Trazodone vs Mirtazapine

How they're similar

Trazodone and mirtazapine are close in many ways. Both are classed as atypical antidepressants, a label that simply means they don't fit the common SSRI or SNRI categories.

• Both are antidepressants, and both are FDA-approved for major depressive disorder.
• Both are sedating, and both are commonly used to help with sleep, often taken at bedtime.
• Both improve sleep quickly. The sedation comes from blocking histamine and arrives the first nights, while the fuller antidepressant effect on mood takes about four to six weeks.
• Both carry the antidepressant FDA boxed warning about suicidal thoughts and behaviors in children, teenagers, and young adults under 25.
• Both are not controlled substances and are not habit-forming.
• Both tend to avoid the sexual side effects associated with SSRIs.
• Both are available as inexpensive generics.

That is a lot of shared ground. Both can do two jobs at once, helping sleep right away and lifting mood over the following weeks, and neither carries the dependence risk that comes with benzodiazepines or z-drugs.

How they differ

For two drugs with so much in common, the differences are narrow. The main one is weight and appetite. The table below sums up the core points, with more detail underneath.

The central difference is weight and appetite. Mirtazapine commonly increases appetite and causes weight gain, an effect tied to its strong blocking of histamine. Trazodone is relatively weight-neutral, which sets it apart from some other antidepressants. For someone who wants to avoid weight gain, that difference favors trazodone. For someone whose depression includes poor appetite and weight loss, mirtazapine's appetite effect can be a deliberate benefit rather than a problem, since gaining back lost weight is part of recovery.

How each drug is used in practice differs too. Trazodone is most often used today purely as a low-dose sleep aid, with its formal approval for depression taking a back seat to that everyday role. Mirtazapine is more often used as a full antidepressant that also happens to help sleep, so it is more commonly the main treatment for depression rather than a sleep add-on.

There is a dosing quirk worth knowing. Mirtazapine can be more sedating at lower doses than at higher ones, so a prescriber may actually raise the dose if daytime drowsiness is a problem. Trazodone's sedation tracks the dose in the usual way, with more sedation at higher doses.

The distinctive risks differ. Trazodone carries a rare risk of priapism, a prolonged and painful erection that is a medical emergency, and it can lower blood pressure on standing, which can cause dizziness or falls. Mirtazapine carries a rare risk of lowered infection-fighting white blood cells, so signs of infection such as fever or sore throat should be reported, and it can raise cholesterol and triglycerides, which a prescriber may monitor.

Side effects compared

The side effects of these two overlap, because both are sedating antidepressants. Both commonly cause drowsiness and sedation, dizziness, and dry mouth, more so early in treatment. Both can cause discontinuation symptoms if stopped abruptly, since the body adjusts to them, so both are best tapered with a prescriber rather than stopped suddenly.

Past that shared ground, the side effect profiles diverge in the ways already described. Mirtazapine's increased appetite and weight gain are prominent and are a main reason some people find it hard to stay on. Trazodone's weight-neutral profile avoids that, but it brings the cautions around priapism and a drop in blood pressure on standing. Mirtazapine causes less nausea than SSRIs, which is sometimes a point in its favor. With either drug, a side effect that is severe or not improving is a conversation to have with a prescriber.

Sleep, weight, and sexual effects

On sleep, the two are alike. Both are sedating because they block histamine, both are usually taken at bedtime, and both help with sleep from the first nights. The dose relationship is the wrinkle, since mirtazapine can be more sedating at lower doses than higher ones, while trazodone's sedation tracks the dose in the usual way.

Weight is where they part. Mirtazapine commonly increases appetite and leads to weight gain. Trazodone is relatively weight-neutral. For someone who wants to avoid weight gain, that favors trazodone, and for someone whose depression includes poor appetite and weight loss, mirtazapine's appetite effect can be a deliberate benefit. On sexual effects, both tend to avoid the reduced sex drive and delayed orgasm associated with SSRIs, which is often a point in favor of either one. The exception worth knowing is priapism with trazodone, the rare prolonged erection that is a medical emergency. Anything bothersome in these areas is worth raising with a prescriber.

Why a clinician might choose one over the other

Because the two are close, the choice often comes down to weight and to what the main target of treatment is.

A clinician might choose trazodone when sleep is the main target and weight gain is unwanted. It is often used as a low-dose sleep aid, and its weight-neutral profile makes it a comfortable longer-term option for someone who wants to avoid the appetite increase that mirtazapine tends to bring.

A clinician might choose mirtazapine when depression comes with insomnia plus poor appetite or weight loss, where the appetite increase actually helps recovery rather than working against it. It can also be a good fit when a sedating antidepressant is wanted as the main treatment for depression and some weight gain is acceptable.

Prior response matters too. Someone who has done well on one of these drugs has a reasonable reason to stay with it. The fuller picture, including the specific shape of a person's depression and sleep, is what a prescriber weighs.

The bottom line

Trazodone and mirtazapine are both sedating antidepressants used to help with sleep, and they share a lot, including quick sleep benefit, the antidepressant boxed warning, no dependence risk, and inexpensive generics. The key difference is weight. Mirtazapine commonly increases appetite and causes weight gain, while trazodone is relatively weight-neutral. That difference, along with whether sleep or full depression treatment is the main goal, usually guides the choice, and it is made with a prescriber.

Common questions

Which one causes more weight gain? Mirtazapine. It commonly increases appetite and leads to weight gain, an effect tied to its strong blocking of histamine. Trazodone is relatively weight-neutral. If avoiding weight gain matters, that difference favors trazodone, and it is worth raising with a prescriber.

Are trazodone and mirtazapine in the same class? Both are classed as atypical antidepressants, a label meaning they don't fit the common SSRI or SNRI categories. They are not identical, but they are relatives, and both are sedating and commonly used to help with sleep.

Do either of them cause dependence? Neither is a controlled substance, and neither is habit-forming in the way benzodiazepines or z-drugs are. The body does adjust to both, so stopping either one is best done as a gradual taper with a prescriber.

Which is better for depression with insomnia? It depends on appetite and weight. If depression comes with poor appetite and weight loss, mirtazapine's appetite increase can be a deliberate benefit. If weight gain is unwanted and sleep is the main target, trazodone is often the better fit. A prescriber matches the drug to the picture.

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.

1. U.S. Food and Drug Administration. Trazodone prescribing information.
2. U.S. Food and Drug Administration. Mirtazapine prescribing information.
3. MedlinePlus, U.S. National Library of Medicine.
4. National Institute of Mental Health. Mental health medications.