Mirtazapine

Also known as

Remeron, Remeron SolTab, avanza, zispin, axit, mirtaz, mirtazon

Classification

Antidepressant, hallucinogen

Overview

Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the FDA to treat depression .

Medical usage

Used to treat depression .

What does it look like?

Tablets

Dosage

Therapeutic

• For oral dosage forms (orally disintegrating tablets, tablets) -
  • For depression -
    • Adults - at first, 15 milligrams 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 .

Abuse

Oral

• threshold 50 - 70 mg,
• light 80 - 130 mg,
• common 140 - 90 mg,
• strong 190 - 240 mg,
• heavy 250 mg + .

What are the different forms?

Mirtazapine is available as regular and oral disintegrating tablets of 15, 30 and 45 mg in multiple generic forms and under the brand name Remeron .

How long do its effects last?

Onset of effects

15 - 30 minutes .

Peak

90 - 180 minutes .

Offset

2 - 6 hours .

After-effects

Up to 12 hours .

Pharmacology

Pharmacodynamics

Mirtazapine, an antidepressant of the piperazinoazepine class, is a tetracyclic compound with an anxiolytic effect. Mirtazapine has fewer ADRs than tricyclic antidepressants and is better tolerated. Selective blockade of specific serotonin receptors by mirtazapine likey minimises side-effects typical of other antidepressants .

Absorption

Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50% .

Bioavailability

50% .

Metabolism

Mirtazapine is extensively metabolised by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low .

Half-life

20 - 40 hours .

Elimination

This drug is known to be substantially excreted by the kidney (75%) . Urine 75% and faeces 15% .

Lethal dosage

LD50 is 600 - 720mg/kg (oral, mice) and 320 - 490mg/kg (oral, rat) .

Tolerance

Tolerance to the effects of mirtazapine are built almost immediately after ingestion. After that, it takes about 3 days for the tolerance to be reduced to half and 7 days to be back at baseline (in the absence of further consumption). Mirtazapine presents cross-tolerance with all psychedelics, meaning that after the consumption of mirtazapine all psychedelics will have a reduced effect .

Mechanism of action

Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT1 receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT1 receptors and as a potent antagonist at 5-HT2 (particularly subtypes 2A and 2C) and 5-HT3 receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors .

Effects

Physical effects

• changes in gravity,
• spontaneous tactile sensations,
• tactile hallucinations,
• appetite enhancement,
• motor control loss,
• sedation,
• constipation,
• dizziness .

Cognitive effects

• conceptual thinking,
• time distortion,
• dream potentiation,
• immersion enhancement,
• increased music appreciation,
• amnesia,
• information processing suppression,
• thought deceleration .

Auditory effects

• auditory distortion,
• auditory enhancement,
• auditory hallucinations .

Visual effects

• tracers,
• geometry,
• autonomous entities,
• external hallucinations,
• internal hallucinations,
• perspective alterations,
• scenarios and plots,
• settings, sceneries, and landscapes .

Minor effects

More common

• constipation,
• dizziness,
• drowsiness,
• dry mouth,
• increased appetite,
• weight gain .

Less common

• abdominal or stomach pain,
• abnormal dreams,
• back pain,
• dizziness or fainting when getting up suddenly from a lying or sitting position,
• increased need to urinate,
• increased sensitivity to touch,
• increased thirst,
• low blood pressure,
• muscle pain,
• nausea,
• sense of constant movement of self or surroundings,
• trembling or shaking,
• vomiting,
• weakness .

Major effects

Less common

• decreased or increased movement,
• mood or mental changes, including abnormal thinking, agitation, anxiety, confusion, and feelings of not caring,
• shortness of breath,
• skin rash,
• swelling .

Rare

• change in menstrual cycle,
• convulsions,
• decreased sexual ability,
• menstrual pain,
• mood or mental changes, including anger, feelings of being outside the body, hallucinations, mood swings, and unusual excitement,
• mouth sores,
• sore throat, chills, or fever .

History

Originally introduced by Organon International in the United States in 1990. Its patent expired in 2004 and hence generic versions are now available .

---