Biomarker Suggests Which Patients With Depression Respond to Cognitive Behavior Therapy Versus SSRI
Not every treatment for mood disorders works for every patient, and for the 60% of depressed patients whose first treatment is ineffective, this wrong guess can translate into months of suffering, wasted money, lost productivity, and risk of suicide. An important trend in treatment research is the search for biomarkers, that is, biological indicators that can predict which patients might be likely (or unlikely) to respond to a particular treatment. A 2013 study by McGrath et al. in the journal JAMA Psychiatry suggests that brain glucose metabolism is one such biomarker.
Patients with untreated major depressive disorder had their brain glucose metabolism measured and then were randomized to receive 12 weeks of treatment either with the SSRI antidepressant escitalopram oxalate (trade name Lexapro) or with cognitive behavior therapy. Low glucose metabolism in a part of the brain called the anterior insula (compared to the rest of the brain) predicted that patients would reach remission on cognitive behavior therapy and respond poorly to escitalopram, while high metabolism in the same area predicted the opposite, that patients would reach remission while taking escitalopram and respond poorly to cognitive behavior therapy.
Researchers will want to test this finding with patients over the long term, but the data from this study suggest that anterior insula glucose metabolism may be a successful biomarker that can guide initial treatment selection for patients with depression.
Cognitive Behavioral Therapy Helps Depression And Inflammation In Inflammatory Bowel Disease
Cognitive behavioral therapy may improve both depression symptoms and inflammatory bowel disease. At a symposium on early-onset depression at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, Eva Szigethy of the University of Pittsburg discussed depression in inflammatory bowel disease (IBD), i.e. Crohn’s disease or ulcerative colitis. Depression and bipolar disorder are often associated with elevated inflammatory markers, such as IL-1b, IL-2, IL-6, INF gamma, TNF alpha, and CRP (C-reactive protein). This kind of inflammation can cause symptoms like decreased appetite, fatigue, anhedonia (loss of pleasure in activities one once enjoyed), and motor slowing.
In children with IBD randomized to cognitive behavioral therapy or just routine supportive care, the somatic symptoms of those receiving cognitive behavioral therapy improved, as did their IBD.
Other treatments may also target both depression and inflammation. Szigethy noted that there is some evidence that the TNF alpha–inhibiting anti-inflammatory drug infliximab has some antidepressant effects in those with high CRP and in patients with the autoimmune condition psoriasis. She indicated that the antidepressant bupropion decreases depression and inflammation in IBD and that bupropion has anti–TNF alpha effects (at least in animals).
Currently levels of inflammation are measured with blood drawn from a vein, but new techniques may be more child-friendly. These include measuring inflammatory markers in hair (which reflects levels over the previous two weeks), saliva, or with a drop of blood from a pinprick (as used by researcher Ben Goldstein).
Cognitive Behavioral Therapy Tailored For Children and Adolescents
At a symposium on early-onset depression at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, Betsy Kennard described a course of cognitive behavioral therapy tailored to eliminating residual symptoms in children with unipolar depression who had no family history of a parent with bipolar disorder. In the same study Graham Emslie discussed, the investigators considered cognitive behavioral therapy for the treatment of childhood- and adolescent-onset depression.
The therapy was aimed at achieving health and wellbeing and focusing on positive attributes and strengths in the child, and it was designed to be a shorter than usual course (i.e. four weekly sessions, then four every other week, and one at three months). This regimen typically also included three to five family sessions. Other key components of the therapy included anticipating and dealing with stressors, setting goals, and practicing all the skills learned.
On a visual timeline, children identified and wrote down past stressors, how they felt when depressed, their automatic cognitions, ways they would know when they were feeling down again (i.e. feeling isolated, angry at parents, etc.), their strengths and skills, what obstacles to feeling better existed and how to circumvent them, and their long-term goals.
The therapy was based on the research of Martin Seligman and Giovanni A. Fava, plus Rye’s Six S’s (soothing, self-healing, social, success, spiritual, and self-acceptance). The children participated in practice and skill-building in each domain. Sleep hygiene and exercise were emphasized. The idea of “making it stick” was made concrete with phrases on sticky notes taken home and put up on a mirror. Postcards were even sent between sessions as reminders and for encouragement.
