mirtazapine (Remeron)

the boxed warning: suicidal thoughts and behaviors, by age

the boxed warning says antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies, that everyone on one should be monitored closely for worsening, and that mirtazapine "is not approved for use in pediatric patients" [label, boxed warning and 5.1]. the number behind it is pooled placebo-controlled trials of antidepressants covering about 77,000 adults and 4,500 children. the label states the difference against placebo per 1,000 people treated: under 18, 14 additional patients; 18 to 24, 5 additional; 25 to 64, 1 fewer; 65 and older, 6 fewer [label 5.1, table 1]. it notes "considerable variation in risk" among drugs, that the risk beyond four months is unknown, and that prescribers should consider changing the regimen, "including possibly discontinuing mirtazapine", in anyone whose depression is persistently worse [label 5.1].

the warning is specific, not blanket: thoughts and behaviors, not deaths; the first months, not years; and above age 24 the pooled trials did not show an increase at all [label 5.1; age-ceiling]. the pediatric line rests on evidence the label describes: two placebo-controlled trials in 258 children and adolescents whose data "were insufficient to establish the safety and effectiveness" of the drug, and in one 8-week trial 49% of children on mirtazapine gained at least 7% of their body weight against 5.7% on placebo, a mean of 4 kg against 1 kg [label 8.4].

sleep and appetite are not approved uses, and what the record says about them

the indications section names one condition, major depressive disorder in adults [label 1]. insomnia is not an approved use, poor appetite is not an approved use, and no sleep or appetite trial appears anywhere in the label. what the label does carry is the dosing instruction to take it "preferably in the evening prior to sleep" [label 2.1], a warning that somnolence "may impair judgment, thinking, and/or motor skills" and that "it is unclear whether tolerance develops to the somnolent effects" [label 5.8], and, in the depression trials, superiority over placebo on the "sleep disturbance factor" of the depression rating scale, which is a cluster of items within a depression trial and not a sleep study [label 14]. the pharmacology section attributes the drowsiness to the drug’s blocking of histamine h1 receptors [label 12.2].

in favour. the two label numbers that drive the off-label uses are real and large: somnolence 54% against 18% and increased appetite 17% against 2% [label 5.7, 5.8]. in a cochrane review of 29 randomised trials in 4,974 people with depression, mirtazapine produced a response faster than ssris at two weeks (odds ratio 1.57) with a small edge remaining at six to twelve weeks (1.19), and caused less nausea and less sexual dysfunction than ssris [watanabe-2011]. in a meta-analysis of antidepressant trials in which sexual function was measured by questionnaire, mirtazapine was among the drugs showing no significant difference from placebo, while sertraline, venlafaxine, citalopram and paroxetine headed the list [serretti-2009]. for someone whose depression comes with insomnia, poor appetite, nausea on an ssri or sexual side effects, those are the facts a prescriber is weighing.

against, or smaller than it sounds. the library holds no randomised trial of mirtazapine for insomnia or for appetite in people who are not depressed, and this page states that absence rather than filling it. in the label’s own trials somnolence was the most common reason for stopping, 10.4% against 2.2% [label 6.1, table 2], and in the pooled premarketing studies 8% of people stopped for weight gain [label 5.7]. in a meta-analysis of 17 placebo-controlled trials in 2,131 adults, mirtazapine roughly quintupled the risk of weight gain (relative risk 4.75; about one extra person affected per ten treated), more than doubled somnolence (2.61; about one per four) and dizziness, and showed a possible but statistically unconfirmed increase in serious adverse events (odds ratio 1.82, confidence interval 0.95 to 3.48); several of its authors are prominent critics of antidepressants and disclosed royalties and consulting tied to deprescribing work, which the library record states [kamp-2025]. in the cochrane review the same sleepiness and weight gain that make the drug attractive for some were the side effects on which it did worse than ssris [watanabe-2011]. the drowsiness has no off switch at the doses the label describes, and its half-life of 20 to 40 hours, longer in women (37 hours) than men (26), means it is still present the next day [label 12.3].

