Watch for nonpsychotropics causing psychiatric side effects

More than one-third (35%) of patients taking clonidine experience sedation or lethargy; less commonly, the drug causes anxiety (3%), agitation (3%), depression (1%), and insomnia (1%).⁵ Acute confusion, delirium, hypomania, and psychosis related to clonidine use have long been recognized, occurring in 5

Box 1

Other cardiovascular drugs. Side effects of nitrates/nitrites include delirium, psychosis (including delusions), anxiety, restlessness, agitation, and hypomania.⁵ Digoxin can cause cardiac glycoside-induced encephalopathy, which may present as sedation, apathy, depression, and psychosis. Patients may develop delirium, even when digoxin/digitoxin serum levels are within a therapeutic range.

Cholesterol-lowering statins might be linked to an increased risk of depression and suicide, but the evidence is inconclusive. Some studies have supported this link,^10,11 whereas others have strongly refuted it^12,13 or had mixed results.¹⁴ A recent review¹⁵ recommends being vigilant for psychiatric side effects in patients taking these drugs.

Steroids: prescription and illegal

Corticosteroids are prescribed for a variety of immune system-related diseases, including asthma, allergic rhinitis, rheumatoid arthritis, inflammatory bowel disease, and dermatologic disorders. Mood changes are the most common psychiatric symptoms caused by corticosteroid use; delirium is less common. Psychiatric side effects include:

• lethargy
  
• insomnia
  
• euphoria
  
• depression
  
• psychosis
  
• “personality changes”
  
• anxiety
  
• agitation.⁵
  

Multiple studies have linked corticosteroids and mood symptoms. The Boston Collaborative Drug Surveillance Program¹⁶ confirmed a direct relationship between corticosteroid dosage and psychiatric effects. More than 18% of patients had severe psychiatric symptoms at corticosteroid dosages >80 mg/d.
A prospective study of asthma patients found statistically significant changes in mood—primarily manic symptoms—during brief corticosteroid courses at modest dosages. Depressed persons did not become more depressed during prednisone therapy, however; in fact, some improved. Some patients with posttraumatic stress disorder reported increased depression and memories of the traumatic event during prednisone therapy.¹⁷

In a study of 50 ophthalmologic patients who did not have psychiatric illness receiving prednisolone (mean starting dose 119 mg/d) for 8 days, 26% developed mania and 10% depression.¹⁸ None reported psychotic symptoms.

The most common adverse effects of short-term corticosteroid therapy are euphoria and hypomania. Long-term therapy tends to induce depressive symptoms.¹⁹ A review of 79 cases of psychiatric syndromes induced by corticosteroids found that 41% reported depression, 28% mania, 6% mixed symptoms, and 14% psychosis.²⁰

A group of 16 healthy volunteers receiving 80 mg/d of prednisone over 5 days exhibited depressed or elevated mood, irritability, lability, increased energy, anxiety, and depersonalization.²¹ Numerous case studies have reported anxiety, agitation, mania, and psychotic symptoms in children and adults taking inhaled corticosteroids.

In general, psychiatric side effects of corticosteroids occur within 2 weeks of starting therapy and resolve with dosage reduction or discontinuation. In severe cases or situations in which the dosage cannot be reduced, the patient may require antipsychotics or mood stabilizers.¹⁹

Female gender and past psychiatric history might be risk factors for developing psychiatric symptoms with corticosteroids,²² although not all studies have confirmed these findings.¹⁸

Anabolic androgenic steroids (AAS) have limited therapeutic benefits but are used illegally by some bodybuilders, wrestlers, and other amateur and professional athletes to increase muscle mass, enhance performance, and gain a competitive edge. AAS can cause acute paranoia, delirium, mania or hypomania, homicidal rage, aggression, and extreme mood swings, as well as a marked increase in libido, irritability, agitation, and anger.

In a large observational cohort study of 320 bodybuilding amateur and recreational athletes,²³ AAS use induced many of these psychiatric side effects. The extent intensified as the abuse escalated. A study that used the Structured Clinical Interview for DSM-III-R to compare 88 athletes using steroids with 68 nonusers found that 23% of the AAS users reported major mood syndromes, including mania, hypomania, and major depression.²⁴