Generally, females are regarded as a high-risk group of QTC interval prolongation. The QTC interval has been reported to be longer in females than in males (Moss, 1993). A meta-analysis of 332 patients exposed to cardiovascular medications suggested that females were more likely to develop torsades de pointes than males in response to drugs that prolong cardiac repolarization (Makkar et al., 1993).
From this evidence, we focused on gender differences in QTC interval distribution and its related factors in people with mental disorders (Ito et al., 2004). We retrospectively reviewed medical charts of 328 patients (145 men and 183 women) taking psychotropics at their admission discharged from a university psychiatric unit between November 1997 and December 2000. The mean QTC interval was 0.408 (standard deviation [SD]=0.036). QTC intervals in women were significantly longer than those in men.
Gender was a significant factor in the tests controlling for diagnosis, antipsychotics and hepatic failure. Cardiovascular disease was the only significant factor other than gender. The mean QTC interval in those with cardiovascular diseases was significantly longer than that in those without cardiovascular diseases. Regarding psychiatric diagnosis using DSM-IV, 94 (28.7%) patients were diagnosed as suffering from schizophrenia, 95 (29.0%) from mood disorders, and 139 (42.4%) from other. There were no significant differences in QTC among the three groups.
The results of our study suggest that a gender difference still exists in QTC lengthening in people with mental disorders after excluding effects of cardiovascular comorbidity. QTC intervals in females were significantly higher than in males among people with mental disorders without cardiovascular comorbidity (Figure).
Precautions Against Drug-Induced Adverse Effects
Adverse effects can be minimized by careful pretreatment evaluation, prescription and monitoring. Special attention should be paid to overdose, patients with cardiovascular disease or other risk factors (Glassman and Bigger, 2001; Yap and Camm, 2000), and concomitant administration of drugs that prolong QTC interval (Yap and Camm, 2000). Checking for an irregular pulse and necessary electrocardiogram should be included in monitoring during treatment, and the advice of a cardiologist is recommended if the QTC interval exceeds 500 ms (Lader, 1999).
Effect of Hormones Is a Matter of Controversy
It is known that the incidence of cardiovascular disease is significantly lower in premenopausal females than males and postmenopausal females, while the risk of heart disease is increasing in females after menopause. This suggests that natural estrogens have a protective effect in the development of cardiovascular diseases (Barrett-Connor and Bush, 1991; Hu et al., 1999; van der Schouw et al., 1996), and factors related to female gender such as steroid hormone receptors and ion channels may possess cardioprotective properties (Collins et al., 2002).The mechanism of hormones, however, is still unclear. Roeters van Lennep and colleagues (2002) found that estrogen alone or estrogen in combination with progestin did not affect the progression of coronary atherosclerosis.