the drug most often set beside mirtazapine for the sleep question is trazodone, which has its own explainer and the same "not an approved use" status for sleep [trazodone-explainer]; the two are compared side by side on this site [compare-trazodone].

weight, appetite and cholesterol, with the label’s numbers

warning 5.7 reports that in the us controlled trials appetite increase was 17% against 2% and weight gain of 7% or more of body weight was 7.5% against 0%; in the larger pool that included long-term open-label treatment, 8% stopped for weight gain; and in the 8-week pediatric trial, 49% against 5.7% gained 7% or more [label 5.7]. warning 5.11 adds the lipids: non-fasting cholesterol rising to 20% or more above the upper limit of normal in 15% against 7%, and triglycerides reaching 500 mg/dl or more in 6% against 3% [label 5.11]. the label gives no mean weight change in adults and no figure beyond six weeks of controlled treatment.

the independent record points the same way. a review of 116 studies of antidepressants and body weight placed mirtazapine, with amitriptyline and paroxetine, among the drugs with the greatest risk of weight gain, while bupropion and short-term fluoxetine tended toward loss; it included non-placebo-controlled studies and is graded conservatively in the library [serretti-2010]. the 17-trial placebo-controlled meta-analysis put the relative risk at 4.75 [kamp-2025]. the cochrane comparison found more weight gain or increased appetite than on ssris [watanabe-2011]. nothing in the label or the library says the weight comes back off.

the other warnings, in plain words

the warnings section runs from 5.1 to 5.15. the label describes mirtazapine as an antagonist at alpha-2 adrenergic, serotonin 5-ht2 and 5-ht3, histamine h1, peripheral alpha-1 and muscarinic receptors, and says its mechanism in depression "is unclear" [label 12.1, 12.2]. beyond those above:

• agranulocytosis [5.2]: in the premarketing trials, 2 of 2,796 people developed agranulocytosis (a white-cell count below 500 with fever or infection) and a third developed severe neutropenia without symptoms, detected on days 61, 9 and 14; all three recovered after stopping. the label’s instruction: "if a patient develops a sore throat, fever, stomatitis, or other signs of infection, along with a low white blood cell count, treatment with mirtazapine should be discontinued". that is about one in a thousand in the trials, and it is a stop-and-test instruction to the prescriber, not routine monitoring.
• serotonin syndrome and maois [4, 5.3, 2.4]: too much serotonin signalling, with agitation, hallucinations or delirium, racing heart, swinging blood pressure, sweating, fever, tremor, rigidity, muscle jerking, overactive reflexes, seizures, nausea and diarrhoea. the risk rises with triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines and st john’s wort, and it can occur on mirtazapine alone. use with an maoi, including the antibiotic linezolid and intravenous methylene blue, is contraindicated within 14 days either way.
• severe skin reactions [4, 5.6]: drug reaction with eosinophilia and systemic symptoms (dress), stevens-johnson syndrome and toxic epidermal necrolysis have been reported after approval, and dress "is sometimes fatal"; the contraindication was added in november 2021 [label, recent major changes]. the instruction is to stop immediately if dress is suspected.
• heart rhythm [5.5]: a 54-volunteer study found a relationship between mirtazapine concentration and qt prolongation, but at 45 mg and at 75 mg, 1.67 times the maximum dose, the prolongation "was not at a level generally considered to be clinically meaningful". after approval, qt prolongation, torsade de pointes, ventricular tachycardia and sudden death have been reported, mostly in overdose or in people with other risk factors or on other qt-prolonging drugs. the label asks for caution in known heart disease or a family history of long qt. in the trials, heart rate rose a mean 3.4 beats a minute against 0.8 [6.1].
• low blood pressure and heart disease [5.15]: significant orthostatic hypotension in early volunteer studies, infrequent in depressed patients; the drug "has not been systematically evaluated" in people with a recent heart attack or other significant heart disease.
• mania [5.9]: treating a depressive episode in someone with bipolar disorder can precipitate a mixed or manic episode; mania or hypomania was reported in 0.2% of trial patients, with bipolar disorder generally excluded; the label asks for screening first [2.3].
• seizures [5.10]: one seizure among 2,796 trial patients; caution in a seizure disorder.
• low sodium [5.12]: hyponatremia, with cases below 110 mmol/l, usually from inappropriate antidiuretic hormone secretion; signs are headache, poor concentration, memory impairment, confusion, weakness and unsteadiness "which may lead to falls"; older people and people on diuretics are at greater risk [8.5].
• liver [5.13]: alt rising to three times the upper limit of normal in 2.0% (8 of 424) against 0.3% (1 of 328); in some people the enzymes returned to normal on continued treatment. clearance is about 30% lower in liver impairment and 30% to 50% lower in kidney impairment, and 75% of the drug leaves by the kidney [12.3].
• glaucoma [5.4]: pupil dilation can trigger an angle-closure attack in an eye with untreated narrow angles.
• benzodiazepines and alcohol [5.8, 7]: the impairment of thinking and motor skills "produced by mirtazapine alone" is additive with alcohol and with diazepam, and the label says to avoid both; alcohol did not change blood levels, the impairment is pharmacodynamic [12.3].
• other drugs [7, 2.5]: carbamazepine and phenytoin roughly double clearance and cut blood levels by 60% and 45%; ketoconazole raises exposure by about 50%; cimetidine by more than 50%; the label says the dose may need to move with each. warfarin: a 0.2 rise in inr, so monitor. lithium and amitriptyline: no relevant change either way; mirtazapine did not change the levels of paroxetine or risperidone.
• pregnancy and breastfeeding [8.1, 8.2]: "prolonged experience with mirtazapine in pregnant women, based on published observational studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes"; animal studies found no malformations at up to 20 times the human dose, with more pup deaths at that dose. in breast milk the relative infant dose was 0.6% to 2.8% in 8 mother-infant pairs, with no adverse effects reported in the infants.
• older people [8.5, 12.3]: about 190 trial patients were 65 or over; clearance was 40% lower in older men and 10% lower in older women; the label warns of confusion and over-sedation and asks for a low starting dose.
• post-marketing reports [6.2]: torsade de pointes, raised prolactin with milk production and breast enlargement, rhabdomyolysis, sleepwalking "and other complex behaviors out of bed", priapism, and the severe skin reactions above. these are voluntary reports, and the label says their frequency and cause cannot be established from them.

what the label says about its own trials

efficacy "was established in 4 placebo-controlled, 6-week trials in adult outpatients", dosed from 5 to 35 mg a day with a mean completer dose of 21 to 32 mg; overall the drug beat placebo "on at least 3 of the following 4 measures", the 21-item hamilton scale, its depressed-mood item, the clinical global impression and the montgomery-asberg scale [label 14]. the label does not report how many people were in each trial or the size of any difference; the adverse-reaction tables indicate the pooled us 6-week trials covered 453 people on mirtazapine against 361 on placebo [label 6.1]. a relapse-prevention study randomised people who had responded over 8 to 12 weeks to continued drug or placebo for up to 40 weeks, with "relapse during the double-blind phase ... determined by the individual investigators", and found lower relapse on the drug [label 14]. the dosing section describes 15 mg at night rising to a maximum of 45 mg, with changes no closer together than one to two weeks [label 2.1]. the label says no more than that, and the approval record on drugs@fda is linked below [approval].

side effects, with the label’s numbers

the label’s one-line summary: the most common reactions, at 5% or more and twice the placebo rate, are "somnolence, increased appetite, weight gain, and dizziness" [label 6]. among the 453 people on mirtazapine against 361 on placebo in the 6-week us trials: somnolence 54% against 18%, dry mouth 25% against 15%, increased appetite 17% against 2%, constipation 13% against 7%, weight gain 12% against 2%, asthenia 8% against 5%, dizziness 7% against 3%, flu syndrome 5% against 3%, abnormal dreams 4% against 1%, abnormal thinking 3% against 1%, tremor, back pain, myalgia, peripheral edema and urinary frequency 2% against 1%, confusion 2% against 0% [label 6.1, tables 3 and 4]. about 16% stopped for a side effect against 7% on placebo, somnolence (10.4% against 2.2%) and nausea (1.5% against 0%) being the reasons at twice placebo [label 6.1, table 2]. the label gives no figures by dose.

