Ketamine and Other Medications: What Can You Take During Treatment?

Often, yes. Most people who start ketamine or Spravato are already taking something else, and many stay on those medications throughout treatment. Being on an antidepressant, a mood stabilizer, or a blood pressure medication does not usually rule you out.

What matters is which medication, at what dose, with which treatment, and alongside which medical conditions. A sedating medication raises different questions than one that raises blood pressure. A drug that might affect how well treatment works is a different conversation than one that affects safety during the session.

One rule holds through everything below. Do not stop, skip, reduce, delay, or otherwise change a prescribed medication on your own to prepare for ketamine treatment. Those decisions belong to your prescriber and your treatment provider, working together. Stopping some psychiatric medications abruptly carries its own real risks.

Why Medication "Interactions" Aren't All the Same

The word "interaction" gets used for very different situations, and blurring them is how ordinary medications end up sounding forbidden.

• A contraindication means the drug should not be given. Spravato's labeled contraindications are aneurysmal vascular disease or arteriovenous malformation, a history of bleeding in the brain, and hypersensitivity to esketamine, ketamine, or the ingredients. No medication appears on that list.
• A labeled drug interaction means the prescribing information names a specific combination and says what to do about it. For Spravato, that instruction is almost always closer monitoring, not avoidance.
• A monitoring precaution means treatment goes ahead with extra attention, such as more frequent blood pressure checks.
• An increased side effect risk means something you already might feel, like sedation, may be stronger.
• A possible reduction in response is about whether treatment works, not whether it's safe. These are separate questions and they get confused constantly.
• A theoretical interaction comes from how drugs work on paper, without patient outcomes behind it.

Keeping those apart is most of what this article is for.

Antidepressants and Ketamine

Taking an antidepressant during ketamine treatment is common and expected. SSRIs, SNRIs, and atypical antidepressants like bupropion aren't known to create a dangerous combination with ketamine, and neither label treats ordinary antidepressant use as a problem.

For Spravato, the current labeling matters here. Spravato is indicated for treatment-resistant depression in adults as monotherapy or in conjunction with an oral antidepressant. You may still read older articles saying every patient must take it with an oral antidepressant. That is out of date for the treatment-resistant depression indication.

The separate indication is different. For depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior, Spravato is indicated in conjunction with an oral antidepressant.

Off-label IV or IM ketamine has no equivalent rule, because there's no FDA-approved psychiatric protocol for it. Clinics generally continue existing antidepressants. Tricyclic antidepressants come up occasionally because of their own blood pressure and heart effects, which is a reason for review rather than exclusion.

Benzodiazepines

This is the class people ask about most, and two very different concerns get mixed together here.

The safety question. Spravato's labeling groups benzodiazepines with other central nervous system depressants and says concomitant use may increase sedation, with close monitoring for sedation advised. The ketamine injection labeling is worded more strongly, warning that combining benzodiazepines with ketamine may result in profound sedation, respiratory depression, coma, or death. That language comes from anesthesia, where doses are far higher than psychiatric ones, but it explains why clinics take the combination seriously and watch breathing and alertness.

The effectiveness question. This one is separate. Some studies have found that higher benzodiazepine doses were associated with a weaker antidepressant response to ketamine. The evidence is limited, and it does not establish a dose at which ketamine stops working. A secondary analysis from a controlled IV ketamine trial found reduced improvement at day one that was no longer apparent by day three.

How much weight should that carry? Less than the internet usually gives it. These findings come mostly from post-hoc and observational analyses with small samples, not from trials built to test the question. A systematic review rated the overall evidence low quality. So a real dose-related signal exists, its size and durability are unsettled, and most data involve IV ketamine rather than Spravato.

None of that is a reason to skip a dose before an appointment. Some clinics do discuss timing with a prescriber, and some don't. That's an individualized medical decision, and stopping a benzodiazepine suddenly can be dangerous on its own.

