Status of neurosurgery for mental disorder in Scotland
Selective literature review and overview of current clinical activity
KEITH MATTHEWS, MD, PhD, MRCPsych and
MUFTAH S. ELJAMEL, MD, FRCSI, FRCS(NS), FABI
Ninewells Hospital and Medical School, Dundee, Scotland, UK
Correspondence: Professor Keith Matthews, Department of Psychiatry, Ninewells Hospital, Dundee
DD1 9SY, UK. Tel: 01382 632121; fax: 01382 633923; e-mail:
k.matthews{at}dundee.ac.uk
Declaration of interest K.M. has received payment for lectures on
the management of depression from various pharmaceutical companies.
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ABSTRACT
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Background Despite the application of ablative neurosurgical
treatments for intractable mental disorder throughout most of the past
century, unequivocal evidence for efficacy has not been provided.
Aims To review the status of ablative neurosurgery for mental
disorder and to describe the activities of the Scottish national service.
Method Relevant literature is reviewed alongside a description of
recent clinical activity.
Results Neurosurgical treatment is offered to a small number of
patients severely disabled by otherwise intractable mental disorder. There are
inequalities in the strength of evidence to support the use of some of these
procedures. The frequency and severity of adverse effects remains unclear. We
are collecting data that should inform future practice.
Conclusions Modern neurosurgery can offer clinically meaningful
symptom relief and improved function for untreatable patients
with chronic, severe depression and obsessivecompulsive disorder.
However, follow-up studies of greater rigour are required. The potential role
of non-ablative alternatives remains unclear.
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INTRODUCTION
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In 1993 a Good Practice Group was established by the Scottish Executive
(then Office) Clinical Resource and Audit Group (CRAG) Working Group on Mental
Illness to evaluate the need for a Scottish neurosurgical service for the
treatment of chronic, intractable mental disorder
(CRAG Working Group on Mental Illness,
1996). Having reviewed a range of complex ethical, legal and
clinical considerations, the key recommendations were:
- neurosurgery for mental disorder should continue to be available in
Scotland, but only as a treatment for intractable obsessivecompulsive
disorder and affective disorders (for example major depressive illness);
- there ought to be a national Standing Advisory Committee;
- an annual report should be made to the Committee by the service
providers.
A framework for best practice was agreed and published in 1996; the second
recommendation was enacted towards the end of 2001, and the first report has
been published on the Scottish Executive Health Department's website
(Matthews & Eljamel,
2001). We here describe the status of neurosurgery for mental
disorder in Scotland.
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ROLE OF NEUROSURGERY IN MODERN PRACTICE
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Originally introduced as a treatment for schizophrenia in the era before
the discovery of effective drug treatments
(Moniz, 1936), the frontal or
prefrontal lobotomy came to be widely used as a treatment for a broad range of
poorly specified mental diseases and behavioural disturbances. These crude and
destructive freehand procedures were overused, with an absence of critical
appraisal of their efficacy and adverse effects. Nevertheless, with refinement
of the precision and targeting of surgery notably the application of
stereotactic neurosurgical techniques evidence has accrued to support
the use of irreversible focal tissue ablation in the management of a few
patients with severely disabling defined psychopathological conditions.
Although different centres have employed different neurosurgical techniques to
target different structures, all modern neurosurgery for mental disorder
involves the ablation, or disconnection, of ventral and medial prefrontal
cortical areas. This is achieved by the precise placement of small lesions in
target structures that are considered to be relevant to the disorder. These
targets evolved on an empirical basis, but recent structural, functional and
neuroanatomical advances confirm that both the main clinical indications for
neurosurgery chronic intractable depression and
obsessivecompulsive disorder (OCD) are associated with
neurobiological changes within these regions or in key projection areas
(Sheline et al, 1996;
Drevets et al, 1997;
Ongur et al, 1998;
Rajkowska et al,
1999; Szeszko et al,
1999). Existing non-surgical treatments remain demonstrably
inadequate for significant numbers of people affected by these conditions. Up
to 40% of patients with depression fail to respond to first-line
antidepressant drug treatments, and of those who do respond, only a modest
proportion achieve full recovery (Judd,
1997). Between 5% and 15% of depressive episodes become chronic
(> 24 months) and potentially 1.5% of the general population suffer from
chronic depression (Judd,
1997). Furthermore, treatment responsiveness decreases with
increasing duration of illness and number of previous episodes of depression.
