Depression is a treatable condition. Evidence-based psychotherapies and antidepressant medications are equally effective in the treatment of mild to moderate depression. For patients with severe recurrent depression, combining pharmacotherapy and psychotherapy is recommended.1
TREATMENT RESISTANCE
Only 40% of patients in primary care respond to the first choice of antidepressant medication. The causes of treatment resistance are multiple. Obviously, patients who do not adhere to their drug regimen often present with what appears to be treatment resistance. Patients who meet the criteria for psychiatric comorbidities are more likely to be resistant to their first antidepressant medication. Those patients with severe depression that has been present for a substantial period of time are also frequently resistant. Chronic social stressors can limit antidepressant response. Finally, one of the more common causes of patients failing to respond to depression therapy is undiagnosed bipolar disorder.2
THE STAR*D TRIAL
The STAR*D trial was designed to compare long-term outcomes of various pharmacologic and nonpharmacologic treatments for depression. This randomized trial also addressed the issue
of treatment resistance. Patients who either did not achieve remission or who could not tolerate a 14-week trial of citalopram (selective serotonin reuptake inhibitor [SSRI]-Celexa) were randomly assigned to one of three groups. Group 1 substituted sustained-release bupropion (atypical antidepressant-Wellbutrin SR) for citalopram. Group 2 substituted sertraline (SSRI-Zoloft), and group 3 substituted venlafaxine (serotonin-
norepinephrine reuptake inhibitor-
Effexor). After treatment with one of these three medications for up to 14 weeks, remission was achieved in 25% of patients and response was achieved in an additional 25%.2
The STAR*D trial also investigated the response of treatment-resistant patients to augmentation of citalopram therapy with either bupropion or buspirone (serotonin type 1A receptor stimulant-BuSpar). Remission was achieved in approximately 30% of patients in both groups. Multiple randomized trials using aripiprazole (atypical antipsychotic-Abilify) as an adjunct medication have shown this regimen to be effective. The use of lithium for augmentation has also been studied and found to be effective. Lithium is the only medication that has been shown to decrease the rate of suicide in major depression.3
The STAR*D trial went on to study patients who did not remit with the medication switching or augmentation. This group of patients was randomized to either switching to nortriptyline (tricyclic antidepressant-Pamelor) or mirtazapine (tetracyclic antidepressant-Remeron) or to augmentation with lithium, triiodothyronine, sertraline, or venlafaxine. Patients who received either mirtazapine or nortriptyline did not demonstrate lower remission rates. Augmentation with either lithium or triiodothyronine was found to be effective for treatment-resistant patients.3
There exists reluctance on the part of both clinicians and patients to push antidepressant treatment to full remission. Additionally, treatment times longer than those used previously are required to achieve remission. A modest improvement at 6 weeks may require a dose increase or a longer time period (up to 12 weeks) at the same dose for a full response.
BOTTOM LINE
Patients who are resistant to monotherapy for depression should be evaluated carefully for medication compliance, substance abuse, bipolar disorder, and social stressors. The combination of antidepressant medication and psychotherapy is more effective than either treatment alone for patients with severe recurrent depression. Patients who fail to remit after the institution of one SSRI may achieve remission when a second SSRI is substituted. Patients who fail to remit after two trials of SSRIs should be switched to a different class of medication, and dual-action medications may be more effective in patients with severe depression. Augmenting SSRI therapy with a second antidepressant or with an atypical antipsychotic medication are also effective strategies. JAAPA
Mary Hewett is Assistant Professor, Division of Physician Assistant Studies, Medical University of South Carolina, Charleston, and the department editor for When the Patient Asks. She has indicated no relationships to disclose relating to the content of this article.
REFERENCES
1. Lyness J, Schwenk T, Solomon D. Depression: clinical manifestations and diagnosis. UpToDate Web site. http://www.utdol.com/online/content/topic.do?topicKey=psychiat/6524&selectedTitle=2%7E150&source=search_result. September 8, 2009. Accessed February 1, 2010.
2. Ciechanowski P, Katon W, Schwenk T, Solomon D. Treatment of resistant depression in adults. UpToDate Web site. http://www.utdol.com/online/content/topic.do?topicKey=psychiat/12876&selectedTitle=5%7E150&source=search_result. September 10, 2009. Accessed February 1, 2010.
3. Fava M, Trivedi M, Wisniewski S, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243-1252.
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