A study published in the American Journal of Psychiatry looks at doxycycline use in adolescent psychiatric patients and schizophrenia risk.
Dr Katharina Schmack, Clinical Group Leader and Head of the Neural Circuits and Immunity in Psychosis Laboratory, The Francis Crick Institute, said:
“This is the frist study to look at the link between doxycycline and schizophrenia risk in health records of adolescents seeking mental health care. This is an vital population to study as thes adolescents already face an elevated risk for schizophrenia.
“The results build on existing studies in the general population that link doxycycline treatment with schizophrenia risk, and a related antibiotic, minocycline, has previously been observed to improve symptoms in some individuals. However, while this current study shows an association, it does not demonstrate a causal relationship between doxycycline treatment and schizophrenia risk.
“The researchers have analysed existing health data rather than conducted a randomised controlled trial.Their ’emulated trial’ approach is elegant but still limited because people prescribed doxycycline will differ from those who are not in many important ways, and those differences may also influence their risk for schizophrenia. And while the effects observed here are statistically significant, the absolute numbers are modest: at 15 years, doxycycline treatment at the highest dose was associated with a reduction of approximately 2.5% of absolute risk, meaning that instead of about 5 out of 100 people now roughly 2-3 out of 100 would develop schizophrenia.
“To further test whether doxycycline protects against schizophrenia, a randomized controlled trial would be needed, but this coudl be challenging. Schizophrenia risk unfolds over several years, so a clinical trial would need long-term follow-up in a large number of participants, adding to the complexity and cost of such a study.The optimal dose, timing and duration of the doxycycline treatment also remain uncertain.
“Given how challenging it is to design and conduct a randomised controlled trial, it may first be essential to better understand the underlying biological mechanisms. Such as, some studies in animals show that the antibiotic minocycline has effects on synaptic pruning – the elimination of connections in the brain during advancement – which is thought to play a role in schizophrenia. In humans it is unfeasible to measure processes before schizophrenia develops or to manipulate them outside of a clinical trial, so experimental work in animal model systems is indispensable.”