How Much Mirtazapine Should I Take For Sleep

Does Mirtazapine Help You Sleep? Mirtazapine is an antidepressant drug that has a sedative effect. Although not a standard treatment for sleeping problems, some doctors prescribe mirtazapine for insomnia because of the drug’s ability to induce drowsiness.

• Mirtazapine is one of several antidepressant medications that are sometimes used to try to improve sleep.
• We discuss mirtazapine’s effects on sleep and explain who may be most likely to benefit from taking it.
• We also describe the typical dosage of mirtazapine, its potential side effects, and alternative ways to improve sleep.

Mirtazapine is a drug primarily used to treat major depression. Mirtazapine is considered an atypical antidepressant because it is generally only prescribed for depression if standard antidepressants have not been effective. Mirtazapine helps regulate mood by increasing the release of certain chemicals in the brain, including serotonin.

Mirtazapine has been approved by the FDA to treat depression since 1996. In addition to its approved use, mirtazapine has also been prescribed off-label National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.

in the treatment of other issues, including:

• Generalized anxiety disorder
• Post-traumatic stress disorder
• Panic disorder
• Tension-type headaches
• Fibromyalgia

Sleepiness is a common side effect of mirtazapine. Up to 53% of people National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. Most of the research about mirtazapine’s effects on sleep come from studies in which the drug was used in people who had both sleeping problems and depression. Insomnia, which is defined as, is common among people with conditions like depression. In a handful of studies, mirtazapine was found to have beneficial effects on sleep, including an improvement in total time spent sleeping and better sleep quality.

1. Mirtazapine may be helpful in both decreasing depressive symptoms and enhancing sleep.
2. Some researchers believe that some of mirtazapine’s impact on depression may come from its ability to reduce sleeping problems National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.

One potential benefit of mirtazapine compared to many other antidepressants is that it does not restrict, which is believed to be important for thinking and memory. However, is most vivid in REM sleep, and there have been some reports of in people taking mirtazapine.

Expert groups generally do not recommend UpToDate More than 2 million healthcare providers around the world choose UpToDate to help make appropriate care decisions and drive better health outcomes. UpToDate delivers evidence-based clinical decision support that is clear, actionable, and rich with real-world insights.

prescribing mirtazapine to treat insomnia in people who do not have depression. Despite this, some doctors will occasionally prescribe mirtazapine for people with insomnia alone. Very little research exists to evaluate the sleep-related effects of mirtazapine in people without depression.

1. In one small study, people who took mirtazapine slept longer and had fewer sleep disruptions.
2. They showed increases in without a reduction in REM sleep.
3. Although most people in research studies have found mirtazapine to be tolerable, it can cause side effects.
4. Given the limited track record in treating insomnia in people without depression, the American Academy of Sleep Medicine does not include mirtazapine in its general recommendations of medications for,

When prescribed for sleeping problems in people without depression, mirtazapine is usually given in a dose of 7.5 or 15 milligrams. Mirtazapine at these dosage levels tends to cause more drowsiness than higher doses of the drug. In most cases, mirtazapine is taken once a day before bedtime as a tablet that is either swallowed or that disintegrates inside the mouth.

For some people, the sleep-inducing effects of mirtazapine appear within one or two days after starting to take the drug. When used for depression, mirtazapine may take multiple weeks to have a noticeable effect. Like most medications, mirtazapine can cause a wide range of side effects. One of the most common side effects is feeling tired or drowsy, which is actually an intended effect when the drug is used to address sleeping problems.

Other side effects that were most frequently experienced across research studies with mirtazapine include:

• Dry mouth
• Increased appetite
• Weight gain
• Dizziness

Additional side effects that can occur when taking mirtazapine include:

• Confusion
• Anxiousness
• Constipation
• Nausea and vomiting

Although uncommon, mirtazapine may lead to potentially serious side effects. Immediate medical assistance should be sought by anyone experiencing:

• Chest pain
• Rapid heartbeat
• Seizures
• Fever, chills, or other flu-like symptoms

As with a number of antidepressants, the FDA warns that people under the age of 24 who take mirtazapine may be more likely to have thoughts of suicide. While this is uncommon, it should prompt immediate care from a doctor, mental health professional, or suicide prevention service. Some side effects may also arise when abruptly stopping mirtazapine. These withdrawal symptoms can include:

• Depression
• Panic attacks
• Insomnia
• Gastrointestinal distress

For this reason, anyone planning to stop taking mirtazapine should consult with a doctor about how to gradually discontinue its use. are not the only way to address insomnia. If you experience difficulty falling or staying asleep, improving your may help.

• Sleep hygiene includes the habits and environmental factors that can influence your sleep at night.
• A series of small changes in your lifestyle and environment may have noticeable impacts on your quality of sleep.
• People who are looking for additional support in making lifestyle changes to improve their sleep may want to consider talking with a health care provider about,

Changes in your daily routine can help you regularly get good sleep at night. While it might be difficult to immediately overhaul your routines, try small steps to incorporate certain changes into your day:

• Make time for or other physical activity
• Follow a for going to bed and waking up
• Aim to be outside for at least 30 minutes of natural sunlight exposure
• Avoid that are long or too late in the day
• Stop drinking by early afternoon at the latest

One part of sleep hygiene is preparing your mind and body for sleep. Practical tips before going to bed include:

• Avoiding and screens for an hour or more before bedtime
• Establishing a consistent and relaxing
• Limiting and heavy foods later in the evening

Your can affect how well you sleep. Some ways to enhance your sleep setting include:

• Keeping the lights off
• Removing electronics and other distractions from the bedroom
• Keeping your bedroom comfortably cool

If sleep hygiene improvements are not bringing about better sleep, about the most appropriate next steps. Your doctor can discuss your sleep habits and the pros and cons of various treatments for insomnia and other sleeping problems. Medical Disclaimer: The content on this page should not be taken as medical advice or used as a recommendation for any specific treatment or medication.

1. Jilani, T.E., Gibbons, J.R., Faizy, R.M., & Saadabadi, A. (2022, September 7). Mirtazapine. In StatPearls. StatPearls Publishing., Retrieved April 12, 2023, from
2. Alam, A., Voronovich, Z., & Carley, J.A. (2013). A review of therapeutic uses of mirtazapine in psychiatric and medical conditions. The Primary Care Companion for CNS Disorders, 15(5), PCC.13r01525.
3. Gandotra, K., Chen, P., Jaskiw, G.E., Konicki, P.E., & Strohl, K.P. (2018). Effective treatment of insomnia with mirtazapine attenuates concomitant suicidal ideation. Journal of Clinical Sleep Medicine, 14(5), 901–902.
4. Neubauer, D.N. (2023, April, 5). Pharmacotherapy for insomnia in adults. In R. Benca, & J.G. Elmore (Eds.). UpToDate., Retrieved April 12, 2023, from
5. 988 Suicide and Crisis Lifeline. (n.d.). Substance Abuse and Mental Health Services Administration., Retrieved April 12, 2023, from

: Does Mirtazapine Help You Sleep?

How much mg of mirtazapine will help me sleep?

