Mirtazapine Stats & Data
CN1CCN2c3ncccc3Cc3ccccc3C2C1RONZAEMNMFQXRA-UHFFFAOYSA-NPharmacology
DrugBankDescription
Mirtazapine is a tetracyclic _piperazino-azepine_ antidepressant agent that was initially approved for the treatment of major depressive disorder (MDD) in the Netherlands in 1994. This drug was first manufactured by Organon Inc., and received FDA approval in 1997 for the treatment of major depressive disorder. The effects of this drug may be observed as early as 1 week after beginning therapy. In addition to its beneficial effects in depression, mirtazapine has been reported to be efficacious in the off-label management of various other conditions. It may improve the symptoms of neurological disorders, reverse weight loss caused by medical conditions, improve sleep, and prevent nausea and vomiting after surgery.
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.
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.
Metabolism
Mirtazapine is heavily metabolized in humans. Demethylation and hydroxylation and subsequent glucuronide conjugation are the major pathways by which mirtazapine is metabolized. Data from in vitro studies on human liver microsomes show that cytochrome 2D6 and 1A2 lead to the formation of the _8-hydroxy metabolite_ of mirtazapine. The CYP3A enzyme metabolizes this drug into its _N-desmethyl and N-oxide_ metabolites. There are various other unconjugated metabolites of this drug that are pharmacologically active, but are measured in the blood at limited concentrations.FDA label, A177826
Absorption
The absorption of this drug is rapid and complete. Due to first pass metabolism in the liver and metabolism in the gut wall, absolute bioavailability is about 50%.FDA label,A177826 Peak blood concentrations are attained within about 2 hours after an oral dose. Food has little effect on the absorption of mirtazapine, and no dose adjustment is required if it is taken with food. Steady-state levels are achieved by about 5 days after the initial dose.FDA label, A177826 Mirtazapine pharmacokinetics vary across gender and age range. Females and the elderly population have been shown to have higher blood concentrations in comparison to males and younger adults.
Toxicity
**LD50** Oral LD50 was 830 mg/kg in male Swiss mice 24 hours after being administered mirtazapine. **Overdose information** Activated charcoal should be administered during an overdose to absorb excess mirtazapine. General supportive therapy should be employed, including maintenance of an adequate airway, oxygen therapy, and ventilation therapy. Vital signs and cardiac rhythm must be monitored. It is not advisable to induce vomiting. Gastric lavage with a large-bore orogastric tube with proper protection of the airway is recommended . There is no antidote for mirtazapine available currently. Consider the possibility of mirtazapine combined with other drugs in an overdose and ensure to contact the local poison control center for guidance on management. **Carcinogenesis** At higher than normal doses, mirtazapine increased the incidence of hepatocellular adenomas and carcinomas in male mice. The highest doses administered to the mice were about 20 and 12 times the maximum recommended human dose (MRHD). Hepatocellular tumors and thyroid follicular adenoma/cystadenomas in male rats occurred at an increased rate at a higher mirtazapine dose (60 mg/kg/day). In female rats, both the medium (20 mg/kg/day) and higher (60 mg/kg/day) doses of mirtazapine increased the rate of hepatocellular adenomas. The relevance of these findings in humans is not known at this time.
Indication
This drug is indicated for the treatment of major depressive disorder and its associated symptoms. Mirtazapine has been used off-label for a variety of conditions including panic disorder, generalized anxiety disorder, dysthymia, tension headaches, hot flushes, post-traumatic stress disorder (PTSD), sleep disorders, substance abuse disorders, and sexual disorders, among others.
Protein Binding
Mirtazapine is about 85% bound to plasma proteins.
Elimination
This drug is mainly excreted by the kidney. It is 75% eliminated in the urine and 15% eliminated in the feces.
Volume of Distribution
The volume of distribution after an oral steady-state dose was measured to be 107 ± 42L in a pharmacokinetic study.
Clearance
Total body clearance in males was found to be 31 L/h in a clinical pharmacokinetics study after intravenous administration. **Clearance in elderly patients** Mirtazapine clearance is slower in the elderly than in younger subjects. Exercise caution when this drug is given to elderly patients. In a clinical trial, elderly males showed a marked decrease in mirtazapine clearance when compared to young males taking the same dose. This difference was less significant when clearance was compared between elderly females and younger females taking mirtazapine. **Clearance in hepatic and renal impairment** Patients with hepatic and renal impairment have decreased rates of clearance and dosage adjustments may be necessary for these patients. Moderate renal impairment and hepatic impairment cause about a 30% decrease in mirtazapine clearance. Severe renal impairment leads to a 50% decrease in mirtazapine clearance.
