Major Depressive Disorder Treatments

Major Depressive Disorder (MDD) is a prevalent, debilitating, and chronic disorder. Contrary to the chronic nature of MDD, however, is the demand for interventions that produce rapid symptom relief. The call for faster acting treatments has naturally led to an increased focus on early stages of and markers for symptom reduction. 

A primary assumption of such a focus is that onset of symptom change occurs prior to treatment response. Empirical work has borne out the validity of this assumption, as outcome studies suggest that symptom change— not complete remission, but change—can be identified during the first 1–2 weeks of treatment. As such, measurement of early symptom reduction that does not meet criteria for response becomes important.

Different criteria of early symptom improvement have been set forth, with a 20% reduction in scores being one frequently used measure. Using this definition of improvement, 92% of a primarily outpatient sample with early improvement by the end of the second week of treatment showed a treatment response by week 8, defined as at least a 50% reduction in symptoms. Moreover, 55% of early responders displayed complete remission by week 8.

More importantly, early onset was the only variable to successfully predict complete remission (4). A separate study reported highly similar results, finding that over 70% of early improvers became responders by week 5. Hence, preliminary research suggests that early response to antidepressant treatment is both identifiable and an indicator of a successful course of outpatient treatment.

Given that change in MDD often occurs during the first 1–2 weeks of outpatient treatment, an important question is whether this change is due to (a) a mild reduction in severity of most symptoms or (b) a greater reduction in certain symptoms but relative stability in others. Evidence regarding specific symptom change in the first 2 weeks of treatment is mixed at best, but the following symptoms have demonstrated a reduction in response to antidepressant treatment: suicidal ideation; guilt;  lack of appetite; depressed mood; poor concentration; anhedonia; and psychomotor retardation.

Evidence suggests that, in contrast to symptoms which may improve quickly, some symptoms show a later response, or even no response, to antidepressant treatment. Such symptoms include anhedonia, anergia, sleep disturbance, and psychomotor agitation or retardation. As readers will note, some symptoms appear on lists of both early responding and late responding symptoms, leading to the conclusion that it is currently unclear which symptoms, if any, reliably respond quickly to treatment, and to which specific treatment they may respond.

The only exceptions to these inconsistencies may be suicidal ideation and guilty feelings, which have more consistently demonstrated early response, and sleep disturbances, which tend to demonstrate a later response to SRIs. If certain symptoms are more likely to show an early response than others, it would be important to identify factors that predict this change. Evidence for predictors of early symptom response is mixed, whichmay result from differences in outcome criteria and predictor variables selected across studies.

Greater initial severity of depression has been associated with faster improvement in some studies, but this effect may be explained in part by the statistical phenomena of regression to the mean and a restricted range of variance to predict among those with lower initial symptoms (i.e., a floor effect). Limited evidence suggests that the presence of a comorbid anxiety disorder and obsessive compulsive personality disorder may be associated with faster improvement. Initial insomnia and older age—that is, mid 40s compared to mid 30s—also have been associated with earlier onset of response. As is the case with early symptom response, however, these findings have often failed to replicate. It is therefore difficult to draw conclusions about predictors of early response to outpatient antidepressant treatment.

Although little empirical evidence exists on predicting response to inpatient treatment for MDD, length of hospitalization is one potential predictor of interest. Lieberman et al  indirectly examined the role of length of hospitalization in MDD treatment response, and found that the length of stay grew significantly shorter for each of 3 successive inpatient cohorts diagnosed with MDD. In general, discharge scores on the HAM-D  were similar across cohorts, but the final cohort had a significantly higher HAM-D at discharge and a significantly lower global assessment of functioning score than the first cohort. These results, while not suggesting a strong effect, indicate that longer length of stay may be associated with higher functioning at discharge.