sexual side effects are not in the label’s tables; "impotence" appears as an infrequent trial report and "abnormal ejaculation" as rare [label 6.1], and raised prolactin with milk production and breast enlargement, and priapism, are post-marketing reports [label 6.2]. the independent record is more informative: when sexual function was measured by questionnaire across antidepressant trials, mirtazapine was among the drugs with no significant difference from placebo, while the ssris and venlafaxine ran from 26% to 80% [serretti-2009], and the cochrane comparison found less sexual dysfunction than on ssris [watanabe-2011]. this site’s page on the sexual side effects of antidepressants has the detail [ssri-sexual].

the discontinuation syndrome

warning 5.14 lists what has followed stopping mirtazapine, particularly abruptly: dizziness, abnormal dreams, sensory disturbances including tingling and electric-shock sensations, agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting and sweating. "a gradual reduction in the dosage, rather than an abrupt cessation, is recommended" [label 5.14, 2.6]. the label gives no schedule, no step size and no duration. the uk guideline for medicines associated with withdrawal says to taper in steps proportionate to the current dose, so the steps shrink as the dose falls, and that withdrawal "may take several months or more" [nice-2022]. in 2019 the royal college of psychiatrists conceded that for some people antidepressant withdrawal is severe and lasts longer than guidelines had said, and asked for tapering at a rate the patient can tolerate, potentially over several months, while stating that antidepressants are not associated with dependence in the addiction sense [rcpsych-2019]. none of this is a reason to stop; it is the reason the label says not to stop abruptly.

what the research says about the approved use, in both directions

in favour. in the network meta-analysis of 522 trials covering 116,477 adults with major depression, mirtazapine was one of seven antidepressants, of 21, that proved more effective than the others in head-to-head comparisons (odds ratios for that group 1.19 to 1.96), with a dropout rate about average; the analysis was publicly funded, most of the underlying trials were industry-funded, and several authors disclosed pharmaceutical fees [cipriani-2018]. the cochrane review of 29 trials found a faster response than ssris at two weeks and a small edge at six to twelve weeks [watanabe-2011]. in the sexual-function comparison it sat with the drugs no different from placebo [serretti-2009].

against, or smaller than it sounds. the one large placebo-controlled trial of the way mirtazapine is now most often added in practice found nothing: in 480 primary-care patients still depressed after at least six weeks on an ssri or snri, adding mirtazapine gave no clinically important benefit over adding placebo at 12 weeks (a difference of 1.83 points on the beck inventory, confidence interval crossing zero), and 46 people on mirtazapine against 9 on placebo stopped because of adverse effects [kessler-2018]. the side-effect meta-analysis found the weight and somnolence risks above and an unconfirmed signal on serious adverse events [kamp-2025]. the label’s own trial record is four 6-week trials reported without per-trial numbers [label 14]. the cochrane review’s early-response advantage came with more sleepiness and weight gain [watanabe-2011].

the warnings, measured. the suicidality warning’s size is the label’s table: 14 extra cases per 1,000 under 18, 5 at 18 to 24, none above [label 5.1]. the weight warning’s size is 7.5% against 0% gaining 7% or more in six weeks, 49% against 5.7% in children, and a relative risk of 4.75 across 17 trials [label 5.7; kamp-2025]. the somnolence warning’s size is 54% against 18% and a one-in-ten dropout for it [label 5.8; 6.1]. the agranulocytosis warning’s size is three people in 2,796 [label 5.2].

questions people ask

what does the remeron (mirtazapine) black box warning mean?

