Efavirenz and psychosis: Is there a link?

To the Editor

Recent advancements in the management of HIV have led to a growing number of ‘combination treatments’ with many antiretrovirals administered in ‘once per day’ tablet forms (Lochet et al., 2003). Atripla is one example, containing emtricitabine, tenofovir and efavirenz. Combination drugs may create a risk of combined side effects with difficulty identifying which pharmaceutical constituent is responsible for adverse events.

Atripla’s safety information lists some potential psychiatric side effects (Atripla, 2011) but does not separate side effects by its drug components. Existing literature suggests a broad association between antiretroviral drugs and acute psychosis (Kashuba, 2008) with more studies suggesting a link between acute psychosis and efavirenz (Lochet et al., 2003; Poulsen and Lublin, 2003; Zalila et al., 2010).

Mr C, a 38-year-old HIV and hepatitis C positive man, was admitted to the psychiatry ward of a large metropolitan hospital after 1 week of paranoid ideation and persecutory delusions. He believed that people were following him and that drug dealers wanted to murder him. He had several aggressive responses to these beliefs, including throwing a brick through a neighbour’s window and breaking into a stranger’s house. Mr C’s symptoms coincided with the initiation (2 weeks prior to admission) of the antiretroviral regime, Atripla.

Mr C had no past psychiatric history and denied experiencing any prior psychotic symptoms. He attributed the psychotic symptoms to his antiretroviral medication.

Complicating his presentation was a history of illicit drug use for 8 years. His daily drug use prior to admission included methamphetamine 1 g/day IV, occasional oral gamma-hydroxybutyric acid (GHB) and smoking cannabis. Urine drug testing on admission confirmed the presence of both amphetamines and cannabis.

Mr C’s Atripla had been ceased 2 days prior to admission and he was commenced on 1 mg risperidone oral twice daily. His HIV biochemistry showed a CD4 count of 286 (16%) and viral load of 162,237. Other investigations (apart from pre-existing HIV and hepatitis C) and physical examination were normal.

Mr C improved rapidly over the next 2 days, displaying a significant reduction in paranoid ideation and persecutory delusions. He was able to identify that he had experienced a brief psychotic illness. After a further 2 days he was discharged.

In consultation with his HIV specialist and with a viral load of 78,000, Mr C. temporarily ceased taking Atripla to minimize the possibility of another psychiatric relapse. There was no immediate plan to begin another antiretroviral.

Three weeks after discharge, Mr C had no psychiatric symptoms. He still used illicit substances, as evidenced by two urine drug tests, which both detected amphetamines and cannabis. He continued to take 1 mg oral risperidone twice daily, and was not taking any antiretrovirals.

Mr C’s brief psychosis appears to have been precipitated by Atripla although HIV patients can experience acute psychosis due to the CNS effects and psychological impact of the disease itself. Nonetheless, this case highlights the need to consider the possible psychiatric implications of taking combined antiretroviral treatments, especially those containing efavirenz, when considering differential diagnoses for new-onset brief psychosis.