Mirtazapine dosage – Mirtazapine is available as 15mg, 30mg and 45mg doses, in both standard tablet form and dispersible tablet form. It’s also available in a liquid form, at a dose of 15mg per ml. When mirtazapine is prescribed to treat depression or anxiety, it’s initially recommended at a dose of 15–30 mg per day, taken at bedtime, for two to four weeks.

After this time, the dose may be adjusted to suit how your body is responding to it. If found necessary, 45mg mirtazapine can be given as a single dose per day or split into two doses during the day. If you are prescribed mirtazapine for sleep problems, it’s usually given at a low dosage. It’s worth noting that the sedative effects of mirtazapine are thought to be greater at low dose and are lost at higher dose.

Generally, it’s given at a starting dose of 7.5mg mirtazapine, to be taken at bedtime. Some people may find that mirtazapine at 3.75mg may be their ideal dose.

Is mirtazapine 7.5 mg better than 15 mg for sleep?

Mirtazapine is commonly used in elderly patients with depression who are also suffering from insomnia. Mirtazapine is often chosen because it is much safer than benzodiazepines, “z-drugs”, and antipsychotics. The mechanisms of mirtazapine (podcast episode on the pharmacology) include the release of norepinephrine via presynaptic adrenergic auto-receptor blockade, increased serotonin production through stimulation of adrenoreceptors on serotonergic cell bodies, and the direct blockade of 5-HT 2 and 5-HT 3 receptors. Mirtazapine has a high H 1 receptor affinity, leading to antihistamine effects. So what does this mean as far as dosing of mirtazapine for insomnia? The recommended initial therapeutic dose for the treatment of depression is 15mg/day. Several studies discuss the predominance of antihistaminergic activity in doses <15mg/day, whereas the use of higher doses results in greater noradrenergic effects that help to negate antihistaminergic effects. If mirtazapine is not aiding the patient in sleeping at their current dose, increasing the dose can make insomnia even worse. The noradrenergic effects of mirtazapine in doses of 15mg/day can result in over-stimulation and insomnia in older adults, especially if given at bedtime. Given this information, if a provider is primarily using mirtazapine for insomnia management, 7.5 mg of mirtazapine is going to be the appropriate dose for most.

1. Aggressive starting doses may have a counter-productive effect and may lead to polypharmacy with the addition of more sedative agents.
2. The American College of Physicians strongly recommends Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment.
3. However, many patients look for a more immediate treatment for their symptoms.

A combination of CBT-I and short-term low-dose mirtazapine use can help promote better sleep. Short-term use is discussed because, as with other antihistaminergic medications, the sedative effects of mirtazapine diminish over time and can dissipate in as little as 7 days in young, healthy adults.

Regardless of the tolerability of sedating side effects, a starting dose of 15-30mg for the treatment of depression should be considered, especially in young, healthy adults. This initial starting dose aims to reduce excessive sedation while the patient gets used to the medication. If the patient is taking mirtazapine doses of 30-45mg/day and is experiencing insomnia, the medication should be taken in the morning to allow for activating noradrenergic effects to decrease by bedtime.

The other adverse effects of mirtazapine can be considered when choosing it for certain patients. Mirtazapine is known to be associated with weight gain. Due to the sedating effects of the medication and weight gain potential, extreme caution should be used in patients with obstructive sleep apnea associated with obesity.

30 medication mistakes PDF 18+ Page Drug Interaction PDF 10 Commandments of Polypharmacy Webinar based on my experiences in clinical practice

Is 30mg mirtazapine more sedating than 15mg?

Somnolence which may be due to its potent antihistaminic effects.1 Common tertiary references report that mirtazapine is more sedating at lower doses (.

Is mirtazapine a strong sleeping pill?

The effects of mirtazapine on sleep in patients with major depressive disorder – PubMed Background: Mirtazapine is a commonly used antidepressant with a well-known ability to produce sedation. At the same time, its sleep-promoting effects in patients with major depressive disorder (MDD) are relatively unclear.

The purpose of this article is to provide clinicians with a detailed review of mirtazapine’s sleep effects in patients with MDD. Methods: A literature search was conducted for studies involving mirtazapine in depressed patients that specifically assessed sleep. Results: Twenty-three studies met selection criteria and were included in this review.

Of the 15 studies that included a general assessment of sleep, all noted improvement from baseline with mirtazapine. Twelve of the 23 trials were randomized, blinded, and controlled. Mirtazapine was superior to placebo but did not clearly differentiate itself from other antidepressants, with the exception of venlafaxine.

Eight studies used detailed measures of sleep and consistently reported that mirtazapine produced significant improvement in sleep efficiency, total sleep time, and sleep quality. Few investigations combined detailed assessments of sleep along with a comparator antidepressant. Conclusion: Mirtazapine is an antidepressant with sleep-promoting effects significantly greater than placebo, similar to tricyclic antidepressants, and somewhat similar to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.

These effects must be balanced with mirtazapine’s ability to cause sedation-related side effects. : The effects of mirtazapine on sleep in patients with major depressive disorder – PubMed

Will 30mg mirtazapine make me sleepy?

Important – Do not stop taking mirtazapine suddenly, or without talking to your doctor first. How does mirtazapine compare with other antidepressants? Mirtazapine is not any better or worse than other antidepressants, Sometimes people get on better with one antidepressant than another.

talking therapy such as cognitive behavioural therapy exercise programmeshelp to get a good night’s sleep

Choosing a treatment that’s most suitable for you depends on:

how long you’ve had depressionyour symptomswhether you’ve had depression beforewhether previous treatment has workedhow likely you are to stick with your treatmentthe potential side effectsyour preferences and priorities

Will it affect my contraception? Mirtazapine will not affect any type of contraception, including the combined pill or emergency contraception, However, if mirtazapine makes you sick (vomit) or have severe diarrhoea for more than 24 hours, your contraceptive pills may not protect you from pregnancy.

Look on the pill packet to find out what to do. Read more about what to do if you’re on the pill and you’re being sick or have diarrhoea, Can I drive or ride a bike? Some people cannot concentrate properly while they are taking mirtazapine. It can also make you feel sleepy. When you first start taking mirtazapine, it’s a good idea to stop driving and cycling for the first few days until you know how this medicine makes you feel.

It’s an offence to drive a car if your ability to drive safely is affected. It’s your responsibility to decide if it’s safe to drive. If you’re in any doubt, do not drive. Talk to your doctor or pharmacist if you’re unsure whether it’s safe for you to drive while taking mirtazapine.

GOV.UK has more information on the law on drugs and driving, Can I drink alcohol while taking mirtazapine? You can drink alcohol while taking mirtazapine but it may make you feel sleepy and unsteady on your feet. It might be best to stop drinking alcohol for the first few days of treatment until you see how the medicine affects you.

Drinking alcohol every day or in large amounts can make your symptoms worse. It also makes it harder for mirtazapine to work properly. Is there any food or drink I need to avoid? You can eat and drink normally while taking mirtazapine. Will I gain or lose weight? Mirtazapine can make you feel more hungry than usual, so you may put on weight.

methadonestimulants like MDMA (ecstasy) or cocainehallucinogens like LSDnovel psychoactive substances (which used to be known as legal highs) like mephedrone

Find out about the side effects of some recreational drugs on the Frank website,

How long does it take mirtazapine to kick in for sleep?

