Gina Johnson
For over a decade, low-dose amitriptyline and mirtazapine have been prescribed off-label for insomnia, despite a lack of placebo-controlled evidence. While both drugs have been shown to be effective in treating depression, it is unclear whether they are more effective than one another. A 2018 Cochrane review called for high-quality trials of antidepressants for insomnia to provide better evidence to inform clinical practice. This article will explore the evidence for the efficacy of amitriptyline and mirtazapine in treating insomnia and discuss the side effects of each drug.
| Characteristics | Values |
|---|---|
| Prescribed for sleep | Amitriptyline and mirtazapine are prescribed off-label for insomnia. |
| Dosage | Amitriptyline: 10–20 mg/day, Mirtazapine: 7.5–15 mg/day |
| Side effects | Amitriptyline: anticholinergic adverse drug reactions, sedative and anticholinergic side effects, weight gain (22% of patients). Mirtazapine: weight gain (13% of patients), sleep disorders, fatigue, restless legs syndrome, periodic limb movements, daytime drowsiness, grogginess, slight hangover feeling. |
| Effectiveness | Mirtazapine has been found to reduce the time it takes for a person to fall asleep and improve the continuity and overall quality of sleep. It reduces the duration of early, light stages of sleep and increases deep sleep. It is well tolerated with a side-effect profile similar to that of a placebo. Amitriptyline was better than a placebo with fewer patients suffering a recurrence of symptoms. |
| Risks | Amitriptyline or mirtazapine is contraindicated based on information known to the GP in usual care, that is, allergy for amitriptyline or mirtazapine; cardiac arrhythmia/cardiac blockade/long QT syndrome/Brugada syndrome/family history of acute cardiac death/recent myocardial infarction (within the past 90 days)/angina pectoris/coronary insufficiency; severe renal insufficiency (Glomerular Filtration Rate, GFR <10); severe liver dysfunction; epilepsy; ocular hypertension/glaucoma; bipolar affective disorder; concurrent alcohol or drug abuse/addiction; suicide risk. |
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What You'll Learn
Amitriptyline and mirtazapine are prescribed off-label for insomnia
Amitriptyline and mirtazapine are two types of antidepressants that are prescribed off-label for insomnia. They are prescribed in low doses, lower than the dosage for antidepressant efficacy, as an alternative to BZRAs. They are thought to be especially effective in treating sleep maintenance problems by antagonising the wake-promoting activities of the central nervous system. However, they are not licensed for insomnia treatment and lack scientific evidence supporting their use for this purpose.
Mirtazapine has been found to reduce the time it takes for a person to fall asleep and improve overall sleep quality. It reduces the duration of early, light stages of sleep and increases deep sleep, while slightly reducing REM sleep. It is usually given at a low dosage of 7.5mg, taken at bedtime. It can take a few weeks for the effects to become noticeable, with some people noticing improvements from the first dose and others experiencing a more gradual effect.
Amitriptyline, on the other hand, has been associated with more adverse events than mirtazapine, particularly sedative and anticholinergic side effects. It has also been linked to objectively measured weight gain in 22% of patients, compared to 13% in those taking mirtazapine.
While mirtazapine may help with sleep while it is being taken, it is important to note that insomnia can develop after stopping the drug. It can cause daytime drowsiness and leave some people feeling groggy. It may also increase the occurrence of restless leg syndrome and periodic limb movements, which can disrupt sleep.
Both medications have their own advantages and disadvantages when used for insomnia. It is important to consult with a healthcare professional to determine the most suitable treatment option based on individual needs and circumstances.
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Mirtazapine has fewer adverse side effects
Mirtazapine has been proven to be as effective as amitriptyline in treating depression and insomnia. However, mirtazapine has been found to have fewer adverse side effects. In a study of patients with alcohol dependence and comorbid depressive disorder, mirtazapine was better tolerated than amitriptyline. Mirtazapine has also been shown to cause fewer and less severe anticholinergic and cardiovascular side effects.
A review of therapeutic uses of mirtazapine in psychiatric and medical conditions found that no serious adverse events, drug interactions, or increases in frequency or severity of seizures occurred. While mirtazapine may cause side effects such as weight gain, daytime drowsiness, and fatigue, these are generally considered mild and well tolerated. Long-term use of mirtazapine is considered safe, with little risk of long-term side effects even when the drug is taken for months or years.
On the other hand, amitriptyline has been associated with a higher number of adverse events than mirtazapine. In particular, amitriptyline has been linked to more sedative and anticholinergic side effects. Additionally, amitriptyline may pose additional risks for patients with certain medical conditions, such as cardiac arrhythmia, severe renal insufficiency, severe liver dysfunction, epilepsy, ocular hypertension, and bipolar affective disorder.
The lower risk of adverse side effects associated with mirtazapine makes it a more attractive option for the long-term treatment of depression and insomnia, especially in vulnerable populations such as the elderly or those with comorbid medical conditions. Mirtazapine's improved side-effect profile, coupled with its efficacy in reducing the risk of relapse and the recurrence of depression, makes it a favourable choice for patients seeking a well-tolerated and effective treatment option.
