US Pharm. 2006;8:34-40.

Depression affects approximately six million men in the United States and is one of the most common psychiatric disorders among the elderly.1,2 Clinically significant depressive symptoms appear in 30% of institutionalized seniors and in 8% to 15% of the community-dwelling elderly.2 It has been shown that patients with any medical diagnosis are twice as likely as those without a medical diagnosis to develop depression. Depression worsens the outcomes of medical disorders and increases medical morbidity, mortality in hospitalized patients, the perception of poor health, the use of medical services, and the economic burden on the health care system.3

It must not be overlooked that depression is the psychiatric disorder most likely to raise the risk of successful suicide in the elderly (Table 1).3 Statistics reveal that suicide rates in the U.S. are highest among people ages 70 and older. Suicide among white males is 45% more common in those ages 65 to 69, about 85% more common in those ages 70 to 74, and more than 3.5 times more common in men older than 85 than in men ages 15 to 19.2 While suicide attempts are less frequent in older people than in younger people, they are more lethal in the elderly as a result of more careful planning, more lethal self-destructive acts, and fewer indications of the intent.3 Younger patients are more likely than the elderly to seek or respond to suicide interventions.2 Although mood disorders are more prevalent in women than in men at any age, successful suicide is disproportionately higher in males, especially in elderly men.3

Individuals who are especially likely to exhibit depressive symptoms associated with their illness include those suffering from cardiovascular disease, cancer, dementia, diabetes, Parkinson's disease, or stroke. These patients may develop somatic complaints (Table 2)--such as pain, low energy, and sexual dysfunctioning--that are typically associated with depression.4 In men, depression can cause erectile dysfunction, which can worsen depression.2

Male Hypogonadism
Serum levels of total testosterone, free testosterone, and bioavailable testosterone--but not dihydrotestosterone--decline with normal aging in many men.5 The decline in serum testosterone with normal aging is mostly due to its decreased production by the testes, which become less responsive to gonadotropin stimulation.5 While age alone has a strong predictive value for lower testosterone levels, comorbid conditions (e.g., diabetes, liver disease, hematochromatosis) and medication therapy (e.g., ketoconazole, glucocorticoids, cimetidine) have also been associated with lower levels of testosterone.5 In males, a decline in sex hormones due to aging may lead to alteration of bone structure and primary osteoporosis.

Male hypogonadism is a clinical condition characterized by a low serum testosterone level (<70 ng/dL [2.4 nmol/L]) in combination with a variety of signs and symptoms, such as depression, reduced libido and vitality, decreased muscle mass and muscle strength, increased fat mass, and altered energy and well-being.2 In elderly men, similar symptoms may be found in combination with subnormal testosterone levels. Research involving depressed hypogonadal and eugonadal men suggests that depressed men may benefit from testosterone augmentation.1 A study examining testosterone intervention in men with treatment-refractory depression and low or borderline-low testosterone levels is currently under way.6

Testosterone Replacement Therapy
Testosterone replacement therapy (TRT) must be carefully considered, especially in elderly patients who are at higher risk of prostate cancer and benign prostatic hypertrophy (BPH).7 In men with symptomatic hypogonadism (Table 3), TRT can be considered in individuals with a normal prostate examination and prostate-specific antigen (PSA) serum level and may improve bone mineral density in those who are able to tolerate the therapy.7 In most cases, TRT clearly improves mood, libido, muscle strength, and sense of well-being.2  

Testosterone transdermal systems (e.g., Testoderm, Androderm) that are applied to the scrotum or elsewhere, intramuscular injections (e.g., Depo-Testosterone, Delatestryl), 1% gels (Testim, Androgel), a pellet for subcutaneous implantation (Testopel), and a buccal system (Striant) are available.2,8 Methyltestosterone (e.g., Testred, Android, Virilon, Methitest) is also available; however, this agent is considered potentially inappropriate for geriatric use independent of diagnoses or conditions. Methyltestosterone has a high severity rating due to potential prostatic hypertrophy and cardiac problems associated with this agent, as per a U.S. consensus panel of experts (Beers criteria).9

Adverse effects of TRT include local skin reactions to topical formulations, presentation or exacerbation of BPH or prostate carcinoma, decreased high-density lipoprotein cholesterol levels, stimulation of erythropoietin secretion, and aggressive behavior (Table 4 ).10 Monitoring parameters for TRT include periodic liver function tests and measures of PSA, cholesterol, hemoglobin, and hematocrit levels. 8 Additionally, patients with diabetes should monitor their serum glucose levels closely, since hypoglycemic requirements may be altered. While studies showing the benefit and safety of TRT are accruing, the risk-benefit ratio for each patient must be assessed.2

Targeted Questioning and the Geriatric Depression Scale
Depression may go unrecognized unless specific questions are asked; it is well known that as many as 70% of seniors who commit suicide were seen by their primary care physicians within the last few weeks of their lives.2,11 Present­ ation of depression in the elderly varies as compared with that in the younger population. Somatic complaints (table 2), rather than psychological complaints, often predominate in the clinical scenario. Although older patients often do not report a dysphoric mood, apathy and withdrawal are common. Loss of self-esteem is prominent, while guilt is less common. The inability to concentrate, resulting in impair­ ment of memory and other cognitive functions, is commonly seen. In addition to a review of systems, health care practitioners can question elderly patients regarding sleep disturbances, appetite changes, trouble concentrating, lack of energy, and loss of interest in activities. Whenever possible, referral for consultation with an experienced geriatric psychiatrist and/or psychologist, in addition to ongoing primary care, is helpful in diagnosing and managing depressive disorders.12 Senior care pharmacists may find the Geriatric Depression Scale (GDS; see Resource) helpful in identifying depressed geriatric patients that should be referred for a full evaluation.12 The GDS may also be used by the pharmacist as an outcomes measure of antidepressant therapy in the management of depression.12 

Pharmacologic Intervention for Depression
A thorough history and physical examination and basic laboratory studies are important to fully evaluate the patient and rule out medical and medication-related causes of depression. The selection of an appropriate antidepressant medication (selective serotonin reuptake inhibitors, tricyclic antidepressants [TCAs], monoamine oxidase inhibitors, or atypical antidepressants), adequate dosages, and a sufficient trial period are imperative in the treatment of depression in the elderly. In seniors, an adequate antidepressant trial is longer than that for younger adults, with a complete response often seen after six to 12 weeks.3 Nuances related to medication therapy in the geriatric population should be clearly expressed by pharmacists in recommendations and educational communications. The impact of aging and of medical conditions associated with aging on the pharmacokinetic profile of a medication and the increased risk of associated side effects must be understood with regard to geriatric dosage guidelines, disease-drug contraindications (e.g., TCAs and cardiac conduction defects), and drug interactions (e.g., CYP-450 inhibition and possible toxicities).

Conclusion
Pharmacists may become involved in identifying those at risk for depression and in facilitating the appropriate evaluation, intervention, and education of patients, their families, and caregivers. It is important to make the distinction between pathological changes and normal aging when caring for older patients. Remaining cognizant of this helps to avoid dismissing a treatable pathology as merely an accompaniment to old age. It also avoids treating natural aging processes as disease and reduces the risk that iatrogenic effects will be overlooked.

REFERENCES
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8. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 10th ed. Cleveland: Lexi-Comp Inc; 2005:815-816, 1211-1213.
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