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Psychiatric Side Effects of Drugs Used to Treat HIV Infection

Many drugs used to treat HIV infection can cause psychiatric symptoms. Patients with HIV disease are particularly sensitive to side effects of medications and, therefore, may be at greater risk of psychiatric reactions to medications. Adverse psychiatric reactions to medications can be idiosyncratic or dosage-related. Generally, in the latter situation, the risk of toxicity for drugs eliminated renally is increased from drug accumulation.

It is important to try to establish a cause and effect relationship because these adverse reactions are usually completely reversible within 24 to 72 hours of stopping the causative drug. In most cases, stopping the suspected drug might be the only method to determine whether or not symptoms are due to the suspected drug.

Antiretroviral Agents

Zidovudine (AZT)-induced mania, seizures, anxiety, auditory hallucinations, and confusion have been described.

Antiviral Agents

Acyclovir and, rarely, ganciclovir (DHPG) can cause visual hallucinations, fearfulness, confusion, insomnia, nightmares, delirium, paranoia, and agitation in patients with renal impairment receiving parenteral or high-dose.

Antimicrobial Agents

Several antimicrobials, including penicillins (>10 MU/ day), ß-lactam antibiotics (eg, cephalosporins, imipenen), quinolones (eg, ciprofloxacin, ofloxacin), arid sulfonamides, including trimethoprim-sulfamethoxazole (TMP-SMX).

Anabolic Steroids

Anecdotal reports suggest that the illicit use in athletes of high doses of anabolic-androgenic steroids are associated with depression, violent behavior, aggression, psychosis, and mania. Psychotic and manic reactions are reported in individuals receiving dosages ten to 100 times greater than recommended or in those using a combination.

Oronabinol (Marinol)

The active agent of' Marinol is beta-9-tetrahydrocannabinol (THC), a major psychomimetic compound. Anxiety or dysphoria are more problematic after acute usage, particularly in elderly patients. Symptoms are dose-related.


All opiates, particularly large doses of tincture of opium and long-acting narcotics, can cause sedation, confusion.


A variety of euphoric and dysphoric mood and behavior changes are reported in patients receiving more than 40 mg per day of prednisone. Recent studies indicate that duration of steroid use, a prior history of psychiatric illness.


Psychiatric Side Effects of Drugs Used to Treat HIV Infection


Adverse Reaction



Zidovudine (AZT)

Mania, anxiety, auditory hallucinations, confusion

Idiosyncratic reaction, resolves within 24 hours after stopping drug.


Didanosine (ddl)

Anxiety, irritability, insomnia

Idiosyncratic reaction, self-limiting, does not require drug discontinuation.

Zalcitabine (ddC)




Lethargy, delirium,

Dosage-related reaction, more common after high oral or parenteral therapy, or in patients with renal impairment. Uncommon with DHPG.

Ganciclovir (DHPG)

hallucinations, agitation, paranoia


Hallucinations, confusion

Association uncertain with foscarnet and psychiatric reactions. Alterations in calcium and magnesium levels are contributory.


Amphotericin B

Delirium, confusion

Rare reports, might be related to hyperthermia and irreversible leukoencephalopathy.

ß-lactam antibiotics

Confusion, paranoia,

Dose-related, high doses in patients with renal dysfunction. Increased risk with procaine penicillin.


Psychosis, delirium, seizures,

Dose-related, high doses in patients with renal dysfunction.

anxiety, insomnia, depression


Psychosis, delirium, confusion,

Dose-related, high doses in patients with renal dysfunction and elderly (?). Direct neurotoxic effect.

depression, hallucinations


Isoniazid (INH)

Paranoia, confusion, anxiety,   hallucinations

Dosages exceeding 17/mg/kg/day. IV pyridoxine recommended.


Mania, psychosis, anxiety

Several reports in patients with overdosages, resolves within 24 hours after discontinuation.

Anabolic Steroids

Mania, psychosis, depression, aggressiveness

Anecdotal reports in patients receiving 10 to 100 times the recommended dosages, abrupt withdrawal after prolonged usage.

Dronabinol (Marinol)

Anxiety, confusion, psychosis, mania, depression, hallucination

Dosage-related, self-limited, usually resolves within 12 hours after acute usage; abrupt withdrawal produces similar symptoms.


Delirium, psychosis, depression, nightmares, hallucinations

Dosage-related, might be more frequent with tincture of opium and long-acting narcotics; responds to dosage reduction.


Mania, "steroid psychosis," depression, euphoria

Dosage-related >40 mg/daily of prednisone; resolves with dosage reduction.

Tricyclic Antidepressants, Neuroleptics, and Other Anticholinergics (see Table 1 )

Confusion, hallucinations, delirium, psychosis, mania, anxiety

Dosage-related, resolves within 24 to 72 hours after stopping the drug. Physostigmine 1-2 mg IM/IV can reverse toxicity.


Anxiety, insomnia, mania

Administer in morning, can inhibit metabolism of TCAs and phenytoin and increase their toxicity.


Confusion, disorientation, paradoxical agitation, paranoia and rage; rebound anxiety and insomnia

Related to abuse and abrupt withdrawal after prolonged therapy. Increased risk with short-acting agents.