Introduction

The ACP-ASIM guideline paper and accompanying background paper on Pharmacological Treatment of Acute Major Depression and Dysthymia were published in the May 2nd issue of Annals of Internal Medicine (Ann Intern Med. 2000; 132:738-742, Ann Intern Med. 2000; 132:743-756). They are based on an evidence report from the San Antonio Evidence-based Practice Center that was published by the AHRQ in January 1999.

The guideline's target audience are all internists, primary care physicians, and other specialists who see patients with depression. The target patient population are healthy adults, including the elderly, diagnosed with mild, moderate or severe acute major depression. The guideline does not apply to patients with psychiatric or medical comorbidities or to patients with recurrent depression. The aim of the guideline and background paper is to present the best currently available evidence on newer pharmacotherapies for depression, including herbal preparations for depression, as compared to placebo and older drugs.

In summary, the recommendations are:

• Older and newer antidepressant drugs (i.e. TCAs and SSRIs) are equally efficacious in treating all forms of major depression. There was no statistically significant difference in drop-out rates due to severe adverse effects between the older and newer agents.
• The decision of which agent to use should be based on a physician-patient discussion of the different side effects profiles and patient preferences.
• For mild to moderate depression, St. John's wort should be used only on a short-term basis (up to six weeks).
• All drug-related adverse events, including those with St. John's wort, should be reported to the FDA.

The guideline contains two important caveats regarding St. John's wort:

• The recommendation is based on data from Europe, where St. John's wort is regulated and standardized by the equivalent of the FDA. Preparations available in the United States are not regulated by the FDA, contain vastly different concentrations of St. John's wort, and may include many other active or inactive compounds in the preparations.
• Recent studies have shown that St. John's wort decreases the serum levels of indinavir and cyclosporine through the induction of the cytochrome P450 system. The possibility exists that other interactions may be reported in the future.

Pharmacotherapy for Acute Major Depression Recommendations

Mild to Moderate Depression

• Older and newer drugs are equally efficacious. The choice of agent depends on side effects profiles, drug-drug interactions, and patient preferences.
• In mild to moderate depression, St. John's wort should be used on a short-term basis only. There is no evidence for treatment beyond six weeks duration.
• After six weeks of treatment, evaluate the patient for clinical improvement. If the patient has improved, then continue treatment for at least four months to decrease relapses.
• If little or no improvement occurs after six weeks of treatment, reassess dose or check serum levels. If patient is at the maximum dose or levels are therapeutic, consider switching drug. There is no evidence for whether it is better to switch drugs within the same class or change the class of drug altogether.
• It is important to educate patients about herbal preparations not being regulated by the FDA and not standardized.

Moderate to Severe Depression

• Older and newer drugs are equally efficacious. The choice of agent depends on side effects profiles and drug-drug interactions
• After six weeks of treatment, evaluate the patient for clinical improvement. If the patient has improved, then continue treatment for at least four months to decrease relapses.
• If little or no improvement occurs after six weeks of treatment, reassess dose or check serum levels. If patient is at the maximum dose or levels are therapeutic, consider switching drug. There is no evidence for whether it is better to switch drugs within the same class or change class of drug altogether.

Disclaimer: Neither the guideline algorithm nor the recommendations are meant to replace physician judgment in assessing and treating the individual patient. Like all guidelines, the algorithm and the recommendations are meant as tool for decision making only.