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Am Fam Physician. 2002;65(7):1395-1397

Questions Addressed

  • What are the effects of treatments for depressive disorders?

  • What are the effects of continuation treatment with antidepressant drugs?

  • Which treatments are most effective at improving long-term outcome?

Tricyclic and heterocyclic antidepressants
Monoamine oxidase inhibitors
Selective serotonin reuptake inhibitors and related drugs
Electroconvulsive therapy
Cognitive therapy (in mild to moderate depression)
Interpersonal therapy (in mild to moderate depression)
Continuation drug treatment (reduces risk of relapse)
Likely to be beneficial
St. John's Wort (in mild to moderate depression)
Problem-solving therapy (in mild to moderate depression)
Combining drug and psychologic treatment (in severe depression)
Continuation of antidepressant treatment (may prevent recurrence)
Unknown effectiveness
Care pathways
Nondirective counseling
Psychologic treatments in severe depression
To be covered in future issues of Clinical Evidence
Behavior therapy
Treatment for bipolar affective disorder
DefinitionDepressive disorders are characterized by persistent low mood, loss of interest and enjoyment, and reduced energy. They often impair function. Older adults: Older adults are generally defined as people 65 years or older. The presentation of depression in older adults may be atypical; low mood may be masked and anxiety or memory impairment may be the principal presenting symptoms. Dementia should be considered in the differential diagnosis of depression in older adults.1
Incidence/PrevalenceYounger adults: Depressive disorders are common, with a prevalence of major depression between 5 and 10 percent of people seen in primary care settings.2 Two to three times as many people may have depressive symptoms but do not meet criteria for major depression. Women are affected twice as often as men. Depressive disorders are the fourth most important cause of disability worldwide, and they are expected to become the second most important cause by the year 2020.3,4 Older adults: Between 10 and 15 percent of older people have significant depressive symptomatology, although major depression is relatively rare in older adults.5
Etiology/Risk FactorsThe causes are uncertain but include childhood events and current psychosocial adversity.
PrognosisAbout one half of people suffering a first episode of major depressive disorder experience further symptoms in the next 10 years.6 Different levels of severity7,8 indicate different prognosis and treatment. Mild to moderate depression is characterized by depressive symptoms and some functional impairment. Many people recover in the short term, but about one half experience recurrent symptoms. Severe depression is characterized by additional agitation or psychomotor retardation with marked somatic symptoms. In this review, treatments are considered to have been evaluated in severe depression if the randomized control trials (RCTs) included inpatients. Psychotic depression is characterized by additional hallucinations, delusions, or both. Older adults: The prognosis may be especially poor in elderly people with a chronic or relapsing course.9
Clinical AimsTo improve mood, social and occupational functioning, and quality of life; to reduce morbidity and mortality; to prevent recurrence of depressive disorder; and to minimize adverse effects of treatment.
Clinical OutcomesDepressive symptoms rated by the depressed person and clinician, social functioning, occupational functioning, quality of life, admission to hospital, rates of self harm, relapse of depressive symptoms, rates of adverse events. Trials often use continuous scales to measure depressive symptoms (such as the Hamilton Depression Rating Scale and the Beck Depression Inventory). Clinician reports and self-reported global outcome measures are also used. Changes in continuous measures can be dealt with in two ways. They can be dichotomized in an arbitrary but clinically helpful manner (e.g., taking a reduction in depressive symptoms of more than 50 percent as an end point), which allows results to be expressed as relative risks and numbers needed to treat. Alternatively, they can be treated as continuous variables, as is done for systematic analysis. In this case, the pooled estimate of effect (the effect size) expresses the degree of overlap between the range of scores in the control and experimental groups. The effect size can be used to estimate the proportion of people in the control group who had a poorer outcome than the average person in the experimental group. A proportion of 50 percent indicates that the treatment has no effect. Older adults: The Hamilton Depression Rating Scale is not ideal for older people because it includes a number of somatic items that may be positive in older people who are not depressed. It has been the most widely used scale, although specific scales for elderly people (such as the Geriatric Depression Scale) avoid somatic items.



Younger adults:Systematic reviews have found that antidepressant drugs are effective in acute treatment of all grades of depressive disorders. We found no clinically significant difference in effectiveness between different kinds of antidepressant drug. However, the drugs differ in their adverse event profiles. On average, people seem to tolerate selective serotonin reuptake inhibitors (SSRIs) a little more than older drugs, but the difference was small. We found no strong evidence that fluoxetine was associated with increased risk of suicide. Abrupt withdrawal of SSRIs is associated with symptoms, including dizziness and rhinitis, and this is more likely to occur with drugs that have a short half-life, such as paroxetine.

Older adults: One systematic review has found that heterocyclic antidepressants and SSRIs are effective in the short term in older people with mild to moderate depression. However, overall treatment effects were modest.


We found limited evidence from RCTs that the effectiveness of drug treatment may be improved by a number of approaches, including collaborative working between primary care clinicians and psychiatrists, case management, intensive patient education, and telephone support.


One systematic review has found that St. John's wort (Hypericum perforatum) is more effective than placebo in mild to moderate depressive disorders and as effective as prescription antidepressant drugs. However, these findings have yet to be repeated in fully representative groups of people using standardized preparations.


Two systematic reviews have found that electroconvulsive therapy (ECT) is effective in the acute treatment of depressive illness.


Younger adults: One systematic review has found that cognitive therapy is effective. Weaker evidence from RCTs suggests that interpersonal psychotherapy, problem-solving therapy, and brief, nondirective counseling may be as effective as drug treatment in mild to moderate depression. We found limited evidence on the relative efficacy of drug and nondrug treatment in severe depression.

Older adults: One systematic review has found that rational psychologic treatments (such as cognitive therapy or cognitive behavior therapy) are effective for older people with mild to moderate depression. However, improvement in people receiving these treatments was no different than in controls who received similar but nonspecific attention. This review was based on a small number of studies, the populations varied (although most were community samples), and many of the studies were short-term.


In severe depression, RCTs have found that the addition of drug treatment to interpersonal or cognitive therapy is more effective than psychologic therapy alone or drug treatment alone. No such effect was observed in mild to moderate depression.


We found limited evidence from one systematic review and one subsequent RCT that exercise may improve depression.


We found limited evidence from one systematic review that bibliotherapy may reduce mild depressive symptoms.


Limited evidence from one small RCT found that befriending reduced symptoms of depression.

Continuation Treatment with Antidepressant Drugs

One systematic review and subsequent RCTs have found that continuation treatment with antidepressant drugs for four to six months after recovery reduces the risk of relapse.

Treatments Most Effective at Improving Long-Term Outcome

One systematic review found no evidence of a difference between treatments in terms of long-term benefits. The systematic review and one additional RCT found limited evidence that cognitive therapy may be an alternative to drug maintenance therapy in preventing relapse.

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