Watch for nonpsychotropics causing psychiatric side effects

In a 2-week, double-blind, fixed-order, placebo-controlled, crossover study of healthy male inpatient volunteers, AAS had both:

• mood-elevating effects—euphoria (“steroid rush”), increased energy, and increased sexual arousal and drive
  
• mood-dysphoric effects, such as irritability, mood swings, increasingly violent feelings, increased hostility, and cognitive impairments.²⁵
  

As with corticosteroids, psychiatric symptoms from AAS become more prevalent and severe as dosage increases. They usually resolve within a few weeks after users discontinue steroids but may persist for up to 1 month, even if adequately treated with antipsychotic medication.

Hormones

Gonadotropin-releasing hormone (GnRH) agonists such as leuprolide and nafarelin are approved for treating endometriosis, advanced prostate cancer, precocious puberty, and uterine leiomyomata. Some studies and case reports suggest that these agents cause depressive symptoms.²⁶

Progestins have complex and variable psychiatric effects. Clinical trials have investigated the antidepressant effects of exogenous estrogens on psychiatric patients, but results have been inconsistent—possibly because of small numbers of subjects and design flaws.²⁶ Some studies suggest a link between estrogen and depression in premenopausal and menopausal women with and without psychiatric illness, but findings remain controversial because other studies have found that estrogens have positive effects on mood.^26,27

Interferon

Various forms of interferon are used to treat hepatitis C, melanoma, multiple sclerosis, chronic myelogenous leukemia, and other illnesses. Psychiatric complications—particularly depression—are the most frequent side effect of interferon therapy and mainly occur within the first 12 weeks of therapy.²⁸

In a prospective observational study of veterans undergoing interferon-alfa/ribavirin treatment for chronic hepatitis C:

• 48% of patients not receiving psychiatric care at baseline required treatment for neuropsychiatric side effects
  
• 23% developed symptoms of major depression.²⁹
  

Treatment with a selective serotonin reuptake inhibitor stabilized these symptoms and allowed patients to continue hepatitis treatment.

Because patients who receive interferon are far more likely to require psychiatric intervention if they have a family history of mood disorders, closely monitor them for depressive symptoms and treat such symptoms aggressively. Also closely monitor patients with multiple psychiatric diagnoses receiving interferon-alfa therapy.³⁰

Jeungling et al³¹ speculated that hypometabolism in the prefrontal cortex may predispose patients to interferon-associated neuropsychological syndromes. Neuropsychiatric symptoms may be a characteristic of hepatitis C, interferon treatment, or both.³²

Antimicrobial agents

Antibiotic and antiviral drugs can cause psychiatric side effects:

• directly by affecting neuronal functions
  
• indirectly by entering the brain rapidly, taking advantage of the compromised blood-brain barrier during sepsis or infection.
  

Delirium is the most common psychiatric complication associated with these agents.⁵

Antibiotics. Penicillin and its analogues are associated with sedation, anxiety, and hallucinations. Delirium has been reported as a side effect of most cephalosporins, especially in patients with compromised renal function. Quinolones such as ciprofloxacin and ofloxacin rarely cause restlessness, irritability, lethargy, tremors, insomnia, mania, depression, psychosis, delirium, seizures, or catatonia (incidence ≤1%).⁵ Though not commonly used, chloramphenicol may cause depression, confusion, and delirium. Many case reports have strongly associated clarithromycin with delirium.³³

Isoniazid is one of the most commonly used antibiotics that can cause psychiatric side effects; it has been linked to delirium, mania, depression, and psychosis. Ethionamide is associated with sedation, irritability, depression, restlessness, and psychosis. Tetracyclines have been known to cause depression, insomnia, and irritability at high dosages.

Sulfonamides can cause delirium. Psychosis and confusion also have been reported, especially when sulfa drugs are combined with trimethoprim.⁵

Antivirals. When used intravenously and at high doses, acyclovir and ganciclovir can cause lethargy, anxiety, hallucinations, and frank delirium.⁵ Foscarnet—an antiviral used to treat herpes viruses—can cause depression, anxiety, hallucinations, and aggressive irritability.

Didanosine—an antiretroviral agent to treat HIV infections—can cause lethargy (5% to 7% of patients), depression (2%), anxiety (2%), emotional lability (25%), delirium (2%), insomnia (1%), and psychotic delusions (1%).⁵ Efavirenz treatment may be associated with major depression and severe suicidal ideation.³⁴ Tenofovir, a nucleotide reverse transcriptase inhibitor, has not been associated with psychiatric side effects.²⁷

Antifungals. Psychiatric side effects are rare.

OTC and other agents

Many common nonprescription agents can cause psychiatric symptoms. The most frequently used classes include cold and allergy preparations, reflux medications, and analgesics (Box 2).^5,35

Cold preparations. Combined antihistamines and decongestants—such as phenylpropanolamine, azatadine, loratadine, ephedrine, phenylephrine, pseudoephedrine, and naphazoline—can cause an atropine-like psychosis that typically manifests as confusion, disorientation, agitation, hallucinations, and memory problems. Decongestants can cause dangerously high levels of norepinephrine when combined with monoamine oxidase inhibitors (MAOIs) and are contraindicated in patients taking MAOIs. Ephedrine can induce restlessness, dysphoria, irritability, anxiety, and insomnia.