The concomitant therapy group participated in a multifaceted program including education, psychiatric referral, pharmacy utilization records, and primary physician feedback. The usual care group received standard antidepressants and follow-up visits from their family physician, with optional referral to a mental health provider.
Psychotherapy has also been shown to decrease the risk of relapse once symptoms have remitted.15 Primary care physicians can also incorporate counseling as adjunctive therapy.
Herbal and nutritional products
St. John’s wort. St. John’s wort (Hypericum perforatum L.) has been used as an herbal medication for more than 2000 years. Its efficacy in the treatment of depression has been studied extensively. Some studies demonstrated that these extracts are more effective than placebo for the short-term treatment of mild and moderate depression.16,17,18 Two randomized controlled trials demonstrated minimal efficacy of St. John’s wort in moderately severe major depression.19,20 The National Institutes of Health is sponsoring a placebo-controlled, double-blinded trial comparing St. John’s wort with SSRIs.21
Omega-3 fatty acids. Chronic deficiencies of essential fatty acids may adversely affect central nervous system function. In a small, 4-week double-blind study, outpatients receiving antidepressant therapy who were also given eicosapentaenoic acid exhibited improvement in core depressive symptoms (eg, worthlessness, guilt, insomnia) compared with the antidepressantplus-placebo group. Larger, long-term prospective trials are needed to confirm an antidepressant effect with omega-3 fatty acids.22
S-adenosyl-L-methionine. S-adenosyl-L-methionine is possibly effective for short-term treatment of major depression. Data for other herbal or nutritional remedies are negligible.23
Exercise
Physical activity may play an important role in relieving depression. One randomized controlled trial showed that an aerobic exercise program, sertraline therapy, or a combination of both were equally effective in the treatment of depression, although there was a more rapid initial response with sertraline.24
A systematic review and meta-analysis concluded that exercise may reduce depression symptoms short term, but much of the evidence is of poor quality.25 Well-controlled studies are needed to clarify the role of exercise in the treatment of depression. However, exercise is promising enough to consider implementation in clinical practice at this time.
Treatment strategy
Guidelines for medicating patients and setting expectations
Start antidepressant therapy promptly when depression is diagnosed. Maintain the initial dosage for at least 3 to 4 weeks before increasing it. A trial of 6 to 8 weeks at maximum dosage (or the maximum tolerated dosage) is necessary to confirm treatment success or failure.26,27,28
An improvement in symptoms will usually not be noted until after 2 to 6 weeks of therapy. Depending on depression severity, schedule weekly or monthly visits for patients during the initial treatment phase. The response rate to initial treatment is only 50% to 60%, but more than 80% of depressed patients will respond to at least 1 medication.1
Response to placebo is highly variable. It is often substantial and has increased in recent years. In an analysis of 75 trials between 1981 and 2001, the mean proportion of patients in the placebo group who responded (50% improvement on the HRSD) was 29.7%, compared with 50.1% in the active medication group.29 The placebo effect may reflect some combination of patient expectations, the natural history of depression with possible spontaneous remission, and limitations of study methods.
Antidepressant therapy is effective compared with placebo for depression secondary to medical illness (number needed to treat [NNT], 4.2; 95% CI, 3.2–6.4), with minimal treatment dropout (number needed to harm, 9.8; 95% CI, 5.4–42.9).30 Although many patients settle for partial improvement of their symptoms, the treatment goal should be complete remission.
Factors in drug selection
Selecting an antidepressant can be challenging: more than 24 drugs are on the market, each working through 1 or more of 7 pharmacologic mechanisms. Theoretically, choosing a drug is made easier by matching patient symptoms to likely medication side effects or by knowing that the patient or a family member responded favorably to a particular antidepressant in the past.
This intuitive model has not been proven superior to any other model of selecting antidepres-sants, but it is clinically sound, pharmacodynamically appealing, and supported by case reports. Its strength may lie in enhancing patient adherence during the critical initial phase of treatment.
A recent randomized, prospective comparison of the SSRIs paroxetine, fluoxetine, and sertraline showed similar effectiveness and tolerability (SOR: A).31 This suggests that efforts to individualize therapy based on comorbidities or likely side effects may not be as useful when choosing from among analogous SSRIs.
Nevertheless, choosing a drug that is effective, convenient, and well tolerated will improve the likelihood of achieving and maintaining a full remission. The data on adverse effects of antidepressants are widely available and well understood. Also consider cost (Table).