Does Mirtazapine Help You Sleep? Mirtazapine is an antidepressant drug that has a sedative effect. Although not a standard treatment for sleeping problems, some doctors prescribe mirtazapine for insomnia because of the drug’s ability to induce drowsiness.

Mirtazapine is one of several antidepressant medications that are sometimes used to try to improve sleep. We discuss mirtazapine’s effects on sleep and explain who may be most likely to benefit from taking it. We also describe the typical dosage of mirtazapine, its potential side effects, and alternative ways to improve sleep.

Mirtazapine is a drug primarily used to treat major depression. Mirtazapine is considered an atypical antidepressant because it is generally only prescribed for depression if standard antidepressants have not been effective. Mirtazapine helps regulate mood by increasing the release of certain chemicals in the brain, including serotonin.

Mirtazapine has been approved by the FDA to treat depression since 1996. In addition to its approved use, mirtazapine has also been prescribed off-label National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.

in the treatment of other issues, including:

• Generalized anxiety disorder
• Post-traumatic stress disorder
• Panic disorder
• Tension-type headaches
• Fibromyalgia

Sleepiness is a common side effect of mirtazapine. Up to 53% of people National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. Most of the research about mirtazapine’s effects on sleep come from studies in which the drug was used in people who had both sleeping problems and depression. Insomnia, which is defined as, is common among people with conditions like depression. In a handful of studies, mirtazapine was found to have beneficial effects on sleep, including an improvement in total time spent sleeping and better sleep quality.

• Mirtazapine may be helpful in both decreasing depressive symptoms and enhancing sleep.
• Some researchers believe that some of mirtazapine’s impact on depression may come from its ability to reduce sleeping problems National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.

One potential benefit of mirtazapine compared to many other antidepressants is that it does not restrict, which is believed to be important for thinking and memory. However, is most vivid in REM sleep, and there have been some reports of in people taking mirtazapine.

• Expert groups generally do not recommend UpToDate More than 2 million healthcare providers around the world choose UpToDate to help make appropriate care decisions and drive better health outcomes.
• UpToDate delivers evidence-based clinical decision support that is clear, actionable, and rich with real-world insights.

prescribing mirtazapine to treat insomnia in people who do not have depression. Despite this, some doctors will occasionally prescribe mirtazapine for people with insomnia alone. Very little research exists to evaluate the sleep-related effects of mirtazapine in people without depression.

In one small study, people who took mirtazapine slept longer and had fewer sleep disruptions. They showed increases in without a reduction in REM sleep. Although most people in research studies have found mirtazapine to be tolerable, it can cause side effects. Given the limited track record in treating insomnia in people without depression, the American Academy of Sleep Medicine does not include mirtazapine in its general recommendations of medications for,

When prescribed for sleeping problems in people without depression, mirtazapine is usually given in a dose of 7.5 or 15 milligrams. Mirtazapine at these dosage levels tends to cause more drowsiness than higher doses of the drug. In most cases, mirtazapine is taken once a day before bedtime as a tablet that is either swallowed or that disintegrates inside the mouth.

• For some people, the sleep-inducing effects of mirtazapine appear within one or two days after starting to take the drug.
• When used for depression, mirtazapine may take multiple weeks to have a noticeable effect.
• Like most medications, mirtazapine can cause a wide range of side effects.
• One of the most common side effects is feeling tired or drowsy, which is actually an intended effect when the drug is used to address sleeping problems.

Other side effects that were most frequently experienced across research studies with mirtazapine include:

• Dry mouth
• Increased appetite
• Weight gain
• Dizziness

Additional side effects that can occur when taking mirtazapine include:

• Confusion
• Anxiousness
• Constipation
• Nausea and vomiting

Although uncommon, mirtazapine may lead to potentially serious side effects. Immediate medical assistance should be sought by anyone experiencing:

• Chest pain
• Rapid heartbeat
• Seizures
• Fever, chills, or other flu-like symptoms

As with a number of antidepressants, the FDA warns that people under the age of 24 who take mirtazapine may be more likely to have thoughts of suicide. While this is uncommon, it should prompt immediate care from a doctor, mental health professional, or suicide prevention service. Some side effects may also arise when abruptly stopping mirtazapine. These withdrawal symptoms can include:

• Depression
• Panic attacks
• Insomnia
• Gastrointestinal distress

For this reason, anyone planning to stop taking mirtazapine should consult with a doctor about how to gradually discontinue its use. are not the only way to address insomnia. If you experience difficulty falling or staying asleep, improving your may help.

Sleep hygiene includes the habits and environmental factors that can influence your sleep at night. A series of small changes in your lifestyle and environment may have noticeable impacts on your quality of sleep. People who are looking for additional support in making lifestyle changes to improve their sleep may want to consider talking with a health care provider about,

Changes in your daily routine can help you regularly get good sleep at night. While it might be difficult to immediately overhaul your routines, try small steps to incorporate certain changes into your day:

• Make time for or other physical activity
• Follow a for going to bed and waking up
• Aim to be outside for at least 30 minutes of natural sunlight exposure
• Avoid that are long or too late in the day
• Stop drinking by early afternoon at the latest

One part of sleep hygiene is preparing your mind and body for sleep. Practical tips before going to bed include:

• Avoiding and screens for an hour or more before bedtime
• Establishing a consistent and relaxing
• Limiting and heavy foods later in the evening

Your can affect how well you sleep. Some ways to enhance your sleep setting include:

• Keeping the lights off
• Removing electronics and other distractions from the bedroom
• Keeping your bedroom comfortably cool

If sleep hygiene improvements are not bringing about better sleep, about the most appropriate next steps. Your doctor can discuss your sleep habits and the pros and cons of various treatments for insomnia and other sleeping problems. Medical Disclaimer: The content on this page should not be taken as medical advice or used as a recommendation for any specific treatment or medication.

1. Jilani, T.E., Gibbons, J.R., Faizy, R.M., & Saadabadi, A. (2022, September 7). Mirtazapine. In StatPearls. StatPearls Publishing., Retrieved April 12, 2023, from
2. Alam, A., Voronovich, Z., & Carley, J.A. (2013). A review of therapeutic uses of mirtazapine in psychiatric and medical conditions. The Primary Care Companion for CNS Disorders, 15(5), PCC.13r01525.
3. Gandotra, K., Chen, P., Jaskiw, G.E., Konicki, P.E., & Strohl, K.P. (2018). Effective treatment of insomnia with mirtazapine attenuates concomitant suicidal ideation. Journal of Clinical Sleep Medicine, 14(5), 901–902.
4. Neubauer, D.N. (2023, April, 5). Pharmacotherapy for insomnia in adults. In R. Benca, & J.G. Elmore (Eds.). UpToDate., Retrieved April 12, 2023, from
5. 988 Suicide and Crisis Lifeline. (n.d.). Substance Abuse and Mental Health Services Administration., Retrieved April 12, 2023, from

: Does Mirtazapine Help You Sleep?

Can you take mirtazapine just for sleep?

Mirtazapine for sleep – While mirtazapine technically isn’t a sleeping medication, its sedative effects can help those with insomnia or poor sleeping patterns. And, unlike some medications whose primary purpose is to treat insomnia (like Ambien or Lunesta ), it does not pose the risks of dependency and tolerance.

Is 15 mg of mirtazapine enough for sleep?

