Skip to main content

Advertisement

SpringerLink
Log in

A Systematic Review of the Psychiatric Side-Effects of Efavirenz

  • Substantive Review
  • Published:
AIDS and Behavior Aims and scope Submit manuscript

Abstract

Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gallant JE, DeJesus E, Arribas JR, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006;354(3):251–60.

    Article  PubMed  CAS  Google Scholar 

  2. Ena J, Pasquau F. Once-a-day highly active antiretroviral therapy: a systematic review. Clin Infect Dis. 2003;36(9):1186–90.

    Article  PubMed  CAS  Google Scholar 

  3. Vrouenraets SM, Wit FW, van Tongeren J, et al. Efavirenz: a review. Expert Opin Pharmacother. 2007;8(6):851–71.

    Article  PubMed  CAS  Google Scholar 

  4. Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available from http://AIDSinfo.nih.gov. Cited Accessed, 1 May 2009.

  5. Sustiva [efavirenz;productinformation].Wilmington, Delaware: DuPont Pharmaceuticals. http://packageinserts.bms.com/pi/pi_sustiva.pdf.

  6. Ruiz N. Clinical history of efavirenz. Int J Clin Pract Suppl. 1999;103:3–7.

    PubMed  CAS  Google Scholar 

  7. Moyle G. In: 6th International Congress on Drug Therapy in HIV Infection, Glasgow, Scotland, November 17–21, 2002.

  8. Munoz-Moreno JA, Fumaz CR, Ferrer MJ, et al. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review. AIDS Rev. 2009;11(2):103–9.

    PubMed  Google Scholar 

  9. Fumaz CR, Tuldra A, Ferrer MJ, et al. Quality of life, emotional status, and adherence of HIV-1-infected patients treated with efavirenz versus protease inhibitor-containing regimens. J Acquir Immune Defic Syndr. 2002;29(3):244–53.

    PubMed  CAS  Google Scholar 

  10. Gutierrez-Valencia A, Viciana P, Palacios R, et al. Stepped-dose versus full-dose efavirenz for HIV infection and neuropsychiatric adverse events: a randomized trial. Ann Intern Med. 2009;151(3):149–56.

    PubMed  Google Scholar 

  11. Rihs TA, Begley K, Smith DE, et al. Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study. HIV Med. 2006;7(8):544–8.

    Article  PubMed  CAS  Google Scholar 

  12. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999;341(25):1865–73.

    Article  PubMed  CAS  Google Scholar 

  13. Fumaz CR, Munoz-Moreno JA, Molto J, et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr. 2005;38(5):560–5.

    Article  PubMed  Google Scholar 

  14. Clifford DB, Evans S, Yang Y, et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med. 2005;143(10):714–21.

    PubMed  CAS  Google Scholar 

  15. Fischl MA, Ribaudo HJ, Collier AC, et al. A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease. J Infect Dis. 2003;188(5):625–34.

    Article  PubMed  CAS  Google Scholar 

  16. Perez-Molina JA. Safety and tolerance of efavirenz in different antiretroviral regimens: results from a national multicenter prospective study in 1, 033 HIV-infected patients. HIV Clin Trials. 2002;3(4):279–86.

    Article  PubMed  Google Scholar 

  17. MedWatch USFaDA. http://wwwfdagov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM164871pdf. Accessed 7 December 2010.

  18. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2008. p. 701.

  19. Markowitz M, Hill-Zabala C, Lang J, et al. Induction with abacavir/lamivudine/zidovudine plus efavirenz for 48 weeks followed by 48-week maintenance with abacavir/lamivudine/zidovudine alone in antiretroviral-naive HIV-1-infected patients. J Acquir Immune Defic Syndr. 2005;39(3):257–64.

    Article  PubMed  CAS  Google Scholar 

  20. Goldenberg D. Psychiatric and neuropsychiatric manifestations of HIV infection. J Int Assoc Physicians AIDS Care (Chic Ill). 2003;2(2):88. author reply 9-90.

