I have received emails in the past about people asking why they feel anxious or moody on Ziagen. This problem has happened to me and others and it is rarely discussed in the literature or in physician-patient conversations.
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In response to the persons who said they cannot sleep and feel anxious on Epzicom (Ziagen+Epivir or Abacavir+ 3TC)…
I took Ziagen and it caused horrible anxiety. I found out it was the drug when I stopped it for a week and restarted it again. The symptoms would disappear and reappear in one or two days. Several friends report the same problem. Only two reports were found in the literature. This problem has not been discussed in most HIV information sources.
More on abacavir-induced neuropsychiatric reactions:
[CORRESPONDENCE]
Foster, Russella; Taylor, Chrisb; Everall, Ian Paulc
aHIV Mental Health Team, Maudsley Hospital, London, UK; bDepartment of Sexual Health, Caldecot Centre, King’s College Hospital, London, UK; and cDepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92083-0603, USA.
Received: 8 September 2004; accepted: 27 September 2004.
It is increasingly recognized that antiretroviral medications may induce severe, but transient, changes in mental state. These are uncommon and idiosyncratic, with the literature containing only two published reports suggesting that abacavir (Ziagen), a nucleoside reverse transcriptase inhibitor, may induce a range of neuropsychiatric disorders in seropositive individuals. These include depression, suicidal thoughts, auditory hallucinations [1] and frank psychosis [2]. Of note is the fact that the subjects in these cases were all female with CD4 cell counts below 500 cells/µl. Here we report, for the first time, a case of a possible abacavir-induced neuropsychiatric reaction in a seropositive Caucasian man with a higher CD4 cell count.
The patient was a 44-year-old gay man who was diagnosed HIV positive in 1993. He was referred to psychiatric services in 2000 after the psychologist whom he had been seeing became concerned about the patient’s ongoing depressive symptoms. He had previously been treated with various antidepressants and triple therapies for HIV, and was currently receiving citalopram 30 mg a day in addition to tenofovir 245 mg per day, nevirapine 200 mg twice a day and abacavir 300 mg twice a day. He had previously been taking didanosine, but this was changed to abacavir because of lipodystrophy.
Approximately one week after commencing abacavir, the patient started to complain of feeling tired and ‘stoned’. He also complained of headaches, which were described as ‘constant and throbbing’ and ‘located in the middle of my brain’. He reported the onset of bad dreams, which he referred to as ‘night terrors’. These were described as vivid and terrifying, but the actual content could not be recalled. He denied any associated physical symptoms such as night sweats or any recent physical illness. His CD4 cell count at this time was 557 cells/µl and his viral load was less than 50 copies/ml. Of note is the fact that despite his dreams he now felt that his previously low mood had improved to the extent that he was expressing the desire to cease taking citalopram.
Two weeks after reporting the above problems, the patient was reviewed by the HIV physician who changed the abacavir back to didanosine. Within 24 h of this the patient reported that his headaches and bad dreams had stopped, and that he was feeling less fatigued. At one month follow-up he remained free of these symptoms, and his mood remained settled. The citalopram was eventually reduced gradually and finally stopped.
This case suggests that abacavir may, in rare cases, induce unpleasant but non-specific neuropsychiatric side-effects, which can resolve rapidly upon stopping this medication. Although it has been suggested that abacavir may be associated with new-onset depression [1], this was not apparent in the current case. In that earlier publication [1], depression and night sweats were reported in one patient, with depression, suicidal ideation, headache, auditory hallucinations and anorexia in the second. The patients in those cases were both HIV positive Caucasian women. Similarly, a more recent publication described a case of putative abacavir-induced psychosis occurring in an African woman [2] who became symptom-free after the cessation and substitution of this medication.
The current report suggests that men can also be adversely affected by abacavir-associated neuropsychiatric problems, even at a higher CD4 cell count accompanied by a low viral load. Furthermore, symptoms may rapidly resolve upon discontinuation of abacavir and the substitution of a suitable alternative antiretroviral agent. It is possible that headache and mood alterations may be early indicators of neuropsychiatric sequelae associated with abacavir. These should be investigated and monitored closely to exclude possible organic factors. Management should be carried out in collaboration with both HIV physicians and specialist psychiatrists.
