Previously unreported NNRTI psychiatric side-effects come to light

Correspondence highlighting previously unreported central nervous system side-effects associated with the two licensed NNRTIs, nevirapine and efavirenz, has been published in the 6 September 2002 edition of AIDS.

Doctors at St Vincent’s Hospital in Sydney report the case of a 47 year old women, who was admitted to hospital with catatonia after three years of efavirenz therapy, and in a separate letter, doctors at the Chelsea and Westminster Hospital, London, report that four patients treated with nevirapine have experienced vivid dreams, a side-effect previously only associated with efavirenz.

In the Sydney case, doctors reported the development of catatonia in a 47 year old woman, who had received three years of HAART including efavirenz, 3TC and d4T, with a CD4 count of 550 cells/mm³ and a viral load of 1,400 copies/mL. The woman had a past history of hepatitis C, injecting drug use and benzodiazepine dependence. Since starting treatment with efavirenz the woman had been admitted to hospital on 21 occasions due to an inability to cope and because of neuropsychiatric symptoms, culminating with admission to hospital with catatonia, psychosis and extreme psychomotor retardation.

Investigation of the woman’s cerebrospinal fluid revealed elevated concentrations of efavirenz, so treatment with efavirenz was halted and anti-psychotic drugs administered. After three weeks the patient recovered.

A study of stored plasma revealed increasing concentrations of efavirenz over time, peaking at 35,000mg/mL shortly before her admission to hospital with catatonia. The patient insisted that she had only taken the prescribed dose of efavirenz, leading doctors to conclude that the long half-life of the drug had led to a gradual accumulation in her plasma. In addition, doctors speculate that the use of benzodiazepines may have contributed to the build-up of efavirenz and conclude that the case demonstrates that efavirenz should not be given to patients with a history of mental illness. They also draw attention to the need to determine levels of efavirenz in the cerebrospinal fluid and plasma of people presenting with central nervous system side-effects.

In a separate letter, doctors at London’s Chelsea and Westminster Hospital report that four men treated with nevirapine experienced vivid dreams, a side-effect previously only reported by people taking efavirenz. The four men were all on their first HAART regimen and none had a previous AIDS-defining illness or history of mental ill-health. Nor did any of the men report recreational drug use. All four had a viral load below 50 copies/mL and had experienced an increase in CD4 count since starting HAART.

The Chelsea and Westminster doctors suggest that the vivid dreams could be due to drug concentrations in the cerebrospinal (CSF) fluid, noting that concentrations of nevirapine and efavirenz in the CSF are similar. They also speculate that cytokine production may be responsible. However, they also note that NNRTIs have similar pharmacokinetic properties, with both efavirenz and nevirapine causing liver problems and rash, and that both NNRTIs are metabolised using the same liver enzyme.

They conclude that “further work needs to be undertaken to describe the prevalence and natural history of the neuropsychiatric complications of nevirapine and to inform patients that such complications may occur.”