Neuroleptic Malignant Syndrome Associated With Use of Risperidone, Ritonavir, and Indinavir: A Case Report

Lee, Stephan I.; Klesmer, Jordan; Hirsch, Bruce Elliot

doi:10.1176/appi.psy.41.5.453

Cited by 20 publications

(9 citation statements)

References 5 publications

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“…62,83 Drugdrug interaction has been reported between risperidone and the antiretroviral ritonavir, resulting in high risperidone serum levels and consequent EPSs 90 , or neuroleptic malignant syndrome. 91 However, there is a lack of controlled studies of the efficacy or side effects of antipsychotic drugs in HIV positive persons, as well as studies of potential interactions with antiretroviral medications. 62 Clearly, such trials are…”

Section: Maniamentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

139

125

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Introduction HIV is a ribonucleic acid (RNA) retrovirus that is the causative agent for AIDS. HIV belongs to the Lentivirus genus in the family Retroviridae, characterized by a replication cycle in which the viral RNA is reverse transcribed into a DNA proviral form that is integrated into the host cell genome. The retrovirus is composed of two copies of single-stranded RNA that codes for the virus's 9 genes. The RNA is non-covalently linked to the core proteins, which in turn is surrounded by a viral envelope, which enables the virus to enter cells by binding to a specific cellular receptor located on the surface of cluster of differentiation 4 (CD4) cells. 1 A few years after the discovery of HIV-1, a second virus, HIV-2, was found in West Africa. HIV-1 and HIV-2 differ regarding their content of the genome, resulting in lower AIDS rates in HIV-2 infected individuals. 2 Once exposed to the body, the HIV virus antibodies may be detected after an acute flu-like illness, and then proceeds to infect specific cells of the immune system during an asymptomatic period that may last for years. In order to enter a cell, HIV must bind to CD4, typically found on T lymphocytes, blood monocytes, macrophages and some dendrite cells, and subsequently to one or a combination of several possible chemokine co-receptors, usually CCR5 and CXCR4. 3,4 The late HIV infection and psychiatric illness B Owe-Larsson, L Säll, E Salamon, C Allgulander Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm, Sweden Abstract Objective: To review the clinical features and current knowledge on the treatment of psychiatric symptoms and disorders in patients with human immunodeficiency virus (HIV) infection. Method: We searched the PubMed database combining HIV/AIDS with different keywords for psychiatric diagnoses and symptoms (e.g. depression, mania, anxiety, psychosis, dementia, substance abuse) and for psychopharmacological treatment. The years covered by these searches included 1980 to 2008. Results: Patients with HIV infection are at an increased risk of psychiatric illness. Major depressive disorder and subsyndromal depressive symptoms, as well as anxiety disorder and substance abuse are more prevalent among HIV infected individuals than among the general population. HIV-associated neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated dementia (HAD) is a serious condition during the acquired immune deficiency syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the first clinical symptom of HIV dementia. The introduction of highly active anti-retroviral therapy (HAART) has resulted in significant decreases in morbidity and mortality for HIV infected patients. HAART has also decreased the incidence of HAD, but does not give complete protection from this condition. The utility of psychotropic medications in HIV patients has not been studied sufficiently as a basis for guidelines, and more controlled trials are n...

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Section: Maniamentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

139

125

View full text Add to dashboard Cite

show abstract

“…20 A 30-year-old woman with AIDS developed neuroleptic malignant syndrome associated with risperidone and ritonavir-boosted indinavir therapy. 21 The proposed mechanism in each of these cases was ritonavir-mediated inhibition of CYP2D6 and CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

Clinically Significant Adverse Events from a Drug Interaction Between Quetiapine and Atazanavir‐Ritonavir in Two Patients

2009

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Clinicians caring for patients infected with the human immunodeficiency virus (HIV) and diagnosed with psychiatric comorbidities must be aware of potential drug-drug interactions, particularly with protease inhibitor-based antiretroviral therapy. Although possible interactions can be predicted based on a drug's pharmacokinetic parameters, the clinical significance is often unknown. We describe two patients who experienced serious quetiapine adverse effects potentially mediated through an interaction with ritonavir-boosted atazanavir. The first patient was a 57-year-old man with HIV and bipolar disease who developed rapid and severe weight gain when quetiapine was added to a stable atazanavir-ritonavir-based antiretroviral regimen. After the patient discontinued both quetiapine and ritonavir, his weight returned to its baseline value. The second patient was a 32-year-old woman with HIV, anxiety disorder, and a history of intravenous drug abuse who developed increased sedation and mental confusion when an atazanavir-ritonavir-based antiretroviral regimen was added to her stable antianxiety drug regimen, which included quetiapine. Her symptoms resolved promptly after discontinuation of the quetiapine. Use of the Naranjo adverse drug reaction probability scale indicated that the adverse effects experienced by the two patients were possibly related and probably related, respectively, to an interaction between quetiapine and atazanavir-ritonavir. Quetiapine is primarily metabolized by cytochrome P450 (CYP) 3A4, and ritonavir is a potent inhibitor of CYP3A4. Thus, it is reasonable to theorize that quetiapine concentrations will increase when these drugs are used concurrently, which would be the likely cause of the toxicities in these two patients. To our knowledge, these are the first published reports of a clinically significant interaction between atazanavir-ritonavir and quetiapine. Clinicians should be aware of the potential for this interaction, and extreme caution should be used when prescribing quetiapine and other atypical antipsychotic agents in HIV-positive patients who are receiving antiretroviral therapy.

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“…118 Development of neuroleptic malignant syndrome due to a DDI between indinavir/ ritonavir and risperidone has also been reported. 119 Another case report described the development of altered mental status that ultimately progressed to a comatose state upon co-administration of indinavir/ ritonavir with risperidone. 120 The patient returned to his baseline mental status 24 hours after discontinuation of all of his medications.…”

Section: Risperidonementioning

confidence: 99%

Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

2018

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Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

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Neuroleptic Malignant Syndrome Associated With Use of Risperidone, Ritonavir, and Indinavir: A Case Report

Cited by 20 publications

References 5 publications

HIV infection and psychiatric illness

HIV infection and psychiatric illness

Clinically Significant Adverse Events from a Drug Interaction Between Quetiapine and Atazanavir‐Ritonavir in Two Patients

Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

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