Pharmacotherapies for Acute Major Depression

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Pharmacotherapies For
Acute Major Depression
(Summary)

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.

Who Should Be Prescribing Your Antidepressants?

There's a debate in the medical community over who can prescribe anti-depressants and other psychotropic drugs in light of a recent New Mexico law that allows psychologists to prescribe antidepressant medication.

Listen to this show with Dr. Charles Faltz, Director of Professional Affairs, California Psychological Association and Clinical Psychologist and Dr. Jack Lewin, Chief Executive Officer, California Medical Association and practicing physician.

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.

Glossary

Major depression: A clinical syndrome lasting at least 2 weeks during which there is either depressed mood or anhedonia with a display of 5 or more of the following symptoms:

depressed mood most of the day, nearly every day
marked diminished interest or pleasure in most activities most of the day
significant weight loss/weight gain, or appetite disturbance
insomnia/hypersomnia
psychomotor agitation/retardation
inappropriate guilt
diminished ability to think or concentrate, or indecisiveness
recurrent thoughts of death, including suicidal ideation.

Mild major depression: Episodes of a major depressive disorder

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whose severity is characterized by the presence of only 5-6 depressive symptoms and either mild disability or the capacity to function normally, but with a substantial and unusual effort. Also defined as a score of 7-17 on the Hamilton Depression Rating Scale.

Moderate major depression: Episodes without psychotic features that occur in a major depressive disorder having symptoms that are midway between mild and severe, or a score of 18-24 on the Hamilton Scale. (Scores of more than 17 are often used as the threshold for including patients in trials.)

Severe major depression: Characterized by the presence of most of the symptoms of major depression and a clear-cut, observable disability such as the inability to work or care for children, or a score of 25 or above on the Hamilton Scale.

Newer pharmacotherapies: Include the selective serotonin reuptake inhibitors (SSRIs) and lesser known "new" agents such as the serotonin and noradrenaline reuptake inhibitors (SNRIs), selective norepinephrine reuptake inhibitors (NRIs), reversible inhibitors of monoamine oxidase (RIMAs), 5-HT₂ receptor antagonists (5-HT₂), 5-HT_1a receptor agonists (5-HT_1a), gabamimetics (GABA), dopamine reuptake inhibitors (DopRI), dopamine antagonists (DopAnt), and herbal remedies such as hypericum (St. John's wort).

Older pharmacotherapies: Include the first and second-generation tricyclics (TCAs), heterocyclics, and monoamine oxidase inhibitors.

Key to Grading of the Recommendations (in the algorithm)

Grade A: Recommendation based on the highest quality evidence such as randomized controlled trials with or without blinding.

Grade B: Recommendations based on case-control studies, cohort studies, or observational studies.

Grade C: Recommendation not based on evidence but rather on clinical experience.

NOTE: You should always check with your doctor before making any changes in your medications.

Source: American College of Physicians-American Society of Internal Medicine

Pharmacotherapies For Acute Major Depression (Summary)