Move over Prozac: New drug offers hope for depression

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The brain chemistry that underlies depression is incompletely understood, but research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor through its receptor TrkB, may contribute to anxiety and depression. Here, researchers describe a screen for stable small molecules that could specifically inhibit TrkB action. They identified one they dubbed ANA-12, which had potent behavioral effects when administered to mice that suggest it will have antidepressant and anti-anxiety activity in humans.

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An estimated 19 million Americans suffer from depression, and though the symptoms might be recognizable, the brain chemistry that underlies them is incompletely understood. Research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor (BDNF) through its receptor TrkB, may contribute to anxiety and depression, and inhibiting this pathway in mice can reduce anxiety and depression-related behaviors. However, translating these findings to clinical studies will require the development of small molecule inhibitors of the BDNF/TrkB pathway that could be used pharmacologically.
In this paper, researchers led by Maxime Cazorla, of Columbia University in New York, and Didier Rognan, of the Université de Strasbourg in France, describe a screen for stable small molecules that could specifically inhibit TrkB action. They identified one they dubbed ANA-12, which had potent behavioral effects when administered to mice that suggest it will have antidepressant and anti-anxiety activity in humans. The researchers are hopeful that this new compound could be used to develop a new class of psychiatric drugs.

Source: http://www.sciencedaily.com/releases/2011/04/110418122314.htm

Depression Medicines

Not only does it take time to get an accurate depression diagnosis, finding the right medication to treat depression can be a complicated, delicate process. Someone may have a serious medical problem, such as heart disease or liver or kidney disease, that could make some antidepressants unsafe. The antidepressant could be ineffective for you or the dose inadequate; there may not have been enough time to see an effect, or the side effects could be too bothersome -- leading to a failure of treatment.

As you approach taking antidepressants to treat depression, it is important to keep these points in mind:

1. Only about 30% of people with depression go into full remission after taking their first course of antidepressants. That’s 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.
2. Some antidepressants work better for certain individuals than others. It's not uncommon to try different depression medicines during treatment.
3. Some people need more than one medicine for depression treatment.
4. Antidepressants carry a boxed warning about increased risk compared to placebo for suicidal thinking and behavior in children, adolescents, and young adults 18-24 years old.

Working with your doctor, you can weigh the risks and benefits of treatment and optimize the use of medication that best relieves your symptoms.

What is an antidepressant?

Antidepressants, sometimes in combination with psychotherapy, are often the first treatment people get for depression. If one antidepressant doesn't work well, you might try another drug of the same class or a different class of depression medicines altogether. Your doctor might also try changing the dose. In some cases, your doctor might recommend taking more than one medication for your depression.

What are the different types of antidepressants?

Here are the main types of antidepressants along with brand names:

• Selective serotonin reuptake inhibitors (SSRIs) were launched in the mid to late 1980s. This generation of antidepressants is now the most common class used for depression. Examples include citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil, Pexeva), fluoxetine (Prozac, Sarafem), vortioxetine (Brintellix), and sertraline (Zoloft). Another SSRI, Viibryd, was approved in early 2011. Side effects are generally mild, but can be bothersome in some people. They include stomach upset, sexual problems, fatigue, dizziness, insomnia, weight change, and headaches.
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer type of antidepressant. This class includes venlafaxine (Effexor),  desvenlafaxine (Pristiq and Khedezla), duloxetine (Cymbalta), and, levomilnacipran (Fetzima). Side effects include upset stomach, insomnia, sexual problems, anxiety, dizziness, and fatigue.
• Tricyclic antidepressants (TCAs) were some of the first medications used to treat depression. Examples are amitriptyline (Elavil), desipramine (Norpramin, Pertofrane), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Side effects include stomach upset, dizziness, dry mouth, changes in blood pressure, changes in blood sugar levels, and nausea.
• Monoamine oxidase inhibitors (MAOIs) were among the earliest treatments for depression. The MAOIs block an enzyme, monoamine oxidase. Examples are phenelzine (Nardil), tranylcypromine (Parnate) , isocarboxazid (Marplan), and transdermal selegiline (the EMSAM skin patch). Although MAOIs work well, they're not prescribed very often because of the risk of dangerous reactions. They can cause serious interactions with other medications and certain foods. Foods that can negatively react with the MAOIs include aged cheese and aged meats.
• Other medications:
  • Bupropion (Wellbutrin, Aplenzin) is different than other antidepressants is thought to affect the brain chemicals norepinephrine and dopamine. Side effects are usually mild, including upset stomach, headache, insomnia, and anxiety. Bupropion may be less likely to cause sexual side effects than other antidepressants.
  • Mirtazapine (Remeron) is usually taken at bedtime. Side effects are usually mild and include sleepiness, weight gain, elevated triglycerides, and dizziness.
  • Trazodone (Desyrel) is usually taken with food to reduce chance for stomach upset. Other side effects include drowsiness, dizziness, constipation, dry mouth, and blurry vision.
  
   Are other medicines used with the antidepressants?
  
  Other medicines may be prescribed in addition to antidepressants, particularly in treatment resistant depression. Here are examples of medicines that may be used to augment as an add-on to antidepressant treatment.
• Antipsychotic medications like Abilify and Seroquel can be used as an add-on to antidepressant treatment. Symbyax, a combination of the antipsychotic drug Zyprexa and an SSRI (fluoxetine), is approved for treatment-resistant depression.
• Your doctor may recommend or prescribe other medications or supplements not FDA approved for use in depression   

Are there suggestions for how to get the most from depression treatment?

• Monitor your mood. Monitoring your moods and behavior from time to time can help your doctor treat your depression before it becomes hard to control. Try to observe any patterns of mood swings each week and call your doctor if you aren’t feeling at the top of your game.
• Strengthen your social support. Although you cannot control your depression diagnosis, there are some things you can control. You can seek or create a positive support system for yourself. Whether your social network stems from your spouse, family members, close friends, co-workers, religious organizations, or community groups, support is available.
• Stick with the prescribed treatment. 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’re not giving it a fair chance to work.
• See a depression expert. It's important to talk with a trained professional during your treatment. Although psychologists cannot prescribe medication, they are well-trained in psychiatric assessment and psychotherapy. You can work with a psychologist while taking antidepressants prescribed by your regular doctor, or you can 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.
• Develop 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 such as 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. 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.
• Let your doctor know if you are prescribed other medicines by another health care professional.  Some medicines can have important interactions with antidepressant medicines.  Tell your doctor if you are already taking, or begin taking, any other medicines so he or she can safely monitor your treatment.
• Never stop taking your depression medicine without your doctor's permission. 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 get worse.
• Don't assume that you can stop taking your depression medicine when you feel better. If you feel that you’d like to come off your medication, talk to your doctor. Don’t stop on your own; quitting abruptly can lead to symptoms associated with discontinuing a drug as well as risk for relapse.

Source: http://www.webmd.com/depression/guide/optimizing-depression-medicines?page=1