Treatment of Depression: When Do Symptoms Go Away?

Abstract & Commentary

Synopsis: Physical symptoms are quite common among patients with depression. These symptoms tend to improve during the first month of therapy with serotonin-antagonists. Most symptoms will plateau in months to follow.

Source: Greco T, et al. J Gen Intern Med. 2004;19:813-818.

This study was aimed at evaluating the prevalence, impact on quality of life, and outcome of physical symptoms in patients with depression. It was designed as an open-label, randomized, intention-to-treat trial and was performed within a research network of 37 primary care clinics over a 6-month period. The study was part of the ARTIST (A Randomized Trial Investigating SSRI Treatment) study. Those patients who were deemed clinically depressed by their primary care physician and considered to be candidates for antidepressant therapy with serotonin-antagonists were eligible for inclusion in this trial. Patients were excluded if they had cognitive impairment, terminal illness, residence in an extended care facility, had recent active suicidal attempts or had been under pharmacological treatment for depression in the prior 2 months, had opiate or cocaine use, or if they had a history of bipolar disorder.

Computer-administered telephone interviews were used to conduct baseline and follow interval at 1, 3, 6, and 9 months after enrollment. Depression outcome was measured with 2 measures of core depressive symptoms (the HSCL-20 survey based on the Hopkins Symptom Checklist, and the Patient Health Questionnaire), and medical comorbidity was also calculated for each patient. The prevalence of symptoms was determined at baseline and the follow-up intervals. A linear regression model was constructed to determine the effect of therapy on individual physical symptoms.

Of the initial 601 patients that gave informed consent, a total of 573 patients completed the telephone assessment and completed the trial. Of the 14 physical symptoms assessed, 13 were present in at least a third-to-half of the patients at baseline measurement.

In follow-up assessments, every symptom showed the greatest improvement during the initial first month of therapy with serotonin antagonists. This improvement in symptomatology reached a plateau after the first month of pharmacotherapy. In contrast, other non-somatic depression symptoms continued to have a steady and gradual improvement over the 9-month study period.

Comment by Joseph Varon, MD, FACP, FCCP, FCCM

Physical, rather than emotional, symptoms are the presenting complaints that the majority of depressed patients voice to their primary care providers. This trial confirms previous studies indicating that many patients with clinical depression have significant physical symptoms.1-3 The study by Greco and associates is important as it presents interesting and compelling data regarding the improvement of physical symptoms with serotonin-antagonists with a peak during the first month of treatment.4

Most standard textbooks still consider that the maximum improvement in depression-related physical symptoms occurs weeks-to-months after the initiation of therapy with serotonin-antagonists. This study reveals that the improvement in physical symptoms will occur primarily during the first month of therapy and then the physical symptoms will plateau. On the other hand, it also notes that the non-physical symptoms of depression continue to improve after the first month.

Clinicians caring for patients with depression in whom somatic symptoms persist beyond one month of antidepressant therapy with serotonin antagonists should consider other treatment strategies.


1. Kroenke K, et al. Arch Fam Med. 1994;3:774-779.

2. Simon G, et al. N Engl J Med. 1999;341:1329-1335.

3. Bair MJ, et al. Arch Intern Med. 2003;163:2433-2445.

4. Greco T, et al. J Gen Intern Med. 2004;19:813-818.

Dr. Varon is Professor at the University of Texas Health Science Center in Houston.