Table 1.
Clinical trials on antipsychotic polypharmacy and corrected QT (QTc) interval
| Study | Year | Design | Diagnosis | Duration | Antipsychotic polypharmacy | Antipsychotic monotherapy | Group difference | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||||||
| Antipsychotics (mean dose, mg/day) | n (male; female) | Mean age, years | Mean QTc baseline to end point difference, ms (within-group difference) | Antipsychotics (mean dose, mg/day) | n (male; female) | Mean age, years | Mean QTc baseline to end point difference, ms (within-group difference) | ||||||
| Anil Yağcioğlu et al16 | 2005 | DB-RCT | Sz and SAD | 6 weeks | CLZ (516) + RIS (6) | 16 (9; 7) | 35.3 | 441 to 430 (n/a) | CLZ (414) + PLB | 14 (11; 3) | 31.2 | 437 to 450 (n/a) | ns |
| Ziegenbein et al17 | 2005 | OL | Sz | 6 months | CLZ (570) + ZIP (147) | 9 (5; 4) | 37.3 | n/a | n/a | n/a | n/a | n/a | n/a |
| Chang et al18 | 2008 | DB-RCT | Sz | 8 weeks | CLZ (304) + APZ (15.5) | 29 (22; 7) | 33.2 | 439 to 443 (ns) | CLZ (291) + PLB | 32 (26; 6) | 31.7 | 440 to 441 (ns) | ns |
| Zink et al19 | 2009 | OL-RCT | Sz and SAD | 6 weeks | CLZ (361) + ZIP (134) | 12 (7; 5) | 31.8 | 388c to 403c (s) | n/a | n/a | n/a | n/a | s |
| CLZ (407) + RIS (3.8) | 12 (7; 5) | 37.3 | 391c to 381c (ns) | n/a | n/a | n/a | n/a | ||||||
| Henderson et al20 | 2009 | OL | Sz and SAD | 6 weeks | CLZ (n/a) or OLZ (n/a) + ZIP (160) | 21 (17; 4) | 49 | 417 to 420 (ns) | n/a | n/a | n/a | n/a | n/a |
| Lin et al21 | 2010 | DB-RCT | Sz | 6 weeks | RIS (2) + HPD (2) | 46a (n/a; n/a) | 38b | 410 to 407 (n/a) | RIS (4) | 42a (n/a; n/a) | 38b | 413 to 405 (n/a) | ns |
| Friedman et al22 | 2011 | DB-RCT | Sz and SAD | 12 weeks | CLZ (519) + PMZ (6.5) | 25 (21; 4) | 45.5 | +9.0 (n/a) | CLZ (478) + PLB | 28 (20; 8) | 44.4 | −1.5 (n/a) | ns |
| Nielsen et al23 | 2012 | DB-RCT | Sz | 12 weeks | CLZ (394) + SER (16) | 25 (15; 10) | 41.8 | 440 to 452 and 405c to 412c (n/a and ns) | CLZ (435) + PLB | 25 (15; 10) | 42.7 | 450 to 450 and 409c to 420c (n/a and n/a) | s and ns |
| Gunduz-Bruce et al24 | 2013 | DB-RCT | Sz and SAD | 12 weeks | CLZ (n/a) + PMZ (4) | 14 (10; 4) | 44.3 | 412 to 420 (n/a) | CLZ (n/a) + PLB | 14 (10; 4) | 41.5 | 409 to 413 (n/a) | ns |
| Muscatello et al25 | 2014 | DB-RCT | Sz | 16 weeks | CLZ (429) + ZIP (80) | 20 (5; 15) | 36.5 | 403 to 408 (s) | CLZ (463) + PLB | 20 (8; 12) | 33.5 | 408 to 405 (n/a) | ns |
a
QTc intervals were measured in 29 patients.
b
For whole patients
c
Calculated with Fridericia’s formula
CLZ = clozapine; DB = double-blind; HPD = haloperidol; n/a = not available or not applicable; ns = nonsignificant; OL = open-label; PLB = placebo; PMZ = pimozide; RCT = randomized controlled trial; RIS = risperidone; s = significant; SAD = schizoaffective disorder; SER = sertindole; Sz = schizophrenia; ZIP = ziprasidone