in Drugs and drugs policy, In the news

In the news – update

coloured drugs

On April 7 2009 I posted about a report by the BBC

The Today Programme reported today that care home children whose behaviour during the 1970s/80s was controlled using large doses  of medication have subsequently given birth to children with birth defects.   The drugs in question included Haloperidol, Droleptan and Depixol.  The BBC have Professor Jeffrey Aronson, professor of clinical pharmacology at Oxford University who says that high doses of such drugs can cause genetic damage.  Presumably he’s suggesting that the drugs cause damage to unfertilized eggs – rather than being teratogenic.  These drugs can currently be given to women of child bearing age.  It’s obviously concerning that large doses of sedatives should be given to anyone without a mental health disorder (or even with…) but if they’re right (nb: it doesn’t sound like a very rigerous report and there could be other causes for what they’re suggesting has happened) this would have wide ranging implications.

I contacted Professor Aronson and he was kind enough to reply

At the moment a possible association between psychotropic drug administration and later birth defects (transgenerational transmission of an epigenetic defect) is hypothetical but worthy of further study.

Transgenerational epigenetic effects have been demonstrated in animals and there is some evidence that they may occur in humans. Diethylstilbestrol was used from the 1940s to the 1970s to prevent spontaneous miscarriages. It was subsequently discovered that the daughters of women who had been given it developed vaginal adenocarcinomas. That was a direct teratogenic effect, albeit an unusual one because of the time it took after birth to occur. However, there is now evidence of a transgenerational epigenetic effect as well–the children of those daughters have abnormalities that include hypospadias in boys [1], menstrual irregularities and possibly infertility in girls [2], esophageal atresia/tracheoesophageal fistulae [3], and possibly ovarian cancers [4]. The data are not conclusive, but they are suggestive. Children of those who were affected by thalidomide may also have an increased incidence of limb deformities [5].

This means that theoretically a genotoxic effect could cause epigenetic birth defects down the line, even though the child was not exposed in utero. Cytogenetic abnormalities have been shown in the blood cells of patients exposed to antipsychotic drugs and benzodiazepines for more than 1 month [6]. I know of no evidence about oocytes.

This combination of observations, taken with the story that has just been reported, suggests that the possibility of a transgenerational epigenetic effect of psychotropic drugs should be investigated. It does not, however, prove the association that has been reported, which is based on circumstantial anecdotal evidence and could be subject to confounding by other factors that the affected women shared. 

1. Brouwers et al. Hypospadias: a transgenerational effect of diethylstilbestrol? Hum Reprod 2006;21(3):666-9.
2. Titus-Ernstoff et al. Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). Int J Epidemiol 2006;35(4):862-8.
3. Felix et al. Esophageal atresia and tracheoesophageal fistula in children of women exposed to diethylstilbestrol in utero. Am J Obstet Gynecol 2007; 197(1): 38.e1-5.
4. Titus-Ernstoff et al. Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation. Epidemiology 2008;19(2):251-7. 5. Holliday R. The possibility of epigenetic transmission of defects induced by teratogens. Mutat Res 1998; 422(2): 203-5.
6. Bigatti et al. Increased sister chromatid exchange and chromosomal aberration frequencies in psychiatric patients receiving psychopharmacological therapy. Mutat Res 1998;413(2):169-75.

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