Mianserin - Side Effects, Contraindications, Dosage, and Warnings

Overview:

Mianserin, an antidepressant, was introduced in the year 1976. Since it had a tetracyclic structure, it was pharmacologically unique from the antidepressants introduced before 1976. A mildly depressed outpatient who is sensitive to the anticholinergic side effects of other antidepressants or who has cardiovascular disease, hypotension, prostration, or glaucoma may benefit from this medication as this does not cause any undesirable cardiovascular side effects. Mianserin could potentially help prevent migraines because it blocks serotonin receptors and has antidepressant effects, but it is not used for migraine primarily.

Drug Group:

Mianserin is a type of medicine known as a tetra-cyclic antidepressant. It works by boosting levels of two natural brain chemicals, noradrenaline and serotonin.

Available Doses and Dosage Forms:

• For adults under 65, start with 30 to 40 mg (milligrams) daily, and increase if necessary as per physicians recommendations. The usual range is 30 to 90 mg daily, with doses up to 200 mg tolerated.

• For adults over 65, use cautiously if other antidepressants do not work. The initial dose should be under 30 mg daily, and further increase should be monitored closely. Taking it once at night is better, and lower doses may work.

• It is not recommended for children and adolescents.

Things to Consider:

• It might take a few weeks for Mianserin to start working, so the person taking it should be patient and keep taking it as prescribed, even if they do not feel better right away..

• If the person ever feels that their depression or anxiety is getting worse or has troubling thoughts about harming themselves, they should talk to their doctor immediately.

• The person should not suddenly stop taking Mianserin, as this can lead to withdrawal symptoms like nausea, shivering, headaches, trouble sleeping, sweating, irritability, restlessness, or anxiety. The doctor will provide instructions on how to stop the medication safely.

• Mianserin can cause drowsiness, so avoid driving or using machinery while on this medication.

• When a person starts taking Mianserin, it might make them feel dizzy or unsteady when getting up from lying down or sitting. Try getting up slowly, and if they feel dizzy, sit or lie down until the phase passes.

• It is important not to drink alcohol while taking Mianserin because it can make a person drowsy or dizzy. This effect can be stronger when they begin treatment or after the dose increases.

• Avoid using recreational drugs like Cocaine, Ecstasy, or Mephedrone while taking Mianserin, as the combination can be risky.

For Patients

What is Depression?

Depression is a serious mood problem known as clinical depression. It makes a person feel very sad, lose interest, and affects their thoughts and actions, leading to various emotional and physical issues.

What Are the Uses of Mianserin?

Mianserin, a type of antidepressant, falls into the group of tetra-cyclic antidepressants. It functions by boosting two natural brain chemicals, noradrenaline and serotonin. The doctor may prescribe Mianserin to alleviate depression symptoms, which include:

• Boosting mood.

• Easing feelings of sadness or hopelessness.

• Enhancing overall well-being.

• Reducing symptoms of depression.

How Does Mianserin Work?

This drug blocks specific receptors in the brain, specifically the alpha 2 adrenergic presynaptic receptor. By doing this, it increases the activity of norepinephrine, which is a neurotransmitter. This mechanism is different from the typical reuptake inhibition seen in many other drugs. Additionally, it blocks alpha 1 adrenergic receptors on serotonin neurons, but this does not lead to a significant increase in serotonin activity. It also blocks various serotonin and histamine receptors. It does not change the personality or instantly make a person happy. It works gradually to fix brain chemical imbalances causing depression. A person should take it daily for several months. It is not addictive, but one should not stop suddenly to avoid withdrawal. Drowsiness is a common side effect, especially at the beginning, so a person should not drive if affected. Avoid alcohol while on Mianserin.

What Are the Things to Inform the Doctor Before Taking Mianserin?

• Liver or kidney problems.

• Heart disease, irregular heartbeat, or recent heart attack.

• Overactive thyroid gland.

• A tumor in the adrenal gland (phaeochromocytoma).

• Enlarged prostate gland.

• A history of high eye pressure or glaucoma.

• Risk of seizures or fits (from epilepsy, alcohol or drug withdrawal, brain damage, or certain other medicines).

