“Sometimes when people have severe depression, they have a partial response to treatment,” says James Seymour, MD, a psychiatrist at Sierra Tucson, a behavioral treatment center in Tucson, Ariz. “They may need an add-on, or second, medication to improve or accelerate their response.” The National Institutes of Mental Health funded a study on this very subject called STAR*D (Sequenced Treatment Alternatives to Relieve Depression). The seven-year study, which released initial results in 2006, looked at more than 4,000 people, ages 18 to 75, with depression. It found that those who did not improve with a single antidepressant medication had an increased chance of getting better with a new medication or through the addition of a second medication. If you’ve noticed an improvement in your depression symptoms since starting an antidepressant but still feel like you could get better control, your doctor may recommend an add-on medication. Keep in mind, though, that you need to give your current medications a reasonable chance to work before looking at this option. It may take six or more weeks for an antidepressant to become fully effective. However, Dr. Seymour concedes that this can feel like a long time to wait if you aren’t seeing results. If after three weeks you see little or no improvement from your antidepressant, he suggests talking with your doctor about whether to wait the full six-week trial period before adjusting your dosage. For example, “if you’re taking 300 milligrams of an antidepressant and getting a partial response," he says, “the next thing your doctor may do is to increase it to 450 milligrams.” If you increase the dosage, hit the maximum, and still see no improvement or have lingering symptoms, then you probably need to change to a different medication or use an add-on medication, Seymour says. Your doctor might suggest adding a second antidepressant or a different kind of drug altogether. Some add-on depression medications are available as a combination pill, and some require that you take separate pills. Add-On Medication Options for Depression Among the different medications used as add-ons in depression treatment are:

Anti-anxiety medications or tranquilizers. Anti-anxiety medications (benzodiazepines) can boost the effectiveness of antidepressants on some depression symptoms. These medications slow down your central nervous system, making you feel more calm and relaxed. However, like all drugs, they can have side effects, and this class of medication does pose a risk of addiction for some.Anticonvulsants. Typically given to prevent seizures in people who have epilepsy, anticonvulsants have been shown to have a calming effect on the brain and are sometimes used as an add-on medication for depression.Antipsychotics. Used to treat delusions and hallucinations, these drugs may also have a benefit as an add-on medication for people with depression. Antipsychotics sometimes cause weight gain and carry an increased risk for insulin resistance (which can lead to diabetes) and cardiovascular disease, however, so this isn’t a first-line add-on medication option for people who already have these conditions.Lithium. Generally well-tolerated as an add-on medication, lithium is usually used to treat bipolar disorder — a condition that involves moods that swing from high to low — and can help improve other mood disorders, including depression.Thyroid hormone. This hormone is sometimes used as a depression treatment because many of the physical symptoms of major depression are similar to those of hypothyroidism (an underactive thyroid): fatigue, malaise, and cognitive impairment.

An add-on medication can help you combat depression if you’re not getting there on an antidepressant alone, but there are drawbacks. For one, taking more drugs can increase your chances of experiencing side effects. You and your doctor have to weigh the risks and benefits of add-on medications and decide what’s best for you. Unfortunately, Seymour says, there’s currently no scientific way to determine which add-on medication will be most effective from the start, so there may be some trial and error involved. If you have relatives who also suffer from depression, look at the depression treatments that work best for them. How a person responds to a particular medication could be genetic, Seymour notes. Their success may give your doctor a starting point. Chances are that with time and effort, you’ll find the best depression treatment for you. Only a small minority of people go through every available antidepressant alone and in combination without finding something that’s effective, Seymour says. “Roughly 60 percent of people get relief from their symptoms on the first try.” Of those who don’t, he says, about half get relief on the second try, and still others get relief on the third try. “So it’s only a small percentage who don’t respond to depression treatments alone or in combination,” he says. “We are blessed to have a wide variety of antidepressants and add-on medications available to us today,” he adds. “Because we have many options, patients shouldn’t give up on finding a depression treatment that’s effective for them.”