Drug update: New antidepressants--beyond SSRIs. (Primary Care).

The newest generation of antidepressants gives physicians some novel options for treating depression that go a step beyond the selective serotonin reuptake inhibitors (SSRIs), but like the SSRIs the new antidepressants are not effective in about 40% of patients with major depression.

Because the SSRIs--citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline--have a longer track record, most experts continue to use them as first-line agents for treating depression. But the newer drugs listed here are generally ranked as comparable to the SSRIs in all other respects.

How would you choose among them? If a patient has been treated successfully in the past, use the same agent. Otherwise, there is no evidence-based way to decide which drug is best for an individual patient.

Some experts recommend matching a patient's symptom complex to the drug's spectrum of effects: for example, using a more sedating agent for a patient whose depression is accompanied by pronounced anxiety. But even this approach has not been supported by study results.

The most significant recent trend in treating depression is to maximize the dosage of whichever drug is used first before switching to a different drug. Also, treatment with the first drug is maintained for up to 12 weeks before it is deemed ineffective and the patient is switched to another drug; in the past, experts recommended sticking with an ineffective drug for only 6 weeks before trying something new The goal of treatment is full remission of symptoms; partial remission is considered inadequate and a reason to switch drugs. When this occurs, some authorities favor picking an agent from a different class, more because it seems sensible than because of any evidence. Others recommend adding lithium or thyroid hormone.

Once remission occurs, treatment should continue for at least 6-9 months. Patients with multiple episodes of depression are likely to require treatment for at least 2 years, and possibly indefinitely.

With depression increasingly viewed as a chronic illness, issues of cost assume more prominence. Fluoxetine is now available in a generic formulation.