Mirtazapine vs Trazodone for Depression and Sleep

Mirtazapine (Remeron) and trazodone are both FDA-approved antidepressants for major depression in adults, and both are sedating, which is why they are so often prescribed at bedtime. Neither is FDA-approved for insomnia, so using either one for sleep alone is off-label, even though antidepressant use for insomnia is widespread. The main trade-offs are weight and appetite with mirtazapine, and dizziness on standing, heart rhythm and a rare risk of priapism with trazodone.

Which one fits depends on whether depression, sleep or both is the main target, your weight and metabolic health, your heart history and your other medicines. That judgment belongs with your prescriber; this guide lays out what the evidence and the FDA labels actually say.

Mirtazapine and trazodone at a glance

Dose ranges above are what the labels describe for depression and are set by the prescriber; they are not instructions.

As antidepressants: how they compare

For depression itself, the evidence favors mirtazapine. In the 2018 network meta-analysis of 522 trials and 116,477 adults, all 21 antidepressants beat placebo, but in head-to-head trials mirtazapine was among the more effective drugs, while trazodone was among the least efficacious and among those with the highest dropout rates. The certainty of the evidence was rated moderate to very low, so these are tendencies rather than verdicts.

Trazodone's labeled dosing for depression starts at 150 mg a day in divided doses, well above the low doses used off-label at bedtime. Its heart rhythm warning is not limited to high doses: the label notes torsade de pointes has been reported at doses of 100 mg or less. A Cochrane review describes antidepressant use for insomnia as widespread even though none is licensed for it.

Prescribers may consider mirtazapine when depression comes with poor sleep, poor appetite or weight loss, given its labeled sleepiness and appetite effects, or when sexual side effects on an SSRI or SNRI have been a problem. A meta-analysis found that mirtazapine, like bupropion, did not differ significantly from placebo in rates of sexual dysfunction, unlike most SSRIs and SNRIs. For where these drugs sit among other first choices, see SSRI, SNRI or bupropion and depression treatment options compared.

For sleep: what the evidence does and does not show

Many people are prescribed one of these drugs "for sleep," so it is worth being precise. Neither is FDA-approved for insomnia. A Cochrane review of antidepressants for insomnia noted that none is licensed for the condition and that the evidence for their efficacy was unclear. Pooling three trazodone studies with 370 participants, it found a moderate improvement in self-reported sleep compared with placebo, but sleep studies showed little or no difference in sleep efficiency, and there was low-quality evidence of more side effects such as morning grogginess and dry mouth. The review found no evidence for long-term antidepressant use for insomnia, and its "other antidepressants" trials covered trazodone and mianserin rather than mirtazapine.

The American Academy of Sleep Medicine's 2017 guideline on drugs for chronic insomnia suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia, a weak recommendation based on its review of the evidence. The American College of Physicians recommends cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia in all adults, a strong recommendation.

What this means in practice

• If insomnia is the main problem and depression is not present, CBT-I is the first-line treatment, and a sedating antidepressant is not the standard starting point. See insomnia treatment options compared and sleep medications compared.
• If depression and insomnia occur together, a sedating antidepressant prescribed for the depression may also help sleep, and the insomnia still deserves its own attention. This article on sleep and depression explains why.
• If you have taken low-dose trazodone for years, it is reasonable to ask whether it is still helping and whether CBT-I could replace or reduce it. Do not stop on your own; the label recommends gradual reduction.
• Snoring, gasping or daytime sleepiness despite enough time in bed can point to sleep apnea, which no sedative fixes. This guide helps you tell the difference.

Weight, appetite and metabolic effects

This is mirtazapine's most important downside. In U.S. controlled trials, increased appetite was reported in 17% of people taking mirtazapine compared with 2% on placebo, and weight gain of at least 7% of body weight in 7.5% compared with 0% on placebo. In a broader pool of studies including long-term use, 8% of people stopped mirtazapine because of weight gain. Nonfasting cholesterol rose to at least 20% above the upper limit of normal in 15% of people on mirtazapine compared with 7% on placebo.

Trazodone's label lists weight loss, not gain, among its most common adverse reactions in trials. For someone with diabetes, prediabetes, obesity or high triglycerides, that difference often matters more than any other.

The appetite effect can be useful. For an older adult who has stopped eating, or someone whose depression has caused weight loss, mirtazapine's appetite boost may be part of the reason it is chosen. If you start mirtazapine, ask your prescriber whether weight and cholesterol should be tracked, and a plan for food and activity makes it easier to catch changes early. See managing antidepressant weight changes and psychiatric medications and metabolic health.

Safety warnings that set them apart

Trazodone: priapism, heart rhythm and dizziness

Trazodone's label warns of priapism, a painful erection lasting more than 6 hours that can cause permanent damage if not treated promptly. Any erection lasting more than 4 hours, painful or not, needs emergency care. The label advises caution in men with conditions such as sickle cell anemia, multiple myeloma, leukemia or Peyronie's disease.

Trazodone prolongs the QT interval. The label notes it may be arrhythmogenic in people with preexisting heart disease and that torsade de pointes has been reported at doses of 100 mg or less, so it should be avoided with other QT-prolonging drugs and strong CYP3A4 inhibitors such as clarithromycin, itraconazole and voriconazole. Its alpha-1 blocking effect can cause orthostatic hypotension and fainting, and people on blood pressure medicines may need adjustments.

Mirtazapine: blood counts, QT and sedation

In premarketing trials, 2 of 2,796 people on mirtazapine developed agranulocytosis, a dangerous drop in white blood cells, and a third developed severe neutropenia. It is rare, but sore throat, fever, mouth sores or other signs of infection should be reported promptly. Mirtazapine also carries a QT prolongation caution for people with risk factors.