Dosage – Mirtazapine is available as an oral tablet or a tablet that dissolves in the mouth. Dosages for both formulations are the same. Tablets are available in a dose of 7.5 mg, 15 mg, 30 mg, and 45 mg. The starting dose is commonly 15 mg per day, taken once daily before bed.

When is the best time to take mirtazapine for sleep?

Dosing – The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

For oral dosage forms (orally disintegrating tablets, tablets):

For depression:

Adults—At first, 15 milligrams (mg) once a day, preferably in the evening just before sleep. Your doctor may adjust your dose if needed. However, the dose is usually not more than 45 mg per day. Children—Use and dose must be determined by your doctor.

Why is mirtazapine so sedating?

Tachyphylaxis to the Sedative Action of Mirtazapine 1 Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Find articles by 1 Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Find articles by 1 Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece 2 Department of Medicine, University of California San Diego, La Jolla, CA, U.S.A.

Patient: Female, 30 Final Diagnosis: Depression Symptoms: — Medication: Mirtazapine Clinical Procedure: — Specialty: Psychiatry

Unusual or unexpected effect of treatment The pharmacological term tachyphylaxis is used to describe rapidly occurring response desensitization, a situation where the biological response to a given drug dose diminishes when it is given continuously. This pharmacological phenomenon is well observed in some drug categories such as ephedrine, nitrates, beta blockers and H 2 antagonists.

• Mirtazapine is a widely-used antidepressant with a multimodal mechanism of action.
• In the present case, we report rapid onset and consistent tachyphylaxis regarding the sedative action of mirtazapine in a 30-year-old female.
• To our knowledge this is the first reported case of rapid onset and consistent tachyphylaxis to the sedative effect of mirtazapine confirming the complexity of the pharmacological profile of the drug.

MeSH Keywords: Conscious Sedation, Histamine Antagonists, Tachyphylaxis The pharmacological term tachyphylaxis is used to describe rapidly occurring response desensitization, a situation where the biological response to a given drug dose diminishes when it is given continuously or repeatedly.

1. It is observed in some drug categories such as ephedrine, nitrates, beta-blockers, and H 2 receptor antagonists,
2. Concerning antidepressants, in most studies tachyphylaxis (or “poop-out”) is usually used to describe a relapse of an episode of major depression after full recovery despite continued treatment with a previously effective antidepressant dose, but pharmacologically, this is rather confusing and the term tolerance is much more comprehensive,

Mirtazapine is a widely-used antidepressant with a multimodal mechanism of action (a noradrenergic and specific serotonergic antidepressant) having no effect as monoamine reuptake inhibitor. It is a potent 5-HT 2A, 5-HT 3, H 1, and central presynaptic a 2 -adrenergic autoreceptor antagonist, a moderate peripheral a 1 -adrenergic and muscarinic receptor antagonist, but also exhibits inverse agonistic properties at 5-HT 2C receptors.

1. Mirtazapine, especially in low doses (7.5 or 15 mg/day), produces sedative effects due to potent histamine H 1 receptor antagonism, and is widely used off-label for sleep disturbances.
2. However, H 1 -antagonism is a target not thought to contribute to its therapeutic antidepressant efficacy,
3. We report a case of a 30-year-old female rapidly developing tachyphylaxis to the sedative action of mirtazapine.

Considering the off-label use of the drug for insomnia, awareness of the possibility of tachyphylaxis is important for the management of the patient. A 30-year-old female presented 2.5 years ago with depressed mood, anhedonia, psychomotor retardation, fatigue, and insomnia receiving a DSM-IV-TR diagnosis of Major Depression.

The patient had no history of drug, tobacco, or alcohol misuse and was free of medical comorbidities. She was put on venlafaxine, gradually increased up to 150 mg daily and 15 mg of mirtazapine at bedtime, aiming to improve her sleep. The core depressive symptoms (depressed mood and anhedonia) gradually improved after 2 weeks and full remission of depression occurred 2 months after treatment initiation.

Nine months later venlafaxine was tapered off. However, during this period her sleep was not successfully managed. It improved initially but after a few days of treatment the patient complained of insomnia. Mirtazapine was increased to 30 mg but couldn’t restore the original response and a benzodiazepine (triazolam) was suggested to improve her sleep.

However, the patient refused to receive a benzodiazepine because she was afraid of its addictive properties and continued to use 15 mg of mirtazapine. Notably, she reported a rapidly decreasing sedative effect after 7 days of use. The recommendations of her physician after the 9-month period was to stop using mirtazapine (and venlafaxine); a follow-up appointment was set up after 3 months.

The patient didn’t show up for the first follow-up appointment but presented a year later after a reminder call for her second follow-up. No symptoms of depression or other mental disorders were diagnosed, and she stated no use of any other licit or illicit substance.

• However, the patient reported that she was still taking mirtazapine at bedtime, but in her own way: after she had noticed that the medication had no effect taking it for 7 days consecutively, she changed to taking a 3-day break for its sedative effect to return.
• So, during this year, she had been taking it 7 days on, 3 days off.

In this case of tachyphylaxis to the sedative action of mirtazapine was evident even in the first period of use, while the physiological effects of tachyphylaxis resolved when dosing was reinitiated after the 3-day hiatus. According to the WHO-UMC system for standardized case causality assessment this clinical event is defined as “certain”,

Tachyphylaxis occurred in a plausible time related to drug administration and cannot be explained by disease or other drugs, since mirtazapine was the only drug used. Drug discontinuation resulted in insomnia and re-exposure produced sedative effects, so the de-challenge and re-challenge criteria are fulfilled.

The term tachyphylaxis describes a decreasing response to a drug that occurs very rapidly, sometimes with its initial administration. Tachyphylaxis and tolerance differ in time to onset, tolerance is defined as a slow decrease in responsiveness to a drug (days/week),

1. Tachyphylaxis can be the consequence of different types of molecular changes in the target tissue (i.e., a decrease or increase in receptor number, known as receptor desensitization or hypersensitization, respectively).
2. Thus, tachyphylaxis correctly refers to a desensitization of response, not necessarily a desensitization of receptors,

The mechanism of mirtazapine tachyphylaxis is speculative. The present case suggests tachyphylaxis to the sedative action of mirtazapine likely resulting from H 1 antagonism. Histamine tachyphylaxis has been described for over 50 years; however, this effect is attributed to H 2 antagonists.

Tachyphylaxis to H 2 antagonists develops rapidly, is evident by the second day of use and does not appear to be progressive. Once tachyphylaxis to an H 2 antagonist has developed, increasing the dose does not appear to be effective in overcoming the loss of its effect, Tachyphylaxis may be also exemplified by the rapid tolerance that develops to the effects of indirect acting drugs, meaning drugs that produce their effects by stimulating the release of a normal neurotransmitter.

Ephedrine, a drug which stimulates the sympathetic nervous system, effects as a model of tachyphylaxis, Mirtazapine indirectly augments monoamine transmission presumably through antagonist activity at multiple receptors including the adrenergic a 2 and serotonin 5-HT 2A/C receptors,

• In the case of tachyphylaxis to beta blockers (e.g., timolol for glaucoma treatment), it has been shown that treatment can lead to a rapid increase in the density of beta-adrenergic receptors, an effect that can occur within a day of the initial dosage,
• However, similar findings with mirtazapine are not reported in the literature.

