Physician's Weekly Article - A Guide for Using Second-Generation Antidepressants

       The American College of Physicians has developed a guideline to help clinicians manage acute, continuation, and maintenance phases of major depressive disorder with second-generation antidepressants.

      Depressive disorders—which include major depressive disorder (MDD), dysthymia, and subsyndromal depression (eg, minor depression)—are serious, disabling conditions that affect about 16% of American adults at some point during their lifetime. These disorders account for an estimated economic burden of $83.1 billion. “Several treatment approaches can be used to manage depression,” explains Amir Qaseem, MD, PhD, MHA, “including pharmacotherapy, psychotherapy, and cognitive behavioral therapy. If physicians choose pharmacotherapy, the most commonly used therapies are second-generation antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and selective serotonin norepinephrine reuptake inhibitors (SSNRIs). Second-generation antidepressants are important medications for treating depressive disorders because they have similar efficacy to and lower toxicity than first-generation antidepressants.”

      Gaining A Better Understanding

      In the November 18, 2008 Annals of Internal Medicine, the American College of Physicians (ACP) released new guidelines. They present available evidence on the pharmacologic management of the acute, continuation, and maintenance phases of MDD and other depressive disorders with second-generation antidepressants (Figure). “The goal of the guideline is to help all clinicians gain a better understanding of the evidence surrounding use of the second-generation antidepressants,” Dr. Qaseem says. “Understanding how patients progress through various phases can help clinicians recognize early depression relapse or recurrence. Relapse is the return of depressive symptoms during the acute or continuation phases. It’s considered part of the same depressive episode. Recurrence, on the other hand, is the return of depressive symptoms during the maintenance phase. It’s considered a new, distinct episode. The key for clinicians is to remember that evidence has shown that there is no difference in efficacy or effectiveness between various second-generation antidepressants.”

      Assessing Efficacy & Quality of Life

      The ACP guidelines make four key recommendations for all clinicians who manage depressed patients with second-generation antidepressants (Table). They note that, based on the current body of evidence, there are no clinically significant differences in terms of efficacy, effectiveness, or quality of life among SSRIs, SNRIs, SSNRIs, or other second-generation antidepressants for the treatment of acute-phase MDD. “As such,” says Dr. Qaseem, “the selection of second-generation antidepressants should be based on adverse effect profiles, cost, and patient preferences. Physicians and their patients should discuss adverse event profiles before selecting medications.”

      The guidelines also point out that 38% of patients fail to achieve a treatment response during 6 to 12 weeks of treatment with second-generation antidepressants; more than half did not achieve remission. Second-generation antidepressants also did not differ in efficacy in patients with accompanying symptoms or in subgroups based on age, sex, race or ethnicity, or other comorbid conditions. Studies evaluating the risk for suicidality demonstrated no differences between second-generation antidepressants, but patients receiving SSRIs did exhibit an increased risk for nonfatal suicide attempts.

      Long-Term Follow Up is Essential

      “When managing patients with second-generation antidepressants, clinicians need to assess status, therapeutic response, and adverse effects of selected therapies regularly,” says Dr. Qaseem. “This should begin within 1 to 2 weeks of initiating therapy. Clinicians should monitor patients for the emergence of agitation, irritability, unusual changes in behavior, or any suicidal ideations. These symptoms can indicate that the depression is worsening. Patients should then be monitored to assess responses to treatment. Changes in therapy may be necessary if responses aren’t sufficient after 6 to 8 weeks of initiation of treatment. The addition of other therapeutic modalities may be required.”

      Durations of antidepressant therapy should depend on risks for relapse or recurrence. “Patients with a first episode of depression and who achieve remission with acute-phase treatment should continue receiving their antidepressant for 4 to 9 months to prevent relapse,” says Dr. Qaseem. “However, patients who have had two or more episodes may benefit from longer durations of therapy.” The guidelines note that there is no evidence indicating differences among second-generation antidepressants in preventing relapse or recurrence.

      More Data Wanted

      Dr. Qaseem says the ACP guidelines will be revisited and revised as new research emerges. “To better assist clinicians, we need more multiple-group and head-to-head trials with second-generation antidepressants. They should assess efficacy and effectiveness in real-world settings. Having data on use of these medications in specific subgroups (eg, the very elderly, patients with comorbid conditions, or different sexes) is also paramount. Additionally, more investigations on the appropriate duration of treatment for maintaining remission and on combination therapy are warranted. As more research emerges, there is hope that the burden of these illnesses can be substantially reduced.”

      Amir Qaseem, MD, PhD, MHA, has indicated to Physician’s Weekly that he has received unrestricted educational grants/research aid from the AHRQ, the Robert Wood Johnson Foundation, Endo Pharmaceuticals, Boehringer-Ingelheim, and Atlantic Philanthropies.