According to the National Institute of Mental Health (NIMH), more than 80 percent of people with major depression can be treated successfully with psychotherapy, medical therapy or a combination of both. However, up to 50 percent may not respond to initial treatment. The treatment options available for depression are quite varied and individualized. Mild forms of the disorder may respond well to psychotherapy alone, whereas moderate to severe forms typically require medication treatment (e.g., antidepressants). The outcome of treatment is generally best with a combination of psychotherapy and medication. During treatment, the patient’s mood will improve gradually, with the patient feeling a little better each day.

Some forms of psychotherapy that may be effective in the treatment of major depression include:

• Cognitive behavioral therapy. Attempts to change negative patterns of thought or behavior that are associated with depression and teach the patient to achieve more satisfaction and rewards from their own actions.
  
  
• Interpersonal therapy. Focuses on the patient’s personal relationships and the problems in these relationships that cause or worsen depression. A form of interpersonal therapy, family therapy, involves the entire family and may be particularly helpful when there are specific family-related stresses.
  
  
• Psychodynamic therapy. Focuses on resolving the conflict in a patient’s feelings, such as the desire for praise coupled with feelings of worthlessness. This therapy is often reserved until symptoms are significantly improved.

Antidepressants can be a valuable treatment option that, in combination with counseling, may provide significant relief of depression. Most antidepressants exert their effect on brain chemicals known as neurotransmitters. Healthy brain function depends on a certain chemical balance of these neurotransmitters.

Two such neurotransmitters are serotonin and noradrenaline, which play roles in the regulation of emotions, behavior, appetite and sleep. A decrease in these neurotransmitters is associated with depressive symptoms. However, it is not known for certain whether an imbalance can be brought on by a traumatic life event, and/or if the threshold for depression is lower due to a pre–existing imbalance.

Antidepressants (which are neither stimulants nor sedatives) work toward restoring and maintaining that balance. This begins immediately, although it may be a number of weeks before individuals see improvement in their symptoms.

The main classes of antidepressants are:

• Tricyclic and tetracyclic antidepressants
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)

Tricyclics (e.g., amitriptyline, nortriptyline, desipramine) have been a mainstay in the treatment of severe depression. As with any medication, there is a risk of side effects. Common side effects with tricyclics include dry mouth, fatigue, constipation and difficulty urinating. There is also a risk of increased blood pressure and heart rate.

MAOIs (e.g., phenelzine, isocarboxazid, tranylcypromine) are generally reserved for depression that does not improve with other classes of antidepressants. MAOIs can provide benefit to individuals with severe anxiety or phobias. Possible side effects include dizziness, headache and muscle tremors.

Antidepressants not falling in the above classes include bupropion, nefazodone, venlafaxine, trazodone and mirtazapine. Possible side effects include weight loss, sexual dysfunction, and increased blood pressure, heart rate and cholesterol levels.

The most recent class of antidepressants is SSRIs, which have found use in mild to moderate depression and tend to cause fewer side effects than the tricyclics. In heart patients, success has been reported with sertraline, a type of SSRI. Early studies demonstrated that the antidepressant was a safe and effective therapy in patients having a recent heart attack or unstable angina (more frequent angina attacks, occurring even at rest). Follow–ups to those studies showed that sertraline also had anti–platelet (anti–clotting) properties. Acting alongside patients’ standard regimen of anti-platelet heart drugs, sertraline further reduced the number of adverse vascular events (e.g., heart attack, stroke). Possible side effects with SSRIs include decreased appetite, insomnia, nervousness and sexual dysfunction.

Combining antidepressants with prescription drugs, over–the–counter remedies, other antidepressants, and even some foods or alcohol, may cause serious adverse reactions. Individuals should talk to their physician and pharmacist about possible interactions between medications. Because many medications cross the placenta, women should confirm the safety of a particular antidepressant during pregnancy or breastfeeding.

The safety and effectiveness of antidepressants not only requires the right dosage, but also involves how the medication is stopped. Abruptly discontinuing antidepressants can result in a relapse of depressive symptoms. This is why antidepressants are typically withdrawn gradually, with a stepwise lowering of the dose.