It is necessary to notice the difference that, regarding antidepressants, the condition in which a depressed patient loses a previously effective antidepressant treatment response despite staying on the same drug and dosage for maintenance treatment should be described as tolerance rather as tachyphylaxis,

1. To our knowledge this is the first reported case of rapid onset and consistent tachyphylaxis to the sedative effect of mirtazapine confirming the complexity of the pharmacological profile of the drug.
2. Since mirtazapine is commonly used off-label for insomnia, clinicians should be aware of the potential for rapid development of tachyphylaxis.

Conflicts of interest None.1. Timmons R, Hamilton L. Drugs, brains and behavior.1990. Available from:,2. Munzel T, Daiber A, Mulsch A. Explaining the phenomenon of nitrate tolerance. Circ Res.2005; 97 :618–28.3. Abelson M, Vashishan A. The truth about tachyphylaxis.

1. Review of Ophthalmology.2006 Marz 16.
2. Available from:,4.
3. McRorie JW, Kirby JA, Miner PB.
4. Histamine 2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing.
5. World J Gastrointest Pharmacol Ther.2014; 5 :57–62.5.
6. Solomon DA, Leon AC, Mueller TI, et al.
7. Tachyphylaxis in unipolar major depressive disorder.

J Clin Psychiatry.2005; 66 :283–90.6. Targum SD. Identification and treatment of antidepressant tachyphylaxis. Innov Clin Neurosci.2014; 11 :24–28.7. Labasque M, Meffre J, Carrat G, et al. Constitutive activity of serotonin 2C receptors at G protein-independent signaling: Modulation by RNA editing and antidepressants.

Mol Pharmacol.2010; 78 :818–26.8. Croom KF, Perry CM, Plosker GL. Mirtazapine: A review of its use in major depression and other psychiatric disorders. CNS Drugs.2009; 23 :427–52.9. World Health Organization. The use of the WHO-UMC system for standardised case causality assessment.2010. Availabe from:,10.

Katzung BG. Basics of clinical pharmacology.8th ed. London: McGraw/Hill; 2001. Articles from The American Journal of Case Reports are provided here courtesy of International Scientific Information, Inc. : Tachyphylaxis to the Sedative Action of Mirtazapine

Is mirtazapine stronger than diazepam?

Comparing Diazepam vs Mirtazapine. Diazepam has an average rating of 8.5 out of 10 from a total of 825 ratings on Drugs.com.82% of reviewers reported a positive effect, while 10% reported a negative effect. Mirtazapine has an average rating of 6.7 out of 10 from a total of 1964 ratings on Drugs.com.

Is mirtazapine calming?

What is mirtazapine? – Mirtazapine⁷ is the active ingredient in a drug called Remeron, and it belongs to a class of medication called tetracyclic antidepressants. Although mirtazapine is an antidepressant, it is also used to treat anxiety, especially for generalized anxiety disorder ⁸.

Neurotransmitters are chemicals in the brain that jump between brain cells (neurons) to relay messages and alter the function of the neurons. The main neurotransmitters associated with anxiety disorders are serotonin and noradrenaline. There is some evidence that people with low serotonin activity and elevated noradrenergic system activity may be more prone to developing anxiety.

How does mirtazapine work? Mirtazapine acts by blocking the alpha-2 receptor⁹, which results in increased levels of serotonin and noradrenaline in the ends, or synapses, of brain cells. Mirtazapine is not usually used as a first-line therapy for anxiety.

First-line therapy for anxiety is normally selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs). However, if you have very symptomatic anxiety, your doctor may decide to start you on mirtazapine. The reason for this is that, unlike the SSRIs and SNRIs, mirtazapine doesn’t aggravate your anxiety symptoms.

Because it has a sedating effect, it can be helpful if your anxiety is so bad you can’t risk having to tolerate an initial exacerbation. Mirtazapine may also be the treatment of choice for you if you are struggling with insomnia due to your anxiety, Its sedating effect can help you get a good night’s sleep.

Can you drink alcohol while taking mirtazapine?

What happens when you mix mirtazapine and alcohol? – When you take mirtazapine and alcohol together, the effects of both can be magnified which can bring feelings of extreme relaxation and happiness. However, mixing the two substances can also cause a range of physical side effects such as nausea, vomiting, dizziness, insomnia and sexual dysfunction.

In some cases, mirtazapine and alcohol blackouts and memory loss can also occur, both of which can put you at risk of accidents, potential crimes and other dangers. If you are taking mirtazapine for a genuine condition like depression, mixing mirtazapine and alcohol can actually make the condition worse.

This is because mirtazapine works by blocking the effects of certain neurotransmitters in the brain, like serotonin and norepinephrine. Alcohol has similar effects on these neurotransmitters, which can lead to an increase in feelings of depression, anxiety and irritability when mixed with mirtazapine.

Does tiredness from mirtazapine go away?

A common side effect is drowsiness, which usually wears off after a few days. Higher doses of Mirtazapine are also less sedative. Mirtazapine may make some people hungrier and cause a slight weight gain. Eating healthily and exercising can help avoid significant weight gain.

Can I overdose on mirtazapine?

Results: We saw two patients after they had overdosed with mirtazapine because of suicidal intention. Both patients had taken 30 and 50 times a normal daily dose and achieved a full recovery without any complications or harm. Conclusions: Mirtazapine seems to be a safe compound in overdose.

What will 30mg mirtazapine do?

Descriptions – Mirtazapine is used to treat depression. Mirtazapine belongs to a group of medicines called tetracyclic antidepressants. These medicines work in the central nervous system (CNS) to make certain chemicals in the brain stronger. This medicine is available only with your doctor’s prescription. This product is available in the following dosage forms:

• Tablet, Disintegrating
• Tablet

Is 15 mg of mirtazapine sedating?

The medication is not as overly sedating at 15 mg because the norepinephrine effects moderate the sedating effects of serotonin, while still maintaining its soporific properties. However, at higher doses, the norepinephrine effects may also interfere with sleep.

Does mirtazapine 40 mg help you sleep?

Key facts –

Mirtazapine usually takes about 4 to 6 weeks to work.Common side effects include headaches, dry mouth and feeling sick. They’re usually mild and go away after a couple of weeks.If you and your doctor decide to take you off mirtazapine, your doctor will probably recommend reducing your dose gradually to help prevent extra side effects.Mirtazapine is not a sleeping tablet but it can make you feel sleepy. This can be helpful if you have depression and difficulties getting to sleep.

Page last reviewed: 15 February 2022 Next review due: 15 February 2025

Is 45mg mirtazapine a sedative?

