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.
Mr. L, a 48-year-old man with a diagnosis of residual schizophrenia [] treated for many years with clozapine 500 mg/d was admitted because of the worsening of his anxiety. The clinical scores and the trough plasma concentrations of clozapine and norclozapine were: CGI : 4; total PANSS: 88; positive: 20/49; negative 25/49; excited component: 9/35; general 40/112. Hamilton-anxiety: 24/56; clozapine: 594 ng/mL; norclozapine: 470 ng/mL, respectively. Aripiprazole 10 mg/d was added to clozapine (dose unchanged) and lorazepam (1 mg/d) was discontinued. The patient was discharged three weeks after the aripiprazole addition.\nA followup over 3 months did not reveal any change in the CGI and PANSS scores (at 3 months: CGI : 4; total PANSS: 73; positive: 20/49; negative: 25/49; excited component: 7/35; general: 40/112), while the Hamilton-anxiety score diminished progressively to 19 and 15 after one and three months, respectively. The clozapine and norclozapine plasma concentrations at three months were 431 ng/mL and 343 ng/mL, respectively.