Opioids and Other CNS Depressants

Prescription opioids, sedating sleep medications, muscle relaxants, and alcohol all fall in the same general category as benzodiazepines. The concern is additive sedation and, at the extreme, slowed breathing.

Spravato's labeling names benzodiazepines, opioids, and alcohol together as CNS depressants that may increase sedation, and calls for close monitoring. Ketamine injection labeling adds that opioid analgesics may prolong recovery time. This is also why Spravato sessions include monitoring for sedation and, when needed, oxygen levels.

Being prescribed an opioid does not automatically exclude you from treatment. It does mean your clinic should know the medication, the dose, and when you take it. If you drink alcohol, say so honestly, because it belongs in the same conversation. So does any history of substance use, which our guide on whether ketamine can be addictive goes into.

Stimulants

Amphetamine products, methylphenidate, modafinil, and armodafinil are common among people seeking depression treatment, and they're not off limits.

Spravato's labeling states that concomitant use with psychostimulants may increase blood pressure, and directs close blood pressure monitoring. That is a monitoring instruction. Stimulants are not listed as a contraindication, and taking one is not by itself a reason to be turned away.

Since both can raise blood pressure, the practical result is usually more attention to your readings before and during a session. For off-label ketamine, there's no labeled psychiatric rule, so clinics apply the same pharmacology using clinical judgment.

MAO Inhibitors

MAOIs such as phenelzine, tranylcypromine, and selegiline are widely described online as incompatible with ketamine. The current labeling doesn't support that framing.

Spravato's labeling says concomitant use with MAOIs may increase blood pressure and advises close blood pressure monitoring. An interaction that calls for monitoring is not the same as a contraindication, and MAOIs do not appear among Spravato's contraindications.

The published clinical experience is limited but reassuring. A systematic review and case series covered roughly three dozen patients across a dozen studies. Blood pressure and heart rate rose in some cases, but the changes were judged clinically insignificant in nearly all. No hypertensive crises and no serotonin syndrome were reported. Unlike serotonergic antidepressants, ketamine works mainly on glutamate, the proposed reason the feared reaction doesn't appear. This is a small evidence base, and it deserves a clinician who knows it rather than a blanket rejection.

Mood Stabilizers

Lamotrigine has the most persistent myth attached to it. Because lamotrigine dampens glutamate release and ketamine acts on the glutamate system, the theory says lamotrigine should blunt ketamine. The research doesn't settle it. A systematic review found mixed results, with two of five studies suggesting attenuation and others finding no clinical difference. More recent real-world data found no significant difference in response or remission, though those samples were small. Some data point toward less dissociation rather than less benefit. No clear reduction in antidepressant response has been established, and anyone telling you confidently that lamotrigine blocks ketamine is ahead of the evidence.

Lithium looks clearer. No clinically important interaction with ketamine has been demonstrated. Two randomized trials found lithium added nothing to ketamine's antidepressant effect, despite animal work suggesting the two might work well together. Encouraging laboratory mechanisms have not translated into human results here.

Valproate and divalproex have very little ketamine-specific research behind them. There's no established interaction to report, and that gap is worth stating plainly rather than filling with speculation.

Antipsychotic Medications

Quetiapine, olanzapine, risperidone, and aripiprazole are often prescribed for depression as add-on treatment, not only for psychosis. Taking one says nothing on its own about whether you can receive ketamine treatment. Our guide on who shouldn't get ketamine therapy covers how clinics think about psychosis itself.

The practical issue is usually sedation, since several of these medications are sedating and ketamine can be too. Whether they change how well ketamine works is unsettled. Brain imaging studies show risperidone dampens some of ketamine's effects, but no clinical trial has tested whether that translates into weaker antidepressant results.

Theophylline and Aminophylline

This pair rarely appears in patient-facing articles, and it's a genuine labeled interaction. Ketamine injection labeling states that concurrent theophylline or aminophylline may lower the seizure threshold, and suggests considering alternative agents for patients already on them.

