Cardiovascular side effects of new antidepressants and antipsychotics: New drugs, old concerns?

Pal Pacher, V. Kecskeméti

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na+, Ca2+ and K+ channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon.

Original languageEnglish
Pages (from-to)2463-2475
Number of pages13
JournalCurrent Pharmaceutical Design
Volume10
Issue number20
DOIs
Publication statusPublished - 2004

Fingerprint

Antidepressive Agents
Antipsychotic Agents
olanzapine
Risperidone
Clozapine
Blood Vessels
Cardiac Arrhythmias
Electrocardiography
Pimozide
Thioridazine
Droperidol
Fluvoxamine
Cardiovascular Agents
Sertraline
Clomipramine
Paroxetine
Citalopram
Orthostatic Hypotension
Desipramine
Amitriptyline

Keywords

  • Antidepressants
  • Antipsychotics
  • Arrhythmia
  • Cardiac ion channels
  • Neuroleptics
  • QT prolongation
  • Repolarization

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Cardiovascular side effects of new antidepressants and antipsychotics : New drugs, old concerns? / Pacher, Pal; Kecskeméti, V.

In: Current Pharmaceutical Design, Vol. 10, No. 20, 2004, p. 2463-2475.

Research output: Contribution to journalArticle

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