Herbal hazards: Which psychotropics interact with four common supplements
Over-the-counter botanicals metabolized by CYP-450 enzymes pose a substantial interaction risk with antidepressants and other drugs
Table 3
Select potential interactions with St. John’s wort
| Cannabinoids ↓ | Fentanyl ↓ |
| Cocaine ↓ | Temazepam ↓ |
| Diazepam ↓ | Triazolam ↓ |
| Donepezil ↓ | |
| ↓= decreased levels/effectiveness | |
| Source: Adapted from reference 12 | |
Efficacy. A meta-analysis of studies found kava more effective than placebo in treating anxiety,25 although most studies suffer from poor design and/or small sample size.
Adverse effects. Reports have associated kava use with hepatic toxicity, liver failure requiring liver transplantation, and death. The European Union and Canada have banned kava sales, and the FDA issued a consumer advisory noting kava’s risks. Emerging information indicates that kava inhibits virtually all CYP-450 enzymes, which would increase levels of and potential adverse effects from any medications taken with kava.26
Other common adverse effects include GI upset, enlarged pupils, extrapyramidal side effects, and dizziness.24,27
Dosage. Kava is usually given at 100 mg (70 mg of kavalactones) three times daily. Urge patients to avoid driving when taking kava because of its side effects. Anxiety symptoms may improve with 1 to 8 weeks of therapy, but adverse hepatic effects can occur within 3 to 4 weeks of starting kava use.
Recommendation. Avoid kava kava use because of substantial risk of hepatotoxicity and drug interactions.
VALERIAN FOR INSOMNIA, ANXIETY
Valerian (Valeriana officinalis) is promoted as a sedative/hypnotic and anxiolytic. The prevalence of valerian use (5.9%) mirrors that of kava.1 An NCCAM study is enrolling patients to evaluate valerian’s effectiveness in treating Parkinson’s disease-related sleep disturbances.
Efficacy. Information on valerian’s mechanism of action and clinical effectiveness is quite limited. In animal studies, its components produced direct sedative effects and inhibited CNS catabolism of GABA.28 Results are mixed in humans with insomnia; some studies have found reduced sleep latency and improved sleep quality with valerian use, whereas others found no improvements.29 Limited, small evaluations suggest that valerian may be useful in treating anxiety.
Adverse effects. The FDA categorizes valerian as an approved food additive, so it is considered safe in usual amounts found in food. FDA lists no amount that it considers safe in food, however, and the federal code covering valerian states that only enough needed to impart the desired flavor should be used.
When taken in therapeutic amounts, valerian’s most common adverse effects are headache and residual morning drowsiness. Because of the herb’s sedative effects, urge caution if patients drive while using it. On discontinuation, withdrawal symptoms similar to those seen with benzodiazepine withdrawal—anxiety, headache, emotional lability—have been reported.
Dosage. For insomnia, valerian is taken 2 hours to 30 minutes before bedtime; doses start at 300 to 400 mg and increase to 600 to 900 mg. Recommended doses vary, as standardization is less common with valerian than with other herbals. Continuous treatment seems more effective than as-needed dosing, as valerian may take up to 4 weeks to improve insomnia.
Recommendation. Well-controlled trials are lacking, and safety data at therapeutic doses are limited. Monitor patients using valerian for adverse effects and drug interactions.
- Natural Medicines Comprehensive Database.www.naturaldatabase.com
- National Center for Complementary and Alternative Medicine. https://nccam.nih.gov
- FDA MedWatch Adverse Event Reporting Program. www.fda.gov/medwatch/how.htm
- ConsumerLab.com. Independent testing of dietary supplements. www.consumerlab.com
Drug brand names
- Alprazolam • Xanax
- Amiodarone • Cordarone, Pacerone
- Amitriptyline • Elavil
- Buspirone • BuSpar
- Cimetidine • Tagamet
- Cyclosporine • various
- Diazepam • Valium
- Digoxin • Lanoxin
- Donepezil • Aricept
- Fentanyl • Duragesic
- Fexofenadine • Allegra
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Indinavir • Crixivan
- Irinotecan • Camptosar
- Methadone • various
- Midazolam • Versed
- Nefazodone • Serzone
- Nevirapine • Viramune
- Omeprazole • Prilosec
- Paroxetine • Paxil
- Phenytoin • Dilantin
- Sertraline • Zoloft
- Simvastatin • Zocor
- Tacrolimus • Prograf
- Temazepam • Restoril
- Theophylline • various
- Triazolam • Halcion
- Venlafaxine • Effexor
- Warfarin • Coumadin
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