• Diabetes.

• Psychotic illnesses like schizophrenia.

• Bipolar affective disorder (manic depression). Mianserin should be stopped if a person enters into a manic phase.

• Treatment with electroconvulsive therapy (ECT).

What Caution Should Be Considered During the Usage of Mianserin?

The person should avoid taking this medicine if:

• They are allergic to Mianserin or its ingredients (maize starch, silica, pregelatinized, colloidal anhydrous, microcrystalline, cellulose, calcium hydrogen phosphate, and magnesium stearate).

• They have severe liver disease.

• They have or are being treated for mania (excessive excitement with unusual behavior).

• They are breastfeeding and are pregnant.

• Selective, reversible monoamine oxidase inhibitors (MAO-A inhibitors) like Moclobemide should be avoided before starting Mianserin within 1 week of taking an MAO-A inhibitor.

What Are the Factors That Indicate a Person Should Avoid Taking Mianserin?

• Children under 18 years old should not use it.

• Breastfeeding mothers should choose bottle-feeding because Mianserin can pass into breast milk.

• People with severe liver disease should not use it.

• If the person has bipolar disorder (manic depression), Mianserin is not suitable.

• People should not take Mianserin if they have used a monoamine oxidase inhibitor antidepressant (MAOI) in the last two weeks.

• Individuals with rare hereditary blood disorders called porphyrias(Uncommon illnesses caused by too many natural chemicals in the body) should avoid it.

• If they are allergic or intolerant to any ingredient in the medicine, they should not use it. Check the medicine's leaflet for ingredient details if known allergies or intolerances exist.

• Some people, especially elderly individuals, may need a lower dose or extra monitoring with Mianserin.

What Are the Side Effects of Mianserin?

Common Side Effects:

• Constipation.

• Dry mouth.

• Feeling drowsy (especially when starting the medication).

Less Common Side Effects:

• Tremors (shaking).

• Headaches.

• Dizziness.

• Feeling weak.

• Feeling dizzy.

• Weight gain.

Rare Side Effects:

• Swelling of the body tissues (edema).

• Joint pain.

• Skin rash.

• Inner restlessness (akathisia).

• Low blood pressure upon standing (leading to dizziness).

• Elevated mood (hypomania).

• Slow heart rate (bradycardia).

• Liver problems (including jaundice).

• Skin rash (exanthema).

Very Rare Side Effects:

• Seizures.

• Blood problems (neutropenia and agranulocytosis).

• Neuroleptic malignant syndrome (a severe drug reaction).

• Restless legs.

• Heart problems (cardiac arrest and failure).

• Nasal congestion.

• Tingling sensations.

• Vision problems (double vision).

• Breast enlargement in males.

• Impotence.

• Muscle aches.

• Itchy skin.

• High blood pressure.

• Rapid heartbeat.

• Ringing in the ears.

• Confusion.

• Agitation.

Overdose: Overdose of Mianserin can cause extreme drowsiness, unconsciousness, low or high blood pressure, a fast heartbeat, and abnormal changes in the heart's electrical activity (QT interval).

Storage:

• Make sure kids cannot reach the medicine.

• Keep it at a cool place below 25 degrees Celsius (room temperature), at a dry spot, and away from sunlight and heat.

For Doctors

Pharmacodynamics: Mianserin is classified as a tetracyclic antidepressant, and it primarily acts as an antihistamine and hypnosedative. Notably, it has minimal anticholinergic effects. While it weakly inhibits the reuptake of norepinephrine, it strongly promotes the release of norepinephrine. Additionally, it interacts with serotonin receptors in the central nervous system. Its therapeutic effects are typically observed within one to three weeks of use. It is worth noting that Mianserin can lead to drowsiness and hematological issues.

Mechanism of Action:

Mianserin, a tetracyclic antidepressant, modulates various brain receptors and neurotransmitters. It is used for depression and exhibits ancillary effects, including anxiolysis, sedation, antiemesis, appetite stimulation, and antihistaminic actions. While it lacks approval in the US, a structurally related compound, Mirtazapine, is available there. Mianserin presents a safer overdose profile compared to older antidepressants.