    Article  Google Scholar 

  21. Wanchu APS, Bambery P, Singh S, Varma S. Adverse drug reactions to generic antiretroviral medications in resource constrained set- tings: implication for scaling up therapy. In: Paper presented at 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO, 2006 (abstract 562).

  22. Lochet P, Peyriere H, Lotthe A, et al. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med. 2003;4(1):62–6.

    Article  PubMed  CAS  Google Scholar 

  23. Journot V, Chene G, De Castro N, et al. Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099. Clin Infect Dis. 2006;42(12):1790–9.

    Article  PubMed  CAS  Google Scholar 

  24. O’Mahony SM, Myint AM, Steinbusch H, et al. Efavirenz induces depressive-like behaviour, increased stress response and changes in the immune response in rats. Neuroimmunomodulation. 2005;12(5):293–8.

    Article  PubMed  Google Scholar 

  25. Moreno A, Labelle C, Samet JH. Recurrence of post-traumatic stress disorder symptoms after initiation of antiretrovirals including efavirenz: a report of two cases. HIV Med. 2003;4(3):302–4.

    Article  PubMed  CAS  Google Scholar 

  26. Damsa C, Bandelier C, Maris S, et al. Recurrence of post-traumatic stress disorder and antiretrovirals. Scand J Infect Dis. 2005;37(4):313–6.

    Article  PubMed  Google Scholar 

  27. Shah MD, Balderson K. A manic episode associated with efavirenz therapy for HIV infection. AIDS. 2003;17(11):1713–4.

    Article  PubMed  Google Scholar 

  28. Peyriere H, Mauboussin JM, Rouanet I, et al. Management of sudden psychiatric disorders related to efavirenz. AIDS. 2001;15(10):1323–4.

    Article  PubMed  CAS  Google Scholar 

  29. Gallego L, Barreiro P, del Rio R, et al. Analyzing sleep abnormalities in HIV-infected patients treated with Efavirenz. Clin Infect Dis. 2004;38(3):430–2.

    Article  PubMed  CAS  Google Scholar 

  30. Tashima K, Staszewski S, Nelson M, et al. Efficacy and tolerability of long-term efavirenz plus nucleoside reverse transcriptase inhibitors for HIV-1 infection. AIDS. 2008;22(2):275–9.

    Article  PubMed  CAS  Google Scholar 

  31. Faggian F, Lattuada E, Lanzafame M, et al. Recreational substance use and tolerance of efavirenz in HIV-1 infected patients. AIDS Care. 2005;17(7):908–10.

    Article  PubMed  CAS  Google Scholar 

  32. Juethner SN, Seyfried W, Aberg JA. Tolerance of efavirenz-induced central nervous system side effects in HIV-infected individuals with a history of substance abuse. HIV Clin Trials. 2003;4(3):145–9.

    Article  PubMed  Google Scholar 

  33. Garey M, editor. Efavirenz (EFV) tolerability in the real world: relation to mental illness, alcohol, and illicit drug use in a large, urban HIV clinic. In: Presented at the XIII international AIDS conference, Durban, SA, July 9–14, 2000 (abstract no. WePeB4288).

  34. Clarke SM, Mulcahy FM, Tjia J, et al. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol. 2001;51(3):213–7.

    Article  PubMed  CAS  Google Scholar 

  35. Marwaha A. Getting high on HIV drugs in South Africa. http://newsbbccouk/2/hi/africa/7768059stm. 2008. Accessed 7 December 2010.

  36. Quereda C, Corral I, Moreno A, et al. Effect of treatment with efavirenz on neuropsychiatric adverse events of interferon in HIV/HCV-coinfected patients. J Acquir Immune Defic Syndr. 2008;49(1):61–3.

