Depression

Drug Treatment Guidelines

Major Classes of Antidepressants and General Treatment Guidelines

Major classes of antidepressants include:

• Selective serotonin-reuptake inhibitors (SSRIs). These have become the standard antidepressants. They target the brain chemical (neurotransmitter) serotonin. They can be effective and usually have moderate side effects.
• Other neurotransmitter inhibitors. These drugs target neurotransmitters other than or in addition to serotonin, such as norepinephrine. Many are proving to be effective in patients who do not respond to standard antidepressants or in specific patients, such as smokers who want to quit or patients with chronic pain.
• Tricyclic antidepressants (TCAs). These drugs are effective but can have severe adverse effects, particularly in older people.
• Monoamine oxidase inhibitors (MAOIs). These drugs include newer selective MAOIs. MAOIs are the most effective antidepressants for atypical depression, but have some severe side effects and require restrictive dietary rules.
• St. John's wort and other herbal remedies are included in the Lifestyle section of this report.

Reviews of studies indicate that there are no substantial differences among SSRIs and other newer types of antidepressants. All of these drugs appear to work equally well, although they may vary in terms of side effects. Your doctor will select an antidepressant based on side effects, cost, and your personal preference.

Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen are as follows:

• Patients should start at a low dose, which is increased over a period of 5 - 10 days.
• Patients should see their doctor every 1- 2 weeks until substantial improvement occurs. It may take 4 - 8 weeks before a patient experiences the effects of any antidepressant.
• Side effects usually diminish within 1 - 4 weeks. (Exceptions may be weight gain and sexual dysfunction.)
• If no improvement occurs within 6- 8 weeks of starting drug treatment, the doctor may either increase the dosage or switch to an alternative drug. More than 80% of patients respond to some antidepressant, although specific drugs are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. In general, the fewer drug treatment strategies required, the better a patient's chances of recovering completely from depression. Patients who become symptom-free have the best chance for complete recovery compared to patients whose symptoms merely improve.
• In general, patients should continue taking antidepressants for at least 4 - 9 months after symptom relief to help prevent relapse. Patients who have had at least 2 episodes of depression may need to continue drug treatment for longer than 9 months. (Patients who improve within 2 weeks of taking medications may not require lengthy treatment.)

Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:

• Patients with at least two episodes of major depression or major depression that lasts for 2 years or longer before initial treatment.
• Patients who continue to have low-level depression for 7 months after starting antidepressant treatments.

Patients may need maintenance therapy. Doctors disagree, however, on the optimal length or the appropriate dosage of maintenance therapy. Some patients may need to stay on antidepressants for 1 - 2 years -- or even indefinitely. Some doctors recommend withdrawing from medication after a year. (This should be done gradually, over 2 - 3 months.) If depression recurs, the patient should go back on the antidepressants.

There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.

Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of patients to tolerate its side effects strongly influences their compliance with therapy. Lack of compliance is probably the major barrier to success. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:

• Sexual dysfunction is a common side effect of many of the standard antidepressants and some of the newer drugs. Some of the newer antidepressants, such as bupropion, may be effective alternatives without as high a risk for this problem. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants. It does not heighten sexual interest, however.
• An increased risk of oral health problems caused by dry mouth is associated with long-term use of most antidepressants. Patients can increase salivation by chewing gum, taking vitamin C tablets, using saliva substitutes, and rinsing the mouth frequently.
• Virtually all antidepressants have complicated interactions with other drugs; some are very important. Patients should inform the doctor of any drugs they are taking, including over-the-counter medications and herbal remedies.
• Nearly all antidepressants are metabolized in the liver, so anyone with liver abnormalities should use them with caution.
• Abrupt withdrawal from many antidepressants can produce severe side effects; no antidepressant should be stopped abruptly without consultation with a doctor.

Suicide Risk and Antidepressant Medications

In recent years, there has been concern that SSRI antidepressants can increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal thoughts and behavior (suicidality). One specific SSRI, paroxetine (Paxil), has been definitely linked with suicidal behavioral risk in adults ages 18 - 30.

In the U.S., all antidepressant medications now carry “black box” warnings on their prescribing label explaining the association between antidepressant use and increased risk for suicidality in children and adolescents, especially during the first few months of treatment. (In general, the average risk is minimal. Data from clinical trials have indicated that children and adolescents treated with these drugs had a 4% risk for suicidality compared with 2% for patients who received placebo.)

There may also be increased risk of suicidal thoughts and behavior in young adults (ages 18 - 24) during the first 1 - 2 months of antidepressant drug treatment. However, there is a decreased risk of suicidality for adults age 65 years and older taking antidepressants.

The U.S. Food and Drug Administration (FDA) recommends that caregivers monitor children being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:

• Agitation
• Irritability
• Anxiety
• Panic attacks
• Insomnia
• Aggressiveness
• Impulsivity
• Hyperactivity in actions and speech
• Worsening of depression
• Increased thoughts of suicide

The FDA’s guidelines for medication usage also recommend that all patients see their doctors regularly after initiating drug treatment. The recommended schedule is:

• Once per week for 4 weeks (1st month)
• Every 2 weeks for the next month (2nd month)
• At the end of week 12 following the start of drug treatment (3rd month)
• More frequently if changes in mood or behavior occur
• Patients should also be closely monitored if their drug dosage is changed.

Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment Guidelines
Medications
Psychotherapy
Other Treatments
Lifestyle Changes
Resources
References

Review Date: 1/22/2009
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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