Two things keep this in proportion. That labeling describes ketamine used as an anesthetic, at doses well above psychiatric ones. Psychiatric ketamine is off-label, so this is safety information rather than a psychiatric treatment rule, and it does not make the combination prohibited. These medications are also prescribed far less often for asthma and COPD than they once were. If you take either, tell your clinic and expect a risk discussion rather than an automatic no.

Sympathomimetics and Medications That Raise Blood Pressure

Ketamine raises blood pressure and heart rate on its own. Ketamine injection labeling notes that sympathomimetics and vasopressin may enhance those effects, and advises close monitoring of vital signs.

Rather than memorizing a list, understand the principle. Anything that pushes blood pressure up gets reviewed, because it stacks with an effect the treatment already produces. That includes some decongestants and some ADHD medications. Clinics check this because your baseline reading and your in-session response both guide what happens next. Our guide on whether ketamine therapy is safe describes that monitoring in more detail.

What About Over-the-Counter Medications and Supplements?

Bring the whole list, not just prescriptions. That means over-the-counter medicines, sleep aids, decongestants, herbal products, and supplements.

Two categories matter most, for the reasons above: anything sedating, and anything that raises blood pressure. Diphenhydramine based sleep aids sit in the first group, and decongestants like pseudoephedrine sit in the second.

"Natural" doesn't mean inert. A supplement can still cause drowsiness or affect blood pressure, and many haven't been studied alongside ketamine. You don't need to research each one. Just disclose them.

Can Medications Make Ketamine Less Effective?

This question deserves separating from safety entirely. A medication can be perfectly safe with ketamine and still, in theory, affect how well it works. The evidence here is thinner than confident websites suggest.

The pattern is worth noticing. Benzodiazepines have the strongest case, and even that rests on studies not designed to answer the question. Everything else is weaker still. None of it justifies changing a medication on your own.

Do You Need to Stop Medications Before Ketamine or Spravato?

Do not make that call yourself. That's the entire answer to this question.

Clinics differ, legitimately. Some continue everything unchanged. Some discuss timing with your prescriber, or add monitoring during sessions. Some coordinate with the clinician who manages your psychiatric medications, postpone treatment until something is stable, or suggest a different approach.

All of those are clinician decisions made with you, and they're most likely to come up with benzodiazepines, opioids, stimulants, antidepressants, and mood stabilizers. What none of them means is that you should preemptively skip a dose because of something you read.

What to Tell Your Ketamine Clinic Before Treatment

Come prepared with:

• Every prescription medication, with doses
• As-needed medications, even ones you rarely use
• Over-the-counter medicines and sleep aids
• Supplements and herbal products
• Any medication change in the last few weeks
• Alcohol or other substance use, answered honestly
• Who prescribes your psychiatric medications

That last one matters more than people expect. If your ketamine provider and your regular prescriber are different people, someone has to connect them.

Questions to Ask About Your Medications

• Can I take my medications on my normal schedule on treatment days?
• Is the concern safety, sedation, blood pressure, or effectiveness?
• Does this apply to Spravato specifically, or to ketamine generally?
• What's the evidence that this medication reduces response?
• Will I need extra monitoring during sessions?
• Will you coordinate with my current prescriber?
• If you recommend a change, who manages it and how?

Finding a Clinic That Reviews Medications Carefully

A careful medication review is a sign of a serious provider, not a warning sign. The clinics worth your time ask for the full list before your first session and can explain where a recommendation comes from. Good answers cite FDA labeling, known pharmacology, published evidence, or individual judgment, and a good clinician will say which one they're relying on.

A clinic that never asks what you take is skipping a basic safety step. A clinic that declares common medications disqualifying, without explaining why, may be applying rules more rigid than the evidence supports.

If you're weighing providers, our guide on how to choose a ketamine clinic covers what else to look for. Who is a good candidate for ketamine therapy covers the broader screening picture. You can search ketamine clinics near you, or browse Spravato treatment centers and IV ketamine infusion clinics if you already know which treatment you're considering.