depression – Michigan Brain & Spine Surgery Center

Severe depression may be treated with deep Brain stimulation DBS

Michigan Brain & Spine — Tue, 15 Oct 2013 16:13:45 +0000

Assessment of deep brain stimulation for patients with treatment-resistant depression has inched forward over the past decade with promising results but remains in its early days with a total worldwide experience of roughly 60 patients.

That total includes patients who have received deep brain stimulation (DBS) leads placed in six different brain regions. However, the results suggest that one of the better target locations for DBS in patients with treatment-resistant depression (TRD) is in the nucleus accumbens, Dr. Bruno Millet said at the annual congress of the European College of Neuropsychopharmacology.

“The nucleus accumbens is a very good target that we will continue to study. It is very safe, and the surgery is easy and rapid. The nucleus accumbens has a good benefit-to-risk ratio,” said Dr. Millet, professor of psychiatry at the University of Rennes (France). “This is a strength of this target.”

The nucleus accumbens became a target because it is “at the center of a circuit involved in major depressive disorder,” and plays a “central role in reward circuitry and its dysfunctions,” he added.

All patients who have received DBS had stage 5 TRD, which meant that their depression was unresponsive to all possible drug classes, including monamine oxidase inhibitors. These patients also failed to adequately respond to electroconvulsive therapy.

Dr. Millet and his associates at nine other French centers ran a pilot study with four patients who received DBS in the nuclear accumbens starting in 2009. Patients received stimulation at a level of 1.5-4 V. All four patients showed gradual improvement in their depression during the first 6 months after treatment. After 1 year of follow-up, all patients had responded, with response defined as at least a 50% decline from the baseline Hamilton Rating Scale for Depression (HRSD) score. One patient went into remission, defined as an HRSD score of less than 10. None of the patients had somatic adverse effects during 15 months of follow-up, but one patient had worsening mood and anxiety and made a suicide attempt; one patient had worsening mood and sleep and increased food intake; and one patient developed paresthesia.

The largest patient series and the longest follow-up of patients who received DBS in their nucleus accumbens for TRD involved 11 patients treated in Germany. The patients had minimal adverse effects, and 5 of the 11 responded, with the response remaining stable during 4 years of follow-up (Neuropsychopharmacology 2012;37:1975-85).

Another target that produced notable results is the medial forebrain bundle, which led to good DBS results in seven patients treated by the same German team. Earlier this year, the investigators reported that six of the seven patients had responded and four patients had reached remission of their depression after 3-7 months of follow-up (Biol. Psychiatry 2013;73:1204-12). Two other brain targets that have been used by other groups with success are the subgenual cingulate gyrus, and the ventral capsule and ventral striatum.

But “one of the striking things in DBS for the moment is the lack of any randomized controlled trials,” Dr. Millet said. He and his French associates have expanded their network to 12 centers, including one in Geneva, and they have designed and are now starting a trial that will place DBS leads in all patients but will withhold active stimulation in half the patients for the first 7 months after lead placement. This trial is sponsored by Medtronic, a company that markets the DBS device Reclaim.

Medtronic primarily markets its DBS device for the treatment of Parkinson’s disease, essential tremor, and dystonia, but in 2009, the Food and Drug Administration also approved its use to treat obsessive-compulsive disorder under a humanitarian device exemption. Some medical ethicists, psychiatrists, and neurosurgeons have questioned the growing use of DBS for obsessive-compulsive disorder in the absence of evidence for its efficacy in a randomized controlled trial, calling this practice “misuse” of the device. One of these critics, Dr. Thomas E. Schlaepfer of Bonn, Germany, also is head of the group with perhaps the largest experience in using DBS to treat patients with depression.

Dr. Millet said he has received grant support from Medtronic, marketer of the Reclaim DBS therapy device. He also said he has been a consultant to, has been a speaker for, or has received research funding from nine other drug or device companies.

CPAP May Ease Depression

Michigan Brain & Spine — Mon, 18 Jun 2012 05:02:19 +0000

By Ed Susman, Contributing Writer, MedPage Today

Published: June 14, 2012.
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Obstructive sleep apnea patients who use — or even try to use — continuous positive airway pressure (CPAP) devices appear to reduce their overall depressive symptom scores, researchers said here.

In every category measured, patients reduced depressive symptoms, even if they were not using the CPAP devices as prescribed, Charles Bae, MD, of the Cleveland Clinic College of Medicine at Case Western Reserve University told attendees at the annual meeting of the Associated Professional Sleep Societies.

In the key endpoint of decrease of symptoms on the Patient Health Questionnaire, patients who used the devices for 4 hours or more achieved a 3.8-point reduction in scores, compared with a two-point reduction among patients who used the devices less than 4 hours a night (P=0.0009).

“All groups that we measured showed decreases in depressive symptom scores,” Bae told MedPage Today. “We observed reductions in people who used the devices correctly; in patients who didn’t use it correctly or used it less than 4 hours; we observed decreases in these scores if patients had daytime sleepiness; or if they were married or not married.”

He suggested that when people get better sleep, it tends to improve their outlook on other aspects of life.

Bae explained that multiple studies have shown that depressive symptoms are associated with sleep apnea, but there have been conflicting reports as to whether treatment with CPAP improves depressive symptoms. Until his work was performed, no studies had looked at the benefit of CPAP therapy on mood using the Patient Health Questionnaire 9 as a measure of the severity of depressive symptoms.

In his retrospective study, Bae reported on outcomes of 769 patients who filled out the questionnaire between 2008 and 2011. These patients had completed the health questionnaires in the office or at their homes.

The study included individuals 18 years of age or older who had been diagnosed with sleep apnea. They were required to have visited their doctors one time before starting treatment with CPAP and then to have made a second visit at least 30 days later. Patients were not included in the study if they failed to make a follow-up visit.

The average age of the patients in the study was 51.8; 47.3% of the cohort were men; about three-quarters were Caucasian; and 62% were married.

The 654 patients who were adherent in use of CPAP had an average baseline depressive symptom score of 11.2 on the Patient Health Questionnaire 9 and that score dropped 3.8 points, while the 115 non-adherent patients’ scores dropped from baseline of 11.8 to 9.8 – a two-point decrease. The difference in change was statistically significant between the groups (P=0.0009).

“The results were more robust if the patients had expressed sleepiness,” Bae reported. The 475 patients adherent with the therapy who had scored 10 or higher on the Epworth Sleepiness Scale achieved a four-point reduction on the Patient Health Questionnaire 9 compared with a 2.8-point reduction among sleepy subjects who did not adhere to therapy (P=0.0032).

In the 475 married patients, the Patient Health Questionnaire 9 showed a four-point drop after therapy; single individuals had a three-point drop and divorced patients achieved a 2.3-point drop. The difference between divorced and married patients was significant (P=0.0083), Bae said.

“Patients with sleep apnea who are adherent with positive airway pressure therapy – using it more than 4 hours a night — compared to those who are not adherent will have a greater decrease in the Patient Health Questionnaire 9 score,” Bae said.

“These results are not surprising,” said George Thommi, MD, clinical assistant professor of pulmonology at Creighton University School of Medicine, in Omaha, Neb., who was not involved in the study. “I have had several patients myself who have improved depressive symptoms after using positive airway pressure devices.”

He told MedPage Today that the devices help improve sleep. “When you sleep better, you are more likely to feel better and not be as depressed. This work is consistent with what I see in my clinical practice.”