Finding the right medication for treatment-resistant depression can be a complicated, delicate process. There is no standard treatment approach for this condition.

While many medications have been approved for depression, no drugs are approved by the FDA specifically for treatment-resistant depression.

Still, many people with treatment-resistant depression can be helped with the right medications at the right doses - it just may take some time to find the right balance. It's important to keep these facts in mind:

• Only 30% of people with depression go into full remission after taking their first course of antidepressants, according to a 2006 study funded by the National Institutes of Health. Those who got better were more likely to be taking slightly higher doses for longer periods than other people.
• Some antidepressants work better for certain individuals than others. It's not uncommon to try a few different depression medicines during treatment.
• And some people need more than one depression medicine.

Work with your doctor closely to try to "optimize" your depression medicines by finding the right dose of the right antidepressants that best relieve your symptoms.

Antidepressants and Depression Medicines

There are a dizzying number of depression medicines, and combinations of medicines, your doctor might try. Here is a rundown of some of the categories.

Antidepressants, in combination with psychotherapypsychotherapy, are often the first treatment that people get for depression. If one antidepressant doesn't work well, you might try another drug of the same class -- which can have different side effects -- or a different class of depression medicines altogether. Your doctor might also try changing the dose. In some cases, your doctor might recommend combining two different antidepressants.

Here are the main types of antidepressants:

• Selective serotonin reuptake inhibitors (SSRIs) are some of the most common antidepressants used for depression. Examples include Celexa, Lexapro, Luvox, Paxil, Prozac (also available as generic fluoxetine), and Zoloft. Side effects are generally mild. They include stomach upset, sexual problems, fatigue, dizziness, weight change, and headaches.
  
  
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer type of antidepressant. This class includes Effexor and Cymbalta. Side effects include upset stomach, insomnia, sexual problems, anxiety, dizziness, and fatigue.
  
  
• Aminoketones, like Wellbutrin, treat depression by an unknown mechanism. It is different than other antidepressants and only weakly affects the brain chemicals influenced by other antidepressants. Side effects are usually mild, including upset stomach, headache, insomnia, and anxiety. Wellbutrin may be less likely to cause sexual side effects than other antidepressants.
  
  
• Tetracyclic antidepressants include Remeron. How Remeron treats depression is unknown, but it does affect both norepinephrine and serotonin, similar to other antidepressants. Side effects are usually mild, and include upset stomach, sleepiness, weight gain, and dizziness.
  
  
• Tricyclic antidepressants (TCAs) were some of the first medications used to treat depression. Examples are Elavil (amitriptyline), Norpramin (desipramine), Tofranil (imipramine), and Pamelor (nortriptyline). Side effects can be severe in some people, which is why they aren't used as often anymore. However, they may help if you haven't responded to newer classes of depression medicine. You may need regular blood tests to monitor the level of tricyclics in your system. These medicines may not be safe for people with heart problems.
  
  
• Monoamine Oxidase Inhibitors (MAOIs) were also an early treatment for depression. Some examples are Nardil (phenelzine), Parnate (tranylcypromine) and Marplan (isocarboxazid.) Although MAOIs work well, they're not prescribed very often because of their side effects. They can cause serious interactions with other medications and with some foods. However, they may help people with treatment-resistant depression that hasn't responded to more common drugs.

Other depression medicines are often prescribed in addition to antidepressants. This is called "augmentation" -- the second drug can help the antidepressant work better.

Here are some of the more common medicines that doctors use to augment antidepressant treatment.

• Some anticonvulsants -- used originally for epilepsy -- may help. Lamictal and Tegretol (carbamazepine) have been studied in people with hard-to-treat depression.
  
  
• Antipsychotic medications like Zyprexa and Risperdal are sometimes used in people with hard-to-treat depression, especially those with hallucinations or delusions.
  
  
• The beta-blocker Visken (pindolol) is often used for high blood pressure and heart problems. But it can also speed up the effects of certain antidepressants.
  
  
• BuSpar (buspirone) is a medicine for anxiety that may help people with hard-to-treat depression.
  
  
• Lithium is one of the most commonly prescribed medications for people with bipolar disorder. It helps level out moods. Studies show that it may also be helpful for people with hard to treat depression. Since lithium is dangerous in high doses, your doctor may need to monitor you closely if you are on it.
  
  
• A synthetic version of a thyroid hormone -- Cytomel (liothyronine) -- has also been shown to help augment the effectiveness of antidepressants.
  
  
• Stimulants like Ritalin or Dexedrine can also help improve the effectiveness of antidepressants for treatment-resistant depression. These medications are commonly used to treat ADHD.

Tips for Getting the Best Treatment for Your Depression

• Stick with it. Antidepressants can take up to eight weeks before they take full effect. Don't skip doses or quit treatment early. If you don't take your depression medicine exactly as prescribed, you won't have given it a fair chance to work.
  
  
• See an expert. Any doctor can prescribe depression medication, but a prescription alone isn't the best treatment. You should seek out an expert, like a psychiatrist or a psychologist. Your condition is, by definition, hard to treat. It's important to talk with a trained professional during your treatment. Although psychologists cannot prescribe medication, they are highly-trained in psychotherapy. You can work with a psychologist while taking antidepressants prescribed by your regular doctor, or see a psychiatrist for both your depression medication and talk therapy. Try to find someone who has a lot of experience helping people with treatment-resistant depression.
  
  
• Get in good habits. Take your depression medicine at the same time every day. It's easier to remember if you do it along with another activity like eating breakfast or getting into bed. Get a weekly pillbox, which will make it easy to see if you've missed a dose. Since people sometimes forget a dose now and then, make sure you know what to do if that happens.
  
