• Depression

When antidepressants don't work: Try, try again?

Medications may cure depression, but it may take several attempts to find the right one. How many will you have to try?

Major depression affects almost 15 million American adults each year. Two-thirds of them can eventually find relief, according to a federal study, if they are willing to keep trying medications until they find one that works for them. But, the odds of beating the depression diminish with every additional treatment strategy needed. The seven-year study by the National Institute of Mental Health, called StarD (Sequenced Treatment Alternatives to Relieve Depression), tracked 4,000 people diagnosed with chronic depression to determine which treatments brought complete remission.

Here how the study worked

Participants proceeded through successive treatment stages, adding and switching meds as needed.

First try: Relief for 33%

Level I

All started with citalopram (Celexa), a selective serotonin reuptake inhibitor (SSRI), for up to 14 weeks. About a third of participants reached remission in about seven weeks.

Second try: Relief for 25%

Level 2

The others, who opted to continue, proceeded to Level 2 and could choose to switch to another medication: sertraline (an SSRI), bupropion-SR (a non-SSRI antidepressant), or venlafaxine-XR. Of those who switched, 25 percent became symptom-free, with similar responses to all three medications.

Or, they could add another medication to the Celexa and received either bupropion-SR (a non-SSRI antidepressant) or buspirone (a medication that enhances the action of an SSRI)] In the add-on group, about one-third of participants became symptom-free, with somewhat better results from bupropion. Those who did not become symptom-free, or who experienced intolerable side effects, could choose to continue to level 3.

Third try: Relief for 12-20%

Level 3

Participants again had the option of either switching to a different medication or adding on to their existing medication. Those who chose to switch their medication were randomly assigned to either mirtazapine (Remeron) - a different type of antidepressant - or to nortriptyline (Aventyl or Pamelor) - a tricyclic antidepressant-for up to 14 weeks. Both work differently in the brain than the SSRIs and other medications used in levels 1 and 2. In the level 3 switch group, 12 to 20 percent of participants became symptom-free, and the two medications used fared about equally well.

Those in the add-on group received either lithium - a mood stabilizer used to treat bipolar disorder - or triiodothyronine (T3) - a medication used to treat thyroid conditions - to add to the medication they were already taking. These medications were chosen because they have been shown to boost the effectiveness of antidepressant medications. About 20 percent of participants became symptom-free, with little difference between the two treatments. However, lithium caused more problem side effects.

Fourth try: Relief for 7-10%

Level 4

Participants who had not yet become symptom-free were taken off all other medications and randomly switched to one of two treatments - the MAOI tranylcypromine (Parnate) or the combination of venlafaxine extended release (Effexor XR) with mirtazapine (Remeron). Seven to 10 percent of these participants became symptom-free. Those taking the venlafaxine-XR/mirtazapine combination experienced more of a reduction in depressive symptoms; those taking tranylcypromine were more likely to quit because of side effects. The STAR*D study showed that about half of participants became symptom-free after two treatment levels. Over the course of all four treatment levels, almost 70 percent of those who did not withdraw from the study became symptom-free. However, the rate at which participants withdrew from the trial rose with each level-21 percent withdrew after level 1, 30 percent withdrew after level 2 and 42 percent withdrew after level 3.

Like other medical illnesses, depression affects different people in different ways, but a wide range of effective treatments exist. People with depression should not give up if their initial treatment attempts do not result in full benefits. They should continue to work with their doctors to find the best treatment strategy. Doctors should provide medication at optimal doses, be aware of and offer treatment choices, and diligently monitor patients during and following treatment. While some people may experience benefits in the first six weeks of a treatment, full benefits may not be realized until 10 or 12 weeks have passed.

Multiple Meds