Hence, there are many for whom neither drug treatments nor psychological
therapies restore function. Similarly, although the clinical course of OCD is
highly variable (Skoog & Skoog,
1999), and most patients experience meaningful symptomatic relief,
at least in the short term, with exposure to modern antidepressant drug
treatments and/or focused psychological interventions, the longitudinal
clinical course appears disappointingly stable
(Mataix-Cols et al,
2002). Indeed, for men with early onset of illness and poor social
adjustment, research suggests that unremitting symptoms are likely
(Skoog & Skoog, 1999).
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DOES NEUROSURGERY WORK?
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These are numerous reviews of the outcome of neurosurgery for mental
disorder. The consistency of the conclusions offered is remarkable
particularly given the heterogeneity of the populations studied, the
neurosurgical procedures used and the outcome measures employed. A detailed
critical review of the literature can be found within the Royal College of
Psychiatrists' report on neurosurgery for mental disorder
(Royal College of Psychiatrists,
2000). Therefore, only a brief review of salient aspects is
presented here.
The accumulated literature on neurosurgery for mental disorder remains
highly unsatisfactory. There has been no prospective, randomised,
double-blind, placebo-controlled trial of any procedure, and none is likely.
To perform sham intracranial surgery, with all its associated hazards, would
probably be unethical. It is also unlikely that a representative sample of
prospective neurosurgery candidates would consent to randomisation, when they
invariably view the procedure as their last resort. Although it
is generally believed that placebo response rates are low with chronic
intractable illnesses, there can be few interventions with greater potential
for eliciting such responses. Indeed, early responses that are not sustained
a potential placebo response are not uncommon (see, for
example, Poynton et al,
1995). The observed and reported clinical responses to
neurosurgery are almost certainly the combined product of surgery-specific and
non-specific influences. However, that placebo or other non-specific effects
might account for consistent reports of long-term clinical improvement seems
implausible. If there is continuing, unjustified exaggeration of the efficacy
of neurosurgery, this is more likely to be attributable to reporting bias than
to placebo response (Hrobjartsson &
Gotzsche, 2001).
A common weakness of published outcome studies is the absence of
demonstrably independent assessments. Generally, outcome has been assessed by
service providers (with obvious potential for bias) and has not been masked.
Also, many studies can be criticised for the short duration of the follow-up
period and the failure to acquire data from all patients. Outcome measures
have usually been categorical global functioning scales, providing limited
detail on crucial domains such as residual symptom burden, social and
occupational functioning and perceived quality of life. Studies have rarely
commented upon the quality of the neurosurgical interventions; for example,
the size and placement of lesions are rarely described. There is no report of
sustained benefit following either deliberate sham or accidentally misplaced
lesions. The absence of anatomical confirmation is a major deficiency of many
older studies in which the neurosurgery was not conducted under stereotactic
guidance. Indeed, it may also be of major relevance for stereotactic
neurosurgery (Lippitz et al,
1999). Similarly, there are usually few (if any) details provided
of postoperative management. Even when rapid and extensive symptom relief
follows neurosurgery, significant psychological and social adjustments are
inevitably required.
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WHAT EVIDENCE SUPPORTS THE USE OF NEUROSURGERY?
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To address the question of efficacy without the use of prospective,
randomised trials, we must evaluate alternative study designs. For example,
there are studies that have employed retrospective control groups. Although
there are many potential interpretative difficulties, each study suggested
improved outcome following neurosurgery: leucotomy for agoraphobia
(Marks et al, 1966);
leucotomy for obsessional disorders (Tan
et al, 1971); subcaudate tractotomy for depression and
OCD (Bridges & Goktepe,
1973); orbitomedial and cingulate lesions for OCD
(Hay et al, 1993);
and subcaudate tractotomy or multifocal leucocoagulation for OCD
(Cosyns et al, 1994).
Consolidated reviews of different neurosurgical procedures, deployed for
different clinical indications, without anatomical quality assessments and
based on global categorical outcome measures, suggest that over half of
patients derived significant benefit from neurosurgery, with around one-third
experiencing dramatic functional improvements
(Kiloh et al, 1988;
Waziri, 1990). Unfortunately,
it is impossible to draw reliable conclusions regarding the comparative
efficacy of different procedures.
For the treatment of intractable depressive disorder, although several
procedures have been deployed, the overwhelming majority of data concern a
procedure no longer performed the subcaudate tractotomy by focal
irradiation (Knight, 1965;
Bridges et al, 1994).
