Remission as the “Gold Standard” of Treatment for Depression With and Without Physical Symptoms

David A. Fishbain, MD

Departments of Psychiatry and Behavioral Sciences, Neurological Surgery, and Anesthesiology, University of Miami Miller School of Medicine, Miami, Fla

Importance of Remission

Remission, not response, has become the “gold standard” for the treatment of patients with depression. While response used to be the focus of treatment, the advantages of treating patients to remission are better prognosis, better functioning, less risk of relapse, and less utilization of medical services by the patient.1,2 However, painful physical symptoms may act as a barrier to remission in patients with major depressive disorder (MDD) by affecting patients’ depression severity, treatment response, and functioning.

Prevalence of Depression and Pain

In a community survey of approximately 21,400 people by Demyttenaere et al.,3 50% of those with MDD reported painful physical symptoms compared with 29% of those without MDD. Further, individuals with more severe depression experienced a greater frequency of painful physical symptoms. Having both MDD and painful physical symptoms decreased patients’ occupational functioning, and the effect was additive. These results indicate that painful physical symptoms not only are common in people with MDD, but also negatively affect patients’ productivity.

In addition to increased rates of pain in patients with depression, people with painful physical symptoms are more likely to have MDD than people with no pain. Currie and Wang4 surveyed 118,533 residents and found that the rate of MDD increased as the severity of chronic lower back pain increased (AV 1AV 1).

Effect of Pain on MDD Treatment Response and Remission

The presence and severity of pain in patients with depression may impact how they respond to antidepressant treatment. In a study5 of 187 patients aged 69 years or older who were treated for MDD with a combination of pharmacotherapy and interpersonal psychotherapy, Karp et al. reported that those who were nonresponders to treatment reported more severe pain at baseline than those who responded. Another study by Karp et al.6 examined 230 patients aged 21 to 65 years with recurrent MDD who also received pharmacotherapy and psychotherapy. The results showed that the presence of pain at baseline (specifically headaches and muscle soreness) increased patients’ time to remission by about 6 weeks, even after controlling for baseline depression severity. These studies5,6 suggested that pain is indicative of difficult-to-treat depression.

The extent to which pain impairs patients’ functioning may affect depression remission. Kroenke et al.7 measured pain interference with daily activities at baseline, 3 months, and 6 months in 405 patients with MDD or dysthymia treated with either collaborative care or usual care. At baseline, 42% of subjects reported that pain caused at least moderate interference with their work and home functioning. At 6 months, 32% of patients still reported at least moderate interference from pain, regardless of the type of depression treatment they received. The extent of baseline pain interference with daily activities and the amount of pain improvement over time were associated with depression response and remission (AV 2AV 2).

Mavandadi et al.8 examined pain severity, pain interference with work and home functioning, and depressive symptoms at baseline, 3 months, 6 months, and 12 months in 524 patients aged 60 years or older who were treated in Veterans Affairs Medical Centers. Although treatment (either integrated care or enhanced specialty referral care) reduced depressive symptoms over time, high levels of pain and pain interference with functioning blunted patients’ improvement in depressive symptoms. Impaired functioning appeared to influence the persistence of depressive symptoms more than pain severity. Both of these studies7,8 stressed the necessity of treating depression and pain simultaneously.


Synergy of Pain and Depression Improvement

Evidence supports a link between improvement in painful physical symptoms and remission of depression. Fava and colleagues9 studied antidepressant effects on painful physical symptoms and remission in 495 patients with MDD. A decrease in overall pain scores was associated with an increase in the probability of achieving remission of depression over time (AV 3AV 3). Remission was especially likely among those whose pain responded within the first 2 weeks of treatment (p = .009), regardless of changes in depression scores in the first 2 weeks. In patients who received active treatment, remission was attained in 39% of pain responders and 25% of pain nonresponders, whereas, in the placebo group, remission occurred in 33% of pain responders and 12% of pain nonresponders. These results imply that if pain improves, remission of depression is more likely than if pain does not improve.


Remission is the goal of treatment for patients with MDD. However, the presence of painful physical symptoms, along with subsequent impaired functioning, can inhibit treatment response and remission of MDD. Evidence shows that the treatment of painful physical symptoms can have an impact on the improvement of depressive symptoms. Therefore, clinicians should target both depression and painful physical symptoms, because patients are more likely to achieve remission of depression if their pain improves.

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