PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Psychotropic Drugs - Cardiotoxicity.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Psychotropic Drugs - Cardiotoxicity

Psychotropic Drugs - Cardiotoxicity

Date Created: 08/03/2001   Last Modified: 24/05/2001   Last Checked: 23/01/2003

Minor cardiovascular adverse effects from antipsychotic drugs are extremely common, in fact they are inevitable because of the broad receptor blocking properties of all psychotropics. They include effects such as postural hypotension from alpha1-adrenoceptor blockade (A1) and tachycardia due to muscarinic receptor blockade. They occur in all patients, at least to some degree, at therapeutic dosages. There are a number of pharmacological effects that are of uncertain clinical significance, such as blockade of calmodulin, sodium and calcium channels, and alpha2-adrenoceptors (A2) in the central nervous system.

The most serious adverse effects of arrhythmias and sudden death are probably uncommon and are most likely to be caused primarily by blockade of cardiac potassium channels such as HERG.

Incomplete evidence suggests that arrhythmias and sudden death may be a particular problem with certain drugs (eg thioridazine and droperidol), and also in high risk populations:--

  • the elderly
  • pre-existing cardiovascular disease
  • inherited disorders of cardiac ion channels
  • poor metabolisers of antipsychotic drugs (cytochrome P450 enzymes - especially 1A2 and 2D6)
  • people taking interacting drugs (such as drugs that prolong the QT interval, e.g. tricyclic antidepressants)
  • drugs that inhibit antipsychotic drug metabolism
  • diuretics (altered potassium levels).

Clozapine may be unique in also causing death from myocarditis and cardiomyopathy.

Much further research is required to more clearly identify high risk drugs and the populations that are at risk of sudden death, as well as the mechanisms involved and the extent of the risk.

Simplistic prohibitions of particular drugs, eg recently thioridazine, may be of some use but they are not a substitute for a proper understanding of the above factors and mechanisms. An understanding of the polymorphicity of cytochrome P450 enzymes and how that determines metabolism is of great assistance:-- see other 'Psychopharmacology Update Notes' especially "blood levels" and cytochrome P450 enzymes.

In this context it is relevant to observe the continuing high use of the tricyclic antidepressant dothiepin. This continues despite longstanding evidence that it is by far the most toxic of the available choices, without, I would suggest, having any counterbalancing redeeming features of significance. It is very probable that avoiding dothiepin would save many more lives than avoiding thioridazine.