it is the antidepressant class warning. in pooled placebo-controlled trials of antidepressants covering about 77,000 adults and 4,500 children, suicidal thoughts and behaviors increased in people under 25: 14 extra cases per 1,000 treated under 18 and 5 extra at 18 to 24, against 1 fewer at 25 to 64 and 6 fewer at 65 and over. the box also says mirtazapine is not approved for anyone under 18; the label reports two pediatric trials in 258 children whose data were insufficient to establish safety or effectiveness, and in one of them 49% of children gained at least 7% of their body weight in eight weeks. the warning says to watch everyone starting an antidepressant, especially in the first months and after dose changes. it describes thoughts and behaviors, not deaths.

is mirtazapine approved for sleep or for appetite?

no. the label approves mirtazapine for one condition, major depressive disorder in adults. insomnia and poor appetite are not approved uses, and no sleep or appetite trial appears anywhere on the label; the library holds none either. what the label has is the instruction to take it in the evening before sleep, somnolence in 54% of trial patients against 18% on placebo, and increased appetite in 17% against 2%, which are side effects recorded in depression trials. off-label prescribing is legal and common; what it means here is that the fda has never reviewed evidence that mirtazapine works for sleep or appetite in people who are not depressed, and the evidence that exists is the side-effect data and the comparisons against ssris in depression.

does mirtazapine cause weight gain?

yes, by the label’s own numbers and by every independent comparison in the library. in six-week trials, 7.5% of people on mirtazapine gained 7% or more of body weight against 0% on placebo, increased appetite was 17% against 2%, and in longer studies 8% stopped for weight gain; in one pediatric trial 49% of children gained 7% or more against 5.7%. cholesterol rose to 20% above normal in 15% against 7%. across 17 placebo-controlled trials the relative risk of weight gain was 4.75, about one extra person affected for every ten treated, and a review of 116 studies placed mirtazapine with amitriptyline and paroxetine among the antidepressants with the greatest weight gain. nothing in the label or the library says the weight comes back off while on the drug.

what are the most common mirtazapine side effects?

in the label’s six-week trials, 453 people on mirtazapine against 361 on placebo: somnolence 54% vs 18%, dry mouth 25% vs 15%, increased appetite 17% vs 2%, constipation 13% vs 7%, weight gain 12% vs 2%, asthenia 8% vs 5%, dizziness 7% vs 3%, abnormal dreams 4% vs 1%, abnormal thinking 3% vs 1%, confusion 2% vs 0%. about 16% stopped for a side effect against 7%, most often for somnolence (10.4% vs 2.2%). the label’s own summary of reactions at twice placebo is somnolence, increased appetite, weight gain and dizziness. it gives no figures by dose. sexual side effects were not measured in the label’s tables; independent comparisons found mirtazapine no different from placebo on that measure and better than ssris.

does mirtazapine cause sexual side effects?

less than most antidepressants, on the evidence in the library. when sexual function was measured by questionnaire across antidepressant trials rather than waited for as a complaint, mirtazapine was among the drugs with no significant difference from placebo, while sertraline, venlafaxine, citalopram and paroxetine headed a list running from 26% to 80% of patients affected; the cochrane comparison of 29 trials found less sexual dysfunction than on ssris. the label itself records impotence as an infrequent trial report, abnormal ejaculation as rare, and priapism and raised prolactin with milk production and breast enlargement as post-marketing reports without a rate.

what happens if you stop mirtazapine suddenly?

the label lists a discontinuation syndrome, particularly after abrupt stopping: dizziness, abnormal dreams, tingling and electric-shock sensations, agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting and sweating, and it recommends a gradual reduction whenever possible. it gives no schedule. the uk guideline says to taper in steps that shrink as the dose falls and that withdrawal may take several months or more, and the royal college of psychiatrists said in 2019 that for some people antidepressant withdrawal is severe and long. the two situations in which the label itself tells a patient to stop are the symptoms of serotonin syndrome and a suspected severe skin reaction, both as emergencies, and it tells the prescriber to stop the drug if a low white-cell count comes with signs of infection. anything else is a prescriber conversation.

does mirtazapine work for depression?

