Buspirone for Depression: What the Evidence Says

Key takeaways

Buspirone’s role in depression treatment

Buspirone (Buspar) is not a standard treatment for depression on its own. It is a prescription medicine approved for anxiety, and prescribers use it for depression off-label, almost always added to an antidepressant that has helped a little. That add-on use is what nearly every mention of buspirone for depression means.

Buspar is the brand name for buspirone, and the two are the same medicine.

Adding a second medicine to an antidepressant that is working partly has a name in psychiatry: augmentation. The antidepressant stays, and something else goes alongside it.

This is not a decision to make alone. Buspirone is prescription-only, and whether an add-on belongs in your treatment sits with whoever manages your depression care.

Is buspirone an antidepressant?

Buspirone (Buspar) is not an antidepressant. It is an anxiolytic, or anti-anxiety medicine, from the azapirone drug class. The FDA has approved it only for anxiety disorders, based on studies in generalized anxiety disorder. In depression it is used off-label, added to an antidepressant that is helping only partly.

The distinction is practical. Antidepressants like sertraline and escitalopram are SSRIs; venlafaxine and duloxetine are SNRIs. Both classes were developed and tested for depression, and carry FDA approval for it. Buspirone was developed and approved for anxiety.

So why does it keep coming up when people talk about depression? Because of the add-on role: when an antidepressant lifts someone part of the way and stalls, a prescriber has a short list of add-ons to consider, and buspirone has been on it since the 1990s.

Off-label prescribing is legal and common: once the FDA approves a drug, clinicians may prescribe it for a use it was not approved for. It also means the FDA has not found the drug safe and effective for that use.

How buspirone works

Buspirone is a partial agonist at the 5-HT1A serotonin receptor. A partial agonist switches a receptor on, but only part of the way. So it acts on one serotonin receptor rather than changing how much serotonin is available overall.

That matters because an SSRI does something different, blocking serotonin from being reabsorbed and raising the amount circulating between nerve cells. Each works at a different point in the same system, which is the argument for using them together instead of swapping one for the other.

Buspirone also does not act at the brain receptors benzodiazepines work on, which is why it behaves so unlike a benzodiazepine. It is not a controlled substance and has shown no potential for abuse. It is less sedating than the older anti-anxiety medicines too, though it is slow to act, taking weeks rather than days. It also does not block benzodiazepine withdrawal, so it is not a stand-in for one.

Making sense on paper is not proof that a drug helps. Plenty of promising drugs have failed in trials.

What the research shows about buspirone and depression

Buspirone (Buspar) has not been shown to treat depression reliably. The evidence for using it on its own rests on one small trial from 1991, in people who had depression plus a lot of anxiety. As an add-on to an antidepressant, it did not beat placebo in the trials that tested it.

The 1991 controlled trial is the one most often quoted. It reported that 70% of the people taking buspirone and 35% of those taking placebo were rated moderately or markedly improved after eight weeks. Everyone in it had major depression alongside moderate anxiety, so it is unclear how much came from the anxiety easing. A 2014 systematic review counted only four placebo-controlled buspirone trials in depression anywhere.

The add-on evidence is larger and less encouraging. The best-known is STAR*D, a 2006 study of 565 people whose depression had not gone into remission on citalopram. Its results sit in the table below with the double-blind trials that tested buspirone against placebo. The other add-on in STAR*D was bupropion, better known as Wellbutrin.

The honest summary is that buspirone is neither a first-line treatment for depression nor a proven one. It carries no dependence risk and is reasonable to try in some situations, though the dropout figures above show it is not always easy to tolerate. Add-ons with better evidence exist: the CANMAT depression guidelines name adding an atypical antipsychotic as the option with the most consistent evidence.

Who buspirone may help, and what else prescribers consider

In our practice, the conversation about adding buspirone starts in one of two situations. The first is a partial response: someone has taken an antidepressant long enough for a fair test and improved, then stalled short of feeling well. Long enough matters: antidepressants usually take four to eight weeks to show what they can do. The second is depression with a lot of anxiety alongside it, where buspirone’s approved use matches what the person needs. Even there the evidence is thin: the most recent study of buspirone for anxiety in depression was an observational study with no comparison group. That argument is weaker for teenagers, where buspirone did no better than placebo in the only trials run in that age group.

