Michael W. Smith, MD, December 2005 If you're coping with long-term depression, you may wonder why you can't feel better. Other people you know may have recovered from their depression more easily -- a few months of therapy or antidepressants and they were back to normal. But it hasn't been like that for you. No matter what treatment you try, you're still suffering. There is no one reason for treatment-resistant depression. For most people, it's probably a combination of different factors. Some of it is beyond your control, such as the genes you were born with. But there are factors that you can control. According to experts, here are the reasons why depression can sometimes be hard to treat. Not staying on a medicine long enough. Antidepressants can take as long as six to eight weeks before they fully take effect. Unfortunately, many people -- and sometimes even doctors -- give up on a depression medicine too early, before it's had a chance to help.
Skipping doses. If you don't take your antidepressant, it can't help you. You'll never really know if a depression medicine is working unless you take it exactly as prescribed.
Unpleasant side effects. Many people who have side effects just stop taking their antidepressants. That isn't a good idea. Instead, talk to your doctor and get some help. You might be able to eliminate or ease the side effects and still get relief from your depression. Also, keep in mind that side effects tend to decrease over time.
Drug interactions. Some other medicines don't mix well with antidepressants. When taken at the same time, neither one may work normally. In some cases, interactions could even be dangerous.
The wrong medicine or the wrong dose. Antidepressant drugs work very differently in different people. Unfortunately, there's no way to predict how well a depression medicine will work without trying it. So finding the right medicine, at the right dose, takes trial and error -- and occasionally, some time. Many people give up before they find the right one.
Your genes. Researchers have found a gene that they believe may make depression harder to treat in some people.
Other medical conditions. Some medical conditions -- like heart disease, cancer, or thyroid problems -- can contribute to depression. Other conditions, like anorexia, can too. It's important that you treat any underlying medical problems in addition to your depression.
Alcohol or drug abuse. Substance abuse often goes hand-in-hand with depression. It can trigger depression or make it worse. If you have a substance abuse problem, you need to get help.
The wrong diagnosis. Some people are simply misdiagnosed with treatment-resistant depression. They might actually have another condition, like bipolar disorder or an anxiety disorder. This is why it's so important to work with an expert. Treatment Doctors do not agree on an approach to controlling treatment-resistant depression. Your treatment will depend on your doctor's experience as well as your own needs, concerns, and medical history. But while the details may vary, most doctors follow the same basic pattern. Here is a rough outline of how your doctor might treat your depression. If you have treatment-resistant depression, you have already typically failed two or more treatments, usually one or more antidepressants and/or psychotherapy. At that point, your doctor may suggest other options. Other antidepressants. If one type of antidepressant hasn't worked -- or has caused unpleasant side effects -- your doctor may suggest that you try another. This might be a new depression medicine in the same class of drugs or one in a different class. Again, you may need to stay on this medicine up to eight weeks to see its full effects. You'll then need to stay on it for at least several months, depending on your doctor's recommendations. If this second one doesn't work, your doctor may try a combination of depression medicines. Your doctor may also recommend older drugs for depression, such as MAOIs or tricyclics.
Augmentation with other medicines. If standard treatments aren't working, your doctor may add other medicines to your antidepressants. The combination can work in cases where antidepressants on their own did not. Types of medicines might include antianxiety drugs, anticonvulsants, antipsychotics, lithium, thyroid hormones, and others. Your doctor may want to try a number of different drugs in different combinations. One drawback is that the more medications you take, the greater potential for side effects.
ECT (electroconvulsive therapy). Although sometimes used as first-line treatment for people with severe, life-threatening depression, ECTECT is usually reserved for people with serious depression that can't be controlled with other treatments. It uses electric impulses to trigger controlled seizures in the brain. This treatment can rapidly relieve depression, although its effects often fade.
