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TitleAntiepileptic Drugs - Combination Therapy and Interactions - J. Majkowski, et al., (Cambridge, 2005) WW
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238 John R. Pollard and Jacqueline French

trial: half dose X � half dose Y; or convert to drug Y titrated up from half dose.

This type of trial was attempted by Deckers et al. (2001) but no attempt was made

to discover if half dose of drug Y was as effective as the combination.

Bourgeois lists other designs as most likely valid such as: failure of drug X,

improvement after addition of drug Y, and then worsening after elimination of

drug X; or adding drug D to drugs X, Y, or Z and obtaining significantly better

results with one of the combinations.

In summary, the total database of proven PD interactions is far from complete.

To date, the best data for a potentially supra-additive effect on efficacy are for the

combination of lamotrigine and VPA. Studies undertaken in the future should

ideally address many of the difficulties identified above. These include: using uni-

versally accepted measures of efficacy, inefficacy, and side effects; accounting for

dropouts; using the concept of drug load; and performing well-controlled studies

that rule out pharmacokinetic interactions. For many reasons, whether cost or

ethics or unavailability of patients, we are unlikely to gain the insights into PD

interactions that the perfect studies would afford.

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Page 515

tricyclic antidepressants (TCAs) 10, 243

interactions with anticonvulsants 357

trilazad, interactions with AEDs

phenytoin (PHT) 161

tuberculosis 4–5, 8

uridine diphosphate (UDP)-glucuronosyl-

tranferases (UDPGTs) 65–6

uridine glucuronyl transferases (UGTs) 28, 51

valproic acid and valproate (VPA) 18

action 210
active metabolites 22

adverse effects 21

effect upon excitatory amino acid receptors

214
effect upon NMDA and AMPA/KA

receptors 218
effects on drug-metabolizing enzyme

systems 81
elimination pathways 78
FEC and FEC index 201
fetal valproate syndrome 310

handicapped and mentally retarded

patients 330–1

influence of excitatory amino acid receptor

antagonists 215
influence of food and drugs on

bioavailability 101

interactions in children 260

interactions in the elderly

analgesics 282

anticoagulants/antiplatelet agents 280–1

CNS agents 287

gastrointestinal agents 283

interactions with newer AEDs 213
interactions with non-AEDs 163

cholestyramine 164

cimetidine 164

cisplatin 164

doxorubicin 164

ibuprofen 164–5

isoniazid 165

ketoconazole 165

mefenamic acid 165

methotrexate 165

naproxen 165

rifampicin 165

salicylic acid 165

tolbutamide 166

tolmetin 166

warfarin 166

zidovudine 166

interactions with other AEDs

effect on other drugs 118

levels through pregnancy 297
non-epileptic disorders 382

pharmacokinetic characteristics 50
pharmacokinetic interactions 21

therapeutic range 393
use of opioids in overdose 251

vecuronium, interactions with AEDs

phenytoin (PHT) 161

venlafaxine 350

verapamil, interactions with AEDs

carbamazepine (CBZ) 143

oxcarbazepine (OCBZ) 150

phenobarbital (PB) 153

vigabatrin (VGB) 18

action 30, 210
clinical trials 232

combination therapies 429

effect upon excitatory amino acid receptors

214
effects on drug-metabolizing enzyme

systems 81
elimination pathways 78
handicapped and mentally retarded

patients 332

influence of food and drugs on

bioavailability 102–3

interactions with non-AEDs 166

interactions with other AEDs

effect of other drugs 127

effect on other drugs 126–7

pharmacokinetic characteristics 50
selection for combination therapy 22

viloxazine 244
vincristine, interactions with AEDs

carbamazepine (CBZ) 145

warfarin, interactions with AEDs

levetiracetam (LEV) 149

oxcarbazepine (OCBZ) 150

495 Index

Page 516

warfarin, interactions with AEDs (contd)

phenobarbital (PB) 153

phenytoin (PHT) 161

tiagabine (TGB) 163

valproic acid (VPA) 166

zidovudine, interactions with AEDs

valproic acid (VPA) 166

ziprasidone 359

zolpidem 33

zonisamide (ZNS)

effects on drug-metabolizing enzyme

systems 81

elimination pathways 78
handicapped and mentally retarded

patients 334

influence of food and drugs on

bioavailability 105

interactions with non-AEDs 167

sulfonamides 167

interactions with other AEDs

effect of other drugs 130

effect on other drugs 128

pharmacokinetic characteristics 50
pharmacokinetic interactions 21

pregnancy, use in 307

496 Index

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