline's effects on sleep physiology

Amitriptyline is a tricyclic antidepressant that has been shown to significantly suppress REM sleep in healthy volunteers and depressed patients. This effect is not simply an epiphenomenon of antidepressant pharmacotherapy, as the initial REM sleep suppression during treatment has been positively correlated with the antidepressant effect after a few weeks. This suggests a potential link between REM sleep suppression and the therapeutic benefits of amitriptyline.

A study by Riemann et al. (1990) compared the effects of a single dose of 150 mg amitriptyline-N-oxide (AMINO) and 75 mg amitriptyline (AMI) on sleep. Both compounds had comparable sleep-inducing effects, but AMI tended to suppress REM sleep more than AMINO, despite the lower dose. This indicates that AMI may have a more pronounced impact on REM sleep suppression.

Another study by Nakazawa et al. (1975) investigated the effects of a single 25 mg dose of amitriptyline on REM sleep in five healthy subjects. They found a significant decrease in REM sleep after administering the drug 30 minutes before sleep. However, this was not followed by any noticeable rebound elevation of REM sleep during the subsequent two recovery nights. When the same dose was given after partial differential REM sleep deprivation (PDRD), a rebound elevation of REM sleep was observed during the following recovery night.

The effects of amitriptyline on REM sleep have also been studied in depressed patients. Gillin et al. (1978) obtained EEG sleep recordings from six hospitalized depressed patients before, during, and after treatment with amitriptyline. They found that amitriptyline significantly reduced the time spent in REM sleep and prolonged the REM latency throughout the treatment period. Interestingly, three patients who improved during treatment showed a REM rebound when amitriptyline was discontinued, while the three patients who did not improve showed no REM rebound.

In summary, amitriptyline has been consistently shown to suppress REM sleep in both healthy individuals and depressed patients. The exact mechanism behind this effect is not fully understood, but it may be related to the modulation of monoamine neurotransmitters, particularly norepinephrine and serotonin, which play a role in suppressing REM sleep. The clinical consequences of REM suppression can include changes in the frequency and intensity of dreaming, as well as the potential exacerbation of disturbing dreams upon discontinuation of the drug.

Amitriptyline and clinical improvement in depressed patients

Amitriptyline is an FDA-approved medication for treating major depressive disorder (MDD) in adults. It is a tricyclic antidepressant (TCA) that works by blocking the reuptake of serotonin and norepinephrine neurotransmitters, increasing their levels in the brain. This helps to maintain mental balance and improve mood. The usual dose for adults is 50mg to 100mg per day, with a maximum dose of 150mg per day. It is typically taken at night due to its sedative effects.

Amitriptyline has been found to suppress REM sleep, which is positively correlated with its antidepressant effect. This suppression has been shown to have a marked antidepressive effect in depressed patients. It is important to note that selective REM sleep deprivation has been found to have an antidepressive effect as well.

While amitriptyline can improve mood and help with sleep and anxiety, it also has common side effects such as weight gain, constipation, dry mouth, dizziness, and somnolence. It is important to note that amitriptyline has a black box warning from the FDA regarding its use in adolescents and young adults, as it can increase the risk of suicidal ideation and behaviour.

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