Valproic acid autoinduction: a case-based review

International Journal of Bipolar Disorders

Table 1 Relationship between age, weight, valproic acid (VPA) formulation, daily VPA dose, average VPA levels, and concentration/dose (C/D) ratio × 1000 mean ± SD and range across cases

Cases	Age	Wt. (kg)	Diagnosis	Hospital Duration	Formulation	VPA dose (mg/day)	VPA level (μg/mL)	C/D ratio × 1000^a	No. of VPA Levels	Mean C/D ratio × 1000: mean ± SD, range^#	Comments
Case 1^*	34	85	Schizophrenia Seizure disorder	> 3 years	VPA	5250	87	17	44	15 ± 2.6, range = 10–21	Significantly lower C/D ratio than the normal range between 112 and 132 µg/mL, suggesting faster VPA metabolism
Case 1^*	34	85	Schizophrenia Seizure disorder	< 1 year	DVPS	2000	78	39	7	39 ± 6.3, range = 28–48	Higher C/D ratio with DVPS than VPA in case 1, suggesting significantly slower DVPS metabolism than VPA
Case 2^*	66	90	Bipolar Disorder Substance Use disorder	8 weeks	DVPS	4000	67	17	10	25 ± 5.6, range = 17–33	Significantly lower C/D ratio than the normal range between 112 and 132 µg/mL, suggesting faster VPA metabolism
Case 3^*	70	71	Tuberous Sclerosis	> 4 years	DVPS	10,500	10	12	137	8 ± 3.5, range = 3–20	Lowest C/D ratio of all cases, suggesting robust autoinduction with DVPS
New Case	51	71	Bipolar disorder Methamphetamine use disorder Recent Traumatic Brain Injury	22 days	VPA	5000	98.8	19.8	7	18.6 ± 2.9, range = 13–20	Similar C/D ratio to case 1 & 2, suggesting similar rate of autoinduction with VPA

*Reference = Jackson et al. (2015) VPA: valproic acid; DVPS: divalproex sodium; C/D = Mean concentration/dose ratio (therapeutic range between 112 to 132 µg/mL); Number of VPA levels drawn over total hospitalization
^#Mean C/D ratio × 1000: mean ± SD, range; Calculated from the total number of VPA levels during hospital duration
^aC/D ratio × 1000; Calculated from the last final VPA dose and the level at that dose