Efavirenz-induced psychosis

In the absence of a cure for HIV infections, the present aim of antiretroviral therapy is to produce the maximal suppression of HIV replication for as long as possible. Current treatment guidelines recommend a combination therapy consisting of a nucleoside reverse transcriptase inhibitor with either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor ^[1].

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that shows good inhibitory activity against HIV-1 ^[2]. It is metabolized in the liver predominantly through cytochrome P450 3A4 and 2B6 isoenzymes, and has been reported to induce cytochrome P450 3A4 in vivo. Although pharmacokinetic interactions have been described among antiretroviral drugs, efavirenz has demonstrated no pharmacokinetic interaction with nucleoside reverse transcriptase inhibitors such as lamivudine or zidovudine ^[3]. Nervous system symptoms such as headache, dizziness, insomnia and fatigue were one of the most frequently reported adverse events associated with combination regimens including efavirenz in a large randomized study ^[4].

We describe a case of psychosis after a combination regimen with efavirenz. A 40-year-old Portuguese woman with HIV disease (CD4 lymphocyte count 27/mm³ and viral load 171 555 copies/mm³ 12 h after admission) was admitted to hospital because of acute changes in her mental status. She was disoriented, confused and reported feeling fearful at home. Paranoid delusions and insomnia were also present.

Laboratory values were generally within normal ranges, toxicological screening was negative, and there were no abnormalities on neurological exploration. Magnetic resonance imaging demonstrated no evidence of cerebral atrophy, toxoplasmosis or lymphomas. The patient had no previous history of mental illness.

Efavirenz (600 mg/day) had been added to the patient's regimen 6 days before admission. Two days later the patient had experienced episodes of confusion, agitation and violent behaviour. Other medication she had received in the daily regimen before admission included zidovudine (300 mg) and lamivudine (100 mg).

Efavirenz was discontinued and haloperidol (9 mg/day) plus lorazepam (3 mg/day) were added to the previous regimen. Nevirapine (200 mg/day) was subsequently added instead of efavirenz, and loratadine was also introduced to prevent the adverse dermatological effects of nevirapine.

After 2 days the patient showed an improvement in mental status and was completely recovered on the seventh day. At follow-up 3 weeks after discharge the patient had no psychotropic drugs in her treatment and showed no disturbances of her mental status.

A temporal relationship between the onset of treatment with efavirenz and the appearance of psychotic symptoms, and the absence of pharmacokinetic interactions between efavirenz, lamivudine and zidovudine may suggest a casual link.

This case illustrates that psychosis can develop in HIV patients taking efavirenz. Therefore caution must be exercised in HIV patients treated with combination regimens including efavirenz, to prevent the occurrence of psychiatric disorders.

César Luis Sanz de la Garzaa

Santos Paoletti-Duarteb

Carlos García-Martínc

Jose Ramón Gutiérrez-Casaresd