Alexopoulos et al14 proposed the “vascular hypothesis theory” that cerebrovascular disease can predispose patients, particularly older adults, to depressive symptoms (Table 2).14 Whether vascular depression is a subtype of MDD remains controversial.
Table 2
Features of vascular depression
| Onset after age 50 |
| Family history of mood disorders is less common |
| Apathy |
| Marked loss of interest in activities |
| Lack of insight |
| Executive dysfunction (problems with planning, organizing, sequencing, abstracting), impaired memory or speed of processing of information |
| History of hypertension, diabetes, or cardiovascular disease |
| May have a neurologic event such as stroke or transient ischemic attack |
| White or gray matter hyperintensities |
| Source: Reference 14 |
Course and prognosis
MDD has been characterized as a self-limited disease, with an average duration of 6 to 9 months. However, newer prospective studies suggest that a substantial number of patients recover more slowly or do not ever fully recover.15 Several factors, such as genetic/biologic vulnerability and psychosocial factors, influence the courses, prognosis, and risk of relapse/recurrence of MDD in all age groups.
Children and adolescents. The typical duration of a major depressive episode for clinically referred children and adolescents is 8 to 13 months.1,16 Approximately 90% of these patients’ major depressive episodes remit by 2 years, but up to 10% persist.1,16 Within 5 years of MDD onset, up to 70% of children and adolescents will experience a recurrence,17 a rate comparable to adults.
Anxiety disorders, panic disorders, phobias, substance abuse, conduct and oppositional disorders, and attention-deficit/hyperactivity disorder occur 2 to 6 times more frequently in children and adolescents with MDD.18,19 Children with MDD who have significant psychiatric and psychosocial comorbidity experience poorer outcomes.18
Older adults. Despite optimal treatment conditions, ≥50% of older patients fail to respond adequately to first-line antidepressant pharmacotherapy.20 Treatment-resistant MDD in older patients increases:
- nonadherence to treatment for comorbid medical disorders
- disability and cognitive impairment
- burden on caregivers
- risk for early mortality, including suicide.20
Differences in treatment
Although MDD often is recurrent, episodic, and in some patients chronic, in general earlier treatment and quicker response lead to better outcomes. A large, naturalistic German study of 795 inpatients with major depression found that early improvement (20% reduction in Hamilton Depression Rating Scale-21 score within the first 2 weeks) with antidepressant therapy may predict later response and remission.21
Regardless of a patient’s age, MDD treatment should begin with education. All patients should be involved in their treatment. Encourage patients to become familiar with their triggers and stressors, improve their coping skills, and adopt a healthy lifestyle, which includes a nutritious diet, frequent exercise, and adequate sleep. As maintenance treatment we recommend that patients participate in frequent socialization and activities (Table 3). Refer patients to self-help books, online help guides, and handouts from sources such as National Institute of Mental Health.22,23 Encourage patients to have patience and perseverance, and guide them through each step of recovery.
In addition to lifestyle modification, other treatment options for depression include pharmacotherapy, interpersonal psychotherapy, cognitive-behavioral therapy (CBT), and electroconvulsive therapy (ECT). All these modalities are effective for acute and maintenance treatment and should be considered when determining the best approach for each patient.
The effectiveness of antidepressants in general is comparable among and within classes.2 Base your initial selection on the patient’s previous response to antidepressants and the medication’s side effects profile and cost.
The benefits of exercise for all patients cannot be underestimated.24 Prescribe 20 to 30 minutes of daily exercise as part of recommended lifestyle changes. Writing “daily exercise” on a prescription pad can effectively remind patients that exercise needs to be taken as seriously as medication compliance.
Children and adolescents. For mild depression, supportive therapy seems to be as effective as CBT and medications.25 A randomized controlled trial of 439 depressed adolescents found that CBT plus fluoxetine conferred quicker benefit, but in the long run may not be any more efficacious than pharmacotherapy alone.25 Researchers also found that CBT plus fluoxetine was no more effective than pharmacotherapy alone for adolescents with moderate to severe depression.25
Older adults. Compared with younger patients, geriatric patients typically require lower antidepressant dosages to achieve a specific blood level, but the blood levels at which antidepressants are most effective appear to be similar.2 Older patients also may be more likely to relapse and less likely to achieve full response to antidepressants than younger patients.2 In older adults, amitriptyline, imipramine, and doxepin are not preferred because these agents may cause orthostatic hypotension and urinary retention.2 A depressed older adult who experiences weight loss might benefit from an antidepressant that improves appetite, such as mirtazapine.26 Some research suggests that maintenance antidepressant therapy in older patients experiencing a first-time episode of MDD should continue for up to 2 years.27