Depression and comorbid medical illness: therapeutic and diagnostic challenges

Journal of Family Practice, Dec, 2003 by F. George Leon, Adam Keller Ashton, Dale A. D'Mello, Bezalel Dantz, Jaye Hefner, Gary A. Matson, C. Brendan Montano, James F. Pradko, Norman Sussman, Bertrand Winsberg

It is estimated that major depressive disorder exists in 36% of patients with coexistent medical conditions and may be more common in hospitalized and elderly patients. (1) This discussion addresses comorbidities in patients with depression and provides treatment strategies for clinicians.

Absent in the general discussion are the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). These agents may have value in treating specific comorbid illnesses (ie, chronic pain syndromes); however, their toxicity makes them inappropriate as first-line medications for depression.

* AGE OF PATIENT AND RISK FOR DEPRESSION AND COMORBIDITIES

Children and adolescents Diagnosis of depression among children and adolescents is often missed. It may be masked by medical or psychiatric comorbidities. (2,3) Parents may not express psychosocial concerns regarding their children to pediatricians, who may not respond. (4) Possibly, 1% to 2% of children and 5% to 8% of adolescents may be affected. (5)

Evaluating the pediatric patient. Various medical conditions can present as depression (eg, anemia, brain injuries, chronic headaches, diabetes, drug abuse, epilepsy, infectious mononucleosis, hypothyroidism, Lyme disease, (6) renal disease, Wilson's disease). Baseline laboratory studies should be considered to rule out organic components of the illness. (7,8)

Treatment strategies. Most of the available treatment strategies are based on data derived from studies with adults. Children are better placebo responders than adults (over 50% in most trials) (9) and benefit highly from structured psychotherapy with support and education for both patient and family.

Limited evidence from clinical trials regarding antidepressants to children. Limited evidence-based research has focused on SSRIs in children. Thus far, fluoxetine, (10) paroxetine, (11) and most recently sertraline (12) are the only antidepressants that have been shown in controlled trials to be effective in children. Caution is indicated regarding paroxetine for patients with major depressive disorder younger than 18 years of age because of a possible increase in suicidal thinking, although no increase in suicides has been documented. (13)

Most antidepressant agents are not FDA-approved for patients under age 18; however, fluoxetine has received approval for use in children ages 7 to 17. (13) Prompt referral and close collaboration with mental health professionals is of the utmost importance in the adolescent who becomes socially disruptive or makes comments of a suicidal nature.

Depression in the elderly

Depression in the elderly often goes undiagnosed and untreated. The prevalence in patients aged more than 65 years can be as high as 30% in outpatient setting and 40% in hospitalized patients. (14) Cognitive impairment can often cloud the differential diagnosis. Depression can simulate dementia: both are associated with memory loss, concentration difficulties, irritability, agitation and distractibility. (15) Medical conditions that become more common with aging are associated with depressive disorders: Up to 50% of cardiac, renal, Parkinsonian, post-stroke, chronic pain, and rheumatoid arthritis patients develop comorbid depressive disorders. (16,17)

Common signs of depression in the elderly that may be overlooked are diminished self-care, increased irritability, and social withdrawal with psychomotor retardation, all of which can impact daily activities, independent living, and compliance with other medical regimens. The greatest risk factors for depression are age over 75, cognitive dysfunction, and severe chronic medical illness.

Barriers to effective screening. Screening may be limited by cognitive impairment. The Mini-Mental State Exam (MMSE) is commonly used for screening global cognitive function. A score of less than 15 cannot be screened with the usual intruments.

An estimated 10% to 30% of the geriatric population will develop mental symptoms as a result of an unrecognized, undiagnosed, and potentially correctable medical condition. (17) Anemia, hypothyroidism, atypical anginal symptoms, pancreatic cancer, hyponatremia, Cushing's disease, post-herpetic neuralgia, and vitamin B12 deficiency are all associated with psychiatric symptoms. (16,17)

Role of multiple medications in diagnosis or onset of symptoms. Multiple medications (including over-the-counter medications) may increase the elderly patient's risk for drug-drug interactions, which may unmask early dementia or produce symptoms of depression, delirium, or mania. (18) Among the many medications that commonly cause psychiatric symptoms in the elderly are steroids, anticholinergics, benzodiazepines, cimetidine, and interferon. (19)

Age-related factors that affect drug accumulation and elimination in the elderly. Age-related pharmacodynamic changes may affect treatment response. The elderly have a higher fat percentage, less volume fat of distribution, less muscle mass, and less total body water. These factors can cause a higher concentration of liposoluble drugs in the brain. (20) Decreased plasma protein levels may lead to diminished drug binding and increased levels of free active drug. Decreased size of both the liver and the kidneys can also inhibit drug elimination and promote drug accumulation.