Editor’s Note: Most depressed kids don’t get completely well (only about 20% after an acute course of medication). Something must be added. This kind of specialized cognitive behavior therapy works and keeps patients from relapsing. This study included only those children with unipolar depression whose parents did not have bipolar disorder. However, Emslie noted that depressed children of a bipolar parent also had an exceedingly low rate of switching into mania (2 to 4%) in his experience, so fluoxetine followed by cognitive behavioral therapy might be considered for treating unipolar depressed children of a bipolar parent.
Once children have developed bipolar disorder, evidenced by hypomania or mania followed by depression, antidepressants are to be avoided in favor of mood stabilizers and atypical antipsychotics, since there is a higher switch rate in these youth when they are prescribed antidepressant monotherapy.
Since children with bipolar disorder are at such high risk for continued symptoms and relapses, the strategy of adding cognitive behavioral therapy to their successful drug treatment would appear appropriate for them as well as those with unipolar depression, especially since there is a large positive literature on the efficacy of cognitive behavioral therapy, psychoeducation, and Family Focused Therapy (FFT) in children and adults with bipolar depression. As noted previously, FFT is very effective for children at high risk because of a parent with bipolar disorder and who are already symptomatic with anxiety, depression or BP-NOS.
Moral of the story: getting kids with unipolar or bipolar depression well and keeping them well is a difficult endeavor that requires specialized, combined medication and therapy approaches and follow-up education and therapy. This is for sure. The hope would also be that good early and long-term intervention would yield a more benign course of recurrent unipolar or bipolar disorder than would treatment as usual (which all too often consists of medication only).
Continuation Cognitive Behavioral Therapy Prevents Relapse in Kids
At a symposium on early-onset depression at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, Graham Emslie of the University of Texas Southwestern Medical Center discussed the role of cognitive behavioral therapy in the long-term treatment of child-and adolescent-onset unipolar depression.
In Emslie’s research, the combination of the antidepressant fluoxetine and cognitive behavioral therapy reduced depressive relapses in children. Using the two treatments together did not speed onset of antidepressant response compared to fluoxetine alone, but once children responded to the medication, the addition of cognitive behavioral therapy reduced relapses over the next year compared to fluoxetine alone (even though the cognitive behavioral therapy ended after the first six months).
Emslie likened the use of cognitive behavioral therapy to the course of rehabilitation that often follows a major surgery and is meant to sustain or enhance the good effects of surgery. Getting patients to full remission (well and with no residual symptoms) was the key to staying well.
Psychotherapy Prevents Recurrence of Depression
New research shows that psychotherapy lowers the risk of relapse in unipolar major depression more than “treatment as usual” does, and also heads off depression in children at high risk.
At the 2013 meeting of the American Psychiatric Association, researcher Pim Cuijpers reviewed 32 trials of cognitive behavior therapy, intensive behavioral therapy, and problem solving therapy used for the prevention of depression and found that these therapies were associated with a 21% lower risk of relapse compared to treatment as usual.
There were five critical elements that made these therapies useful: they supported coping with depression, and they included exercise, mindfulness, internet-based cognitive behavior therapy, and problem solving.
Among those who presented at the meeting, Greg Clarke of Kaiser Permanente, Oregon discussed an 8-week course on coping with stress given to a group of adolescents (aged 14 to 16) who had four times the normal risk of developing depression because each had a parent with depression. Clarke found a significant reduction in depression among the adolescents who received therapy compared to controls.
Insomnia can be a precursor to a first depression or to recurrent depression. Cognitive behavior therapy was more effective in improving sleep than a comparative sleep hygiene course.
Researcher Judy Garber presented data showing that cognitive behavior therapy was effective in 13- to 17-year-olds who had a parent with depression and had themselves had a prior depression or were currently sub-syndromal. The effect of the therapy was only significant if the parent was not depressed at intake.