Savvy Psychopharmacology

Which psychotropics carry the greatest risk of QTc prolongation?

Current Psychiatry. 2012 October;11(10):36-39

References

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Clinical Point

QTc prolongation has been associated with long-term ziprasidone use more often than with risperidone, olanzapine, or quetiapine

Cardiovascular adverse effects associated with clozapine—including QTc prolongation—are dose-dependent.³ Olanzapine prolongs QTc interval, although the mean change is less than with other agents unless other variables were present, such as:

concomitant use of medications that may prolong QTc interval (ie, amantadine, hydroxyzine, or tamoxifen²)
preexisting cardiovascular conduction disorders
higher doses (>40 mg/d).^3,23

In 17 case reports of cardiac changes associated with quetiapine use, doses ranged from 100 mg/d²⁴ to an overdose of 36 g/d.²⁵ Only 1 patient death was reported secondary to overdose and preexisting dysrhythmia and hypertension.²⁶ QTc prolongation associated with risperidone was minor¹ based on oral doses in the normal therapeutic range and incidences of overdose.¹⁰ Paliperidone²⁷ and lurasidone²⁸ are associated with clinically insignificant QTc prolongation. Changes in QTc interval were positively correlated with asenapine dose, although at the highest dose of 40 mg/d, the increase was <5 milliseconds.²⁹

Clinical Point

Paliperidone and lurasidone are associated with clinically insignificant QTc prolongation

Mrs. A presents with a number of risk factors for QTc prolongation, including older age, female sex, and psychiatric and medical comorbidities that require medication. A pill count revealed that she was taking more than the prescribed daily doses of her medications. During the interview, Mrs. A said that if she missed her medication time, she would take them when she remembered. If she could not remember if she took her pills, she would take them again. Her physicians will explore strategies to increase medication adherence.

Table

Examples of QTc prolongation associated with select antipsychotics^a

Antipsychotic	Approximate QTc interval prolongation in milliseconds^b
Aripiprazole^4,17	-1 to -4
Clozapine⁴	10
Haloperidol^1,2	7 to 15
Mesoridazine¹⁶	39 to 53
Olanzapine¹	2 to 6.5
Paliperidone⁴	2 to 4
Pimozide²	19
Quetiapine^1,2	6 to 15
Risperidone^1,2	3.5 to 10
Sertindole¹	30
Thioridazine^2,16	33 to 41
Ziprasidone^1,2	16 to 21
^aList is not comprehensive. Other antipsychotics may be associated with QTc prolongation ^bQTc prolongation interval may depend on the route of administration

Related Resources

De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126.
Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26(12):997-1012.
Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics. 2005;46(5):464-494.

Drug Brand Names

Amantadine • Symmetrel
Amitriptyline • Elavil
Aripiprazole • Abilify
Asenapine • Saphris
Chlorpromazine • Thorazine
Citalopram • Celexa
Clozapine • Clozaril
Desipramine • Norpramin
Fluoxetine • Prozac
Furosemide • Lasix
Haloperidol • Haldol
Hydroxyzine • Atarax, Vistaril
Iloperidone • Fanapt
Lisinopril • Prinivil, Zestril
Lorazepam • Ativan
Lurasidone • Latuda
Maprotiline • Ludiomil
Mesoridazine • Serentil
Metformin • Glucophage
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Paliperidone • Invega
Paroxetine • Paxil
Pimozide • Orap
Quetiapine • Seroquel
Risperidone • Risperdal
Tamoxifen • Nolvadex, Soltamox
Thioridazine • Mellaril
Venlafaxine • Effexor
Ziprasidone • Geodon

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. No similar work by the authors is under review or in press. No funding was requested or received in conjunction with this manuscript.