Table. Effects of psychotropic drugs on QTc and the occurrence of torsade de pointes (TdP).
| Drug | QTc prolongation | QTc (Bazett) prolongation compared to baseline in ms (n); reference no. | Reported cases of TdP | TdP risk (Arizona CERT) | DDD in Germany, 2009 (millions) | References |
| Typical high-potency antipsychotic drugs | ||||||
| Thioridazine1 | +++ | +28 to 36.6 (n = 60); 10 | +++ | 1 | 1.3 | 2, 4– 6, 10, 12– 14, 23, 24, e6 |
| Haloperidol1 | + | +3.8 to 8.9 (n = 147; 4–15 mg); 4 | +++ | 1 | 18.4 | 2, 4– 6, 8, 10, 12– 15, 19, 23, 24, e1, e6 |
| Pimozide1 | +++ | +19 to 24 (n = 97); 10 | + | 1 | 1.0 | 2, 5, 6, 10, 19, 23, 24, e29 |
| Perphenazine1 | + | -55 to -16.6 (-35.7; n = 4); 7 | + | 0.5 | 5, 7 | |
| Fluphenazine1 | + | + | 8.2 | 5– 7, 24, 25 | ||
| Flupentixole1 | + | N.R. | 9.6 | 5, 6, 25 | ||
| Benperidol1 | Ø | -17.1 (n = 1); 7 | N.R. | 9.0 | 7, 12) | |
| Bromperidol1 | + | -15.6 to 19.2 (+1.8; n = 5); 7 | N.R. | 9.0 | 7, 12 | |
| Zuclopenthixole1 | Ø | -25.5 to 1.1 (-12.2; n = 9); 7 | N.R. | 5.3 | 5, 7 | |
| Perazine1 | N.R. | N.R. | 15.2 | |||
| Fluspirilene | N.R. | N.R. | 3.2 | |||
| Typical low-potency antipsychotic drugs | ||||||
| Chlorpromazine1 | ++ | ++ | 1 | N.R. | 6, 12, 13, 23– 25, e30, e31 | |
| Melperone1 | +++ | +30 (n = 23); e32 | + | 12.2 | 5, 24, e32 | |
| Levomepromazine1 | ++ | -18 to 11.8 (-31; n = 6); 7 | N.R. | 3.8 | 5, 7, 12, e33 | |
| Promethazine1 | + | + | 32.4 | e34 | ||
| Pipamperone1 | + | -10.8 to 9.6 (-0.6; n = 15); 7 | + | 9.3 | 5, 7, e35 | |
| Prothipendyl1 | Ø | N.R. | 3.3 | 5 | ||
| Chlorprothixene1 | Ø | N.R. | 6.6 | 5 | ||
| Newer antipsychotic drugs | ||||||
| Ziprasidone1 | ++ | +9.7 (n = 3095); 13 | +++ | 2 | 5.3 | 2, 3, 13, 19, 23 |
| Sertindole1 | +++ | +11 to 30 (n = 510); 10 | + | 2 | N.R. | 2, 10, 13, 14, 18, 23, 24 |
| Quetiapine1 | +++ | -2 to +19.7 (n = 312); 10 | ++ | 2 | 33.3 | 2, 5, 10, 19, 23, 24, e36, e37 |
| Risperidone1 | ++ | +2 to 11.6 (n = 185); 10 | + | 2 | 29.0 | 2, 5, 6, 10, 14, 17, 19, 24, e3, e38 |
| Clozapine | ++ | +10 (n = 13); 10 | + | 2 | 13.3 | 2, 5, 6, 10, 13, 23, 24, e6, e7 |
| Paliperidone1 ER | Ø | +1.7 to 3.7 (n = 1300); e4 | N.R. | 2 | 3.2 | e4 |
| Sulpiride1 | ++ | + | 4.1 | 5, 13, 24, e12, e13 | ||
| Amisulpride1 | + | -5.9 (n = 12); 13 | ++ | 7.0 | 2, 5, 13, 23, 24, e9, e39 | |
| Zotepine1 | + | +8.3 (n = 537); 13 | N.R. | 0.8 | 5, 13, 23, e40 | |
| Olanzapine1 | + | -4.5 to +8.4 (n = 1342); 10 | N.R. | 32.7 | 2, 5, 10, 13, 14, 23, 24, e10 | |
| Aripiprazole | Ø | -4 to -3.5 (n = 828); 10 | N.R. | 8.0 | 2, 10, 14, e11 | |
| Tri-and tetrayclic antidepressants | ||||||
| Amitriptyline1 | +++ | +1 to 21 (n = 117); 10 | ++ | 3 | 94.5 | 7, 10, 18, 23, 24, e21, e23 |
| Doxepine | +++ | +8 to 22 (n = 20); 10 | ++ | 3 | 54.2 | 7, 10, 18, 23, 24, e24 |
| Imipramine1 | +++ | +4 to 20 (n = 76); 10 | + | 3 | 2.6 | 7, 10, 23, 24, e25 |
| Clomipramine1 | ++ | -1.6 to 14.7 (+6,6; n = 19); 7 | ++ | 3 | 8.1 | 7, 10, 18, 23, 24 |
| Desipramine1 | +++ | +11 to 24 (n = 74); 10 | + | 3 | N.R. | 10, 18, 23, 24 |
| Nortriptyline1 | +++ | +7 to 30 (n = 129); 10 | N.R. | 3 | 2.5 | 7, 10, 23 |
| Trimipramine1 | Ø | N.R. | 3 | 31.6 | e41 | |
