Effect of phenothiazines on serum antiepileptic drug concentrations in psychiatric patients with seizure disorder.

The intrapatient effect of starting (group A, n = 16), increasing (group B, n = 19), decreasing (group C, n = 23), and discontinuing (group D, n = 34) the phenothiazines (PHZs) thioridazine, chlorpromazine, or mesoridazine on serum phenytoin (PHT), phenobarbital (PB), and primidone (PRI) was studied at a constant antiepileptic drug regimen and between two consecutive steady-state concentration determinations in 92 institutionalized epileptic patients with psychiatric disorders. For PHZ initiation or dosage increase (groups A and B), serum PHT and PHT concentration-to-dose ratio (C/D) decreased by 44 (p less than 0.001) and 41.6% (p less than 0.001) in group A, and 32.9 (p less than 0.001) and 35.3% (p less than 0.005) in group B, respectively. For PHZ dosage decrease or discontinuation (groups C and D), serum PHT and C/D ratio increased by 54.8 (p less than 0.001) and 51.3% (p less than 0.01) in group C, and 71.2 (p less than 0.001) and 69.2% (p less than 0.001) in group D, respectively. The changes for PB were in the same direction, although to a lesser extent. No statistically significant differences were noted for PRI. For groups A and B, the clinical trend was for increase in number of seizures when PHZs were started or dosage increased. For groups C and D, a clear trend for PHT intoxication was evident when PHZ dosages were decreased or discontinued.