June 1st, 2012

Treatment resistance: a complex problem that requires multiple approaches

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PHOTO BY Tom Croke
Benjamin D. Greenberg, M.D., Ph.D. is an associate professor at Brown University and chief of outpatient services at Butler Hospital where tests are underway for possible interventions for treatment resistant/refractory patients.

Individuals who suffer with mental illness have several treatment options from which to choose, including psychotherapy, behavioral therapy, short-term residential placement and selective serotonin reuptake inhibitors (SSRIs) or other pharmacological agents. In spite of this robust therapeutic menu, some patients remain significantly impaired, posing a challenge for effective treatment.

Treatment resistance, present across a number of diagnoses and common in depression, posttraumatic stress disorder, and personality disorders, involves multiple variables, according to Rick Barnett, Psy.D., LADC, MS clinical psychopharmacology and president of the Vermont Psychological Association (VPA). Those variables include who is defining treatment resistance, treatment approach, diagnosis, co morbid illnesses and compliance. “In a biologically informed model of depression for example, patients may be deemed treatment resistant when a trial of psychotropic medication fails to show some symptom improvement after six to 10 weeks,” he says. “In psychotherapy, providers may determine after 12 or more weeks that a patient is treatment resistant and may need to augment or change treatment strategies. It is important to distinguish between no response to treatment, a partial response to treatment and remission.”

M. Gerard Fromm, Ph.D., director of the Erikson Institute at the Austen Riggs Center in Stockbridge, Mass., recommends developing a working relationship with the patient so that problems are, first of all, approached from the patient’s perspective. For example, if a patient misses treatment sessions or stops taking medication, a clinician needs to explore how and why the patient believes this behavior makes sense. “Put yourself in their place and trust they had a good reason. You need to get it on the table as something to talk about and perhaps trace back to the last session what happened between the two of you that upset the patient,” he says. “This is reparative and strengthening and conveys to the patient that others can stand their feelings. Trust in the engineering sense, that is, the capacity of the relationship to withstand stress, develops in this way.”

“For a trauma patient, the relationship to authority is not simple. Their sense of self is fragile,” Fromm adds. “The  issue is not compliance with the treatment; it’s much more about alliance. The clinician has to begin where the patient is and negotiate. Trust cannot be taken for granted. In fact, the trust that is necessary is the therapist’s for the patient, not vice versa.”

The tenuous relationship between patient and clinician may be the main reason for poor medication compliance among psychotic patients, according to Fromm. He says, “Physical side effects are also problematic, but the major issue in such treatment resistance may well be the lack of a true alliance between patient and clinician.”

Barnett indicates that motivational interviewing, cognitive behavioral and interpersonal strategies may be effective. “These approaches have focused, practical and meaningful ways of engaging patients and helping them adhere to treatment regimens,” he says. “Where treatment resistance exists, it is important to recognize it as early as possible, recognize co morbid issues as quickly as possible and treat all co morbid conditions as aggressively as possible at treatment onset in order to increase the likelihood of treatment response or even remission.”

Co morbidity – patients who present with as many as four or five diagnoses – adds to the problem of treatment-resistance, according to Fromm. “In psychotherapy, we treat the whole person, rather than dealing with diagnoses separately. Other treatment interventions may be very valuable for one or another symptom, but these interventions will have the best chance of success if the core problem is worked with in psychotherapy based on strong alliance with the patient in which the question `How is the patient right?’ is the foundation of the work.”

Benjamin D. Greenberg, M.D., Ph.D., chief of outpatient services at Butler Hospital and associate professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University in Providence, R.I., runs a translational program for individuals with obsessive compulsive disorder (OCD) and finds co morbidity common in this population. “Sixty to 80 percent over a lifetime will develop one major depressive diagnosis. They have increased rates of anxiety and tic disorder,” he says.

Sarah Garnaat, Ph.D., a postdoctoral fellow who works with Greenberg, says, “There is a fairly high rate of OCD in schizophrenia. One interesting thing is that when you treat OCD, a lot of other anxiety or depressive symptoms get better.” The order in which symptoms are treated matter, notes Garnaat. “By addressing other symptoms first, it enables the person with OCD to deal with the OCD,” she says.

Greenberg, who prefers to use the term “refractory” for patients who are “intractably ill after having a reasonable combination of medication and behavioral therapy,” emphasizes the importance of an accurate diagnosis. He says, “The fundamental problem is misdiagnosis. You have to get to the basic questions. Do we really know what they have? What’s been tried? Is there good documentation?”

Butler Hospital is currently testing a couple of possible interventions for treatment resistant/refractory patients. Garnaat says, “We are asking someone with intractable OCD to do some treatment exposures, face what they are afraid of. But it’s like asking them to jump off a cliff, their degree of fear is so intense.” This approach is designed to increase overall resilience and reduce anxiety. “It is intended to make them stronger, braver in the face of the exposure,” she says.

However, this option proves ineffective or impossible for some patients. “These patients may have a defect in safety learning,” says Greenberg, who explains that deep brain stimulation may be a better choice. “We are always looking for ways of treating people who are refractory, when symptoms remain despite good conventional therapy.” While partial response is common, some individuals may have to continue using behavioral tools for the rest of their lives.

Determining the numbers of patients who are treatment resistant can be challenging, since these individuals have a higher than normal dropout rate, according to Barnett. “Perhaps, up to 15 to 20 percent of my patients may be or have been treatment resistant at some point during the course of therapy,” he says.

By Phyllis Hanlon

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