| Maprotiline | +++ | +17 (n = 95); 10 | ++ | 3.8 | 7, 10, 18, 23, 24, e22, e42 | |
| Mirtazapine | + | +3.1 (n = 338); 9, 10 | + | 123.1 | 7, 10, 19 | |
| Trazodone1 | + | -4 to +7 (n = 52); 10 | + | 2.0 | 10, 23, 24, e15, e16 | |
| Mianserine | + | -10.3 to 6.9 (-1,7; n = 20); 7 | + | N.R. | 7, 23 | |
| Opipramol | Ø | N.R. | 74.0 | e43 | ||
| SSRI/SSNRI/SNRI2 | ||||||
| Venlafaxine1 | + | +4.7 (n = 357); 10 | + | 2 | 75.1 | 7, 10, 14, 24, e44, e45 |
| Citalopram1 | + | -10 to 0 (n >900); 10 | ++ | 3 | 241.7 | 7, 8, 10, 14, 19, 20, e18– 20 |
| Fluoxetine | ++ | 0 to 10 (n = 370); 10 | ++ | 3 | 43.3 | 8, 10, 19, 20, 23, 24 |
| Paroxetine | Ø | -3.1 to 4.2 (+0.6; n = 111); 7 | ++ | 3 | 42.3 | 7, 10, 19, 20, 24 |
| Sertraline | Ø | 0 (n = 2500); 10 | N.R. | 3 | 55.1 | 7, 10 |
| Escitalopram1 | + | N.R. | 17, 20 | |||
| Fluvoxamine | Ø | 0 to 2 (n = 99); 10 | N.R. | N.R. | 7, 10 | |
| Reboxetine | Ø | N.R. | 6.8 | e46 | ||
| Duloxetine | Ø | N.R. | 34.7 | e47– 50 | ||
| Other antidepressants | ||||||
| Lithium1 | +++ | 0.7 to 19.4 (+10.1; n = 18); 7 | N.R. | 2 | 20.3 | 6, 7, 12, 14, 24, e16 |
| Bupropion | + | -6.4 to -0.3 (n = 80); 10 | + | 6.5 | 7, 10, 23, 24 | |
| Buspirone | N.R. | N.R. | 1.0 | |||
| Hypericum | Ø | -5 (n = 84); 10 | N.R. | 27.7 | 10 | |
| Moclobemide | Ø | -0.3 (n = 3); 7 | N.R. | N.R. | 7 | |
| Tranylcypromine | Ø | +4 (n = 10); 10 | N.R. | 2.7 | 7, 10, 24 | |
| Sedatives and other psychotropic drugs | ||||||
| Methadone1 | +++ | 17 ± 5 (n = 55); 22 | +++ | 1 | 2.8 | 22, 24, e26– 28, e51 |
| Levomethadone1 | +++ | 27 ± 4.5 (n = 55); 22 | + | 1 | 5.4 | 22, 24, e51 |
| Chloral hydrate1 | + | + | 2 | 1.8 | 23, 24, e52 | |
| Methylphenidate | Ø | N.R. | 3 | 55.3 | e53, e54 | |
| Atomoxetine1 | Ø | N.R. | 3 | 2.6 | e55, e56 | |
| Tiapride1 | + | + | 5.0 | 2, 23, 24 | ||
| Carbamazepine | Ø | N.R. | 53.9 | 6, 12, e57– e59 | ||
| Valproate | Ø | N.R. | 53.1 | 12, 24, e60 | ||
| Lamotrigine | Ø | N.R. | 20.2 | e59, e61 | ||
| Biperidene | Ø | N.R. | 9.9 | 12 | ||
| Diazepam | Ø | N.R. | 31.0 | 12 | ||
1The summary of product characteristics (SPC) warns of QTc prolongation/TdP, esp. with overdose in combination with other QTc-prolonging drugs or in case of hypokalemia. 2 Selective serotonin-reuptake in hibitors(SSRI), selective norepinephrine-reuptake inhibitors (SNRI), selective serotonin/norepionephrine-reuptake inhibitors (SSNRI).
QTc prolongation::
Ø, none at therapeutic concentrations;
+, mild (>5 and <9 ms) or only in case of overdose or intoxication;
++, moderate (≥9 and <16 ms);
+++, severe (≥17 ms);
ER, extended-release formulation;
n, number of study participants.
Reported cases of TdP:
N.R., not reported;
+, rare cases in combination with other drugs that elevate the risk of TdP, or in the setting of overdose or intoxication;
++, rare cases under monotherapy and/or at therapeutic concentrations;
+++, multiple case reports or studies.
TdP risk according to the Arizona CERT (9):
1, generally accepted elevated risk of TdP;
2, rare case reports of TdP, possible but not adequately documented TdP risk;
3, weak association with TdP, unlikely at therapeutic doses, elevated TdP risk in the presence of congenital QT syndrome.
DDD, number of defined daily doses in Germany (11)