My Account Area – 1. Name of the medicinal product Mirtazapine 45 mg tablets 2. Qualitative and quantitative composition Each film coated tablet contains Mirtazapine 45 mg. Excipient(s) with known effect: Each Mirtazapine 45 mg tablet contains 306 mg lactose (as monohydrate). For the full list of excipients, see section 6.1 3. Pharmaceutical form Film coated Tablet (tablet) Mirtazapine 45 mg tablets are White, biconvex, capsule shaped film coated tablets with “45” debossed on one side and “MI” debossed on the other side 4. Clinical particulars 4.1 Therapeutic indications Mirtazapine tablets are indicated in adults for the treatment of episodes of major depression.4.2 Posology and method of administration Posology Adults The effective daily dose is usually between 15 and 45 mg; the starting dose is 15 or 30 mg. Mirtazapine begins to exert its effect in general after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response within 2-4 weeks. With an insufficient response, the dose can be increased up to the maximum dose. If there is no response within a further 2-4 weeks, then treatment should be stopped. Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms. It is recommended to discontinue treatment with mirtazapine gradually to avoid withdrawal symptoms (see section 4.4). Elderly The recommended dose is the same as that for adults. In elderly patients an increase in dosing should be done under close supervision to elicit a satisfactory and safe response. Renal impairment The clearance of mirtazapine may be decreased in patients with moderate to severe renal impairment (creatinine clearance <40 ml/min). This should be taken into account when prescribing Mirtazapine to this category of patients (see section 4.4). Hepatic impairment The clearance of mirtazapine may be decreased in patients with hepatic impairment. This should be taken into account when prescribing Mirtazapine to this category of patients, particularly with severe hepatic impairment, as patients with severe hepatic impairment have not been investigated (see section 4.4). Paediatric population Mirtazapine should not be used in children and adolescents under the age of 18 years as efficacy was not demonstrated in two short-term clinical trials (see section 5.1) and because of safety concerns (see sections 4.4, 4.8 and 5.1) Method of administration Mirtazapine has an elimination half-life of 20-40 hours and therefore Mirtazapine is suitable for once daily administration. It should be taken preferably as a single night-time dose before going to bed. Mirtazapine may also be given in two divided doses (once in the morning and once at night-time, the higher dose should be taken at night). The tablets should be taken orally, with fluid, and swallowed without chewing.4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, Concomitant use of mirtazapine with monoamine oxidase (MAO) inhibitors (see section 4.5).4.4 Special warnings and precautions for use Paediatric population Mirtazapine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking. Suicide/suicidal thoughts or clinical worsening Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany therapy with antidepressants especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present. With regard to the chance of suicide, in particular at the beginning of treatment, only a limited number of Mirtazapine film-coated tablets should be given to the patient consistent with good patient management, in order to reduce the risk of overdose. Bone marrow depression Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis, has been reported during treatment with Mirtazapine. Reversible agranulocytosis has been reported as a rare occurrence in clinical studies with Mirtazapine. In the postmarketing period with Mirtazapine very rare cases of agranulocytosis have been reported, mostly reversible, but in some cases fatal. Fatal cases mostly concerned patients with an age above 65. The physician should be alert for symptoms like fever, sore throat, stomatitis or other signs of infection; when such symptoms occur, treatment should be stopped and blood counts taken. Jaundice Treatment should be discontinued if jaundice occurs. Conditions which need supervision Careful dosing as well as regular and close monitoring is necessary in patients with: – epilepsy and organic brain syndrome: Although clinical experience indicates that epileptic seizures are rare during mirtazapine treatment, as with other antidepressants, Mirtazapine should be introduced cautiously in patients who have a history of seizures. Treatment should be discontinued in any patient who develops seizures, or where there is an increase in seizure frequency. – hepatic impairment: Following a single 15 mg oral dose of mirtazapine, the clearance of mirtazapine was approximately 35 % decreased in mild to moderate hepatically impaired patients, compared to subjects with normal hepatic function. The average plasma concentration of mirtazapine was about 55 % increased. – renal impairment: Following a single 15 mg oral dose of mirtazapine, in patients with moderate (creatinine clearance < 40 ml/min) and severe (creatinine clearance ≤10 ml/min) renal impairment the clearance of mirtazapine was about 30 % and 50 % decreased respectively, compared to normal subjects. The average plasma concentration of mirtazapine was about 55 % and 115 % increased respectively. No significant differences were found in patients with mild renal impairment (creatinine clearance < 80 ml/min) as compared to the control group. – cardiac diseases like conduction disturbances, angina pectoris and recent myocardial infarction, where normal precautions should be taken and concomitant medicines carefully administered. – low blood pressure. – diabetes mellitus: In patients with diabetes, antidepressants may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted and close monitoring is recommended. Like with other antidepressants, the following should be taken into account: – Worsening of psychotic symptoms can occur when antidepressants are administered to patients with schizophrenia or other psychotic disturbances; paranoid thoughts can be intensified. – When the depressive phase of bipolar disorder is being treated, it can transform into the manic phase. Patients with a history of mania/hypomania should be closely monitored. Mirtazapine should be discontinued in any patient entering a manic phase. – Although Mirtazapine is not addictive, post-marketing experience shows that abrupt termination of treatment after long term administration may sometimes result in withdrawal symptoms. The majority of withdrawal reactions are mild and self-limiting. Among the various reported withdrawal symptoms, dizziness, agitation, anxiety, headache and nausea are the most frequently reported. Even though they have been reported as withdrawal symptoms, it should be realized that these symptoms may be related to the underlying disease. As advised in section 4.2, it is recommended to discontinue treatment with mirtazapine gradually. – Care should be taken in patients with micturition disturbances like prostate hypertrophy and in patients with acute narrow-angle glaucoma and increased intra-ocular pressure (although there is little chance of problems with Mirtazapine because of its very weak anticholinergic activity). – Akathisia/psychomotor restlessness: The use of antidepressants have been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental. – Cases of QT prolongation, Torsade de Pointes, ventricular tachycardia, and sudden death, have been reported during the post-marketing use of mirtazapine. The majority of reports occurred in association with overdose or in patients with other risk factors for QT prolongation, including concomitant use of QTc prolonging medicines (see section 4.5 and section 4.9). Caution should be exercised when Mirtazapine is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QTc interval. Severe cutaneous adverse reactions Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), bullous dermatitis and erythema multiforme, which can be life-threatening or fatal, have been reported in association with Mirtazapine treatment. If signs and symptoms suggestive of these reactions appear, Mirtazapine should be withdrawn immediately. If the patient has developed one of these reactions with the use of Mirtazapine, treatment with Mirtazapine must not be restarted in this patient at any time. Hyponatraemia Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported very rarely with the use of mirtazapine. Caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatraemia. Serotonin syndrome Interaction with serotonergic active substances: serotonin syndrome may occur when selective serotonin reuptake inhibitors (SSRIs) are used concomitantly with other serotonergic active substances (see section 4.5). Symptoms of serotonin syndrome may be hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma. Caution should be advised and a closer clinical monitoring is required when these active substances are combined with mirtazapine. Treatment with mirtazapine should be discontinued if such events occur and supportive symptomatic treatment initiated. From post marketing experience it appears that serotonin syndrome occurs very rarely in patients treated with Mirtazapine alone (see section 4.8). Concomitant administration of serotonergic agents, such as MAO inhibitors, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants, and buprenorphine-containing medicinal products may result in serotonin syndrome, a potentially life-threatening condition (see section 4.5). If concomitant treatment with buprenorphine-containing medicinal products is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. Elderly Elderly are often more sensitive, especially with regard to the undesirable effects of antidepressants. During clinical research with Mirtazapine, undesirable effects have not been reported more often in elderly patients than in other age groups. Lactose This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction Pharmacodynamic interactions • Mirtazapine should not be administered concomitantly with MAO inhibitors or within two weeks after discontinuation of MAO inhibitor therapy. In the opposite way about two weeks should pass before patients treated with mirtazapine should be treated with MAO inhibitors (see section 4.3). In addition, as with SSRIs, co-administration with other serotonergic active substances (L-tryptophan, triptans, tramadol, linezolid, methylene blue, SSRIs, venlafaxine, lithium and St. John's Wort – Hypericum perforatum – preparations) may lead to an incidence of serotonin associated effects (serotonin syndrome: see section 4.4). Caution should be advised and a closer clinical monitoring is required when these active substances are combined with mirtazapine. • Mirtazapine may increase the sedating properties of benzodiazepines and other sedatives (notably most antipsychotics, antihistamine H1 antagonists, opioids). Caution should be exercised when these medicinal products are prescribed together with mirtazapine. • Mirtazapine may increase the CNS depressant effect of alcohol. Patients should therefore be advised to avoid alcoholic beverages while taking mirtazapine. • Mirtazapine dosed at 30 mg once daily caused a small but statistically significant increase in the international normalized ratio (INR) in subjects treated with warfarin. As at a higher dose of mirtazapine a more pronounced effect cannot be excluded, it is advisable to monitor the INR in case of concomitant treatment of warfarin with mirtazapine. • The risk of QT prolongation and/or ventricular arrhythmias (e.g. Torsade de Pointes) may be increased with concomitant use of medicines which prolong the QTc interval (e.g. some antipsychotics and antibiotics). Pharmacokinetic interactions • Carbamazepine and phenytoin, CYP3A4 inducers, increased mirtazapine clearance about twofold, resulting in a decrease in average plasma mirtazapine concentration of 60 % and 45 %, respectively. When carbamazepine or any other inducer of hepatic metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with such medicinal product is discontinued, it may be necessary to reduce the mirtazapine dose. • Co-administration of the potent CYP3A4 inhibitor ketoconazole increased the peak plasma levels and the AUC of mirtazapine by approximately 40 % and 50 % respectively. • When cimetidine (weak inhibitor of CYP1A2, CYP2D6 and CYP3A4) is administered with mirtazapine, the mean plasma concentration of mirtazapine may increase more than 50 %. Caution should be exercised and the dose may have to be decreased when co-administering mirtazapine with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, cimetidine or nefazodone. • Interaction studies did not indicate any relevant pharmacokinetic effects on concurrent treatment of mirtazapine with paroxetine, amitriptyline, risperidone or lithium. Buprenorphine-containing medicinal products Mirtazapine should be used cautiously when co-administered with Buprenorphine-containing medical products as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4). Paediatric population Interaction studies have only been performed in adults.4.6 Fertility, pregnancy and lactation Pregnancy Limited data of the use of mirtazapine in pregnant women do not indicate an increased risk for congenital malformations. Studies in animals have not shown any teratogenic effects of clinical relevance, however developmental toxicity has been observed (see section 5.3). Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN to mirtazapine treatment, this potential risk cannot be ruled out taking into account the related mechanism of action (increase in serotonin concentrations). Caution should be exercised when prescribing to pregnant women. If Mirtazapine is used until, or shortly before birth, postnatal monitoring of the newborn is recommended to account for possible discontinuation effects. Breast-feeding Animal studies and limited human data have shown excretion of mirtazapine in breast milk only in very small amounts. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Mirtazapine should be made taking into account the benefit of breastfeeding to the child and the benefit of Mirtazapine therapy to the woman. Fertility Non-clinical reproductive toxicity studies in animals did not show any effect on fertility.4.7 Effects on ability to drive and use machines Mirtazapine has minor or moderate influence on the ability to drive and use machines. Mirtazapine may impair concentration and alertness (particularly in the initial phase of treatment). Patients should avoid the performance of potentially dangerous tasks, which require alertness and good concentration, such as driving a motor vehicle or operating machinery, at any time when affected.4.8 Undesirable effects Depressed patients display a number of symptoms that are associated with the illness itself. It is therefore sometimes difficult to ascertain which symptoms are a result of the illness itself and which are a result of treatment with Mirtazapine. Summary of safety profile The most commonly reported adverse reactions, occurring in more than 5 % of patients treated with Mirtazapine in randomised placebo-controlled trials (see below) are somnolence, sedation, dry mouth, weight increased, increase in appetite, dizziness and fatigue. Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), bullous dermatitis and erythema multiforme have been reported in association with Mirtazapine treatment (see section 4.4). Tabulated list of adverse reactions All randomised placebo-controlled trials in patients (including indications other than major depressive disorder), have been evaluated for adverse reactions of Mirtazapine. The meta-analysis considered 20 trials, with a planned duration of treatment up to 12 weeks, with 1,501 patients (134 person years) receiving doses of mirtazapine up to 60 mg and 850 patients (79 person years) receiving placebo. Extension phases of these trials have been excluded to maintain comparability to placebo treatment. Table 1 shows the categorized incidence of the adverse reactions, which occurred in the clinical trials statistically significantly more frequently during treatment with Mirtazapine than with placebo, added with adverse reactions from spontaneous reporting. The frequencies of the adverse reactions from spontaneous reporting are based on the reporting rate of these events in the clinical trials. The frequency of adverse reactions from spontaneous reporting for which no cases in the randomised placebo-controlled patient trials were observed with mirtazapine has been classified as 'not known'. Table 1. Adverse reactions of Mirtazapine

