Ms. A, a 40-year-old woman diagnosed with a residual schizophrenia [] was admitted following an exacerbation of psychotic symptoms with a predominance of anxiety despite 700 mg/d of clozapine for two years. The clinical scores and the trough plasma concentrations of clozapine and norclozapine at admission were CGI : 5; total PANSS: 123; positive: 17/49; negative: 18/49; excited component: 12/35; general: 39/112; Hamilton-anxiety: 14/56; clozapine: 896 ng/mL; norclozapine: 551 ng/mL, respectively (clozapine therapeutic range: 350–600 ng/mL [–]). Because of the risks of seizures, the dose was reduced to 500 mg/d, and aripiprazole (10 mg/d) was added. Clozapine and norclozapine plasma concentrations measured after 10 days were decreased according to the reduction of the dose (615 ng/mL and 478 ng/mL, resp.). The aripiprazole plasma concentration after 10 days was 282 ng/mL. Following a clinical reduction of the anxiety, the patient was discharged from the hospital three weeks after the addition of aripiprazole.\nA followup over 6 months did not reveal any change in the CGI and PANSS scores (at 6 months: CGI : 5; total PANSS: 125; positive: 18/49; negative: 23/49; excited component 10/35; general: 38/112). On the other hand, the Hamilton-anxiety score diminished progressively to 12, 7, and 8 after one, three, and 6 months, respectively. Clozapine and norclozapine plasma levels were stable over this period (at the sixth month: 608 ng/mL, 443 ng/mL, and 75 kg, resp.), and the comedications (clorazepate 20 mg/d, valsartane 40 mg/d, zopiclone 7,5 mg/d, and tamsulosine 0.4 mg/d) were not modified. No reports are describing an impact on anxiety by the antihypertensive comedication by valsartane (an angiotensin II receptor antagonist) and tamsulosine (peripheral α1-antagonist). There is no significant pharmacokinetic or pharmacodynamic interactions of that comedication and the antipsychotic/anxiolytic treatments.
A 27-year-old, Caucasian, male patient, diagnosed with substance-induced psychotic disorder, was hospitalized due to exacerbation of psychotic symptoms despite clozapine dose of 150 mg/day for two years. His family reported exacerbation of obsessive-compulsive symptoms, such as contamination obsessions and frequent handwashing, for 3 months. Clozapine and norclozapine plasma levels were lower than therapuetic level on admission. a 15-mg/day aripiprazole was added on and clozapine dose increased to 200 mg/day. At the end of the first week, aripiprazole dose was increased to 30 mg/day. Plasma clozapine and norclozapine levels were found to be higher than therapeutic level with a clozapine dose of 200 mg/day, and clozapine dose decreased to 100 mg/day. The clozapine and aripiprazole doses, plasma drug levels, and the clinical rating scale scores are given in Table \n. At the end of the fourth week, during discharge, his scores of PANSS was 46 (159 at admission), and YBOCS was 10 (30 at admission).