Suicidality and divalproex sodium: analysis of controlled studies in multiple indications

Table 1 Study descriptions and number of subjects

Indication	Study and year of publication	Description	Treatment duration, weeks	Dose and/or target trough drug level	Treatment group		Total, N = 2,319
					DVPX, N = 1,327	Placebo, N = 992
Placebo-controlled studies
Epilepsy	Willmore et al. 1996 [30]	Adjunctive therapy in CPS	16	90 mg/kg/day max	77	70	147
	Total				77 (6%)	70 (7%)	147 (6%)
Psychiatric	Pope et al. 1991 [31]	Acute mania^a	3	50-100 μg/ml	20	23	43
	Bowden et al. 1994 [32]	Acute mania^a	3	150 μg/ml	69	74	143
	Bowden et al. 2000 [33]	Mania maintenance	52	71-125 μg/ml	187	94	281
	Sachs et al. 2001 [34]	Bipolar depression	16	250 mg/day initial with titration^b	23	22	45
	Hirschfeld et al. 2010 [35]	Acute mania^a	3	20 mg/kg/day with increases allowed	146	78	224
	Tariot et al. 2001 [36]	Dementia^a	6	30 mg/kg/day max	87	85	172
	Bowden et al. 2006 [37]	Acute mania^a	3	85-125 μg/ml	192	185	377
	Hollander et al. 2003 [38]	Impulsive aggression	12	80-120 μg/ml, 30 mg/kg/day max	124	122	246
	Placebo-controlled study^c	Dementia^a	6	500 or 1,000 mg/day	78	43	121
	Total				926 (70%)	726 (73%)	1652 (71%)
Migraine	Mathew et al. 1995 [39]	Migraine prophylaxis	12	70-120 μg/ml	70	37	107
	Klapper 1997 [40]	Migraine prophylaxis	12	500, 1,000 or 1,500 mg/day	132	44	176
	Freitag et al. 2002 [41]	Migraine prophylaxis	12	500 or 1,000 mg/day	122	115	237
	Total				324 (24%)	196 (20%)	520 (22%)
High-dose DVPX vs low-dose DVPX
				Trough levels	High-dose DVPX	Low-dose DVPX
Epilepsy	Beydoun et al. 1997 [42]	Monotherapy in CPS	24	25-50 μg/ml and 80-150 μg/ml	131	134	265

^aInpatient study; all others were conducted in an outpatient setting; ^binitiated at 250 mg, titrated by 250 mg/day on alternate days until reaching one of three criteria: serum trough concentration ≥45 μg/ml and HAM-D improvement ≥60% from baseline, ≥75 μg/ml and HAM-D ≥50% from baseline, or ≥95 μg/ml and HAM-D ≥30% from baseline; cData obtained from Abbott Protocol M99-082 clinical study report (unpublished). CPS = complex partial seizures; DVPX = divalproex sodium; HAM-D = Hamilton Rating Scale for Depression.

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