Minor cardiovascular adverse effects from antipsychotic drugs are extremely
common. They include effects such as postural hypotension and tachycardia
due to anticholinergic or alpha(1)-adrenoceptor blockade, and may occur in
the majority of patients at therapeutic dosages. There are a number of phar
macological effects that are of uncertain clinical significance, such as bl
ockade of calmodulin, sodium and calcium channels and alpha(2)-adrenoceptor
s in the central nervous system. The most serious consequences of treatment
, arrhythmias and sudden death, are probably uncommon and are most likely t
o be caused primarily by blockade of cardiac potassium channels such as HER
G. Incomplete evidence suggests that arrhythmias and sudden death are a par
ticular problem with certain drugs (thioridazine and droperidol), high risk
populations (elderly, pre-existing cardiovascular disease, inherited disor
ders of cardiac ion channels or of antipsychotic drug metabolism) or people
taking interacting drugs (such as drugs that prolong the QT interval, e.g.
bicyclic antidepressants, drugs that inhibit antipsychotic drug metabolism
, or diuretics). Clozapine may be unique in also causing death from myocard
itis and cardiomyopathy. Much further research is required to more clearly
identify high risk drugs and the populations that are at risk of sudden dea
th, as well as the mechanisms involved and the extent of the risk.