Although a substitute method has been described obviating the need to secure a
supply of radioactive yttrium-90 rods
(Malhi & Bartlett, 1998),
the Geoffrey Knight Unit in London no longer offers neurosurgery for mental
disorder. The two remaining centres in the UK (Dundee and Cardiff) have
favoured anterior capsulotomy (bilateral thermal lesions of the anterior limbs
of the internal capsule): or anterior cingulotomy (bilateral thermal lesions
of the anterior cingulate gyri) for such patients (Figs
1 and
2). However, the efficacy of
the anterior capsulotomy procedure for depressive disorder is poorly
established. The most informative data are those presented by Herner
(1961), who reported that 9 of
19 anterior capsulotomy procedures were associated with substantial benefit
when patients were followed over a period of up to 24 months; 4 patients were
reported to have deteriorated. Thus, the evidence base for performing anterior
capsulotomy for depression is restricted to a single, 40-year-old, open study
of 19 patients of uncertain diagnostic status. With the Dundee and Cardiff
neurosurgery services having performed over 50 such procedures for depressive
disorder within the past decade, there is a compelling case for a
collaborative outcome study. In Dundee, we offer anterior cingulotomy for
resistant depressive disorder, in the light of the favourable outcomes
reported by other centres (e.g. Ballantine
et al, 1987; Spangler
et al, 1996) and our own clinical experience. For
intractable OCD, although subcaudate tractotomy and multifocal
leucocoagulation have been reported to offer benefit (reviewed by the
Royal College of Psychiatrists,
2000), anterior capsulotomy
(Waziri, 1990) and anterior
cingulotomy (Dougherty et al,
2002) are the best-established current treatment options. Although
there is no compelling evidence either way, it is possible that anterior
capsulotomy may offer marginal superiority.

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Fig. 1 Anterior capsulotomy. Horizontal section through human brain at the level
of the basal ganglia; fibres appear white, cellular material is stained dark
grey. The marked areas [UNK] represent the site and extent of typical thermal
anterior capsulotomy lesions.
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Fig. 2 Anterior cingulotomy. Sagittal section through human brain exposing the
medial cerebral hemisphere surface. The marked area [UNK] represents the site
and extent of a typical thermal anterior cingulotomy lesion.
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ADVERSE EFFECTS OF NEUROSURGERY
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Advances in neuroimaging techniques and stereotactic targeting technology
(stereotactic frames and software) have made it possible to place
millimetre-scaled lesions accurately and precisely in neural structures
implicated in the symptoms of depression and OCD. The same advances have also
made it possible to define the topography of lesions and to correlate this
with clinical effects. The adverse effects associated with neurosurgery for
mental disorder can be considered under two categories: general risks
associated with any intracranial surgery, and risks specific to the particular
procedure carried out.
The main general risks are those of vascular events, confusional states and
postoperative epilepsy. The surgical death rate in neurosurgery for mental
disorder is extremely low and no higher than for stereotactic intracranial
surgery performed for other indications. The current risk of acquiring major
neurological deficit (usually by vascular injury) as a consequence of
frame-based stereotactic surgery is less than 1%. Transient confusional states
(<21 days) are not uncommon following intracranial neurosurgery, with
increased rates following larger, nonstereotactic lesions and in elderly
patients. Rates following anterior capsulotomy and anterior cingulotomy are
very low. Epilepsy rates are also low following stereotactic neurosurgery,
even where lesions are large. We inform potential patients that the risk of at
least one seizure following anterior cingulotomy (with no previous history of
epilepsy) approaches 10% over 10 years
(Jenike et al, 1991).
However, such seizures are generally responsive to anticonvulsant monotherapy.
Weight gain of clinical significance has been reported with both anterior
capsulotomy (Herner, 1961) and
subcaudate tractotomy procedures (Bridges
et al, 1994), but not with anterior cingulotomy. It is,
of course, difficult to dissociate the impact of neurosurgery from that of
other influences such as changes in general levels of activity, medication and
catering arrangements.
Despite concerns that surgical interference with the frontal lobes must
lead to adverse personality change, there is surprisingly little evidence to
support its occurrence with modern neurosurgery. Indeed, there is some
evidence to the contrary (e.g. Mindus
& Nyman, 1991). Personality changes following lobotomy, or
other widespread lesions, would have been very common. Reports of adverse
change following neurosurgery for mental disorder (for example, the
development of irritability, aggression and loss of responsiveness to social
cues) are allegedly infrequent (0.4-4%;
Kiloh et al, 1988),
even in patients treated with large frontal lesions such as subcaudate
tractotomy (<7%; Goktepe et al,
1975). There is one report of adverse personality change following
anterior cingulotomy, where 3 of 27 (11%) patients were considered to show
postoperative indifference or lack of judgement
(Vilkki, 1977). It must be
noted, however, that valid, sensitive and repeatable methods for the
measurement of personality are lacking, and underestimation is likely.
