Treating Depression: What Works?

By Debra Gordon

Types of Depression

The National Institute of Mental Health defines three major forms of depressive illness:

1. Major depression - Also referred to as unipolar or clinical depression, major depressive episodes last at least two weeks. They may last for several months or longer and may occur several times over the lifetime.

2. Dysthymia - While milder and longer-lasting (at least two years), the symptoms of dysthymia are the same as those for major depression. People with dysthymia frequently lack zest and enthusiasm for life, living a joyless and fatigued existence that seems almost a natural outgrowth of their personalities. They can also experience major depressive episodes.

3. Manic-depression (or bipolar disorder) - This is a less common form of depression that involves cycles of depressive symptoms alternating with mania.

Numerous studies find that a combination of medication and psychotherapy works best for treating severe depression, while psychotherapy alone may work just as well as medication for mild or moderate depression. Here's a look at your options in both cases:


Today, doctors have dozens of medications from which to choose. None is better than the other; everyone reacts to medications differently, and you may even find that a medication that's worked for you in the past suddenly stops working.

  • Selective serotonin reuptake inhibitors (SSRIs) - These include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and citalopram (Celexa). They work by blocking the brain's reuptake of serotonin, a neurotransmitter that helps regulate mood, sleep, eating and more. SSRIs allow serotonin to remain available to the brain. Side effects include loss of libido, nervousness, nausea, diarrhea and insomnia, most of which tend to disappear over time.

  • Tricyclics (TCAs) - Includes drugs like Elavil and Ludiomil. These drugs inhibit norepinephrine reuptake or both norepinephrine and serotonin reuptake. Side effects include fainting, weight gain and headaches.

  • Monoamine oxidase inhibitors (MAOI) - These drugs include phenelzine (Nardil), isocarboxazid (Marplan) and tranylcypromine (Parnate). These drugs inhibit the action of monoamine oxidase, an enzyme that breaks down brain chemicals like serotonin implicated in depression. Can produce life-threatening interactions with common foods like aged cheese.

  • Mixed reuptake inhibitors - Bupropion (Wellbutrin) and venlafaxine (Effexor), which regulate transmission of norepinephrine, dopamine and/or serotonin. Buproprion tends to have very few side effects, while venlafaxine's side effects include nausea, headaches and loss of libido.

  • 5-HT modulators - Nefazodone (Serzone) and trazodone (Desyrel). These drugs block receptors in the brain for the 5-HT enzyme, a precursor of serotonin. They have a low risk of side effects, but they may cause sudden drops in blood pressure upon standing, headaches and daytime drowsiness. In rare cases, nefazodone may cause liver damage.

  • Norepinephrine and 5-HT modulators: Mirtazapine (Remeron) - Blocks serotonin receptors and tends to relieve symptoms sooner than the SSRIs. Side effects include weight gain and daytime drowsiness.


The two most common and best-researched types of therapy for depression are interpersonal therapy (IPT) and cognitive behavioral therapy (CBT).

  • Interpersonal therapy defines depression as a treatable mental illness that is not the patient's fault. It focuses on connections between current life events and the beginning of depression to help patients understand and overcome their depression, while also helping patients develop positive life events to counteract the negative cycle of depression.

  • Cognitive behavioral therapy helps people change the negative perceptions of the world that contribute to their depression.

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