Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Divalproex Sodium

Divalproex Sodium brand name: Depakote.

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

Divalproex Sodium falls into 3 drug categories that Gamma-hydroxybutyrate (ghb) can interact with; the most serious is rated major. GHB may increase the risk of serious CNS and respiratory depression.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Gamma-hydroxybutyrate (ghb) and Divalproex Sodium

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Gamma-hydroxybutyrate (ghb) interacts with whole categories of medication. Divalproex Sodium falls into 3 of those categories, so it can interact with Gamma-hydroxybutyrate (ghb) in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 3

Why this applies to Divalproex Sodium

Divalproex Sodium falls under CNS DEPRESSANTS — the group Gamma-hydroxybutyrate (ghb) interacts with.

GHB may increase the risk of serious CNS and respiratory depression.
Concomitant use of GHB with CNS depressants may increase the risk of serious CNS and respiratory depression.
Severity Major Likelihood Probable Evidence D

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version: both GHB and your Depakote (divalproex sodium) calm down the nervous system. Depakote does this to control seizures, mood, or migraines, but it also tends to make people feel drowsy on its own. Stack a powerful brain depressant like GHB on top, and that sedation can pile up fast.

When you combine the two, the real worry is going too deep, meaning heavy drowsiness, confusion, very slow or shallow breathing, and in a worst case, slipping into unconsciousness. The evidence here is mostly anecdotal, but the risk is taken seriously because GHB is so unpredictable and can be dangerous even by itself. Please don't change anything on your own, but do talk with your pharmacist or doctor before mixing these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Major

DIVALPROX SODIUM (Depakote)

2 of 3
Divalproex sodium can increase the levels and clinical effects of GHB.
Concomitant use of GHB with divalproex sodium may increase the plasma levels and clinical effects of GHB. Concomitant use of the prescription form of GHB (sodium oxybate) with valproic acid results in approximately 25% increased exposure to GHB. It is recommended that the dose of the prescription form of GHB (sodium oxybate) be decreased by at least 20% if divalproex sodium is initiated in patients already receiving GHB (sodium oxybate) and that a lower starting dosage of GHB (sodium oxybate) is used in patients who are already receiving divalproex sodium.
Severity Major Likelihood Likely Evidence A

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the key thing to understand: in this pairing, it's the GHB that gets boosted, not your Depakote. When divalproex sodium is on board, your body holds onto more GHB. Studies with the prescription form (sodium oxybate) show roughly a 25% jump in GHB exposure when valproic acid is added. That's a meaningful bump for a drug that already strongly slows the brain down.

Since GHB is a powerful central nervous system depressant, more of it can mean deeper sedation, heavy drowsiness, slowed or stopped breathing, and in serious cases coma. I'll be honest with you: non-prescription GHB isn't a safe supplement to begin with, and adding Depakote makes it riskier. Please don't change your Depakote on your own. Talk with your doctor or pharmacist before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Moderate

ANTICONVULSANTS

3 of 3

Divalproex Sodium also falls under ANTICONVULSANTS.

Theoretically, GHB may reduce the effects of anticonvulsant medications.
GHB has been reported to cause seizures, and may theoretically reduce the effectiveness of anticonvulsants. Also, concomitant use of GHB with sedative anticonvulsants may increase the risk of serious CNS and respiratory depression.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

First, a real safety note: GHB sold outside of a doctor's care is dangerous and illegal, so this isn't something I'd ever recommend mixing with anything. But here's the concern with your Depakote (divalproex sodium). There are two worries, and both rest on weaker, anecdotal evidence rather than solid studies.