There is no evidence that stereotactic neurosurgery for mental disorder
results in significant intellectual impairment. Indeed, improvements in
general measurements of IQ have been reported
(Kelly, 1980), presumably
following improved attentional capacity associated with symptom relief.
Although some measures of frontal functioning have detected transient
impairments with some neurosurgical procedures
(Kartsounis et al,
1991), evidence for enduring deficit is scant. However, sensitive,
specific tests of frontal function have not generally been applied. Three
more-recent reports have highlighted previously unrecognised adverse effects.
Two single-case studies suggest that anterior capsulotomy may exert subtle
adverse effects on social insight (Happe
et al, 2001) and that anterior cingulotomy may impair
attentional and executive processes
(Ochsner et al,
2001). In a 20-year follow-up of 16 patients who received
stereotactic ventromedial frontal leucotomy for intractable OCD, 8 developed
significant substance dependence postoperatively
(Irle et al, 1998).
Clearly, each of these observations requires detailed evaluation in other
neurosurgical series.
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DOES NEUROSURGERY DESTROY HEALTHY BRAIN TISSUE?
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Ablative neurosurgery has always been subject to special consideration by
the medical and legal communities, as well as by the public, because of the
perception that it is controversial, hazardous and irreversible. The essence
of the controversy has always been that neurosurgery for mental disorder
represents a destructive physical treatment for
psychological disorders in which the brain tissue targeted for
ablation is healthy. Indeed, the recently published Millan
Committee report on proposed reforms to the Mental Health (Scotland) Act 1984
retains this outdated, dualist perspective: we agree that any operation
to destroy brain tissue, where this is not for treatment of a physical
illness, requires stringent safeguards
(Millan Committee, 2001). The
importance of recent research demonstrating discrete changes in cerebral
metabolism and anatomical structure in defined mental disorders
(Sheline et al, 1996;
Drevets et al, 1997;
Ongur et al, 1998;
Rajkowska et al,
1999; Szeszko et al,
1999) cannot be overstated. Destructive and irreversible
neurosurgical treatments are used without legal provision or restriction to
manage distressing and treatment-refractory medical problems such as the motor
symptoms of Parkinson's disease, epilepsy and chronic pain. The techniques and
technologies used to perform such surgery are identical to those used in
neurosurgery for mental disorder. Conceptually, they are also identical
specific areas of the brain are destroyed, or functionally
inactivated, to alleviate otherwise intractable symptoms. With rapidly
accruing evidence from multiple sources that depression and OCD are associated
with distinctive, regionally specific changes in brain function and structure,
we must consider at which point these conditions cease to be
non-physical. To assert that the brain of an individual with
chronic, severe depression or OCD represents healthy tissue now
seems illjudged and implausible. We can no longer conclude that neurosurgery
for mental disorder is targeting healthy tissue.
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THE DUNDEE SERVICE
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The first modern neurosurgical procedures for mental disorder performed in
Dundee took place in 1992. The clinical service was established by Professor
George Fenton (Department of Psychiatry, University of Dundee) and Mr T. R. K.
Varma (Department of Surgical Neurology, Dundee Royal Infirmary). Between
January 1990 and December 2001, a total of 34 such procedures were performed
(Table 1). Since its inception,
the configuration and activities of the service have evolved to reflect the
need for expert multi-disciplinary input. For example, assessment of the
adequacy of previous psychological treatments and of potential suitability for
further psychological therapy before consideration for neurosurgery now
involves detailed, independent assessment by a senior academic clinical
psychologist and a consultant psychotherapist. Operational policies for
neurosurgery for mental disorder have been extended and refined following
discussion and correspondence with other specialist treatment services for
intractable depression and OCD within the UK. Independent clinical assessments
are provided for all patients by representatives from the Mental Welfare
Commission for Scotland. Such assessments include a consideration of
diagnostic issues, the degree of functional impairment, the adequacy of
previous treatments, the suitability of the proposed rehabilitation plan and
the appropriateness of neurosurgery. These assessments are provided as a
statutory requirement for all patients liable to detention under UK mental
health legislation and as an informal agreement for all non-detained patients.
Mental Welfare Commission assessments are conducted by a group of three
commissioners with at least one medical representative. Thus, before
proceeding to neurosurgery, the individual's suitability and capacity to
provide informed consent will have been assessed by the referring mental
health team (including the consultant psychiatrist and the responsibile
medical officer), the Dundee team and the Mental Welfare Commission for
Scotland.