  
• Don't ignore side effects. Side effects are one of the main reasons that people give up on medication. For instance, in a British study of just over 1,000 people with depression, 65% said they stopped taking their medicine at some point. Of this group, about 45% said side effects were the reason. The results were published in Current Medical Research and Opinion in 2003. So if you have side effects, talk to your doctor. See if there's any way to minimize or eliminate them. However, keep in mind that side effects might be worse when you first start a medicine. Side effects often ease up over time.
  
  
• Never stop taking your depression medicine without your doctor's OK. If you need to stop taking your medicine for some reason, your doctor may want to reduce your dose gradually. If you stop suddenly, you could have side effects and your depression could worsen.
  
  
• Don't assume that you can stop taking your depression medicine when you feel better. If you have treatment-resistant depression, you will need to take your antidepressant for several months -- or possibly a year -- even after you're feeling better. This type of "maintenance medication" can help prevent you from getting more depressed in the future.

Psychotherapy

Psychotherapy - or "talk therapy" -- is an effective treatment for depression. While it may not be enough on its own to resolve treatment-resistant depression, it can play an important role when used together with other treatments.

What Can Psychotherapy Offer?

Many studies have shown that therapy can be a powerful treatment for depression. Some, although not all, have found that combining depression medicine with therapy can be particularly effective. A 2004 review published in the Archives of General Psychiatry concluded that therapy combined with antidepressants worked better than depression medicine alone. It also found that therapy can help people stick with their drug treatment in the long term.

There are few conclusive studies of psychotherapy specifically in people with treatment-resistant depression, according to a review of treatments published in the Journal of Clinical Psychiatry in 2005. But many experts still recommend it. Therapy can help you:

Types of Psychotherapy Treatments

The first step is to find a qualified therapist -- usually a psychiatrist, psychologist, social worker, psychiatric nurse, or counselor. If possible, find someone who has expertise in helping people with treatment-resistant depression. Ask your health care provider for recommendations. Or get in touch with an organization like NAMI, The Nation's Alliance on Mental Illness, or the Depression and Bipolar Support Alliance (DBSA).

There are many different types of therapy. Here are some of the most common.

• Cognitive therapy, behavioral therapy, and cognitive behavioral therapy all focus on how your own thoughts and behaviors contribute to your depression. Your therapist will help you learn new ways to react to situations and challenge your preconceptions. You and your therapist might come up with concrete goals. You might also get 'homework' assignments, like keeping a journal, or applying problem-solving techniques in particular situations.
  
  
• Interpersonal therapy focuses on how your relationships with other people play a role in your depression. It focuses on practical issues. You will learn how to recognize unhealthy behaviors and change them.
  
  
• Psychodynamic therapy is a more traditional form of therapy. You and your therapist will explore the roots of your depression. You might focus especially on any traumas of your childhood.
  
  
• Group therapy gives you a chance to talk about your depression with other people who might have a similar condition. A therapist leads the group, which is what makes it different from a support group. The therapist might use any one or a combination of the approaches discussed above.

While there are many types of therapy, don't worry too much about the approach. Focus on finding a therapist whom you like and trust. Many therapists use a combination of approaches anyway.

While some people only need therapy for short periods of time, people with treatment-resistant depression might need it for longer. This is called maintenance therapy. Studies show that this lowers your risk of relapse. You and your therapist can watch for signs that your depression might be worsening. Over time, you will also learn about the patterns in your life that lead to depression.

Trying Psychotherapy Again

If you have treatment-resistant depression, you may have already tried psychotherapy. Maybe you didn't feel like it worked. But it may be time to give it a second chance. Here are some things to consider before you try again.

• Think about the reasons you didn't like therapy before. Why didn't it work? What did you need from therapy that you weren't getting?
  
  
• Decide what you want out of therapy now. Do you want to tackle specific problems? Do you want to work through upsetting events from your past? Come up with goals.
  
  
• Consider going back to your old therapist. Even if therapy didn't work last time, that doesn't mean that the therapist was at fault. The experience may be different if you approach therapy with specific goals this time. Going back to a previous therapist may be easier, since he or she will already know your history and situation.
  
  
• Consider trying someone new. It's very important that you like and respect your therapist. If you and your therapist didn't 'click,' therapy is unlikely to work. So you could try someone new. You might even want to meet with a few different therapists before choosing one. Ask about their approaches. Talk about your goals.
  
  
• Give it time. Once you have settled on a therapist, you need to give therapy a chance to work. Don't give up after a few sessions. Like depression medicine, therapy can take a little while before you feel the benefits.

SOURCES: American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depression, 2000. American Psychological Association, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, American Psychiatric Association, 2000. Cadieux, R.J. "Practical Management of Treatment-Resistant Depression," American Family Physician, December 1998; vol 58: pp 2059-62. Compton M.T., "Depression and Bipolar Disorder," ACP Medicine, Psychiatry II, 2003. Depression and Bipolar Support Alliance web site, "Psychotherapy: How It Works and How It Can Help," "Treatment Challenges: Finding Your Way to Wellness." Fochtmann, L.J. and Gelenberg, A.J., Focus, Winter, 2005; vol 3: pp 34-42. Keller, M.B. Journal of Clinical Psychiatry, 2005; vol 66 (supp. 8): pp 5-12. Pampallona, S. Archives of General Psychiatry, 2004; vol 61: pp 714-719. Plakun, E. "A Psychodynamic Perspective on Treatment-Refractory Mood Disorders," Psychiatric Times, October 2002; vol 19. Stimmel, G. "Options for Treatment-resistant Depression," Psychiatric Times, July 2002; vol 19.