VNS (vagus nerve stimulation). VNSVNS is a new approach used in people with serious depression that hasn't responded to other treatments. Through a pacemaker-like device implanted in the body, VNS delivers regular electrical impulses to the vagus nerve, one of the nerves that relays information to and from the brain. Other experimental techniques. Researchers are working on experimental techniquesexperimental techniques to tackle treatment-resistant depression, like TMS (transcranial magnetic stimulation), MST (magnetic seizure therapy), and deep brain stimulation. These have not been approved by the FDA for treating depression. But if you're interested in trying them, talk to your doctor about joining a clinical trial. Lifestyle Changes There's a lot that you can do on your own to ease the symptoms of depression. Changing your lifestyle can have a big effect on your mood. But the problem is that it's not always easy to change our ways. It's one thing to say that you'll exercise five days a week, sleep at least eight hours a night, and eat three healthy meals and two snacks a day. But it's not that easy to actually do. It's especially difficult when you're depressed. The key is to try not to get overwhelmed at the idea of changing your behavior. You also shouldn't try to kick all your bad habits and reform totally overnight. That won't work. Instead, start by making a few small changes to your life. As you start feeling better, make some more changes. Gradually ease yourself into a healthy lifestyle. If you have treatment-resistant depression, you may have already tried one or more of these options. Lifestyle changes continue to be important as you and your doctor decide next steps for you. Here are some suggestions. - Get some exercise. Studies show that regular exercise can improve your mood and help you sleep better. For instance, one study found that three sessions of aerobic activity each week worked as well as antidepressants in treating nearly two-thirds of depressed people. And after 10 months of regular exercise, only 33% of the people who exercised were depressed, compared to 52% of the people who took antidepressants. The results were published in the journal Psychosomatic Medicine in 2000.
When you start an exercise program, take it slowly at first. You could begin with walks around the neighborhood with a friend. Gradually, work up to exercising on most days of the week. Try out different activities to find one that you really enjoy. Exercise with a friend or relative or sign up for a class. Doing things you like to do and having other people involved may help you stick with it.
- Sleep well. Depression, and sometimes antidepressants, can interfere with your sleep. Some people with depression sleep too much. Others can't fall asleep or wake up too early. So get into some good sleep habits. Get on a regular schedule: go to bed and get up at the same time each day. Avoid naps. Before getting in bed, unwind with a good book or soothing music, but not in the bedroom. It might help to reserve the bedroom only for sleep and sex.
- Eat a healthy diet. There's no diet that will cure or prevent depression. But a sensible eating plan will keep you feeling healthy and give you the nutrients you need. Don't rely on popular diets that cut out food groups and sharply restrict what you can eat. Just focus on the basics: watch your calories, eat lots of vegetables, whole grains, and fruits, and limit fat and sugar. Since caffeine can make you anxious, cut back on soda, coffee, tea, and chocolate. Ask your health care provider if seeing a nutritionist would be a good idea.
- Avoid alcohol and drugs. Alcohol and drugs can add to your depression and make it worse. Depression and substance abuse often go together. In addition, alcohol and drugs can prevent your antidepressants from working as well as they should. If you have a substance abuse problem, you need to get help now. Addiction or abuse can prevent you from fully recovering from depression.
- Get some sunlight. Some people find that they get depressed at certain times of the year, most often during the winter when the days are short and the nights are long. This form of depression is called seasonal affective disorder (SAD). If you have SAD, ask your doctor whether light therapy -- exposure to artificial sunlight with a special lamp -- might help.
- Stay connected and involved. Depression can rob you of your energy. You may feel like you can barely get across the room, let alone go out to dinner and a movie. But push yourself a little. Set aside time to do things that you used to enjoy doing. Get out with your family or friends. Or take up a hobby that used to give you pleasure. Staying active -- and connected with the people in your life -- may help you feel better.
If you have treatment-resistant depression, you may have already tried one or more of these options. Lifestyle changes continue to be important as you and your doctor decide next steps for you. Optimizing Medications 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.
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