Antidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolizing genes of the CYP450 family

Yolande Lucire, Christopher CrottyEdgecliff Centre, Edgecliff, NSW, AustraliaPurpose: To examine the relation between variant alleles in 3 CYP450 genes (CYP2D6, CYP2C9 and CYP2C19), interacting drugs and akathisia in subjects referred to a forensic psychiatry practice in Sydney, Australia.Patients and methods: This paper concerns 10/129 subjects who had been referred to the first author’s practice for expert opinion or treatment. More than 120 subjects were diagnosed with akathisia/serotonin toxicity after taking psychiatric medication that had been prescribed for psychosocial distress. They were tested for variant alleles in CYP450 genes, which play a major role in Phase I metabolism of all antidepressant and many other medications. Eight had committed homicide and many more became extremely violent while on antidepressants. Ten representative case histories involving serious violence are presented in detail.Results: Variant CYP450 allele frequencies were higher in akathisia subjects compared with random primary care patients tested at the same facility. Ten subjects described in detail had variant alleles for one or more of their tested CYP450 genes. All but two were also on interacting drugs, herbals or illicit substances, impairing metabolism further. All those described were able to stop taking antidepressants and return to their previously normal personalities.Conclusion: The personal, medical, and legal problems arising from overuse of antidepressant medications and resulting toxicity raise the question: how can such toxicity events be understood and prevented? The authors suggest that the key lies in understanding the interplay between the subject’s CYP450 genotype, substrate drugs and doses, co-prescribed inhibitors and inducers and the age of the subject. The results presented here concerning a sample of persons given antidepressants for psychosocial distress demonstrate the extent to which the psychopharmacology industry has expanded its influence beyond its ability to cure. The roles of both regulatory agencies and drug safety “pharmacovigilantes” in ensuring quality and transparency of industry information is highlighted.Keywords: adverse drug reaction, drug therapy, safety pharmacogenetics, CYP1A2, CYP3A4 CYP2D6, CYP2C9, CYP2C19, drug metabolism, public health, suicide, violence, human right

Stigmatization of Repetitive Hand Use in Newspaper Reports of Hand Illness

Failure to provide a balanced evidence-based consideration of the role of activity in illness can stigmatize individuals and their activities. We assessed the prevalence of language that stigmatized repetitive hand use and those that use their hand repetitively in newspaper coverage of common hand illnesses. The LexisNexis Academic database was used to search five major US newspapers for articles containing keywords about common hand illnesses during a 3-year period. Article language was assessed for stigmatization of activities involving repetitive hand use as well as for stigmatization of patients who use their hand repetitively. One hundred and twenty-four articles on hand illnesses were identified. Of these, 65.3% of articles stigmatized activities involving repetitive hand use, including 96.6% of articles discussing overuse injury of the hand, 90% of articles discussing tendonitis or tenosynovitis, and 51.8% of articles discussing carpal tunnel syndrome. Patient stigmatization was documented in 30.6% of the newspaper articles. Stigmatizing statements were most commonly made by journalists (94.8%), followed by patients (3.1%), and physicians (2.1%). Language that stigmatizes repetitive hand use and patients who use their hand repetitively is prevalent among US newspaper articles. Both health professionals and journalists reporting health-related news should be more sensitive to the use of stigmatizing language and provide a more balanced, measured, and evidenced-based account of hand illnesses