One, GHB has been reported to trigger seizures, so it could theoretically work against what your Depakote is doing and make a breakthrough seizure or mood episode more likely. Two, both GHB and divalproex can calm the nervous system, so together they may stack up and cause heavy drowsiness, confusion, or even slowed breathing. Please don't change your Depakote on your own. Talk with your doctor or pharmacist about anything you're combining it with.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Stomberg MW, Knudsen K, Stomberg H, Skärsäter I. Symptoms and signs in interpreting gamma-hydroxybutyrate (GHB) intoxication - an explorative study. Scand J Trauma Resusc Emerg Med. 2014 Apr 23;22:27. PubMed
  3. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Gamma-hydroxybutyrate (ghb) Also Interacts With Other Medications

Gamma-hydroxybutyrate (ghb) has 248 major, 21 moderate, 5 minor known drug interactions in our database — the Divalproex Sodium one above is among them. If you take anything else, check it against the full list below.

Major 248 Moderate 21 Minor 5 No known interaction 2,556 (incl. Divalproex Sodium)
Taking anything else?

Check Another of Your Medications Against Gamma-hydroxybutyrate (ghb)

Covers the 2,830 medications we’ve checked against Gamma-hydroxybutyrate (ghb). Pick one to open its full report.

From our Q&A

Questions About Gamma-hydroxybutyrate (ghb) or Divalproex Sodium

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Gamma-hydroxybutyrate (ghb) or Divalproex Sodium, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Divalproex Sodium

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Divalproex Sodium page lists 134 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Kava (major) and L-tryptophan (major).

By severity: 7 major · 110 moderate · 17 minor.

Open the Divalproex Sodium interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Divalproex Sodium Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Gamma-hydroxybutyrate (ghb)
Steady interest

#938 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Divalproex Sodium
Top 25%

#446 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Gamma-hydroxybutyrate (ghb)

What is Gamma-hydroxybutyrate (ghb)?

  • Narcolepsy (cataplexy and excessive daytime sleepiness)
  • Sleep aid
  • Misused as a recreational 'party drug'
  • Bodybuilding/muscle building (unproven)
  • Alcohol withdrawal (in some countries)

GHB (gamma-hydroxybutyrate) is a powerful central nervous system depressant that is NOT a safe dietary supplement. In the U.S. it is a controlled substance, and only a tightly regulated prescription form (sodium oxybate) is legal for narcolepsy. Non-prescription GHB can cause coma, breathing failure, and death, and it is also a known 'date-rape' drug — it should not be taken outside of medical supervision.

Read the full Gamma-hydroxybutyrate (ghb) monograph & all interactions
Medication

About Valproic Acid

What Is Valproic Acid Used For?

Brand name: Depakote

Valproic acid capsules (brands Valproic and Valproic Acid) and valproic acid oral solution (brand Valproic Acid) are both used to treat epilepsy. Specifically, they are approved for complex partial seizures (either alone or with other seizure types) as monotherapy or add-on therapy, and for simple and complex absence seizures as sole therapy or add-on therapy.

Both forms are intended for adults and pediatric patients. Always follow your prescriber's guidance on which product and regimen is right for you.

See full Valproic Acid drug information
Keep checking

Other Drugs & Gamma-hydroxybutyrate (ghb)

Browse every other medication we’ve checked against Gamma-hydroxybutyrate (ghb) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

248Major
21Moderate
5Minor
2,555No known interaction
248 Major 21 Moderate 5 Minor 2,555 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Gamma-hydroxybutyrate (ghb) page.

Moderate

21 interactions

Minor

5 interactions

No interaction 2,555 drugs checked — show the list

We also checked Gamma-hydroxybutyrate (ghb) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,555 medications checked with no known interaction — see the full Gamma-hydroxybutyrate (ghb) list.

See the full Gamma-hydroxybutyrate (ghb) interactions page
See every supplement checked against Divalproex Sodium, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Gamma-hydroxybutyrate (ghb) monograph › Uses, safety, and every drug interaction in one place Divalproex Sodium supplement interactions › Every supplement checked against Divalproex Sodium, ranked by severity Valproic Acid drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Gamma-hydroxybutyrate (ghb) and Divalproex Sodium Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Divalproex Sodium?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Gamma-hydroxybutyrate (ghb) and Divalproex Sodium?
Divalproex Sodium belongs to more than one drug category, and Gamma-hydroxybutyrate (ghb) interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Gamma-hydroxybutyrate (ghb) and Divalproex Sodium interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.