Ettinger

Table (E)T-3 Randomized double-blind clinical trials of psychotropic effects of AEDs in patients with psychiatric disorders

Drug / Disorder/symptom / Study design / Treatment (n) / Results
Traditional AEDs
Phenytoin
Mishory 200019 {ref}
Mishory 200320 {1326}
Nemets 200521{1327}
Stanford 200522{1349} / Bipolar I, acute mania
Bipolar I, prophylaxis
Major depression, recurrent episode
Impulsive aggression / PC, 5 week, adjunct (to haloperidol)
PC, CO, 6 months
Comparative (vs fluoxetine), 6 weeks
PC, parallel group, 6weeks / PHT, mean level from
9.4 μg/ml at week 1 to 21.4μg/ml at week 5 (6)
Placebo (6)
PHT, mean level from 2.5μg/ml at week 1 to 10.7μg/ml at month 6; placebo (23)
PHT, dose adjusted to levels of 10-20 µg/ml (14)
Fluoxetine, 21-28 mg/day (14)
PHT, 300 mg/day (7)
CBZ, 450 mg/day (7)
VPA, 750 mg/day (7)
Placebo (8) / Greater improvement, PHT vs placebo, on BPRS but not YMRS.
Prophylactic effect of PHT, p = 0.02 for time to relapse vs placebo
12 PHT-treated and
12 fluoxetine-treated had >50% improvement on HAM-D
OAS AS vs placebo was lower for PHT (p = 0.001) and VPA (p = 0.001) but not CBZ (p = 0.083)
Carbamazepine
Hartong 200323
{1310}
Weisler 200424
{1359}
Weisler 200525
{1360}
Stanford 200522 {1349} / Bipolar disorder, outpatients
Bipolar I disorder with current manic or mixed episode bipolar I
Bipolar I disorder with current manic or mixed episode
Impulsive agression / Double-dummy, 2years, maintenance
PC, parallel group, 21days
PC, parallel group, 21days
See study details under “Phenytoin” / CBZ (50) Li (44)
Doses based on serum level (Li, 0.6-1.0 mmol/L; CBZ, 610mg/L)
CBZ (ER) 400 titrated to maximum 1,600 mg/day (94)
Placebo (98)
CBZ (ER) 400 titrated to maximum 1,600 mg/day (120)
Placebo (115) / Longer time to mood episode for Li vs CBZ (p0.05 for patients with prior hypomanic but no manic episodes)
YMRS ↓ from baseline to day 21; p=0.032, CBZ vs placebo
YMRS ↓ from baseline to day 21; p< 0.0001, CBZ vs placebo
Valproate
Sival 200226
{1346}
Hollander 200327
{1312}
Stanford 200522 {1349}
Porsteinsson 200128 {1338} / Aggressive behavior with senile dementia
Impulsive aggression, Cluster B personality disorder
Impulsive aggression
Agitation associated with dementia / PC, CO; 8 weeks
PC, parallel-group, MC, 12 weeks
See study details under “Phenytoin”
PC, parallel-group, MC, 6 weeks / VPA 480 mg/day, placebo (42)
DVPX 80-120 µg/ml, maximum 30 mg/kg/day (47)
Placebo (49)
DVPX (28)
Placebo (28) / SDAS-9 and CGI, VPA vs placebo, no difference
OAS-M scores better for DVPX vs placebo, p=0.047
BPRS Agitation factor ↓ with DVPX vs placebo, p=0.08
Newer AEDs
Gabapentin
Pande 200029 {1333}
Pande 199930 {1332}
Pande 200031 {1334}
Frye 200032 {1302} / Bipolar I with manic/hypomanic or mixed symptoms
Social phobia
Panic disorder
Resistant bipolar spectrum disorders / PC, parallel group, MC, add-on, 10 weeks
PC, parallel-group, 2centers, 14 weeks
PC, parallel group, MC, 8-week.
PC, CO; 3 phases, 6weeks each / GBN 600-3,600 mg/day (58)
Placebo (59)
GBN 300-3,600 mg/day (34)
Placebo (35)
GBN 600-3,600 mg (52)
Placebo (51)
Gabapentin up to 4,800mg/day
LTG up to 500 mg/day / Improvement on YMRS, placebo vs GBN, p=0.03
↓ in LSAS, GBN > placebo, p=0.008
Difference between treatments (PAS score) NS; p = 0.04 in favor of GBN in subset of more severely ill patients
