19368080 - Deep Brain Stimulation for Psychiatric Disorders--state of the Art

Offprint from

Advances and Technical Standards in Neurosurgery, Vol. 34

Edited by J.D. Pickard

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Springer-Verlag/Wien 2008 – Printed in Austria – Not for Sale

Deep brain stimulation for psychiatricdisorders – state of the art

T. E. S

CHL

€

AAPFER

and B. H. B

EWERNICK

Brain Stimulation Group, Department of Psychiatry and Psychotherapy,University Hospital Bonn, Germany and Departments of Psychiatryand Mental Health, The Johns Hopkins University MD, USAWith 3 Figures and 4 Tables

Contents

Abstract IntroductionHistory of deep brain stimulationPrinciples of DBSNeurobiology of depression and OCDNeurobiology of depressionStudies of DBS and psychiatric disordersProblems in target selection Targets in depression Targets in OCDSafety and advantages of DBSEthical aspects and standards in DBSEthical considerations The path towards mandatory standards for DBS in psychiatric disordersConclusions The future of DBSReferences

Abstract

A substantial number of patients suffering from severe neuropsychiatricdisorders do not respond to conventional therapeutic approaches. Results

from functional neuroimaging research and the development of neuromod-ulatory treatments lead to novel putative strategies. Recently, one of thosemethods, deep brain stimulation (DBS) has been applied in selected patient with major depression and obsessive-compulsive disorder (OCD) and majordepression. We summarize in this review, the state of art of knowledge about theneurobiology of depression and OCD and historical treatment methods.Principles of DBS and reasons for the use of DBS in neuropsychiatry arediscussed. Different targets have been chosen in a hypothesis-guided way and ﬁrst results have demonstrated that DBS might be able to modulate dys-functional neural networks in both major depression and OCD. Although DBSis a unique and promising method for otherwise treatment resistant psychiatricpatients, mandatory treatment standards have to be applied for patient andtarget selection. Therefore, a distinct focus of this review lies on ethical aspectsfor DBS in neuropsychiatric disorders.

Keywords:

Deep brain stimulation (DBS); depression; obsessive compulsive disor-ders; neuroethical aspects.

Introduction

Today, different well established forms of drug treatment and psychothera-py are available for the treatment of neuropsychiatric disorders, alone orin combination they are effective in most patients [4, 37]. However, thereremain a sizable number of patients that cannot be helped with theseinterventions. Indeed, 8–13% of patients suffering from major depressionhave a poor outcome after ﬁve years of treatment [31]. A more recent study found that 63.2% of patients included in the STAR-D study werenot treated to remission in the acute study phase [49]. These patients arecalled ‘‘treatment-resistant’’ and have been treated with several antidepres-sants (e.g. tricyclica, selective serotonine reuptake inhibitors) augmentationagents (e.g. lithium, neuroleptics), psychotherapy and often electroconvul-sive treatment. In obsessive-compulsive disorder (OCD) the number of treatment-resistant patients is estimated to be 10–40% [30, 16]. Thesepatients have little hope of recovery, are almost always stigmatized andremain in a state of extremely poor quality of life. Treatment resistant psy-chiatric disorders are a signiﬁcant source of worldwide disability [43]. Thus,it clearly is a moral imperative to develop alternative treatment methods forthese patients.In this review, we will outline putative new options for treatment-resistant depression and OCD. A special focus lies on the establishment of mandatory research guidelines.

2 T. E. S

CHL

€

A APFER

and B. H. B

EWERNICK

History of deep brain stimulation

Directly neurosurgical interventions for psychiatric indications have a long andsomewhat tainted history [34]. Psychiatric neurosurgery began in the 30s of thelast century when Egas Moniz performed the first frontal lobotomy [42]. Thismethod was further developed and widely used in the 1940s, when Freemanand Watts performed frontal lobotomies lacking any other treatment for severemental disorders [13]. These operations were crude, not guided by scientifichypotheses, were associated with high mortality and lead to unacceptable ad- verse effects. With the invention of psychotropic drugs in 1954 and their broadapplication, the interest for surgery waned [13]. Due to severe side effects of psychopharmacological medications and the availability of new operating tech-niques (stereotactic surgery), interest in functional neurosurgery for psychiatricdisorders returned [13]. Today, stereotactic operations allow reaching a target precisely with minimal lesions and minimal side effects. Methods are cingulot-omy (bilateral lesioning of cingulate gyrus) for OCD, major depression andpain disorders [25, 55], capsulotomy (anterior limb of the internal capsule asrelay between cortex and thalamus) for OCD, subcaudate tractotomy (inter-rupts cortical pathways to striatum and to thalamus) for OCD and depression[25, 55] and limbic leucotomy (combination of cingulotomy and a ventral lesionsimilar to that of subcaudate tractotomy) for OCD, depression and self-muti-lation [25, 47, 55]. The efficacy of neurosurgery for otherwise therapy resistant patients lies between 30 and 70%, depending on the disorder and the selectedtarget [13].Electric stimulation of the brain probably had its beginnings in 1879, wherelimb movement were elicited by stimulating the motor cortex in dogs, humanstudies followed in 1884 [22]. The first chronic brain stimulation was per-formed in the mid 20

th

century, when the Nucleus Caudatus was stimulatedfor eight weeks in a case of a severe depressed patient [17].Insights from lesioning studies, imaging studies and animal models havecontributed to the development of deep brain stimulation (DBS). Adams was a very early pioneer who stimulated the internal capsule for relief of chronic pain[2]. The technique of chronic DBS used today was invented in the 80s by Benabid and coworkers for the treatment of movement disorders [10]. Today,this method is clinically used for the treatment of tremor associated withParkinson’s disease, chronic pain and dystonia. The observation of inducedpsychiatric side effects (e.g. changes in mood, hypomania, reduction of anxiety)gave the impulse to try DBS also for psychiatric disorders [36]. Another im-pulse was the fact that the effective but irreversible ablative neurosurgical interventions could now be emulated using DBS with a focused, fully reversibleand titratable technique (see Fig. 1). Insights from a somewhat different meth-od of electric brain stimulation (vagal nerve stimulation) further encouraged thedevelopment of DBS [52].

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