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Table 1 Activity of the Dundee neurosurgery for mental disorder programme
1990-2001: referral and operation rates, separated by gender
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On receipt of a formal, written referral, the assessment procedure begins.
This may vary for geographical reasons and according to the nature of the unit
making the referral. Psychiatric assessment can be conducted at home, at the
patient's base hospital, or during a period of in-patient assessment in
Dundee. Community-based assessment facilitates scrutiny of local medical and
psychiatric case records, collection of information from relatives and from
members of the local health care team. In-patient assessment is preferred when
the source of referral is geographically distant and it is necessary to
complete a detailed review of previous psychological treatment methods and
responses, particularly for patients referred from centres with limited access
to such treatment methods. The aims of the initial assessment are to confirm
diagnosis, to determine the appropriateness, vigour and adequacy of previous
treatments, and to consider the impact of illness on physical and mental
status, social and occupational function, and quality of life. Almost all
patients referred for neurosurgery for mental disorder are then directed
towards treatment strategies that have not previously been explored or that
have been of dubious adequacy. The major inclusion and exclusion criteria for
consideration for neurosurgery are detailed in Appendix 1. These criteria are
used to guide clinical decision-making, but are not applied rigidly. Indeed,
the criteria are subjected to regular review to ensure that treatment advances
are incorporated as necessary. We have adopted the view that the presence of a
personality disorder (the presence of significant maladaptive personality
traits prior to the development of mental disorder) might represent a relative
contraindication to surgery. Our screening has identified three candidates for
neurosurgery for mental disorder who met criteria for a diagnosis of
personality disorder: however, none met criteria for treatment adequacy and
none has had neurosurgery.
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WHEN IS PREVIOUS TREATMENT ADEQUATE?
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Appendix 2 details the framework for determination of the adequacy of
previous physical treatments. The guiding principle is that it is necessary to
determine whether patients have been exposed to a sufficiently broad range of
different treatments (pharmacological and psychological), in adequate
dosage, for adequate periods. The reader will be able to
identify drug treatment strategies, particular combination treatments, that do
not appear on the Dundee framework. These treatments are not listed as
required because evidence for their efficacy falls below that
for neurosurgery itself. However, it should be appreciated that most people
referred for neurosurgery for mental disorder have been exposed to many more
drug treatments and combinations than are listed. The most problematic
assessments usually concern the adequacy of previous psychological treatments.
In general, judgements involve detailed scrutiny of previous treatment
records, an assessment of the likely responsiveness in terms of presenting
characteristics and, in some cases, a brief trial of a potentially suitable
treatment approach. Although there are specific psychological treatment
approaches with proven efficacy in depressive disorder and OCD (although not
for presentations of such complexity and chronicity), the availability of
suitably trained, expert therapists varies from one region to another. We
place particular emphasis upon adequate trials of expertly delivered
cognitivebehavioural therapy. Although there is evidence for the
efficacy of interpersonal therapy in less severe depressive disorder, suitably
trained therapists are even more difficult to access than
cognitivebehavioural therapists. Hence, interpersonal therapy does not
feature as a mandatory requirement. Although there is no compelling evidence
to support the efficacy of psychodynamically oriented psychological treatment
approaches, an assessment of previous treatment exposures and potential
suitability for subsequent treatment by such methods is routinely conducted.
To date, none of those screened has been considered a suitable candidate for
such treatment. Indeed, the patients referred for consideration for
neurosurgery are almost invariably too ill to engage in therapy, or have
previous experience of therapy leading to worsening of symptoms and intense
personal distress.
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ALTERNATIVES TO ABLATIVE NEUROSURGERY
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Two potentially non-destructive alternatives to ablative
neurosurgery have emerged: vagus nerve stimulation and deep brain stimulation.
The former, an approved and effective treatment for refractory epilepsy,
involves intermittent electrical stimulation of afferent fibres within the
vagus nerve. This has been reported to achieve a significant improvement in
symptom burden and function after 12 weeks of stimulation in 18 people who
were participants in an open study of 59 patients with chronic, refractory
depression (Rush et al,
2000). Of this cohort, 13 of 28 were reported to have met criteria
for response after 12 months of stimulation. However, there are early
indications that the most chronic, treatment-refractory study entrants (i.e.
those most similar to those referred for neurosurgery for mental disorder in
the UK) exhibited the poorest responses to vagus nerve stimulation
(Sackeim et al,
2001). Similarly, there is a single open study reporting
short-term efficacy for the application of deep brain stimulation in OCD
(Nuttin et al, 1999).
