Med Check
This is Part 2 of a special edition of Med Check featuring summaries of new research posters presented in May at APA's 2009 annual meeting in San Francisco.
These presentations are usually preliminary in nature and often involve results that have not been peer reviewed for publication. In addition, the reports, which may involve the use of medications or procedures for indications that the FDA has not approved, are largely funded by product manufacturers.
Deep Brain Stimulation
• Researchers at the Mayo Clinic described findings from their deep brain stimulation (DBS) study in 17 patients who received stimulation in the ventral capsule/ventral striatum area, with an average follow-up of over three years. At 6 and 12 months after implantation, eight (47 percent) and nine (53 percent) patients, respectively, achieved response. Response was defined as a greater than 50 percent reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score. Five (29 percent) and seven (41 percent) of the patients achieved remission (MADRS score <10) at 6 and 12 months, respectively. These patients had had an average of six courses of antidepressants and six additional courses of drug combination/augmentation treatment. All had been refractory to ECT.
Most adverse events were minor and reversible after adjustments to the stimulation parameters. Serious adverse events included hypomania in a patient with bipolar disorder, syncope, broken leads of the device, pain at the implant site, and suicidality/increased depression. One person committed suicide after receiving the stimulation for five years. The study was supported by Medtronic Inc., which manufactures the stimulation device.
• In a study of 21 patients with refractory major depressive disorder who received DBS stimulation for at least six months, 13 patients (62 percent) achieved response at six months. Response was defined as a reduction of at least 40 percent from baseline in 17-item Hamilton Rating Scale for Depression (HRSD-17) scores. The stimulation was applied to the subgenual cingulated gyrus (SCG) and the procedure was performed at the University of British Columbia, McGill University, and the University of Toronto. Of the other eight patients, four (19 percent) had partial response, defined as 20 percent to 40 percent reduction in HRSD-17 scores, and four (19 percent) were nonresponders. Twenty of the 21 patients had been evaluated for at least one year. Among the 13 patients who achieved response at six months, all but one patient (92 percent) maintained the response at their last evaluation.
The study patients had had an average of seven depressive episodes in the past and had been in the current episode for five years. All had failed at least four courses of treatments. Eighteen (90 percent) had been treated with ECT.
Other than safety risks inherent in brain surgery and device implantation, the researchers did not see any unexpected adverse events related to the device. Two serious adverse events due to a broken extension of the device occurred. Three patients had four depression-related serious adverse events, including three suicide attempts and one suicide. One attempt was related to symptom recurrence because of treatment discontinuation; the other events were judged to be unrelated to the device. The authors pointed out that placebo-controlled studies should be conducted in future research to replicate the findings. The study was supported by St. Jude Medical Neuromodulation Division, which holds the patents for this particular DBS device.
• Canadian researchers tested the cognitive function and emotional information processing in patients receiving DBS in the SCG area and found an initial improvement in executive functions, memory, and emotional information processing tests before any significant stable mood improvement was observed. They hypothesized that cognitive symptoms in severe depression are not secondary to mood disorder but rather related to different frontal-limbic neural circuits that are modulated by the DBS.
Transcranial Magnetic Stimulation
• In a randomized, sham-controlled clinical trial, four and six weeks of daily transcranial magnetic stimulation (TMS) treatment on patients with major depressive disorder did not produce adverse effects on cognitive functioning. Patients (n=155) who received active TMS did not differ significantly from those who had sham TMS (n=146) in global cognition, as measured by the Mini Mental Status Examination; in short-term memory, as measured by the Buschke Selective Reminding test; and in long-term memory, as measured by the Autobiographical Memory Interview-Short Form. The study was sponsored by Neuronetics Inc., the maker of a TMS device recently approved by the FDA to treat adult patients with depression who have failed one adequate course of antidepressant treatment.
• Australian researchers at the Adelaide Clinic at Ramsay Health Care Mental Health Services randomized 22 referred outpatients with major depressive disorder to two TMS treatment schedules: three-days per week for six weeks (n=9) or five days per week for four weeks (n=13). Overall, the mean reduction from baseline was significant for HRSD, Hamilton Rating Scale for Anxiety (HRSA), and MADRS scores. Ten of the 22 patients (46 percent) met the criteria for response, defined as at least 50 percent improvement in HRSD score from baseline. Seven (32 percent) reached remission, or a score of 7 or less on HRSD at the end of the acute treatment course. The two TMS schedules did not differ in HRSD score reduction at the end of each course (four weeks for the five days/week schedule and six weeks for the three days/week schedule). Interestingly, the symptom reduction was not significantly different between the two schedules at four weeks. The authors concluded that three days/week TMS for four weeks was as effective as three days/week for six weeks and five days/week for four weeks as acute treatment of depression. However, whether these schedules would result in different relapse rates is unknown. The study was funded by Ramsay Health Care Mental Health Services.
• Researchers at the University of Pennsylvania have been conducting an open-label study on the feasibility and safety of low-frequency (1 Hz) TMS treatment for pregnant women with antenatal depression at 14 to 34 weeks in gestational age. The TMS was administered at a one-minute-on, one-minute-off schedule for 10 minutes per session. Each patient received a total dose of 6,000 pulses during the study. Four women had completed treatment at the time the poster was presented. No abnormality in fetal heart rate, uterine tocometry, or fetal ultrasound associated with the treatment was observed. Three of the four women achieved clinical response, defined as at least 50 percent reduction in HRSD-17. No serious adverse events were reported in the mothers or fetuses. The study was funded by Penn Comprehensive Neuroscience Center and Neuronetics Inc.
Bipolar Disorder
• Researchers at the Karolinska Institutet in Sweden reported observing micrometer-sized particles in the cerebral spinal fluid (CSF) of patients with bipolar disorder type I and type II. Fifty-nine patients treated at the bipolar outpatient unit and 21 controls with no psychiatric diagnosis consented and provided their CSF samples through lumbar puncture. The CSF was filtered and dried using vacuum suction, then examined under scanning electron microscopy. Twenty-two of the bipolar patients had thread-like structures, 42 patients had spherical particles, and six had threads with spherical particles closely attached. Some patients had more than one type of particles. Eleven of the bipolar patients had no particles at all in the CSF. None of the control subjects had any particles in their CSF. A previous study found spherical particles in the CSF of patients with schizophrenia that appeared similar to those in some of these bipolar patients. Ullvi Båve, M.D., Ph.D., the lead author of the poster presentation, and colleagues hypothesized that the particles in CSF may be related to the pathology of bipolar disorder, either as an inducer or a product of the disease process, and that this similarity provides further evidence that schizophrenia and bipolar disorder may have overlapping pathogenesis.
• Self-reported mood in patients with bipolar disorder does not appear to have a seasonal pattern, according to a study conducted by multinational researchers from Europe, North and South America, and Australia. Three hundred and sixty adult patients residing in these regions and under treatment for bipolar disorders reported their daily mood ratings using a computer software program. Climate, latitude, and seasonal variations did not have a statistically significant association with self-reported mood ratings.▪