CGI-BD, improvement with LTG, GBN comparable to placebo
Lamotrigine
Calabrese 199933
{1090}
Ichim 200034
{1093}
Calabrese 200035
{889}
Normann 200236 {1330}
Barbosa 200337 {1288}
Tritt 200538 {1352}
Frye 200032 {1302} / Bipolar I depression episode
Bipolar, acute mania, inpatient
Bipolar, rapid cycling
Acute depressive episode
Bipolar disorder or major depression, depressive episode
Borderline personality disorder
Resistant bipolar spectrum disorders / PC, parallel-group, MC, 7 weeks
Parallel-group, 4 weeks
PC, parallel-group, MC, 6 months
PC, parallel-group, 9weeks, add-on to paroxetine
PC, 42 days, augmentation (fluoxetine)
PC, parallel-group, 8weeks
PC, CO; three phases, 6weeks each / LTG 50 mg/day (66)
LTG 200 mg (63)
Placebo (66)
LTG 100 mg/day (15)
Li 800 mg/day (15)
LTG up to 500 mg (93)
Placebo (89)
LTG 150 mg (20)
Placebo (20)
LTG up to 100 mg/day (13)
Placebo (10)
LTG up to 200 mg/day (18)
Placebo (9)
See under “Gabapentin” / HAM-D improved in both LTG groups more than placebo (p < 0.05)
↓ from baseline on MRS in both groups
In time to need for additional pharmacotherapy, NS trend favoring LTG, (p = 0.177)
HAM-D difference between groups, NS
HAM-D difference between groups, trend favoring LTG, NS
Improvement on 4 of 5 STAXI scales, LTGplacebo, p0.05
See under “Gabapentin”
Levetiracetam / No randomized
controlled trials
Oxcarbazepine / No randomized controlled trials
Pregabalin
Feltner 200339 {1299}
Pande 200440{1335}
Pohl 200541
{1337} / Generalized anxiety disorder
Social anxiety
Generalized anxiety disorder / PC, MC, 4 weeks, comparative (lorazepam)
PC, parallel-group, MC, 10weeks
PC, parallel-group, MC, 6 weeks / PGN 150 mg/day (70)
PGN 600 mg/day (66)
Lorazepam 6 mg/day (68)
Placebo (67)
PGN 150 mg/day (42)
PGN 600 mg/day (47)
Placebo (46)
PGN 200 mg/day (78)
PGN 400 mg/day (89)
PGN 450 mg/day (88)
Placebo (86) / HAM-A ↓, PGN 600mg/day > placebo (p=0.0013), both PGN doses vs lorazepam, NS
LSAS ↓, PGN 600mg/day >placebo (p=0.024)
HAM-A ↓, for each PGN dose vs placebo (p£0.006)
Tiagabine / No randomized trials
Topiramate
Nickel 200442 {1328}
Nickel 2005 / Borderline personality disorder, women
Borderline personality disorder, men / PC, parallel-group, 8weeks
PC, parallel groups,
8 weeks / TPM 250 mg/day (19)
Placebo (10)
TPM 250 mg/day (22)
Placebo (20) / Improvement on 4 of 5 STAXI subscales, TPMplacebo, p0.05
Improvement on 4 of 5 STAXI subscales, TPMplacebo, p0.05
Zonisamide / No randomized trials

AED = antiepileptic drug; PC = placebo-controlled; PHT = phenytoin; BPRS = Brief Psychiatric Rating Scale; YMRS = Young Mania Rating Scale; CO = crossover; HAM-D = Hamilton Rating Scale for Depression; OAS-AS = Overt Aggression Scale Aggression Score; CBZ = carbamazepine; VPA = valproate; Li = lithium; ER = extended release; SDAS = Social Dysfunction and Aggression Scale; CGI = Clinical Global Impression; MC = multicenter; OAS-M = Overt Aggression Scale–Modified (for outpatients); DVPX = divalproex; GBN = gabapentin; NS = not significant; LSAS = Liebowitz Social Anxiety Scale; CGI-BD = Clinical Global Impression–Bipolar Disorder; LTG = lamotrigine; STAXI = State-Trait Anger Expression Inventory; PGN = pregabalin; HAM-A = Hamilton Rating Scale for Anxiety; TPM = topiramate.