    Article  PubMed  CAS  Google Scholar 

  37. Bickel M, Stephan C, Rottmann C, et al. Severe CNS side-effect and persistent high efavirenz plasma levels in a patient with HIV/HCV coinfection and liver cirrhosis. Scand J Infect Dis. 2005;37(6–7):520–2.

    Article  PubMed  Google Scholar 

  38. Gill MJ, Rachlis A, Walmsley S, et al. Canadian Expert Panel recommendations on the management of CNS symptoms related to efavirenz. Can J Infect Dis. 2001;12:20c–30c.

    Google Scholar 

  39. Skeie L, Maeland A. Can efavirenz be taken in the morning? Scand J Infect Dis. 2006;38(11–12):1089–91.

    Article  PubMed  CAS  Google Scholar 

  40. Kappelhoff BS, van Leth F, Robinson PA, et al. Are adverse events of nevirapine and efavirenz related to plasma concentrations? Antivir Ther. 2005;10(4):489–98.

    PubMed  CAS  Google Scholar 

  41. Haas DW, Ribaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 2004;18(18):2391–400.

    PubMed  CAS  Google Scholar 

  42. van Luin M, Brouwer AM, van der Ven A, et al. Efavirenz dose reduction to 200 mg once daily in a patient treated with rifampicin. AIDS. 2009;23(6):742–4.

    Article  PubMed  Google Scholar 

  43. Bartlett JA, Johnson J, Herrera G, et al. Long-term results of initial therapy with abacavir and lamivudine combined with efavirenz, amprenavir/ritonavir, or stavudine. J Acquir Immune Defic Syndr. 2006;43(3):284–92.

    Article  PubMed  CAS  Google Scholar 

  44. Martinez-Picado J, Negredo E, Ruiz L, et al. Alternation of antiretroviral drug regimens for HIV infection. A randomized, controlled trial. Ann Intern Med. 2003;139(2):81–9.

    PubMed  Google Scholar 

  45. Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr. 2004;36(5):1011–9.

    Article  PubMed  CAS  Google Scholar 

  46. van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet. 2004;363(9417):1253–63.

    Article  PubMed  Google Scholar 

  47. Hawkins T, Geist C, Young B, et al. Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients. HIV Clin Trials. 2005;6(4):187–96.

    Article  PubMed  Google Scholar 

  48. Spire B, Carrieri P, Garzot MA, et al. Factors associated with efavirenz discontinuation in a large community-based sample of patients. AIDS Care. 2004;16(5):558–64.

    Article  PubMed  CAS  Google Scholar 

  49. Blanch J, Martinez E, Rousaud A, et al. Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. J Acquir Immune Defic Syndr. 2001;27(4):336–43.

    Article  PubMed  CAS  Google Scholar 

  50. Boly L, Cafaro V, Dyner T. Depressive symptoms predict increased incidence of neuropsychiatric side effects in patients treated with efavirenz. J Acquir Immune Defic Syndr. 2006;42(4):514–5.

    Article  PubMed  Google Scholar 

  51. Brokaw DK, Fulco PP, Klinger R. Efavirenz use in HIV infected patients with a psychiatric history. In: Presented at the 35th American Society of Health-System Pharmacists annual mid-year clinical meeting, Las Vegas, NV, December 3–7, 2000.

  52. Gaughan DM, Hughes MD, Oleske JM, et al. Psychiatric hospitalizations among children and youths with human immunodeficiency virus infection. Pediatrics. 2004;113(6):e544–51.

    Article  PubMed  Google Scholar 

  53. Goldenberg D, Boyle B, Vaamonde C, et al., editors. Psychiatric illness and efavirenz study (PIES). In: Presented at the XIII international AIDS conference, Durban, SA, July 9–14, 2000.

  54. Jena A, Sachdeva RK, Sharma A, et al. Adverse drug reactions to nonnucleoside reverse transcriptase inhibitor-based antiretroviral regimen: a 24-week prospective study. J Int Assoc Physicians AIDS Care (Chic Ill). 2009;8(5):318–22.