Effect Profile
Curated + 66 ReportsStrong auditory effects with mild visuals and body load, low headspace
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Formal human data on tolerance are limited. Clinically, sedation often diminishes over 1–4 weeks of regular nightly dosing (partial tolerance), while antidepressant benefits generally require sustained dosing and do not show euphoric tolerance patterns. No reliable evidence for cross‑tolerance with classic serotonergic psychedelics; many reports suggest mirtazapine blunts them. Data quality is mainly clinical observation and user reports.
Cross-Tolerances
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 66 experience reports (66 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 9
Adverse Effects 7
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Threshold (n=39) |
|---|---|
| Anxiety Suppression | 51.3% |
| Stimulation | 51.3% |
| Sedation | 48.7% |
| Color Enhancement | 25.6% |
| Visual Distortions | 20.5% |
| Euphoria | 17.9% |
| Body High | 15.4% |
| Nausea | 12.8% |
| Music Enhancement | 12.8% |
| Auditory Effects | 12.8% |
| Focus Enhancement | 10.3% |
| Confusion | 10.3% |
| Sweating | 10.3% |
| Memory Suppression | 7.7% |
| Dissociation | 7.7% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 66 experience reports.
Limited tier coverage — most reports fall within the Threshold range. Effects at other dose levels may not be represented.
| Effect | Threshold (n=39) | |
|---|---|---|
| anxiety suppression | ||
| stimulation | ||
| sedation | ||
| color enhancement | ||
| visual distortions | ||
| euphoria | ||
| body high | ||
| nausea | ||
| music enhancement | ||
| auditory effects | ||
| focus enhancement | ||
| confusion | ||
| sweating | ||
| memory suppression | ||
| dissociation | ||
| hospital | ||
| closed-eye visuals | ||
| headache | ||
| time distortion | ||
| empathy |
Showing top 20 of 22 effects
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 93 individual dose entries
Oral (n=89)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 55 reports
Harm Reduction
drugs.wikiMirtazapine blocks central presynaptic α2‑adrenergic auto/heteroreceptors and is a potent antagonist at 5‑HT2 and 5‑HT3 as well as H1 histamine receptors; H1 antagonism largely explains strong sedation, weight gain, and next‑day grogginess, especially at lower doses. Older adults and people with hepatic/renal impairment are more susceptible to sedation, orthostatic hypotension, and falls; dose conservatively and rise slowly. Additive CNS depression occurs with alcohol, benzodiazepines, Z‑drugs, sedating antihistamines, and opioids; avoid driving or hazardous tasks until individual response is known. Serotonin syndrome from mirtazapine alone is rare but reported; risk increases with MAOIs, methylene blue/linezolid, and other serotonergic agents (e.g., DXM, tramadol, triptans); seek urgent care if symptoms such as agitation, tremor, clonus, hyperreflexia, or hyperthermia emerge. Rare but serious blood dyscrasias (neutropenia/agranulocytosis) can occur; stop and obtain urgent evaluation for fever, sore throat, mouth ulcers, or signs of infection. Weight gain and increased appetite are common; monitor weight and lipids during long‑term use. Elevations in liver enzymes and rare liver injury have been reported; evaluate persistent RUQ pain, jaundice, or dark urine. Mania/hypomania may emerge in bipolar disorder; screen for bipolarity prior to starting and monitor for mood switches. Orthostatic hypotension may occur due to peripheral α1 antagonism; rise slowly and hydrate, particularly at initiation. Psychedelics (LSD/psilocybin) are commonly blunted owing to 5‑HT2A antagonism; subjective responses vary, and combinations can be unpredictable. Fluvoxamine and other CYP inhibitors may raise mirtazapine exposure; monitor for excess sedation and consider dose adjustment. For overdose, there is no antidote; management is supportive with airway protection and cardiac monitoring.
References
Drugs.wiki References
- DrugBank – Mirtazapine DB00370 (mechanism, targets, half‑life, α1/H1 antagonism)
- DrugBank – Review A177856 (dosing, sedation, alcohol/benzodiazepine caution, hepatic/renal considerations)
- DrugBank – Review A559 (somnolence more frequent at lower doses; tolerability profile)
- NCBI StatPearls – Mirtazapine (adverse effects: drowsiness, weight gain, cholesterol; hematologic and hepatic events; clonidine interaction; overdose management)
- NCBI PDQ – Depression in Cancer (mechanism summary; sedation/weight gain; agranulocytosis; rare serotonin syndrome, especially with potent serotonergic combinations)
- DrugBank – Case report A255153 (mirtazapine‑induced serotonin syndrome, rare)
- DrugBank – Animal study A13525 (mirtazapine attenuates 5‑HT syndrome hyperthermia via 5‑HT2A antagonism)
- NIHR/NCBI – Therapeutics Letter summary NBK598513 (rates incl. neutropenia/agranulocytosis; strong sedation; impairment warning)
- Drugs‑Forum – Community reports on psychedelics blunting/variability with mirtazapine (anecdotal)