During a 12-month period, 7% of all adults are affected by major depressive disorder, and approximately 1 in 6 individuals is affected by this major public health problem during his/her lifetime. A Seminar published Online First by The Lancet examines novel developments associated to this disabling condition, and concludes that the majority of individuals with the condition require multiple treatment steps for remission. In addition, it reveals why deep brain stimulation is a treatment that shows promise for the future. The Seminar is written by Professors David J Kupfer, Ellen Frank, and Mary L Phillips, all of University of Pittsburgh Medical Center, PA, USA.

The negative impact depression has on health is equivalent to other chronic diseases, such as diabetes and arthritis, although sometimes this is not recognized. In addition, depression can integrate with other chronic diseases, resulting in considerably worse patient outcomes.

The researchers explain:

“A crucial implication is that primary care providers should not ignore the presence of depression when patients have a chronic physical disorder.”

According to the researchers the risk of depression may be increased by some of the risk factors for obesity, and individuals who are depressed are more likely to become obese. Two-way relationships such as this may be the cause for increased connection between coronary artery disease and depression. In addition, investigations have concluded that clinical depression is linked to a 65% increased risk of elderly individuals developing diabetes.

Evidence indicates that depression specific psychotherapy and medication treatments, either alone or combined, are effective treatments for depression. Many large investigations in Europe and the U.S., support interpersonal psychotherapy and cognitive behavioral therapy. The internet and telephone can be used to deliver cognitive therapy, which can result to substantial financial savings.

The researchers highlight that the most prevalently prescribed type of medication in hospital outpatient-based practice and general practice are antidepressants. However, the use of antidepressants is low in racial and ethnic minorities.

The team point out the STAR*D investigation that analyzed up to 4 successive treatment steps, beginning with citalopram, and included a change to augmentation with further medication or cognitive therapy in the following steps. In steps 1 to 4 remission rates were disappointing at 37%, 31%, 14%, and 13%, with a cumulative remission rate of 67%, lower than indicated by effectiveness investigations of the various antidepressants.

The team say this “suggests that, in actual practice, most patients need several sequential treatment steps to achieve remission.”

In addition they note novel approaches that have been used, such as intravenous ketamine for acute treatment of treatment-resistant depression, and ademetionine for major depression.

The safety of selective serotonin reuptake inhibitors (SSRIs) has been substantially debated, however the researchers explain that evidence in association with the use of these medications and suicide is conflicting, with some investigations revealed lower risk of suicide after starting SSRI treatment, particularly in men, and with sertraline, and other investigations showing an increased risk of suicide. Furthermore, the team go over the risk of using SSRIs during pregnancy, with data indicating that paroexetine may result in major disfigurement, especially cardiac defects.

SSRI use during late pregnancy can be connected with persistent pulmonary hypertension in newborns, and continuously depressed mothers and continuous SSRI use during pregnancy were more likely to give birth prematurely than those without depression or using SSRIs. The researchers explain:

“Guidelines suggest that SSRIs should be used with caution during pregnancy and that paroxetine be avoided.”

A novel prospect for using deep brain stimulation for treatment for major depression has yet to be approved by the US Food and Drug Agency (FDA) or the European Medicines Agency, however it shows promising results.

Electrodes that are connected to an internal pulse generator, that can be adjusted to the patient’s needs, are inserted bilaterally in the brain. The FDA has already approved Transcranial magnetic stimulation (TMS), although repetitive TMS may not be as effective as deep brain stimulation.

However, the researchers conclude that, even though the recent clinical, neurobiological, and treatment advances made in the past five years, “no fully satisfactory treatments for major depression are available.”

Written by Grace Rattue