System organ class	Very common (≥1/10)	Common (≥1/100 to <1/10)	Uncommon (≥1/1,000 to <1/100)	Rare (≥1/10,000 to <1/1,000)	Frequency not known (cannot be estimated from the available data)
Blood and the lymphatic system disorders					• Bone marrow depression (granulocytopenia, agranulocytosis, aplastic anemia thrombocytopenia) • Eosinophilia
Endocrine disorders					• Inappropriate antidiuretic hormone secretion • Hyperprolactinemia (and related symptoms e.g. galactorrhea and gynecomastia)
Metabolism and nutrition disorders	• Increase in appetite 1 • Weight increased 1				• Hyponatraemia
Psychiatric disorders		• Abnormal dreams • Confusion • Anxiety 2, 5 • Insomnia 3, 5	• Nightmares 2 • Mania • Agitation 2 • Hallucinations • Psychomotor restlessness (incl. akathisia, hyperkinesia)	• Aggression	• Suicidal ideation 6 • Suicidal behaviour 6 • Somnambulism
Nervous system disorders	• Somnolence 1, 4 • Sedation 1, 4 • Headache 2	• Lethargy 1 • Dizziness • Tremor • Amnesia 7	• Paraesthesia 2 • Restless legs • Syncope	• Myoclonus	• Convulsions (insults) • Serotonin syndrome • Oral paraesthesia • Dysarthria
Vascular disorders		• Orthostatic hypotension	• Hypotension 2
Gastrointestinal disorders	• Dry mouth	• Constipation 1 • Nausea 3 • Diarrhea 2 • Vomiting 2	• Oral hypoaesthesia	• Pancreatitis	• Mouth oedema • Increased salivation
Hepatobiliary disorders				• Elevations in serum transaminase activities
Skin and subcutaneous tissue disorders		• Exanthema 2			• Stevens-Johnson Syndrome • Dermatitis bullous • Erythema multiforme • Toxic epidermal necrolysis • Drug reaction with eosinophilia and systemic symptoms (DRESS)
Musculoskeletal and connective tissue disorders		• Arthralgia • Myalgia • Back pain 1			• Rhabdomyolysis
Renal and urinary disorders					• Urinary retention
Reproductive system and breast disorders					• Priapism
General disorders and administration site conditions		• Oedema peripheral 1 • Fatigue			• Generalised oedema • Localised oedema
Investigations					• Increased creatinine kinase

