What herbs should be avoided when taking lurasidone (Lurasidone) and divalproex acid (Valproic acid)?

Herbs to Avoid with Lurasidone and Divalproex Acid

Avoid St. John's wort completely when taking lurasidone, as it is a strong CYP3A4 inducer that is explicitly contraindicated with this medication. 1

Critical Herb Contraindications

St. John's Wort (Hypericum perforatum)

• Absolutely contraindicated with lurasidone as a strong CYP3A4 inducer that will significantly reduce lurasidone blood levels and therapeutic efficacy 1
• Also problematic with divalproex acid, as it induces CYP3A4 and can reduce levels of multiple medications 2
• Can cause serotonin syndrome when combined with other serotonergic agents 2, 3
• May decrease platelet aggregation, adding bleeding risk 2

Grapefruit and Grapefruit Juice

• Must be avoided with lurasidone as they inhibit CYP3A4 and can cause dangerous elevations in lurasidone concentrations 1
• The FDA label explicitly states grapefruit should be avoided in patients taking lurasidone 1

Herbs Requiring Caution or Avoidance

Kava (Piper methysticum)

• Hold 2 weeks before any procedure due to potential additive sedation with anesthetics and benzodiazepines 2
• May act additively or synergistically with CNS depressants, causing excessive sedation 2
• Has resulted in coma when combined with alprazolam 4
• Particularly concerning given lurasidone's CNS effects

Valerian (Valeriana officinalis)

• Should not be used concomitantly with barbiturates due to excessive sedation risk 4
• May cause additive CNS depression when combined with sedatives 2
• The American Academy of Sleep Medicine suggests against its use for restless legs syndrome, indicating limited evidence for efficacy 2

Herbs with Antiplatelet Effects (Bleeding Risk)

The following herbs inhibit platelet aggregation and should be held 2 weeks before surgery or used cautiously with any anticoagulants:

• Ginkgo (Ginkgo biloba): Displaces platelet-activating factor, may potentiate bleeding with warfarin or aspirin 2, 5
• Garlic (Allium sativum): Inhibits thromboxane synthetase and decreases platelet aggregation 2, 6
• Ginger (Zingiber officinale): Laboratory evidence of decreased platelet aggregation 2
• Ginseng (Panax ginseng): May alter bleeding time 4, 5
• Saw palmetto: May increase bleeding time 2
• Turmeric: Inhibits platelet aggregation via thromboxane metabolism 2

Herbs Affecting Drug Metabolism

Goldenseal (Hydrastis canadensis)

• Hold 2 weeks due to high potential for drug interactions through CYP3A4 and CYP2D6 metabolism 2
• These are the same pathways involved in lurasidone metabolism 1

Schisandra

• Hold 2 weeks due to effects on drug metabolism 2
• Has multiple bioactive compounds that may interact with medications 2

Sedating Herbs (Additive CNS Depression Risk)

Lemon balm (Melissa officinalis)

• Hold 2 weeks as combination with sedatives or alcohol may result in additive CNS depression 2

Skullcap (Scutellaria lateriflora)

• Hold 2 weeks due to dose-dependent sedation 2
• Concern for additive CNS depressive effects 2

Hops (Humulus lupulus)

• Consider continuing but avoid alcohol, as sedative effects may be additive with valerian 2

Herbs Affecting Glucose and Metabolic Function

Given that both lurasidone and divalproex acid can affect metabolic parameters:

• Gymnema: Hold 2 weeks as it inhibits glucose absorption and increases insulin secretion 2
• Karela and ginseng: May affect blood glucose levels 4

Common Pitfalls to Avoid

• Do not assume "natural" means safe: Many patients fail to disclose herbal supplement use to clinicians 3
• Grapefruit in any form is contraindicated: This includes juice, fresh fruit, and extracts when taking lurasidone 1
• Multiple herb interactions may compound: Using several herbs simultaneously increases interaction risk 6
• Quality control issues: Herbal preparations lack standardization, making interactions unpredictable 2, 5

Clinical Approach

Screen all patients taking lurasidone and divalproex acid for:

• Current use of St. John's wort (immediate discontinuation required) 1
• Grapefruit consumption in any form (must be eliminated) 1
• Any herbal supplements with CYP3A4 effects 1
• Sedating herbs that may cause excessive CNS depression 2, 4
• Antiplatelet herbs if patient has bleeding risk or takes anticoagulants 2, 4

Develop a trusting relationship that encourages patients to disclose dietary supplement use, as most patients do not volunteer this information 3.