yes, on the trial record, and better than average against other antidepressants. the label describes four placebo-controlled six-week trials in which it beat placebo on at least three of four rating measures, without giving the numbers. in the network meta-analysis of 522 trials and 116,477 adults, mirtazapine was one of seven of 21 antidepressants that proved more effective in head-to-head comparisons, with about average dropout; the cochrane review of 29 trials found a faster response than ssris at two weeks with a small edge remaining at six to twelve weeks. the clear negative is the add-on use: in 480 primary-care patients still depressed on an ssri or snri, adding mirtazapine gave no clinically important benefit over placebo at 12 weeks and five times the dropout for side effects.

how is mirtazapine different from trazodone or sertraline?

all three carry the same boxed warning and the same not-approved-under-18 line. the label facts that differ: mirtazapine’s somnolence (54%), appetite (17%) and weight figures are the largest of the three, its sexual side-effect profile is the mildest, and it carries an agranulocytosis warning and a severe skin reaction contraindication the others do not; trazodone carries the priapism and heart-rhythm warnings and the same unapproved status for sleep. the trazodone and sertraline labels each have their own explainer on this site [trazodone-explainer; sertraline-explainer], and the drugs are compared side by side on the comparison pages [compare-trazodone; compare-sertraline]. nothing in any of the labels is a reason to prefer one drug; that is a prescriber’s decision.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

1. mirtazapine tablets prescribing information, fda label on dailymed (set id e38c96d4-ea33-3f1a-e053-2a95a90a0903, version 2, effective august 26, 2026; nucare pharmaceuticals, anda 076921): boxed warning; sections 1, 2.1 to 2.6, 4, 5.1 to 5.15 with table 1, 6, 6.1 tables 2 to 4, 6.2, 7 table 5, 8.1, 8.2, 8.4, 8.5, 10, 12.1 to 12.3, 14; recent major changes
2. drugs@fda, nda 020415 (remeron, organon), approved june 14, 1996
3. ahrq medical expenditure panel survey, prescribed medicines public-use files 2014 (hc-168a) and 2024 (hc-254a): people with at least one mirtazapine purchase and prescriptions, weighted; the 2014 to 2024 prescription change is within the survey’s margin of error; computed by veisund, method on the usage section of this page
4. the antidepressant suicidality warning’s age ceiling, from the labels themselves, as a library row (library row)
5. national institute for health and care excellence. medicines associated with dependence or withdrawal symptoms (ng215), 2022 (library row)
6. royal college of psychiatrists. position statement on antidepressants and depression (ps04/19), 2019 (library row)
7. cipriani a, et al. comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. lancet 2018 (library row)
8. watanabe n, et al. mirtazapine versus other antidepressive agents for depression. cochrane database of systematic reviews 2011 (29 trials, 4,974 participants) (library row)
9. kessler ds, et al. mirtazapine added to ssris or snris for treatment resistant depression in primary care: phase iii randomised placebo controlled trial (mir). bmj 2018 (480 participants) (library row)
10. kamp cb, et al. the risks of adverse events with mirtazapine for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis. bmc psychiatry 2025 (17 trials, 2,131 participants; the library record notes the authors’ disclosed deprescribing interests) (library row)
11. serretti a, mandelli l. antidepressants and body weight: a comprehensive review and meta-analysis. journal of clinical psychiatry 2010 (116 studies; graded conservatively in the library) (library row)
12. serretti a, chiesa a. treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. journal of clinical psychopharmacology 2009 (library row)
13. the sexual side effects of antidepressants, a separate evidence page on this site
14. what the trazodone (desyrel) warnings mean, the companion explainer on this site for the other antidepressant most often prescribed for sleep, also not an approved use
15. what the sertraline (zoloft) warnings mean, the companion explainer on this site
16. mirtazapine vs trazodone, the side-by-side comparison page on this site
17. mirtazapine vs sertraline, the side-by-side comparison page on this site

Weight gain on the mirtazapine label

The mirtazapine FDA label names weight gain in its Adverse Reactions section, in the list below.

Most-reported reactions

• Nausea5,028
• Fatigue4,903
• Drug ineffective4,788
• Fall4,168
• Diarrhoea4,114
• Off label use3,998
• Toxicity to various agents3,837
• Dizziness3,586
• Anxiety3,582
• Dyspnoea3,535