The term “depression” refers to multiple different disorders that share a group of common symptoms. For instance, depression in the context of bipolar disorder is related to but different from depression in a person without bipolar disorder. Psychotic depression, i.e., depression with hallucinations and/or delusions, is related to but different from non-psychotic depression.

Depressive episodes can occur in otherwise healthy individuals. Mild to moderately severe uncomplicated depression may be recognized by a primary care physician. A person with such a depression may respond well to supportive care coupled with either antidepressant medication or brief, evidenced-based psychotherapy. On the other hand, there are treatment-resistant depressions often complicated by comorbid medical illnesses and substantial psychosocial stressors. Alcohol and/or other substance use disorders may also co-exist. Individuals with moderate to severe treatment-resistant depression often are referred to specialists in a mental healthcare setting.

There have been very few studies investigating treatment outcomes in individuals with persistent depression who receive treatment by mental health care specialists. These patients are often individuals with complicated depressions that haven’t responded to routine treatments. In a paper published recently in Lancet Psychiatry, Richard Morriss and colleagues report the results of a treatment trial comparing intensive, integrated specialty treatment of persistent depression with routine specialty treatment. The intensive treatment involved expert pharmacological management by a team of psychiatrists together with intensive cognitive behavioral therapy (CBT). This intensive approach was compared to “routine” specialty care provided by a psychiatrist and mental health team in an outpatient setting. 

The study took place in three outpatient mental healthcare settings in England. All of the participants suffered from persistent moderate to severe depression that had not responded to at least six months of treatment and, at the time of the study, were under the care of mental health specialists. At entry into the study, the participants’ current depressive episode had been present, on average, for about 6 to 7 years and was associated with substantial impairment of function. The level of treatment received by the participants in the intensive treatment group was remarkable. The pharmacologic treatment strategy was carefully reviewed every two to four weeks. CBT sessions occurred weekly for up to 10 months and then were gradually spread out. The overall length of treatment was also remarkable. The intensive specialty treatment continued for 12 months followed by a 3-month transition to more usual care. Outcome was measured at 6, 12, and 18 months after initiation of treatment using standardized assessments of depressive symptoms and global function. Results of even longer term follow-up will be reported in the future.

Perhaps the most sobering finding in this study is that when outcomes were measured 18 months after the beginning of intensive treatment, only 26% of the participants were considered to be in remission (typically defined as having few or no depressive symptoms). In contrast, only 13% of the participants who received “treatment as usual” psychiatric care were considered to be in remission. These results highlight the fact that complicated, treatment-resistant depression is a tough illness to treat successfully, a finding that replicates prior large-scale effectiveness trials.

Importantly, improvement in both groups increased over time. For instance, in the intensive treatment group, only about half of the improvement evident at 18 months was noted at 6 months. In other words, if an individual is going to improve, treatment must continue for months to years.

Morriss and his colleagues indicate that at the 12 month follow-up, the participants who received intensive treatment did not show better outcomes in either depressive symptoms or function than those receiving “usual” specialty treatment. At 18 months, those in the intensive group demonstrated, on average, statistically better improvement in depression scores when compared with the treatment as usual group, although the difference was small. As mentioned previously, the intensive treatment group did have an overall estimated 2-fold increase in remission at the 18 month follow-up when compared to the treatment as usual group. Disappointingly, improvement in the ability to function at 18 months was no different between the two groups. The intensive treatment was also much more expensive to administer.

There are many types of depressions, and some types may be more responsive to specific treatment modalities than other types. Patients with treatment-resistant depression are suffering from a devastating, disabling, and life-altering illness. Even with the best psychologic and pharmacologic tools available, the majority of these individuals do not show marked improvement. The chronicity and poor outcomes of treatment-resistant depression highlight the need for continued development of novel treatments including ongoing research with brain stimulation methods (electroconvulsive therapy, transcranial magnetic stimulation, and vagus nerve stimulation among others), ketamine-like drugs, and new psychotherapies.

Much more needs to be learned about treatment-resistant depression. Hopefully, future research will lead to more effective treatments.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.

References

Morriss, J., Garland, A., Nixon, N., et al. Lancet Psychiatry 2016; 3:821-831.

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