    Article  Google Scholar 

  55. Ward DJ, Curtin JM. Switch from efavirenz to nevirapine associated with resolution of efavirenz-related neuropsychiatric adverse events and improvement in lipid profiles. AIDS Patient Care STDS. 2006;20(8):542–8.

    Article  PubMed  Google Scholar 

  56. Welch KJ, Morse A. Association between efavirenz and selected psychiatric and neurological conditions. J Infect Dis. 2002;85(2):268–9.

    Article  Google Scholar 

  57. Koppel BS, Bharel C. Use of amitriptyline to offset sleep disturbances caused by efavirenz. AIDS Patient Care STDS. 2005;19(7):419–20.

    Article  PubMed  Google Scholar 

  58. de la Garza C, Paoletti-Duarte, García-Martín, et al. Efavirenz-induced psychosis. AIDS. 2001;15(14):1911–2.

    Article  Google Scholar 

  59. Lowenhaupt EA, Matson K, Qureishi B, et al. Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. Clin Infect Dis. 2007;45(10):e128–30.

    Article  PubMed  CAS  Google Scholar 

  60. Hasse B, Gunthard HF, Bleiber G, et al. Efavirenz intoxication due to slow hepatic metabolism. Clin Infect Dis. 2005;40(3):e22–3.

    Article  PubMed  CAS  Google Scholar 

  61. Poulsen HD, Lublin HK. Efavirenz-induced psychosis leading to involuntary detention. AIDS. 2003;17(3):451–3.

    Article  PubMed  Google Scholar 

  62. Allavena C, Le Moal G, Michau C, et al. Neuropsychiatric adverse events after switching from an antiretroviral regimen containing efavirenz without tenofovir to an efavirenz regimen containing tenofovir: a report of nine cases. Antivir Ther. 2006;11(2):263–5.

    PubMed  Google Scholar 

  63. Dawson S, Woods C. Neuropsychiatric effects of efavirenz: delayed onset. Int J STD AIDS. 2005;16(11):769–70.

    Article  PubMed  CAS  Google Scholar 

  64. Puzantian T. Central nervous system adverse effects with efavirenz: case report and review. Pharmacotherapy. 2002;22(7):930–3.

    Article  PubMed  Google Scholar 

  65. Sabato S, Wesselingh S, Fuller A, et al. Efavirenz-induced catatonia. AIDS. 2002;16(13):1841–2.

    Article  PubMed  Google Scholar 

  66. Blanch J, Corbella B, Garcia F, et al. Manic syndrome associated with efavirenz overdose. Clin Infect Dis. 2001;33(2):270–1.

    Article  PubMed  CAS  Google Scholar 

  67. Boscacci RT, Buclin T, Furrer H, et al. A case of voluntary intoxication with efavirenz and lamivudine. AIDS. 2006;20(9):1352–4.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Disclosures

Dr. Kenedi has received no financial or material support. Dr. Goforth has received past grant support from Forest Pharmaceuticals. Dr. Goforth has also previously served as a consultant to Eli Lilly and Bristol-Myers-Squibb Pharmaceuticals. That work was independent of this paper and no member of Bristol-Myers-Squibb has been involved with this work or is aware of the project or submission for publication.

Author information

Authors and Affiliations

  1. Auckland City Hospital, Liaison Psychiatry, Support Building, Level 4, Private Bag 92024, Auckland, 1142, New Zealand

    Christopher A. Kenedi

  2. Duke University Medical Center, Durham, NC, USA

    Christopher A. Kenedi & Harold W. Goforth

Authors
  1. Christopher A. Kenedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harold W. Goforth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher A. Kenedi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kenedi, C.A., Goforth, H.W. A Systematic Review of the Psychiatric Side-Effects of Efavirenz. AIDS Behav 15, 1803–1818 (2011). https://doi.org/10.1007/s10461-011-9939-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10461-011-9939-5

Keywords

Search

Navigation