Diazepam with Valerian Interaction Details
Brand Names Associated with Diazepam
- Diazepam
- Diazepam Intensol®
- Valium®
- Valrelease®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 19, 2023
Interaction Effect
Additive CNS depression or reduced effectiveness of the benzodiazepine
Interaction Summary
In one case report, valerian and passionflower used concurrently with lorazepam resulted in additive CNS depressive effects. Valerian extracts have shown affinity for central and peripheral benzodiazepine receptors as well as barbiturate and GABA-A receptors . Valerian extract displaced the benzodiazepine fluorodiazepam from the receptor . The clinical effect may be additive or reduced effectiveness of benzodiazepines depending on the nature of the binding. It is recommended that patients be asked about herbal product use during intake of personal history . Monitoring for altered effectiveness of the benzodiazepine should be considered with concurrent use.
Severity
Moderate
Onset
Rapid
Evidence
Theoretical
How To Manage Interaction
Concomitant use of valerian and benzodiazepines may resulted in additive CNS depressive effects or may decreased the effectiveness of benzodiazepines. It is recommended that patients be asked about herbal product use during intake of personal history. Monitor for altered effectiveness of the benzodiazepine during concurrent use.
Mechanism Of Interaction
Additive effects on the benzodiazepine receptor, possible displacement of the benzodiazepine from its receptor
Literature Reports
A) A case report describes a potentiated CNS depressive effect in a 40-year-old man following concomitant use of lorazepam with valerian and passionflower. The patient, who had been treating with lorazepam 2 mg/day for 2 months with no adverse effects, self-administered an infusion of valerian subterranean parts (estimated dose, 300 mg). 2 hours before going to bed for 2 consecutive days. On day 3, he instead ingested 3 oral tablets of dry extract from valerian rhizomes (300 mg/tablet) plus roots and aerial parts of passionflower (380 mg/tablet) at 1 hour intervals before bedtime. Nervousness and mild shaking dissipated after going to bed followed by extreme somnolence. After taking the same dose of the valerian root/passionflower product on day 4, he experienced more severe symptoms including substantial hand shaking, dizziness, and palpitations before bedtime followed by profound somnolence. Upon presentation after 32 hours of experiencing these CNS symptoms, he was observed to have nervousness while speaking and demonstrated anxious behavior without shaking. He had a history of general anxiety disorders and dream disorders. His family history was negative for essential tremor and there were no metabolic, renal, or hepatic disorders, high blood pressure, or drug allergies. Because a drug interaction was suspected, the patient was continued on lorazepam but withdrawn from valerian and passionflower and symptoms resolved. It is postulated that the valerian root and passionflower have additive or synergistic effects on the inhibitory activity of benzodiazepines binding to the gamma-aminobutyric acid (GABA) receptors .
B) The amount of the amino acid gamma-aminobutyric acid (GABA) in aqueous and hydroalcoholic extracts of valerian is sufficient to explain its (3H)muscimol displacement effect at GABA receptor sites during in vitro tests. The GABA content of the aqueous extract is also sufficient to cause release of (3H)GABA in synaptosomes through homologous exchange, accounting for this in vitro effect as well. Since GABA cannot effectively cross the blood-brain barrier when given in the amounts available in the extracts, it appears unlikely that the influence of valerian on GABA neurotransmission contributes to central nervous system sedation . Valeriana officinalis extracts significantly displaced fluorodiazepam from benzodiazepine receptors, and a fraction containing sesquiterpene alcohols and ketones showed 80% inhibition at concentrations of 1.5 x 10(-3) moles/liter. A fraction containing valepotriates also produced significant displacement. Statistical values were not provided . In local cerebral glucose utilization, valerian extracts reacted in a way analogous to that observed with the GABA agonist, progabide. Therefore, the interaction at the GABA-A-benzodiazepine receptor complex may differ from that of diazepam . Valerian extracts inhibit (3H)flunitrazepam binding to benzodiazepine receptors; however, the amount of benzodiazepine-like molecules present in the plants is below pharmacologically-active doses .
C) Hydroalcoholic and aqueous extracts of Valeriana officinalis roots showed affinity for the GABA-A receptors with lesser affinity for the peripheral benzodiazepine receptors in vitro. Inhibition of 3H-PK 11195 binding to benzodiazepine and GABA-A receptors was measured and expressed as IC50 values. IC50 values for the hydroalcoholic extract were 0.04 milligrams/milliliter (mg/ml) and 3.9 x 10(-3) mg/ml for peripheral and central benzodiazepine receptors and GABA-A receptors, respectively. The lipophilic fraction of the hydroalcoholic extract showed affinity for the barbiturate receptor and to some extent for peripheral benzodiazepine receptors. The aqueous total extract A, the aqueous fraction B derived from the hydroalcoholic extracts, as well as the hydroalcoholic extracts demonstrated affinity for GABA-A receptors. This interaction at the receptor level could represent the molecular basis for the sedative effect noted with Valeriana officinalis .
Diazepam Overview
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Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.