Treatment Considerations for Psychiatric Syndromes Associated with HIV Infection

Tami Benton; Joshua Blume; Benoit Dubé


HIV Ther. 2010;4(2):231-245. 

In This Article

HIV & Psychosis

Studies have demonstrated both higher prevalences of HIV infection in the severely mentally ill relative to the general population,[87,88] as well as increased HIV-risk behavior.[40] These two consistently reproducible findings taken together among the severely mentally ill suggest that many patients presenting with HIV and psychotic symptoms are suffering from a primary psychotic illness, whether or not it has been previously diagnosed. In the absence of a clear history of pre-existing or premorbid symptomatology, it is rarely possible to exclude an HIV-associated etiology based on psychopathology alone.[88] In cases where the HIV infection preceded the onset of psychotic symptoms, the clinical presentations are heterogeneous and the causal link between HIV and the psychosis unclear.[87,89,90]

The emergence of psychotic symptoms in patients infected with HIV presents a diagnostic challenge. The clinician should consider a primary psychiatric illness (e.g., schizophrenia or bipolar disorder) that is distinct from HIV, an opportunistic CNS infection or malignancy, previously undiagnosed 'AIDS dementia complex', delirium, medication-induced psychosis, and 'primary HIV psychosis'.

New-onset psychosis in HIV-seropositive patients has prevalence estimates ranging from 0.5 to 15%,[91] and is most often seen in neurocognitive disorders, such as delirium, HIV-associated dementia and HIV minor cognitive motor disorder. When delirium is present, an underlying medical cause should be sought and treated.

When an HIV-seropositive patient without a pre-existing psychiatric diagnosis presents with psychotic symptoms in the absence of delirium or structural findings, the clinician should consider substance-induced psychosis, including ARV-associated psychosis. Case studies[92–94] and uncontrolled studies suggest that the initiation of antiretroviral therapy may be implicated in the onset of psychotic symptoms based on higher frequency of symptoms within 1 month of initiation of therapy[95] and resolution of symptoms following the discontinuation of the offending agent.[19,94] The agents cited include efavirenz, zidovudine, abacavir, nevirapine and combivir. Conversely, there is also limited evidence that antiretrovirals may have a protective effect against psychotic symptoms.[96]

While psychotic symptoms can be seen in AIDS dementia complex and minor cognitive motor disorder, psychotic symptoms in the absence of gross cognitive deficits are encountered in HIV patients,[89,96–99] yet the mechanistic link between HIV and psychosis is not well understood.[100] One study suggested that HIV psychosis may be a harbinger of dementia,[97] and another suggested that it was associated with decreased survival time.[98,101]

When psychosis occurs in the setting of delirium or is thought to be substance-induced; the first step in case management is the correction of the underlying disturbance or removal of the offending agent, respectively. Whether or not antipsychotic medication should be initiated depends upon the severity of the behavioral disturbance, the persistence of symptoms and whether the patient needs to be rechallenged with an offending antiretroviral agent.

Antipsychotic agents are the treatments of choice regardless of the underlying diagnosis. Open studies and case reports support the use of antipsychotic agents for psychotic symptoms in HIV;[99] one study of 21 patients with HIV-related psychosis found risperidone to be efficacious with a more favorable side-effect profile than the traditional agents (haldol and thioridazine).[102]

A small open study found clozaril to be effective for reducing psychotic symptoms while not producing extrapyramidal symptoms.[103] Despite some reports of efficacy, its side-effect profile, especially its risk for agranulocytosis, limits its use to treatment-resistant psychosis. Another important consideration is HIV-infected patients' increased sensitivity to antipsychotic-induced extrapyramidal symptoms, thought to be related to the damage to basal ganglia observed in HIV.[101] As such, commonly used high-potency antipsychotic agents, such as haloperidol, are best avoided in favor of lower-potency agents or atypical antipsychotics, such as olanzapine, quetiapine[99] and risperidone.[102]

Another consideration when choosing antipsychotic agents for treatment in HIV-infected individuals is the high risk for dyslipidemia and hyperglycemia in those receiving antiretroviral treatments,[104] in addition to the potential for the metabolic syndrome that has been observed in general psychiatric patients receiving atypical antipsychotic agents. This syndrome, defined by the National Cholesterol Education Program Expert Panel, is an inter-related constellation of cardiovascular disease risk factors, linked by insulin resistance, including obesity, dyslipidemia, impaired glucose tolerance and hypertension.[105]

Evidence suggests potential interactions between ART and some antipsychotic agents. Cytochrome P450 inhibitors have the potential to increase the concentration of clozaril and pimozide, thus contraindicating these medications in combination with agents such as ritanovir. Ritanovir also significantly decreases olanzapine plasma levels by enhancing CYP1A2 and UDP-glucoronyl transferase.[106]

In the absence of guidance from the literature, the decision as to whether or not to maintain the patient on antipsychotic therapy is purely clinical, depending upon the severity of the symptoms being treated and their likelihood of recurrence. The atypical antipsychotic agents risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone have demonstrated efficacy with psychotic symptoms without causing excessive sedation or cognitive impairment.[107] Quetiapine has been shown to have the least parkinsonian effects.[108]


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