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Amitriptyline has more sedative side effects
For over a decade, low-dose amitriptyline and mirtazapine have been prescribed off-label for insomnia. However, amitriptyline has been associated with significantly more adverse events than mirtazapine, particularly sedative and anticholinergic side effects. While mirtazapine has also been shown to have sedative effects, leading to daytime drowsiness, amitriptyline's sedative side effects are more pronounced.
Amitriptyline's sedative side effects may be due to its pharmacological mechanism of action, which involves antagonising the wake-promoting activities of the central nervous system mediated by histamine H1-receptors. By blocking these receptors, amitriptyline can cause drowsiness and promote sleep. However, this same mechanism can also lead to excessive daytime sleepiness and fatigue, particularly if the dosage is not carefully monitored.
Mirtazapine, on the other hand, has been found to have a more favourable side-effect profile. While it can also cause sedation and daytime drowsiness, these effects are typically milder and more manageable. Mirtazapine has been shown to reduce the time it takes for a person to fall asleep, decrease night-time waking, and improve the overall quality of sleep. Additionally, mirtazapine's sedative effects are thought to be greater at low doses and may even be lost at higher doses, further emphasising the importance of careful dosage management.
In terms of safety, mirtazapine has been well tolerated in various studies, with a side-effect profile similar to that of a placebo. In a study comparing mirtazapine and amitriptyline in the long-term treatment of depression, mirtazapine demonstrated fewer relapses during treatment and a longer time to relapse. Additionally, mirtazapine was better tolerated than amitriptyline, particularly in patients with alcohol dependence and comorbid depressive disorder.
While both amitriptyline and mirtazapine can be effective in treating insomnia, amitriptyline's more pronounced sedative side effects may be a cause for concern. It is important to carefully consider the potential benefits and risks of each medication and to follow the prescribed dosage to minimise adverse events.
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Mirtazapine may cause sleep disorders
Mirtazapine is an antidepressant that has been prescribed off-label for insomnia for over a decade. While it may help people sleep better, it is well recognised that insomnia can develop after stopping the drug. Mirtazapine's sedative effects can lead to daytime drowsiness, and it can also leave some people feeling groggy or like they have a slight hangover. It is important to follow the prescribed dosage.
Mirtazapine has been found to reduce the time it takes for a person to fall asleep and the occurrence of night-time waking, while improving the continuity and overall quality of sleep. It reduces the duration of early, light stages of sleep and increases deep sleep, and also slightly reduces REM sleep (dream sleep).
However, mirtazapine may cause 'sleep disorders', with fatigue also being a common side effect. It may also increase the occurrence of restless legs syndrome and periodic limb movements, both of which can significantly disrupt sleep. Weight gain is also considered a common side effect of mirtazapine, with one study concluding that the drug may change the user's metabolism and increase cravings for sweet foods.
While mirtazapine is generally well tolerated, it is important to note that it may not be suitable for everyone. For example, it is contraindicated in cases of allergy, cardiac arrhythmia, severe renal insufficiency, severe liver dysfunction, epilepsy, ocular hypertension/glaucoma, bipolar affective disorder, concurrent alcohol or drug abuse/addiction, and suicide risk.
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Amitriptyline and mirtazapine are both effective antidepressants
Amitriptyline is associated with more adverse events than mirtazapine, particularly sedative and anticholinergic side effects. Weight gain is also more frequent with amitriptyline, occurring in 22% of patients compared to 13% with mirtazapine. However, amitriptyline has been shown to be advantageous in the first 20 weeks of treatment, with fewer patients relapsing compared to those on mirtazapine or placebo.
Mirtazapine has a more favourable side-effect profile, with fewer and less severe anticholinergic and cardiovascular side effects. It is well tolerated, with a side-effect profile similar to that of a placebo. The only adverse event reported significantly more frequently with mirtazapine was weight gain. Mirtazapine has also demonstrated a faster median response time compared to other antidepressants, with effects seen as early as 1-2 weeks after treatment initiation.
Both drugs have been found to improve sleep. Mirtazapine reduces the time it takes to fall asleep, improves continuity and overall quality of sleep, and increases deep sleep. Amitriptyline, on the other hand, is often prescribed for its sedative effects, which can help with sleep maintenance problems.
In terms of their effectiveness as antidepressants, mirtazapine has been found to be equally effective as tricyclic antidepressants and trazodone in patients with moderate to severe depression. It also demonstrated comparable efficacy to amitriptyline in treating depression in patients with alcohol dependence and comorbid depressive disorder.
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Frequently asked questions
Amitriptyline and mirtazapine are two types of well-known antidepressants that are often prescribed off-label for insomnia.
Amitriptyline has been associated with anticholinergic and sedative side effects. It has also been linked to weight gain in 22% of patients.
Mirtazapine has been linked to weight gain in 13% of patients, as well as fatigue and daytime drowsiness. It may also increase the occurrence of restless leg syndrome and periodic limb movements.
There is limited scientific evidence to support the use of either drug for insomnia. However, mirtazapine has been found to reduce the time it takes for a person to fall asleep and improve overall sleep quality. It has fewer side effects than amitriptyline and is better tolerated.