Two side-effect claims here need correcting. Weight gain is not among buspirone’s common side effects, though the FDA label lists both weight gain and loss as uncommon ones. Buspirone is also widely described as a fix for the sexual side effects antidepressants can cause. The trial built to test exactly that found buspirone no better than placebo, and a Cochrane review later called the evidence in this area rather limited.

Buspirone is a poor fit for someone who has not yet given a first-choice treatment enough time to work. It is not a replacement for an antidepressant either.

Adding a medicine is one option among several. The American Psychiatric Association notes that when improvement stalls a prescriber may adjust the current antidepressant or switch to a different one, and that talking therapy works for depression too. Among add-ons, prescribers weigh bupropion, lithium, thyroid hormone, and the atypical antipsychotics, some of which carry FDA approval as an add-on for major depressive disorder that buspirone lacks. Supplements such as SAM-e and L-methylfolate come up too, and sorting through them is what a medication management visit does.

Buspar side effects and the interactions that matter

Buspar’s most common side effects, from the controlled trials on its FDA label:

• Dizziness (12%)
• Drowsiness (10%)
• Nausea (8%)
• Headache (6%)
• Nervousness or restlessness (5%)

Three interactions are worth bringing up before you start. MAOI antidepressants must not be taken with Buspar, and the 14-day gap runs both ways: not within 14 days of stopping Buspar, and not within 14 days of stopping an MAOI. The risk is serotonin syndrome and raised blood pressure. Serotonin syndrome has also been reported with Buspar on its own, and more often alongside other medicines that raise serotonin. That matters when the plan is to add it to an antidepressant. And grapefruit blocks CYP3A4, the enzyme that breaks Buspar down, which raises Buspar levels sharply. MedlinePlus advises avoiding large amounts of grapefruit while taking it. Some prescription medicines act on the same enzyme, so the prescriber needs your full list.

Serotonin syndrome is a reaction to too much serotonin activity, and it can be a medical emergency. Get medical care right away if you notice any of the signs the label describes after a medication change: agitation, confusion, a fast heartbeat, heavy sweating, shivering, muscle twitching or stiffness, or a fever.

Buspar is taken on a steady schedule rather than when symptoms flare, and it works gradually. Whether to keep taking it or stop is a prescriber conversation.

Common questions about buspirone and depression

Does buspirone make you feel happier?

Buspirone (Buspar) is not a mood lifter in the way people expect an antidepressant to be. It works on anxiety, and it does not lift mood directly. Any benefit in depression is usually modest and comes from adding it to an antidepressant.

How long does buspirone take to work?

Buspirone (Buspar) works gradually, and its clinical effect typically takes two to four weeks, so taking it only when symptoms spike does little. If several weeks have passed with no change at all, that is worth raising with the prescriber who started it.

Can buspirone cause depression?

Buspirone (Buspar) does not list depression among its common side effects. The FDA label names dizziness, drowsiness, nausea, headache and nervousness as the most frequent ones. Mood can still shift after any medication change, so tell your prescriber if yours drops after starting it.

Can I just stop taking buspirone?

Buspirone (Buspar) is not associated with a withdrawal syndrome the way benzodiazepines are, but that is not a reason to stop on your own. NIMH advises that people should not stop a prescribed medication, even when feeling better, without help from a health care provider.

Is buspirone used for depression in teenagers?

Buspirone (Buspar) has weak evidence in this age group. Across two placebo-controlled trials in 559 patients aged 6 to 17 with generalized anxiety, buspirone did no better than placebo, and there are no long-term safety or efficacy data in children or teenagers. It is worth asking a prescriber about directly.

Talk to a prescriber about your treatment

If an antidepressant helped part of the way and then stopped, book a medication-management evaluation with Zellig. The visit reviews what you take and whether to add anything. We see patients ages 12 and up by video across Pennsylvania. Appointments are usually available within the week.

Buspirone may be a reasonable addition for some people, depending on what you have tried and how you are doing now.

If you are in crisis or thinking about harming yourself, call or text 988 to reach the Suicide and Crisis Lifeline, any time.

This is general information and not a substitute for medical advice. For a diagnosis or any treatment decision, talk with your own prescriber or a qualified clinician.