Combination Therapies

When you’re first diagnosed with major depressive disorder (MDD), your doctor will likely prescribe one antidepressant for you. This is called monotherapy, and this first-line treatment will help 30 percent of patients reach remission (no symptoms). That leaves more than two-thirds of MDD patients untreated or undertreated for what can be a very debilitating disease.

To date, researchers cannot predict how patients will respond to medications. Doctors cannot know if a first-line treatment will help a patient, or if they will suffer residual symptoms and need additional treatment. For this reason, it’s important to work closely with your doctor so you can react to and treat the symptoms of MDD best. This may include considering combination drug therapy. A relatively new horizon for MDD treatment, many doctors are beginning to see the benefit of using a combination of medications, including other antidepressants or drugs to treat other mood disorders, in depression treatment.

The Role of Medications
Until recently, doctors typically prescribed antidepressant medication from only a single class of drugs at one time. If that drug failed, they might try another medicine within that class or switch to another class of antidepressants entirely. They did not consider combining antidepressants from multiple classes, but research suggests that may be the best way to treat MDD.

A study in the American Journal of Psychiatry found that patients who began initial treatments for MDD with combination drug therapy (medicine from more than one class of antidepressants) showed significantly greater improvements in symptoms and reduced remission rates compared to patients who were treated with a single drug. In this same study, 40 percent of patients who had been using a combination therapy who were later reduced to monotherapy (one type of pill) relapsed. Although this study was done in people being treated for MDD for the first time, it holds promise for people who are looking for an improved treatment for existing MDD.

Atypical Antidepressants
Bupropion is the most commonly used combination therapy medication, and it’s often used with SSRIs and SNRIs. On its own, the medication is very effective at treating major depression disorder, but it may also be used in conjunction with other medications in difficult-to-treat depression. It is well tolerated in people who have experienced severe side effects from other antidepressant medication, and it can also relieve some of the sexual side effects of the more popular selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinphrine reuptake inhibitors (SNRIs).

For people experiencing loss of appetite and insomnia, mirtazapine may be welcomed as its most common side effects are weight gain and sedation. However, mirtazapine has not been studied in depth as a combination medication.

Antipsychotics
Research suggests there may be some benefit in treating residual symptoms in people taking SSRIs with atypical antipsychotics, such as aripiprazole. The possible side effects associated with these medicines (weight gain and metabolic disturbances) should be carefully considered as they may prolong or worsen some symptoms of depression.

Lithium
Lithium is typically used to treat biopolar disorder, but it has a well-researched history of treating other mood disorders, too. In most cases, lithium is used in conjunction with monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs). However, small studies have shown it is also effective with more popular (and most frequently prescribed) SSRIs and SNRIs.

Despite its success, many doctors will not treat with lithium because of the potential for toxicity. Patients using lithium will have to have frequent serum level blood measurements to check for lithium buildup in the blood.

L-Triiodothyronine (T3)
Some doctors may use L-Triiodothyronine in combination therapy with TCAs and MAOIs. Research suggestions T3 is better at speeding up the body’s response to treatment than increasing the likelihood a person will enter remission.

Stimulants
D-amphetamine (Dexedrine) and methylphenidate (Ritalin), both stimulants, are used to treat depression. They can be used as a monotherapy, but they may also be used in a combination therapy with other antidepressant medications. They’re most helpful when the desired effect is a quick response: patients who are debilitated, or those who have comorbid conditions (such as a stroke) or chronic medical illnesses, may be good candidates for this combination.

Combination Therapy as First-Line Treatment

Success rates of treatment with a single type of medication (monotherapy) are so low, many researchers and doctors believe the first and best approach to treating MDD is combination treatments. Still, many doctors will begin treating with a single antidepressant medication. Before making a decision about the medication, give it time to work. The 2008 American College of Physicians guideline suggests medications should be adjusted only after they have been given six to eight weeks to show efficacy. After that trial period, if you do not show an adequate response, your doctor may wish to change medications or add an additional medication to see if the combination helps your treatment plan succeed.

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