Table 2: Summary of the included in vitro, animal, and clinical studies on interactions between carbamazepine and herbal products, dietary supplement, and food.

Types of herbal product*Herbal productsStudy typeSubject/model (number)Study designOutcome measuresEffectMechanismReferences

TCMAcorus calamus Linn.AnimalMale Wistar rats with pentylenetetrazole-induced seizure model
(6 in each group)
Randomized controlled studyPK and PD parametersNo effect on plasma level of CBZ
Additive antiepileptic activity
Increased GABAergic activityKatyal et al. 2012 [35]

TCMBerberine (active compound in Coptidis rhizome)AnimalMale Wistar rats (5 in each group)Randomized parallel designPK parametersNo effect on pharmacokinetic parameters of CBZ or CBZ 10,11-epoxideDid not affect in vivo intestinal or hepatic CYP3A activityQiu et al. 2009 [36]

TCMCardiospermum halicacabum  Linn.AnimalMale Wistar rats (10 in each group)Randomized crossover designPK and PD parametersNo significant effect on CBZ plasma level
No change in drug-related toxicity
(including general behavior, liver function, haematological parameters, and kidney function)
N.D.Thabrew et al. 2004 [37]

TCMCassia auriculata  Linn.AnimalMale Wistar rats (10 in each group)Randomized crossover designPK and PD parametersIncreased plasma level of CBZ
No change in drug-related toxicity
(including general behavior, liver function, haematological parameters and kidney function)
N.D.Thabrew et al. 2004 [37]

TCMChai-hu-jia-long-gu-mu-li- tangAnimalWistar rats
(5-6 in each group)
Randomized parallel designPK parametersNo effect on pharmacokinetic parameters or protein binding of CBZ or CBZ 10,11-epoxideDid not alter in vivo CYP3A activityOhnishi et al. 2001 [38]

TCMGinsenoside
(active compound in ginseng)
In vitro Human liver microsomes
(3 in each group)
N/APK parametersIncreased CBZ metabolismActivated CYP3A4 activity by interacting with CBZ in the active siteHaop et al. 2008 [39]

TCMGinkgo biloba AnimalRats
(6 in each group)
Randomized parallel designPK parametersDecreased bioavailability and increased rate of elimination of CBZN.D. Chandra et al. 2009 [40]

TCMHu-gan-ning pianAnimalMale Sprague-Dawley rats
(7 in each group)
Randomized parallel designPK parametersDecreased bioavailability
No effect on , , , CL, and elimination K of CBZ
Decreased absorption but not metabolism of CBZZheng et al. 2009 [41]

TCMHypericum perforatum Linn.HumanHealthy subjects
(8)
Open label studyPK parametersNo effect on PK parameters of CBZAutoinduction or greater clearance by CBZBurstein et al. 2000 [42]

HPIspaghula Husk
(Psyllium)
HumanHealthy male volunteer (4)Open label studyPK parametersDecreased bioavailability by reducing absorption and plasma levels of CBZDecreased amount of biological fluid in GI tract and thereby reduced dissolution rate of CBZ Also adsorb CBZ onto their surfaces Etman 1995 [43]

TCMJia-wei-xiao-yao-sanHumanPatients with major depression or bipolar disorder (61)Randomized double-blinded control trialPK parametersDecreased plasma level of CBZIncreased metabolism of CBZ by inducing CYP3AZhang et al. 2007 [44]

HPMentatAnimalNew Zealand white rabbits
(8 in each group)
Randomized parallel designPK parametersIncreased bioavailability of CBZN.D.Tripathi et al. 2000 [45]

TCMPaeoniae RadixAnimalMale Sprague-Dawley rats
(6 in each group)
Randomized parallel designPK parametersDecreased of CBZ
Decreased protein binding rate of CBZ
No effect on AUC, , , CL, and F of CBZ
Improved dissolution of CBZ
N.D.
Chen et al. 2002 [46]

TCMPiperine
(active compound in Piper longum  
Linn.)
HumanPatients with epilepsy
(10 in each group)
Open label, crossover studyPK parametersIncreased bioavailability of CBZ
Increased elimination rate and decreased elimination
Decreased metabolism/ elimination and/or increased absorption of CBZPattanaik et al. 2009 [47]

TCMPlatycodonis RadixAnimalRabbits
(4 in each group)
Randomized parallel designPK parametersIncreased plasma level of CBZImprove CBZ absorption by increasing its solubility and stimulating bile secretionLiu and Wei 2008 [48]

TCMPolygonum cuspidatum AnimalMale Sprague-Dawley rats
(6 in each group)
Randomized crossover designPK parametersIncreased level of CBZ and CBZ 10,11-epoxide in plasma, brain, liver, and kidney
Decreased formation rate of CBZ 10,11-epoxide
Inhibited CYP3A in intestine and MRP2 in the kidneyChi et al. 2012 [49]

HPSeptilinAnimalMale rabbits
(8 in each group)
Randomized crossover studyPK parametersDecreased absorption of CBZAffected gastric emptying time or intestinal transit timeGarg et al. 1998 [50]

TCMXiao-cha-hu-tangAnimalFemale Sprague-Dawley rats
(4 in each group)
Randomized parallel designPK parametersIncreased , decreased of CBZ and AUC of CBZ 10,11-epoxide
No effect on , and MR of CBZ
Decreased GI absorption of CBZ by decreasing gastric emptying rateOhnishi et al. 2002 [51]

TCMXiao-qing-long-tangAnimalMale Wistar rats (4–6 in each group)Randomized parallel designPK parametersIncreased , elimination K of CBZ and decreased MR of CBZ
No effect on and AUC of CBZ and CBZ 10,11-epoxide
Decreased gastric emptying rate and accelerated metabolism of CBZOhnishi et al. 1999 [52]

TCMXiao-yao-sanHumanPatients with major depression or bipolar disorder Randomized double-blinded control trialPK and PD parametersDecreased plasma level of CBZ and increased incidence of dizziness, blurred vision, skin rash, and nauseaN.D.Li et al. 2005 [53]

 *Types of herbal product: traditional Chinese medicines (TCM)/other herbal products (HP); N.D.: not determined by authors; N/A: not applicable.