Mentally ill bring new issues to brain research
Use of research requires extra attention to consent
The use of deep brain stimulation (DBS) in the treatment of Parkinson's disease and other neurological disorders has been the subject of many research studies and has been approved by the Food and Drug Administration since 1997.
But as researchers explore its potential for helping people with mood and behavior disorders, they and IRBs will have to grapple with new issues, says Peter V. Rabins, MD, MPH, a professor of psychiatry at Johns Hopkins University's School of Medicine in Baltimore, MD.
Rabins was among the coordinators of a 2007 conference of researchers, bioethicists, patient advocates, research policymakers and other experts discussing the use of DBS in trials for treatment of mood and behavior disorders.
The goals of the conference were to establish a consensus about how such trials should be designed and to develop standards for the protection of participants.
Rabins anticipates that more IRBs will face protocols proposing the use of DBS for these new purposes in the years ahead.
"Clinical depression is a relatively common condition," he says. "And even if 95% of patients eventually get better, either through treatment or spontaneous recovery, there is a small but meaningful percentage of people who remain chronically depressed.
"I think the number of people with severe, treatment-resistant depression means that interest in doing the research might well be fairly widespread."
Past concerns inform debate
Deep brain stimulation uses a surgically implanted, battery-operated device called a neurostimulator to deliver electrical stimulation to targeted areas in the brain, similar to a heart pacemaker. Its potential as a treatment for mental illness was discovered when Parkinson's patients who used DBS showed changes in mood and behavior.
Rabins says the use of DBS in mentally ill patients is a delicate issue, in light of past controversies over psychosurgical treatments for mental illness. One question that was raised immediately, he says, was whether people with mental illness should be treated differently in a DBS trial than those with neurological conditions such as Parkinson's.
"Are there needs for special safeguards, given the past history of seeming abuse of psychiatric patients during the lobotomy era, and given the possibility that mental illness might impair consent capacity differently than physical illness?" Rabins says.
"If this kind of research becomes widespread, what are the issues that researchers and IRBs should consider? Are there unique issues here that IRBs might not think of based on their prior experiences reviewing research?"
The group eventually reached consensus on 16 statements related to the experimental use of DBS for mood and behavior disorders such as depression and obsessive-compulsive disorder. While many of the statements deal with technical aspects such as the target sites for implantation, the group also made several recommendations about protecting research participants:
• Research centers — DBS trials should be conducted only at expert centers by multidisciplinary teams that include neurosurgeons and neurologists with extensive experience in DBS, as well as psychiatrists and neuropsychologists.
• Capacity to consent — Rabins says that for now, conference members believe that participants must be able to give consent themselves, rather than relying on surrogates. The consensus document recommends that researchers assess subjects' capacity to consent, taking into account the potential effects of mental illness on consent capacity.
Beyond that, however, the group did not feel it was appropriate to place further restrictions on participation by adults, Rabins says. He notes that research shows some people with depression and schizophrenia, for example, are fully capable of giving consent for research.
"Some researchers actually require that a person have a surrogate as a cosigner, in case the patient loses capacity," he says. "But there was a consensus (among his group) that surrogate consent is not a requirement," because of concerns for participants' autonomy.
Too soon for pediatric studies
• Pediatric use — The conference group agreed that at this point, DBS trials for mood and behavior disorders should generally be confined to adults, despite the fact that DBS is currently used with children for treatment of severe dystonia, a neurological condition. Rabins says there isn't a lot of information about how DBS affects a growing brain.
"We thought it ought to be shown that it's beneficial in adults whose brains might be adaptive and changing but wouldn't be growing, before extending it into adolescents or even children," he says.
Rabins notes that there are still questions about the long-term effects of DBS, since most of the patients who receive it have Parkinson's disease and they often don't live for many years past treatment.
"People with Parkinson's disease who get deep brain stimulation aren't likely to live beyond 10 or 15 years," he says. "So we really don't have knowledge of what happens after 10 or 15 or 20 years."
• Consent — Conference participants said the informed consent should tell patients that participating in a DBS study could limit their ability to use other treatments or tests, such as a pacemaker or some MRIs. The consent document should make clear the conditions under which the stimulator would be turned off or even removed and who would pay for that removal.
It should state that DBS alone is unlikely to improve all aspects of mental illness, and that patients should continue to receive other complementary treatments.
Rabins says that raises another point that should be considered by IRBs: Most researchers involved in the conference believe that in addition to DBS, many patients need a psychosocial rehabilitation program.
"Is that a responsibility of researchers? Whether that kind of treatment needs to be part of the protocol is a question that I think IRBs need to consider," he says.
He says IRBs also should consider who should be responsible for the implanted device over time. He notes that this problem also arises in other trials of permanent implantable devices.
"If the study ends and the device remains in, are the researchers or the manufacturers still responsible in some way or does their responsibility end at the time the study ends?" Rabins says. "Eventually, the batteries need to be replaced and the electrode may move or become less functional over time — again, who's responsible for that?"
He says those questions need to be answered very clearly in the informed consent.
There have been reports of increased rates of suicidality associated with patients who underwent DBS, but it's unclear whether it's a risk of the procedure itself, Rabins says, comparing it to the suicidality issue that arose in trials of SSRIs. He says studies of DBS need to assess the risk of suicide among patients.
Reference
- Rabins P, Appleby BS, Brandt J, et al. Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior and thought. Arch Gen Psychiatry 2009 Sep;66(9):931-7.
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