Sedation is common: in U.S. controlled studies, somnolence was reported in 54% of people on mirtazapine compared with 18% on placebo, and the label says it is unclear whether tolerance develops. Both drugs can impair driving, and both add to the effects of alcohol and other sedatives; psychiatric medications and alcohol covers this in detail.

Older adults

Both drugs are used in older adults, and both need care. Mirtazapine's label notes that sedating drugs may cause confusion and over-sedation in the elderly, that clearance was lower in older people in a pharmacokinetic study, and that older adults may be at greater risk of low sodium. Trazodone's label says experience in the elderly is limited and advises caution. Both labels note that low sodium can cause unsteadiness that may lead to falls, and trazodone's label warns of orthostatic hypotension and fainting, so night-time trips to the bathroom deserve thought. For an aging parent, see geriatric psychiatry for aging parents.

Children and teens

Neither drug has established safety and effectiveness in children or adolescents. In an 8-week pediatric trial, 49% of young people on mirtazapine gained at least 7% of their body weight, compared with 5.7% on placebo. Both carry the boxed warning about suicidal thoughts and behaviors in young people. For teen depression, our parent's guide covers the medications with stronger pediatric evidence.

Using one with another antidepressant

Either may be added to an SSRI or SNRI: trazodone mostly for sleep, mirtazapine for sleep, appetite or as an augmentation strategy. Combining serotonergic drugs raises the risk of serotonin syndrome, which both labels describe, so combinations should be deliberate and monitored. As an augmentation strategy for depression that has not responded, the evidence for adding mirtazapine is mixed: in a UK primary care trial of 480 adults still depressed on an SSRI or SNRI, adding mirtazapine did not produce a clinically important benefit over placebo, and side effects were more common. Stronger-evidence add-on options are compared in antidepressant augmentation options.

Stopping either one

Both labels recommend reducing the dose gradually rather than stopping abruptly, because discontinuation symptoms can occur. Mirtazapine's half-life is about 20 to 40 hours. Insomnia is among the discontinuation symptoms the trazodone label lists, which is easier to manage when it is expected and paired with behavioral sleep strategies. Plan any change with the prescriber; discontinuing long-term medication explains the general approach.

Common scenarios and how they tend to play out

These are starting points for a discussion, not rules. A drug that has worked well for you before, or one that has caused trouble, usually weighs more than any table.

Questions to ask your prescriber

• Is the goal here to treat depression, insomnia or both, and does that change which drug makes sense?
• Given my weight, cholesterol or blood sugar, is mirtazapine's appetite effect a problem for me?
• Do I need an ECG, given my heart history or my other medications?
• Would CBT-I be a better first step, or something to add?
• How will we judge whether this is working, and when would we reconsider?
• If I want to stop later, how would we taper?

Never start, stop or change the dose of a prescription sleep or antidepressant medication on your own. If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.

How the practice approaches depression with poor sleep

Dr. Lewis's practice offers psychiatric evaluation and medication management together with psychotherapy, including CBT, and nutrition and lifestyle psychiatry, so a sleep complaint can be addressed with more than a prescription. You can read about medication management or start with a free discovery call to talk through care options. Other medication comparisons are collected in the Choosing Psychiatric Care guide.

Frequently asked questions

Is low-dose trazodone addictive?

Trazodone's label states that it is not a controlled substance and that no drug-seeking behavior was seen in its clinical studies. The label does describe discontinuation symptoms and recommends tapering rather than stopping abruptly. For chronic insomnia, CBT-I is the recommended first treatment.

Can I take trazodone with my SSRI?

Prescribers sometimes combine them, but the combination adds serotonergic load, and the trazodone label warns about serotonin syndrome with other serotonergic drugs, SSRIs included. Your prescriber should know every medicine and supplement you take, and you should report agitation, fever, sweating, tremor or confusion promptly.

Can mirtazapine cause serotonin syndrome?

Its label says the risk is increased when it is combined with other serotonergic drugs such as SSRIs, SNRIs and triptans, but that it can also occur when mirtazapine is taken alone, and it must not be combined with MAOIs. Seek care urgently for agitation, fever, sweating, muscle stiffness or confusion.

What is RemeronSolTab?

It is an orally disintegrating tablet form of mirtazapine that dissolves on the tongue. The label says to use it immediately after removing it from the blister pack, because it cannot be stored once removed.

Does mirtazapine help anxiety?

Mirtazapine is FDA-approved only for major depression. It is sometimes used when anxiety accompanies depression, but that is not a labeled indication. See anxiety treatment options compared for options with stronger evidence.

Sources

1. REMERON (mirtazapine) tablets and REMERONSolTab orally disintegrating tablets prescribing information. Organon via DailyMed (U.S. National Library of Medicine), 2025. dailymed.nlm.nih.gov
2. Trazodone hydrochloride tablets prescribing information. DailyMed (U.S. National Library of Medicine), 2026. dailymed.nlm.nih.gov
3. 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. The Lancet (Cipriani et al.), 2018. pubmed.ncbi.nlm.nih.gov
4. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. Journal of Clinical Psychopharmacology (Serretti and Chiesa), 2009. pubmed.ncbi.nlm.nih.gov
5. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine (Sateia et al.), 2017. pubmed.ncbi.nlm.nih.gov
6. Antidepressants for insomnia in adults. Cochrane Database of Systematic Reviews (Everitt et al.), 2018. pubmed.ncbi.nlm.nih.gov
7. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine (Qaseem et al.), 2016. pubmed.ncbi.nlm.nih.gov
8. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). BMJ (Kessler et al.), 2018. pubmed.ncbi.nlm.nih.gov

Educational information, not medical, tax or legal advice. Decisions about diagnosis, medication and treatment belong with a clinician who knows your history.