Mianserin interacts with multiple receptors: H1, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, and α2-adrenergic, and inhibits norepinephrine reuptake. It acts as a potent H1 receptor inverse agonist, primarily responsible for its sedative and weight gain effects. Importantly, it exhibits minimal affinity for mACh receptors, lacking anticholinergic properties. Recent findings also highlight its strong kappa opioid receptor agonism and potent antagonism of the neuronal octopamine receptor. Although the precise mood implications remain elusive, octopamine's role in regulating sleep, appetite, and insulin production may contribute to mianserin's overall side-effect profile. In summary, Mianserin addresses depression while intricately interacting with various neural receptors.

Pharmacokinetics: Mianserin exhibits a bioavailability of 20 to 30 percent. Approximately 95 percent of mianserin is bound to plasma proteins. Metabolism of mianserin occurs in the liver through N-oxidation and N-demethylation processes, primarily facilitated by the CYP2D6 enzyme. The elimination half-life of mianserin ranges from 21 to 61 hours. A small portion, around four to seven percent, is excreted in the urine, while a larger fraction, approximately 14 to 28 percent, is eliminated in feces.

Toxicity: Taking too much mianserin can lead to symptoms such as excessive drowsiness, coma, abnormally low or high blood pressure, rapid heart rate, and prolongation of the QT interval on an electrocardiogram.

Clinical Studies: Mianserin is a type of antidepressant medication that affects certain receptors in the brain. It helps with depression and anxiety, makes a person sleepy, reduces nausea, increases appetite, and has antihistamine effects. Mianserin was one of the first antidepressants in the United Kingdom that was safer in case of overdose. It mainly works on receptors for histamine, serotonin, and norepinephrine, causing drowsiness and weight gain. Unlike some other drugs, it does not affect certain other receptors that cause side effects like dry mouth. It also acts on the kappa opioid receptor and the octopamine receptor, but how these affect mood is not clear yet.

What Are the Contraindications of Mianserin?

• Minaserin is contraindicated in individuals with a history of hematological (blood) disorders.

• Usage of Minaserin should be avoided by patients who have taken Monoamine Oxidase Inhibitors (MAOIs) within the preceding 14 days.

• It is not recommended for individuals with a high sensitivity or allergy to Minaserin.

• Avoid Minaserin in the presence of urinary tract infections.

Warnings and Precautions:

• Discuss the medical history with a healthcare professional if a person has a seizure history or risk factors like head injuries, specific medications, or changes in alcohol intake that could increase the likelihood of seizures.

• Exercise caution if a person has underlying heart conditions, including cardiovascular insufficiency, recent heart attacks, heart block, or irregular heart rhythms.

• Inform the healthcare provider if a person has a history of bipolar disorder.

• If a person is pregnant, consult the healthcare professional before using this medication.

• Notify the healthcare provider if a person has a tumor in their adrenal gland (phaeochromocytoma).

• Diabetes patients should know that their diabetes medication might require adjustment; discuss this with the healthcare provider.

• If a person has kidney or liver problems, share this information with the healthcare provider.

• Inform the healthcare provider if a person has a history of conditions like narrow-angle glaucoma (high eye pressure), urinary retention, or symptoms related to bladder obstruction.

• Be prepared for regular blood tests, especially in the initial three months of treatment, to monitor blood and liver function.

• If a person experiences signs of infection, such as fever, sore throat, or mouth sores, contact the healthcare provider.

Special Considerations:

• If a person is pregnant or planning to become pregnant while on Mianserin, consult the doctor.

• Mianserin is not recommended during pregnancy, especially in the first and third trimesters, as its safety is still not confirmed.

• Using Mianserin in the third trimester may lead to fetus-related side effects or withdrawal symptoms, requiring extra baby monitoring after birth.

• If a patient becomes pregnant and wants to stop Mianserin, they should not quit abruptly. The doctor will guide a gradual tapering-off plan to prevent withdrawal symptoms.

• Avoid drinking alcohol while driving because it leads to drowsiness.

• Breastfeeding women should avoid this medication.