With electrical stimulation electrodes sited bilaterally within the anterior
limbs of the internal capsule, three of four patients with refractory OCD
experienced benefit from deep brain stimulation over a period of weeks.
Although the same technology has successfully replaced some ablative
neurosurgical procedures for the management of pain and some of the symptoms
of refractory Parkinson's disease, there are no longer-term follow-up data to
support its use in mental disorder. Nevertheless, such procedures may offer
promise for the development of reversible surgical treatments for refractory
mental disorder.
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CAPACITY FOR INFORMED CONSENT
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Perhaps the most controversial of the recommendations made by the Good
Practice Group was that neurosurgery for mental disorder should be able
to be performed on patients who are mentally incapable of giving consent to
it, provided they do not resist or oppose it
(CRAG Working Group on Mental Illness,
1996). With the recent implementation in Scotland of Part 5 of the
Adults with Incapacity (Scotland) Act 2000, much media interest has focused on
this proposal. As the sole service in Scotland providing neurosurgery for
mental disorder, we wish to clarify our position while awaiting parliamentary
affirmation of law. Treatment of some forms of mental disorder in the absence
of consent is an established principle in mental health care. However, a
critical aspect of such treatments is their reversibility and
limited potential for serious adverse consequences. Essentially, such
treatments are considered not to result in permanent changes in brain
structure or function. Clearly, this does not describe neurosurgery. A body of
evidence suggests that neurosurgery does improve outcome for some sufferers;
however, we have no ability as yet to predict which patients might benefit. We
also know that neurosurgery for mental disorder is not without risk: serious
adverse events can and do occur. We cannot reliably predict these. Therefore,
while aware of the moral, ethical and other arguments, the Dundee service has
decided to maintain a policy of not offering neurosurgery for mental disorder
to anyone who is incapable of providing sustained, informed consent.
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CONCLUSIONS
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We must continue to evaluate the efficacy of neurosurgery for mental
disorder against a constantly evolving knowledge base, both in terms of the
underlying neuroscience of mental disorder and with respect to advances in
treatment. It is also necessary rigorously to evaluate
reversible alternatives such as vagus nerve and deep brain
stimulation. It is our view (and our experience) that neurosurgery still
represents a potentially useful strategy to augment the management of chronic
depression and OCD in a small number of patients. Like all other treatments
for these two conditions, neurosurgery is not curative. There is a
compelling need to review the long-term outcomes of the Dundee and Cardiff
cohorts who have undergone neurosurgery for mental disorder.
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Clinical Implications and Limitations
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CLINICAL IMPLICATIONS
- Modern neurosurgery for mental disorder bears little relation to the early
procedures and clinical practice that brought discredit upon psychiatry.
- Ablative neurosurgery remains available as a treatment option for chronic,
intractable depression and obsessivecompulsive disorder.
- Despite developing empirically, modern ablative neurosurgery targets neural
structures that have been shown to exhibit functional and structural
abnormalities and cannot be considered to represent healthy
tissue.
LIMITATIONS
- The evidence base for ablative neurosurgery for mental disorder remains
unsatisfactory.
- A plausible mechanism of action for such neurosurgery has yet to be
identified.
- The importance of defining and describing key features of postoperative
management has been neglected.
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APPENDIX 1
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Criteria for consideration for ablative neurosurgery
Treatment-refractory depression
Inclusion criteria
- Age > 20 years.
- Legal status: both formal and informal patients can be considered.
- Confirmation of diagnosis: the individual will fulfil ICD10 criteria
for one of the following:
- F32.2 severe depressive episode without psychotic symptoms
- F32.3 severe depressive episode with psychotic symptoms
- F33.1F33.3 recurrent depressive disorder, current episode moderate
to severe
- F31.4F31.5 bipolar affective disorder, current episode severe
depression with or without psychotic symptoms.
- Duration of illness: an absolute minimum of 3 years, with at least 2 years
of unremitting symptoms despite treatment. Only in exceptional circumstances
would a duration of illness of < 5 years be considered.
- Consent: the patient must be capable of providing sustained, informed
consent.
Exclusion criteria
- Age < 20 years.
- Failure to fulfil ICD10 criteria for F32.2, F32.3,
F33.1F33.3, F31.4F31.5
- Incapacity to give sustained, informed consent.
- A current diagnosis of substance misuse fulfilling criteria for
ICD10 F10F19 Mental and behavioural disorders due to
psychoactive substance use.
- A diagnosis of organic brain syndrome fulfilling criteria for ICD10
F00F09, including Alzheimer's disease, vascular and other
dementias.
- A diagnosis of disorder of adult personality fulfilling criteria for
ICD10 F60F69.
