Achieving the best outcome in treatment of depression

Journal of Family Practice, March, 2003 by John E. Sutherland, Steven J. Sutherland, James D. Hoehns

Practice recommendations

* Combined treatment with psychotherapy or psychiatric consult and drug therapy has shown better response in several studies than either therapy alone (A).

* Although not proven by clinical trials, selecting a medication by matching its side-effect profile to patient characteristics is supported by case reports and likely enhances compliance.

* Patients who do not improve with initial therapy often benefit from being switched to another class of antidepressants (A), or having a drug from another class added to their therapy (B).

You are more likely to see depression in your practice than any other disorder except hypertension. (1) Given the prevalence of depression * and the variability of its clinical symptoms and comorbidities, how do you determine the optimal therapy for a given patient?

A sobering thought: nearly half of all patients stop taking their antidepressant prescription medication within the first month of treatment. (1) We discuss the critical factors you can address to help patients stick with treatment and achieve the best outcome.

* THERAPEUTIC OPTIONS

Pharmacotherapy

Antidepressants are thought to exert their therapeutic and adverse effects through 3 chemical monamine neurotransmission systems; by increasing levels of norepinephrine, serotonin, or dopamine in the synapse; and by resultant secondary changes in presynaptic and postsynaptic receptor physiology. (3,8,9) Newer medications--such as selective serotonin reuptake inhibitors (SSRIs)--have simpler dose schedules, different (and for some patients more favorable) adverse effect profiles, and less likelihood of causing death from overdose compared with older tricyclic antidepressants (TCAs) and monamine oxidase inhibitors (MAOIs).

Patients are less likely to discontinue treatment with SSRIs than with TCAs (odds ratio=1.21; 95% confidence interval [CI], 1.12-1.30). (10)

However, there are no clinically significant differences in effectiveness between SSRIs and TCAs (strength of recommendation [SOR]: A). (11) Importantly, although practice patterns in the use of antidepressants have changed, some reasons for the preference of newer effective agents have not been substantiated. For instance, we do not know whether the patient population taking newer agents has a lower rate of suicide, despite the difference in fatality risk mentioned earlier.

Combined pharmacotherapy and psychiatric consultation

Combining pharmacotherapy and psychotherapy can be more effective than either modality alone. In one study, 73% of patients with chronic depression treated with combination therapy showed a reduction of 50% or more on the Hamilton Rating Scale for Depression (HRSD), compared with just 48% in the nefazodone-only and psychotherapy-only groups (SOR: A). Among those who completed the study, the rates of response were 85%, 55%, and 52%, respectively (although the results considered compliant patients only, which biases the results in favor of treatment). (2)

Among elderly depressed patients who received home care, 58% of those who underwent intervention by a psychogeriatric team recovered, compared with just 25% in the control group (SOR: A). (12) The intervention group received a multidisciplinary team evaluation and an individualized management plan, which could include any combination of physical, psychological, or social interventions. The control group received usual care from their general practitioner.

Studies of combination therapy have yielded mixed results, but guidelines from the psychiatric literature based on clinical experience advocate concomitant psychotherapy and medication (SOR: A). (13) For patients with persistent symptoms after 6 to 8 weeks of taking antidepressant medication, concomitant psychotherapy improved compliance, satisfaction, and outcomes when compared with usual care. (14)

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 antidepressant-plus-placebo group. Larger, long-term prospective trials are needed to confirm an antidepressant effect with omega-3 fatty acids. (22)