Clinical Depression: Complexities of Diagnosis and Management

Major depression is at once simple and complex. At one level, the treatment of this disorder is straightforward. Yet, at a multitude of other levels, it is a complex condition for which available treatments remain suboptimal. Ongoing clinical and translational research in the biology, treatment, and outcome of depression has continued to enlighten the management of this common human affliction. The articles in this special issue highlight the state of the art of depression research and management. Issues as varied as the use of serotonin reuptake inhibitors in pregnancy and the use of imaging to optimize depression outcomes are discussed. In addition to the clinical value of these articles, the reader should note the broad diversity of research being done today.

Studies that have restrictive criteria have been criticized as not being reflective of real-world treatments. This has been labeled the "efficacy-effectiveness gap," or the difference between what studies show and what we see in the clinical setting. For this reason, the NIMH sponsored several large effectiveness studies: STEP-BD, CATIE for schizophrenia, and STAR*D. One of the major lessons these effectiveness studies have taught us is that the restrictive efficacy studies are generally accurate. This is also true when we examine the role of cognitive-behavioral therapy in the treatment of depression as examined in the STAR*D study and analyzed in the cover article of this issue by Edward S. Friedman, MD, "Cognitive Therapy: What Is Its Role in Depression Treatment?"

Chronic depression is a growing problem, and yet the definition of chronic depression is not clear. How is chronic depression different from dysthymia? How is chronic depression different from treatment-resistant depression? What is the best approach to the treatment of chronic depression? Research into long-term disorders is difficult to perform. In a field in which so much of our data are generated by industry, finding good information about chronic depression is not easy. That is one of the reasons why "Never-Ending Winter: Chronic Depression" by Francis Mondimore, MD, is an important article.

Research is ultimately an attempt to predict the future. We administer treatments to our patients with the promise that in the near future they will improve. However, we frequently fail and modify our treatment recommendations. Would it not be advantageous if we had tools that would allow us to predict who will respond to which treatment option? Work in major depression is heading in that direction, and the state of the art is described by Jeffrey M. Miller, MD, and Ramin V. Parsey, MD, PhD, in "Can We Predict Response to Antidepressants?"

The placebo effect is frequently invoked when some unexpected improvement occurs. But what is the placebo effect? Is it a reflection of the natural history of an episodic illness? Is it related to the hope or support that naturally occurs when patients come in for treatment? Is it related to the patient's belief that the treatment will help him or her? It is likely all of these and more. We need to understand the placebo effect not only to understand and interpret studies more accurately but also to improve the outcome of our treatments. That is why "Placebo Effects on Pharmacotherapy Outcomes in Major Depression" by Aimee M. Hunter, PhD, is an important article to read.

Nearly 60% of all psychiatric hospital admissions are related to suboptimal adherence to chronic medication regimens. This is a significant problem that may also be an important issue in chronic depression. Factors influencing treatment adherence, and what clinicians can do to improve treatment outcome are discussed in "Adherence to Treatment Regimens in Major Depression: Perspectives, Problems and Progress," by Melvin G. McInniss, MD.

We believe that there is an advance, a progression, from the primitive to the exquisite. However, this is not always absolute. Older treatment options continue to have their utility and their niche. One of our oldest somatic treatments, electroshock therapy, continues to be one of the most effective short-term treatments available. Consequently, it is important to understand how we can use all the tools at our disposal. "Not Obsolete: Continuing Roles for TCAs and MAOIs," by J. Alexander Bodkin, MD, and Jessica L. Gören, PharmD, places these older pharmacological options in proper perspective.

Depression has its onset in young adults and is more common in women. Thus, concomitant occurrence of depression and pregnancy may be expected. Given that nearly 60% of pregnancies in the United States are unplanned, information about the effect of antidepressants in pregnancy is very important. The article by Ruta M. Nonacs, MD, PhD, "SSRIs and Pregnancy: Putting the Risks Into Perspective" will help when addressing this issue with your patients.

Research is the future of our field. Thus, examination of these articles can provide a look into our future. The next generation of psychiatrists can expect to have new formulations of medications that can be administered topically, by injection, or even by genetic manipulation. Imaging of brain activity is likely to be more routine.

The developing field of "personalized medicine" will affect depression treatment. Personalized medicine is based on the belief that specific biological or genetic variants can be predictive of specific treatments. Such a case may already exist for the treatment of alcoholism with naltrexone. A genetic variation of the µ-opioid receptor gene in which the 118th base is occupied by a guanine instead of an adenine, is highly predictive of response to naltrexone. Studies are under way that will lead to routine genotyping before initiation of naltrexone therapy. This may be the case within 2 years.

This is an exciting time for our field. We are confronting the deficiencies in our treatments and learning more about how to address them to improve our patients' lives and to alter the prognosis of a disease that has tortured humanity for thousands of years.