Psychiatry 2008 - September 2008 - (Page 31)

or depression. On the basis of standard outcome measures, 36 to 50 percent of patients were considered to be treatment responders.26 A recent study by Cho, et al., of 16 patients with intractable major affective disorders who underwent a limbic leucotomy, followed patients for seven years post-surgery. In the seven-year follow-up, mean scores on the Hamilton Depression Rating Scale and the Beck Depression Inventory declined significantly from 42±5.76 to 20±11.98 (p<0.01) and from 32±9.13 to 19±14.29 (p<0.05), respectively. There was no surgical mortality, and only three patients experienced temporary minor complications.27 Neuromodulation. Deep brain stimulation has several advantages over the lesioning procedures as just described. Surgeons using DBS can potentially achieve a clinical effect without producing an irreversible lesion. In DBS procedures, stimulation electrodes are implanted into specific brain regions and continuous electrical high frequency stimulation is delivered from an implanted, externally programmable pulse generator, similar to a cardiac pacemaker. DBS is reversible in that the stimulator can be turned on or off, and the output of the device and stimulation can be controlled at the discretion of the clinician. This also allows researchers to create sham conditions that allow for blinded placebo controlled trials, a method that is unavailable for practical and ethical reasons in lesioning operations. However, DBS still requires neurosurgery and has the potential for serious medical and neurological side effects. Symptomatic hemorrhage, infection, and seizure may occur in 1 to 4 percent of cases, but death is exceedingly rare.28 Contemporary use of clinical brain stimulation began in 1987 with Benabid, et al., reporting on the first successful use of thalamic DBS as a treatment for Parkinson tremor.28 The subthalamic nucleus (STN) subsequently became a prime target in Parkinson’s disease, with the finding that STN lesions reversed motor signs of Parkinsonism in experimental animals. Currently, DBS is FDA approved to treat Parkinson’s disease and essential tremor. The mechanism of action of DBS is still unknown. Because clinical effects of DBS are similar to lesioning neurosurgery, it is hypothesized that DBS disrupts pathological neural activity, although there are several competing hypotheses regarding how this occurs.29 DBS in OCD. Recent trials of deep brain stimulation in OCD at several targets have indicated distinct benefit. One target is the anterior limb of the internal capsule, the site used in capsulotomy. Targeting of the anterior capsule is believed to disrupt activity in the loop fibers that connect the cortex with the thalamus, thus, in theory, disrupting that pathological circuit. Greenberg, et al., reported on results from data collected by four groups, which worked in collaboration over eight years, for a total of 26 patients.30 The percentage of patients meeting the full response criterion (≥35% YBOCS decrease) increased from 28 percent at one month to 61.5 percent at last followup. Conversely, the percentage with less than a 25-percent YBOCS decrease (no response) declined from 68 percent at one month to 27 percent at last follow-up. Overall, a total of 73 percent of patients had at least a 25-percent YOBCS improvement at last follow-up; a large majority of those improvements were a 35-percent or greater YBOCS reduction. Depression and anxiety also improved, as did self care, independent living, and work, school and social functioning. Surgical adverse effects included two asymptomatic, intracerebral hemorrhages, a single seizure, and a superficial wound infection. Devicerelated adverse events included a break in a stimulating lead and extension wire requiring a replacement in one patient each. Psychiatric adverse effects included transient hypomanic symptoms and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. Abelson, et al., examined the effects of DBS for treatmentrefractory OCD in four patients with leads placed bilaterally in the anterior limbs of the internal capsule in a blinded, on-off design, with one patient experiencing substantial benefit in mood, anxiety, and OCD symptoms both during the blinded study and open, long-term follow-up. One patient committed suicide despite her OCD symptoms improving as per self report. One patient showed moderate benefit during open follow-up.31 Other small case series and a case report have reported benefit.32,33 Other brain regions have also received attention, including the nucleus accumbens with one case series reporting observed, but not quantified, clinical improvement in three out of four patients.34 DBS in depression. Based on neuroimaging findings that implicate hyperactivity of the subgenual cingulate region (BA 25) in treatment-resistant depression and association of decreases in cg25 activity with clinical improvement, Mayberg and colleagues targeted this area in a study of six patients implanted with bilateral leads in this area.35 At one month postoperatively, 2 of the 6 patients met the criteria for clinical response, which was defined as a decrease in the Hamilton Depression Rating Scale (HRDS-17, also known as HAM-D17) of 50 percent or more from the pretreatment baseline. At the sixmonth study endpoint, antidepressant response was maintained in four subjects (66%). Three of these responders attained remission or near remission of illness. From a safety standpoint, two of the patients developed persistent wound infections and required explantation of the device. Another site utilized in DBS for depression is the nucleus accumbens, a site implicated primarily in the reward systems of the brain. Schlaepfer, et al., have reported on three patients suffering [SEPTEMBER] Psychiatry 2008 31

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Psychiatry 2008 - September 2008 Editor’s Message Editorial Advisory Board Contents Psych Rx Letters to the Editor Use of Benzodiazepines in the Treatment of Anxiety Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician Treatment of Comorbid Adolescent Cannabis Use and Major Depressive Disorder Risperidone Long-acting Injections: Successful Alternative Deltoid Muscle Injections for Refractory Schizophrenia Alcohol/Substance Misuse and Treatment Nonadherence: Fatal Attraction Transforming the Psychiatric Inpatient Unit from Short-term Pseudo-asylum Care to State-of-the-art Treatment Setting Journal Watch Classified Advertising Information for Authors

Psychiatry 2008 - September 2008

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