MIRZA 30

Indications

• Major depressive disorder
• Anxiety disorders
• Appetite stimulation in cancer patients

Dosage

Children: Mirtazapine is not recommended for children.

Adults: Initially 15-30 mg daily, increased as necessary, with a maximum dose of 45 mg daily in 2 divided doses.

Mechanism of action

Mirtazapine's exact mechanism of action is not fully understood, but it is believed to involve antagonism at presynaptic α2-adrenergic receptors, which enhances noradrenergic and serotonergic activity in the central nervous system. It also acts as a strong antagonist at serotonin 5-HT2 and 5-HT3 receptors, while indirectly increasing 5-HT1A transmission. Additionally, mirtazapine exhibits peripheral α1-adrenergic antagonist properties and is a potent histamine (H1) receptor antagonist, contributing to its sedative effects.

Pharmacodynamics

Mirtazapine is effective in alleviating symptoms associated with moderate to severe depression, such as disturbed sleep, lack of appetite, and anhedonia. The drug stimulates appetite and can help reduce nausea. However, there is an increased risk of suicidality, particularly in younger patients, necessitating careful monitoring for any emergence or worsening of suicidal thoughts during treatment.

Pharmacokinetics

Mirtazapine is well absorbed following oral administration, and its effects can be observed relatively quickly. The half-life of mirtazapine is approximately 20 to 40 hours, allowing for once-daily dosing. It undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, with renal excretion of metabolites. Caution is advised in patients with hepatic or renal impairment, as these conditions may affect drug clearance.

Contra-indications

• Hypersensitivity to mirtazapine or any excipients
• Concurrent use of monoamine oxidase inhibitors (MAOIs)
• History of mania or severe hepatic impairment

Adverse effects

• Drowsiness
• Increased appetite
• Weight gain
• Dry mouth
• Dizziness
• Fatigue
• Confusion
• Constipation
• Diarrhea
• Tremor
• Hallucinations
• Syncope
• Seizures
• Urinary retention
• Suicidal thoughts
• Aggression
• Pancreatitis
• Severe cutaneous adverse reactions

Interactions

• Cimetidine (increases exposure)
• Mitotane (decreases exposure)
• Rifampicin (decreases exposure)
• Cobicistat (increases exposure)
• Idelalisib (increases exposure)
• Clarithromycin (increases exposure)
• Pitolisant (decreases efficacy)

Precautions

• Use with caution in patients with cardiac disorders
• Diabetes mellitus
• Elderly patients
• History of seizures
• History of urinary retention
• Hypotension
• Psychoses (may aggravate symptoms)
• Susceptibility to angle-closure glaucoma
• Withdrawal effects may occur if treatment is stopped abruptly

Pregnancy

Use with caution; limited experience available. Monitor neonate for withdrawal effects.

Breast-feeding

Present in milk; use only if potential benefit outweighs risk.

Storage

Store below 25 degrees Celsius. Protect from light. Keep out of reach of children.

Formulations

• Mirtazapine 15 mg tablets
• Mirtazapine 30 mg tablets
• Mirtazapine 45 mg tablets
• Mirtazapine 15 mg/ml oral solution
• Mirtazapine 15 mg orodispersible tablets
• Mirtazapine 30 mg orodispersible tablets
• Mirtazapine 45 mg orodispersible tablets

Mechanism of action

**Summary** The mechanism of action of mirtazapine is not fully understood but may be explained by its effects on central adrenergic and serotonergic activity. This drug exhibits a fast onset of action, a high level of response, a manageable side-effect profile, and dual noradrenergic and serotonergic effects that are unique from the effects of other antidepressants. **Effects on various receptors** It has been shown that both noradrenergic and serotonergic activity increase following mirtazapine administration. The results of these studies demonstrate mirtazapine exerts antagonist activity at presynaptic α2-adrenergic inhibitory autoreceptors and heteroreceptors in the central nervous system. This is thought to lead to enhanced noradrenergic and serotonergic activity, which are known to improve the symptoms of depression and form the basis of antidepressant therapy. Mirtazapine is a strong antagonist of serotonin 5-HT2 and 5-HT3 receptors. It has not been found to bind significantly to the serotonin 5-HT1A and 5-HT1B receptors but indirectly increases 5-HT1A transmission. In addition to the above effects, mirtazapine is a peripheral α1-adrenergic antagonist. This action may explain episodes of orthostatic hypotension that have been reported after mirtazapine use. Mirtazapine is a potent histamine (H1) receptor antagonist, which may contribute to its powerful sedating effects. The pain-relieving effects of mirtazapine may be explained by its effects on opioid receptors.

Pharmacodynamics

**General effects and a note on suicidality** Mirtazapine is effective in treating moderate to severe depression and treats many symptoms normally associated with this condition. These symptoms may include disturbed sleep, lack of appetite, and anhedonia, in addition to anxiety.. It is important to note that suicidal ideation and behavior may emerge or increase during treatment with mirtazapine, as with any other antidepressant. This risk is especially pronounced in younger individuals. Patients, medical professionals, and families should monitor for suicidal thoughts, worsening depression, anxiety, agitation, sleep changes, irritable behavior, aggression, impulsivity, restlessness, and other unusual behavior when this drug is taken or the dose is adjusted. Do not administer mirtazapine to children. When deciding to prescribe this drug, carefully consider the increased risk of suicidal thoughts and behavior, especially in young adults. **Effects on appetite and weight gain** In addition to the above effects, mirtazapine exerts stimulating effects on appetite, and has been used for increasing appetite and decreasing nausea in cancer patients. Some studies and case reports have shown that this drug improves eating habits and weight gain in patients suffering from anorexia nervosa when administered in conjunction with psychotherapy and/or other psychotropic drugs. In a clinical trial, women with depression experienced a clinically significant mean increase in body weight, fat mass, and concentrations of leptin when treated with mirtazapine for a 6-week period, with a lack of effect on glucose homeostasis. **Effects on sleep** The use of mirtazapine to treat disordered sleep has been leveraged from its tendency to cause somnolence, which is a frequently experienced adverse effect by patients taking this drug. Mirtazapine has been shown to exert beneficial effects on sleep latency, duration, and quality due to its sedating properties. Insomnia is a common occurrence in patients with depression, and mirtazapine has been found to be efficacious in treating this condition.