1 In clinical trials these events occurred statistically significantly more frequently during treatment with Mirtazapine than with placebo.2 In clinical trials these events occurred more frequently during treatment with placebo than with Mirtazapine, however not statistically significantly more frequently.3 In clinical trials these events occurred statistically significantly more frequently during treatment with placebo than with Mirtazapine.4 N.B.

dose reduction generally does not lead to less somnolence/sedation but can jeopardize antidepressant efficacy.5 Upon treatment with antidepressants in general, anxiety and insomnia (which may be symptoms of depression) can develop or become aggravated. Under mirtazapine treatment, development or aggravation of anxiety and insomnia has been reported.6 Cases of suicidal ideation and suicidal behaviours have been reported during mirtazapine therapy or early after treatment discontinuation (see section 4.4).7 In most cases patients recovered after drug withdrawal.

In laboratory evaluations in clinical trials transient increases in transaminases and gamma-glutamyltransferase have been observed (however associated adverse events have not been reported statistically significantly more frequently with Mirtazapine than with placebo).

Paediatric population : The following adverse events were observed commonly in clinical trials in children: weight gain, urticaria and hypertriglyceridaemia (see also section 5.1). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.4.9 Overdose Present experience concerning overdose with Mirtazapine alone indicates that symptoms are usually mild.

Depression of the central nervous system with disorientation and prolonged sedation have been reported, together with tachycardia and mild hyper- or hypotension. However, there is a possibility of more serious outcomes (including fatalities) at dosages much higher than the therapeutic dose, especially with mixed overdoses.

In these cases QT prolongation and Torsade de Pointes have also been reported. Cases of overdose should receive appropriate symptomatic and supportive therapy for vital functions. ECG monitoring should be undertaken. Activated charcoal or gastric lavage should also be considered.

Paediatric population The appropriate actions as described for adults should be taken in case of an overdose in paediatrics.5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: other antidepressants, ATC code: N06AX11 Mechanism of action/pharmacodynamic effects Mirtazapine is a centrally active presynaptic α2-antagonist, which increases central noradrenergic and serotonergic neurotransmission.

The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors, because 5-HT2 and 5-HT3 receptors are blocked by mirtazapine. Both enantiomers of mirtazapine are presumed to contribute to the antidepressant activity, the S(+) enantiomer by blocking α2 and 5-HT2 receptors and the R(-) enantiomer by blocking 5-HT3 receptors.

Clinical efficacy and safety The histamine H1-antagonistic activity of mirtazapine is associated with its sedative properties. It has practically no anticholinergic activity and, at therapeutic doses, has only limited effects (e.g. orthostatic hypotension) on the cardiovascular system. The effect of mirtazapine on QTc interval was assessed in a randomised, placebo and moxifloxacin controlled clinical trial involving 54 healthy volunteers using a regular dose of 45 mg and a supra-therapeutic dose of 75 mg.

Linear e-max modelling suggested that prolongation of QTc intervals remained below the threshold for clinically meaningful prolongation (see section 4.4). Paediatric population: Two randomised, double-blind, placebo-controlled trials in children aged between 7 and 18 years with major depressive disorder (n=259) using a flexible dose for the first 4 weeks (15-45 mg mirtazapine) followed by a fixed dose (15, 30 or 45 mg mirtazapine) for another 4 weeks failed to demonstrate significant differences between mirtazapine and placebo on the primary and all secondary endpoints.

Significant weight gain (≥7%) was observed in 48.8% of the mirtazapine treated subjects compared to 5.7% in the placebo arm. Urticaria (11.8% vs 6.8%) and hypertriglyceridaemia (2.9% vs 0%) were also commonly observed.5.2 Pharmacokinetic properties Absorption After oral administration of Mirtazapine, the active substance mirtazapine is rapidly and well absorbed (bioavailability ≈50 %), reaching peak plasma levels after approx.

two hours. Food intake has no influence on the pharmacokinetics of mirtazapine. Distribution Binding of mirtazapine to plasma proteins is approx.85 %. Biotransformation Major pathways of biotransformation are demethylation and oxidation, followed by conjugation.

In vitro data from human liver microsomes indicate that cytochrome P450 enzymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.

Elimination Mirtazapine is extensively metabolised and eliminated via the urine and faeces within a few days. The mean half-life of elimination is 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded and shorter half-lives have been seen in young men.

• The half-life of elimination is sufficient to justify once-a-day dosing.
• Steady state is reached after 3-4 days, after which there is no further accumulation.
• Linearity/non-linearity Mirtazapine displays linear pharmacokinetics within the recommended dose range.
• Special populations The clearance of mirtazapine may be decreased as a result of renal or hepatic impairment.5.3 Preclinical safety data Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.

In reproductive toxicity studies in rats and rabbits no teratogenic effects were observed. At two-fold systemic exposure compared to maximum human therapeutic exposure, there was an increase in post-implantation loss, decrease in the pup birth weights, and reduction in pup survival during the first three days of lactation in rats.

1. Mirtazapine was not genotoxic in a series of tests for gene mutation and chromosomal and DNA damage.
2. Thyroid gland tumours found in a rat carcinogenicity study and hepatocellular neoplasms found in a mouse carcinogenicity study are considered to be species-specific, non-genotoxic responses associated with long-term treatment with high doses of hepatic enzyme inducers.6.

Pharmaceutical particulars 6.1 List of excipients Mirtazapine 45 mg tablets contain Core: Lactose monohydrate, Maize starch, Low substituted Hydroxypropyl Cellulose, Magnesium Stearate (E 470b), Hydroxypropyl cellulose and Silica Colloidal anhydrous Film Coating: Hypromellose (E464) and Titanium dioxide (E 171) 6.2 Incompatibilities Not applicable.6.3 Shelf life 4 years.6.4 Special precautions for storage This medicinal product does not require any special storage conditions.6.5 Nature and contents of container Blister packs comprising of 250 µ PVC coated with 60 gsm PVdC & 25 µ aluminium foil.10/14/28/30/40/50/56/60/70/84/90/100/200/250/500 tablets.

Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.7. Marketing authorisation holder Milpharm Limited Ares Block, Odyssey Business Park West End Road Ruislip HA4 6QD United Kingdom 8.

Marketing authorisation number(s) PL 16363/0631 9. Date of first authorisation/renewal of the authorisation 31/07/2006 10. Date of revision of the text 02/08/2021

What does mirtazapine 30 mg do to you?

Descriptions – Mirtazapine is used to treat depression. Mirtazapine belongs to a group of medicines called tetracyclic antidepressants. These medicines work in the central nervous system (CNS) to make certain chemicals in the brain stronger. This medicine is available only with your doctor’s prescription. This product is available in the following dosage forms:

• Tablet, Disintegrating
• Tablet