- A diagnosis of pervasive developmental disorder fulfilling criteria for
ICD10 F84.
Treatment-refractory obsessivecompulsive disorder
Inclusion criteria
- Age > 20 years.
- Legal status: both formal and informal patients can be considered.
- Confirmation of diagnosis: individuals will normally fulfil criteria for a
primary diagnosis according to ICD10 F42.0F42.9. Individuals
with treatment-refractory obsessional and/or compulsive symptoms in the
presence of other comorbid mental disorder (e.g. depression, schizophrenia)
can be considered for surgery but additional criteria for adequacy of
treatment will be applied.
- Duration of illness: an absolute minimum of 3 years, with at least 2 years
of unremitting symptoms despite intensive psychopharmacological and
psychological treatment. Only in exceptional circumstances would a duration of
illness of < 5 years be considered.
- Consent: the patient must be considered capable of providing sustained,
informed consent.
Exclusion criteria
- Age < 20 years.
- Failure to fulfil ICD10 criteria for F42.0F42.9.
- Incapacity to give informed consent.
- A current diagnosis of substance misuse fulfilling criteria for
ICD10 F10F19, Mental and behavioural disorders due to
psychoactive substance use.
- A diagnosis of organic brain syndrome fulfilling criteria for ICD10
F00F09, including Alzheimer's disease, vascular and other
dementias.
- A diagnosis of disorder of adult personality fulfilling criteria for
ICD10 F60F69.
- A diagnosis of pervasive developmental disorder fulfilling criteria for
ICD10 F84.
- Absence of an adequate therapeutic trial of psychological treatment
methods.
- Absence of adequate therapeutic trials of psychopharmacological treatment
methods.
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APPENDIX 2
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Assessment of treatment adequacy
Treatment-refractory depression
As a guiding principle, all physical treatments that have been shown to be
effective in randomised, controlled trials must have been tried in adequate
dosage for an adequate period. In general terms, this will reflect the
prescription of antidepressant drugs within, or above, the dose range
recommended by the British National Formulary (BNF) for a period of
at least 6 weeks. At present, the use of plasma drug concentration monitoring
(where possible) is not included as a mandatory requirement, but is clearly
desirable and may become obligatory. Most patients referred for assessment
will have been exposed to many different treatment trials. The following
represent those deemed essential before proceeding to neurosurgery:
- At least two courses of treatment with a tricyclic antidepressant drug.
- At least one course of treatment with a selective serotonin reuptake
inhibitor.
- At least one course of treatment with a non-reversible monoamine oxidase
inhibitor.
- At least one of the above plus lithium augmentation for a period of 4-6
weeks, with a 12-h post-medication plasma level of 0.4-0.8 mmol/l.
- At least one course of treatment with an antidepressant drug as defined
above, plus the prescription of a typical or atypical antipsychotic drug for a
period of 6 weeks at a dose within the BNF recommended range (where psychotic
symptoms are prominent in the clinical presentation, trials of both typical
and atypical drugs should be performed).
- At least two trials of electroconvulsive therapy, spaced 6 months apart.
Adequacy is defined as a minimum of eight bilateral applications of the
therapy with recorded evidence of seizure duration exceeding 15 s per
treatment. Failure to respond is defined as no clinical response, minimal
clinical response, or a brief response with relapse within a period of 4
weeks, despite antidepressant maintenance treatment.
- At least one of the following for a period of at least 6 weeks:
- combination therapy with clomipramine, lithium and L-tryptophan;
clomipramine to be administered at the maximum tolerated dose (150-250 mg per
day), with a 12-h post-medication plasma lithium level of 0.4-0.8 mmol/l;
- combination therapy with phenelzine, lithium and L-tryptophan; phenelzine
to be administered at the maximum tolerated dose (45-90 mg per day), with a
12-h post-medication plasma lithium level of 0.4-0.8 mmol/l.
Alternative drug treatment strategies are desirable, but not essential. For
each, there may be either an absence of unequivocal evidence of efficacy, or
restricted suitability for selected patients on the basis of increased risk to
physical health.
- Prescription of at least one antidepressant drug at a dosage beyond the BNF
recommended maximum daily dose, with regular physiological monitoring; for
example, gradual escalation to highest tolerated dose of venlafaxine (> 500
mg per day). Alternatively, gradual escalation to highest tolerated dose of
imipramine (> 300 mg per day). Measurement of plasma levels may be
indicated, with a target concentration of 200-250 ng/ml. This level ought to
be maintained for 6 weeks.
- Thyroid hormone augmentation of antidepressant drug treatment. This
involves the administration of liothyronine sodium/T3 hormone
(not T4) to augment the action of a tricyclic
antidepressant. The tricyclic drug ought to be given at the maximum tolerated
dose and then T3 is added (increasing to 20 µg three times
daily). Where the patient is known to suffer from hypothyroidism and is taking
replacement T4 (biochemically euthyroid), the strategy of
T3 augmentation is still advised.
- Anticonvulsant drugs. Some evidence exists for the efficacy of
carbamazepine and lamotrigine in resistant bipolar depression. Carbamazepine
or lamotrigine ought to be prescribed either in combination with a tricyclic
drug, or on their own at a dose of 800-1200 mg (carbamazepine) or 200 mg
(lamotrigine) daily in divided dose. Plasma level monitoring may be helpful
with carbamazepine.
- Psychostimulant drug treatment. Patients ought to be exposed to the maximum
tolerated dose of a tricyclic drug, to which methylphenidate is added,
initially as a single 10-mg test dose, gradually increasing to 30 mg three
times daily.
Psychological treatment methods. At least one sustained
trial of structured, manualised, cognitivebehavioural therapy of 20
sessions duration (with either a cognitive or a behavioural emphasis), with
long-term follow-up. Treatments ought to be delivered by a therapist with
British Association for Behavioural and Cognitive Therapies (BABCP)
accreditation. Where there is significant doubt over the adequacy of previous
trials of psychological treatment, it may be appropriate to offer the patient
at least a brief trial of a suitable psychological therapy. In some cases,
this might suggest that a more intensive course of therapy ought to be
instigated either in Dundee or elsewhere.
Treatment-refractory obsessivecompulsive disorder
As a guiding principle, all of the physical treatments that have been shown
to be effective in obsessivecompulsive disorder (OCD) (preferably in
randomised, controlled trials) must have been tried in adequate dosage for an
adequate period. In general terms, this will reflect the prescription of
antidepressant drugs within, or above, the dose range recommended by the BNF
for a period of 12-16 weeks. Most patients referred for assessment will have
been exposed to many different treatment trials. The following represent those
deemed essential before proceeding to neurosurgery.
- At least one course of treatment with the tricyclic antidepressant drug
clomipramine for 16 weeks at a dosage in excess of 150 mg per day. Except in
exceptional circumstances, the dosage should be titrated upwards towards a
target of 250 mg per day (or above) depending on tolerability. Compliance
ought to be determined by plasma level estimation where deemed necessary.
- At least two courses of treatment with different selective serotonin
reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, citalopram
or sertraline) at the maximum tolerated dose for a period of 16 weeks. This
may involve the prescription of these drugs at a dose in excess of the BNF
maximum recommended dosage. Except in exceptional circumstances, all
drugs from the SSRI class ought to be tried, sequentially, in full dosage (or
maximum tolerated dosage) for an adequate period (the minimum target daily
dose would be fluoxetine 60 mg, fluvoxamine 300 mg, sertraline 200 mg,
citalopram 60 mg and paroxetine 50 mg).
- At least one of the above plus lithium augmentation for a period of 12
weeks with a 12-h post-medication plasma lithium level of 0.4-0.8 mmol/l.
- At least one of the above, plus neuroleptic augmentation for a period of 12
weeks (particularly where comorbid tic disorder or psychotic symptoms are
present). Both typical and atypical agents may be tried (haloperidol and
risperidone are recommended).
- At least one of the above plus augmentation with buspirone (10-60 mg per
day), clonazepam (0.5-3.0 mg per day) or nefazodone (200-600 mg per day) for a
period of 12 weeks.
It is also anticipated that additional augmentation strategies may have
been tried (e.g. L-tryptophan). Electroconvulsive therapy may be tried and
becomes obligatory where depressive symptoms are prominent. The longer-term
usefulness of intravenously administered clomipramine remains to be
established.
Psychological treatment methods. At least one sustained
trial (>26 weeks) of exposure and response prevention under the supervision
of a BABCP-accredited therapist (minimum therapist contact time 90 min per
week). Whenever possible, we would expect a period (12 weeks) of in-patient
behavioural therapy, conducted in a specialist unit. However, many sufferers
are unwilling, for a variety of reasons, to consent to this. Cognitive therapy
can also be an effective adjunct to exposure treatment if intrusive thoughts
and ruminations are prominent. Again, trials of cognitive therapy ought to be
conducted under the supervision of a BABCP-accredited therapist.
 |
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Received for publication November 8, 2001.
Revision received October 23, 2002.
Accepted for publication November 12, 2002.