References
1. Colebunders R, Hilbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med 2002; 113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report and brief review of the literature. HIV Med 2003; 4:139–144. Accession Number: 00002030-200412030-00021
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Neuropsychiatric Reaction Induced by Abacavir in a Pediatric Human Immunodeficiency Virus-Infected Patient
[Departments: Letters to the Editors]
Palacin, Pere Soler MD; Aramburo, Angela; Moraga, Fernando A.; Cabañas, Maria Josep; Figueras, Concepció
Pediatric Infectious Diseases Unit, Vall d’Hebron Hospital, Barcelona, Spain(Palacin, Aramburo, Moraga, Figueras)
Pharmacy Service, Vall d’Hebron Hospital, Barcelona, Spain(Cabañas)
To the Editors:
Although most commonly reported abacavir-related side effects are mild and transient, and because of hypersensitivity reactions in the first 1 or 2 weeks after starting treatment with this drug, even severe neuropsychiatric reactions have been recently described in human immunodeficiency virus (HIV)-infected adult patients. These may include depression, suicidal thoughts, auditory hallucinations and frank psychosis. To our knowledge, there is no case described in pediatric HIV-infected population receiving abacavir (Ziagen; GlaxoSmithKline).
The patient we here describe is now an 11-year-old Caucasian boy who was found to be vertically transmitted HIV-positive at the age of 2 years. At the age of 3 years, he started taking antiretroviral drugs (zidovudine and lamivudine). He started highly active antiretroviral therapy (stavudine, lamivudine and nelfinavir) when he was 5 years old. He had been well since the present time with good virologic (plasma viral load below 50 copies/mL), immunologic (CD4% always >35%) and clinical situation (Centers for Disease Control and Prevention classification 1994 B2). The patient was admitted to the hospital at the age of 6 years because of indinavir-related nephrolithiasis. He did not present any acquired immunodeficiency syndrome-defining illness.
At the age of 11 years, his antiretroviral regimen was simplified to abacavir, lamivudine and efavirenz with the aim to change to lamivudine-abacavir when available, to reduce pill burden. One month after the initiation of this regimen, the parents referred that the patient had mood changes and complained of headaches, anxiety and bad dreams. During the following weeks, he developed major depression with refusal to attend school and to have any social interaction with both his friends and family. He was then referred to our center’s Department of Pedopsychiatry, the diagnosis of major depression was confirmed (DSM IV) and no exogenous triggering factor was observed. He then weighed 29 kg, and his height was 139 cm. No abnormalities were observed at physical examination. His CD4+ lymphocyte count was 888/mm3 (38%), and his plasma viral load was below 50 copies/mL. Neither the patient nor his parents had a history of psychiatric disorders.
Because of the coincidence of the beginning of neuropsychiatric manifestations and the start of a new antiretroviral drug (he had been taking lamivudine and efavirenz for a long period before) and the risk of abacavir-induced neuropsychiatric reactions, the drug was then discontinued and treatment was changed to stavudine. No other clinical or analytical signs of abacavir-related side effects were observed. Two weeks after the drug discontinuation, the patient began to improve without adding any antidepressive agent, bad dreams and headache disappeared and he accepted school attendance. After 3 months of follow-up, psychiatric problems did not reappear and the patient’s mood remained settled.
This case supports the idea that, as described in the adult HIV-infected population,1–3 abacavir can induce several neuropsychiatric side effects in pediatric patients that resolve rapidly when this medication is stopped. The appearance of symptoms a few weeks after starting the new antiretroviral regimen, coupled with the rapid resolution of symptoms with cessation of treatment, provides further support for abacavir as a possible cause of neuropsychiatric symptoms in our patient.
Because headache and mood alterations may be early indicators of neuropsychiatric manifestations in patients receiving abacavir or other antiretroviral drugs, these symptoms must be closely investigated. If early recognized, this situation can be easily managed by cessation of abacavir and change to other suitable antiretroviral regimen with symptomatic treatment (antipsychotics, antidepressive agents, etc) if necessary.
2Pere Soler Palacin, MD
Angela Aramburo
Fernando A. Moraga
Pediatric Infectious Diseases Unit
Maria Josep Cabañas
Pharmacy Service
Concepció Figueras
Pediatric Infectious Diseases Unit
Vall d’Hebron HospitalBarcelona, Spain
REFERENCES
1. Colebunders R, Hillbrands R, De Roo A, Pelgrom J. Neuropsychiatric reaction induced by abacavir. Am J Med. 2002;113:616.
2. Foster R, Olajide D, Everall IP. Antiretroviral therapy-induced psychosis: case report an brief report of the literature. HIV Med. 2003;4:139–144. 3. Foster R, Taylor C, Everall IP. More on abacavir-induced neuropsychiatric reactions. AIDS. 2004;18:2449.
