Two rapid-dose titrations of sertindole in patients with schizophrenia.
The novel antipsychotic sertindole has demonstrated efficacy in psychosis with an extrapyramidal syndrome profile indistinguishable from placebo. Prior trials of sertindole have increased the dose by 4 mg every third day, whereas the present study evaluated the safety and tolerability of two, previously untested, more rapid dose escalation regimens. Sixteen schizophrenic inpatients entered a 4-day, single-blind placebo washout period in two consecutive groups. All patients received sertindole in 4-mg dose increments up to a maximum dose of 24 mg, which was maintained for 5 days. Dose increases were every other day for group 1 (N = 8) and daily for group 2 (N = 8). Adverse events, electrocardiograms, routine laboratory tests, and plasma sertindole concentrations were recorded. No patient was discontinued because of adverse events. The most frequent adverse events were tachycardia upon orthostatic challenge, nasal congestion, dry mouth, and headache; except for dry mouth, the incidence of these was greater in group 2. All cases of tachycardia were asymptomatic. No clinically significant laboratory abnormalities were detected in either group. In conclusion, 4-mg increases of sertindole every other day seems to be safe. Daily titration was, in general, not well tolerated.
Sramek
J J
JJ
California Clinical Trials, Beverly Hills, USA.
Mack
R J
RJ
Awni
W
W
Hourani
J
J
Jhee
S S
SS
Barto
S
S
Cutler
N R
NR
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole