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Correspondence

Schizophrenia in the early middle ages: some Whenever he lay on the ground, a horrible swarn of frogs
negative evidence seemed to hop over him, and he heard voices openly
reproaching him and saying: Martin, whom you have
Peter Dendle, Department of English, Pennsylvania State supplicated, cannot help you because you are under our
University, Mont Alto, Pennsylvania, US: authority. [3]
The existence of schizophrenia before the modern era,
especially prior to the eighteenth century, has remained a According to Gregory, Landulf is cured through his sup-
contested point. As a medievalist studying the history of plications to this saint. The third reference comes from a
mental disorder and demonology who is in the process letter by Boniface, the Anglo-Saxon missionary in Ger-
of compiling a database of early medieval possession ac- many, to King Aethelbald of Mercia, England (dated ca.
counts, I believe I can contribute an observation pertinent 746747 ce). Boniface refers to Aethelbalds predecessor
to the discussion. Specifically, I wish to address a chal- King Ceolred, who suffered from a sudden fit of some
lenge posed by Edward Hare in the course of a debate in sort while at the dinner table: he was apparently left rav-
the Australian and New Zealand Journal of Psychiatry ing after his fit and conversing with devils (cum diabolis
over the history of schizophrenia [1]. In that dialogue, J. sermocinans) [4]. We may or may not interpret convers-
Ellard questions our ability to determine the early history ing with devils as an indication that Ceolred was hearing
of schizophrenia with any confidence, focusing on the antagonistic voices.
problematic nature of schizophrenias changing profile. These are the only cases of auditory hallucinations un-
Hare responds to Ellard that hearing illusory voices is a accompanied by visual hallucinations from the early Mid-
symptom as common as any in schizophrenia: dle Ages that have come to my attention. They are the
rare exceptions in a large body of literature documenting
Ellard mentions the need for at least one defining char-
a rich spectrum of mental and behavioural disorders. In
acteristic of schizophrenia. I wonder if voices might do
fact, auditory hallucinations seem to be very poorly at-
here that is, hallucinatory voices in the absence of vi-
tested in early medieval sources, sources which otherwise
sual hallucinations . . . Voices of this kind are common in
supply a wide range of detailed symptoms of madness and
schizophrenia and are rare in other conditions. In a search
possession (falling to the ground, frothing at the mouth,
of the literature before 1800 I found scarcely any refer-
tearing clothes, breaking chains or fetters etc.). My hope
ences to voices . . . I can find no account of voices in
is that this observation, though it is only negative evi-
Burtons Anatomy, nor in the main psychiatric treatises
dence, may contribute toward the broader dialogue on
of the eighteenth century.
the history of schizophrenia.

For a forthcoming monograph on demon possession in


the early Middle Ages, I have been compiling a database References
1. Hare E. Commentary one (addendum to Ellard J.). Did
of possession cases from the time of the New Testa-
schizophrenia exist before the eighteenth century? Australian and
ment through around 1050 ce. Out of the 274 specific New Zealand Journal of Psychiatry 1987; 21:315316.
cases of demonic possession I have collected about which 2. Ward B, trans. The sayings of the desert fathers: the alphabetical
detailed symptoms and/or demographic information are collection. Kalamazoo: Cistercian Publications, 1975:187 (saying
139).
given, only three suggest something like auditory hallu- 3. Gregory of Tours. Libri de virtutibus sancti Martini episcopi 2.18:
cinations unaccompanied by visual hallucinations. Quodsi se subderet terrae, ranarum super eum multitudo horribilis
The first is from the Greek Apothegmata Patrum (Say- desilire videbatur, sed et voces publice ab eo audiebantur
ings of the Fathers), a collection of monastic anecdotes exprobrantium et dicentium: Martinus, quem expetisti, nihil tibi
poterit subvenire, quia nostris es ditionibus mancipatus. In:
and proverbs compiled around the fourth century and Krusch B, ed. Gregorii Episcopi Turonensis Miracula et Opera
disseminated in a number of languages throughout the Minora. Hanover: Hahn, 1885:165.
Middle Ages. A saying attributed to Abba Poemen men- 4. Letter 73.Tangl M. Die Briefe des Heiligen Bonifatus und Lullus.
tions auditory hallucinations in this context: Abba Po- MGH, Epistolae Selectae 1. Berlin: Weidmann, 1955:153.
emen said, If you have visions or hear voices do not
tell your neighbor about it, for it is a delusion in the Outcomes of an early psychosis intervention
battle [against demons][2]. A second instance comes program
from Gregory of Tours Books on the Miracles of Saint
Martin the Bishop (581 ce). This miracle collection in- Anthony J. Pelosi, Hairmyres Hospital, East Kilbride,
cludes a strikingly vivid description of a certain Landulf UK:
of Vienne, who apparently suffered from tactile as well Nash and Gorrell and their colleagues are rightly cau-
as auditory hallucinations: tious when discussing the outcome study of their early
CORRESPONDENCE 523

psychosis intervention program, not least because of the the generic service provided better care and it is possible
high proportion of patients who declined to participate in they used less seclusion, fewer community treatment or-
the research and frequent non-completion of intake and ders and lower doses of neuroleptic agents. It is important
follow-up assessments [1]. The headline finding that the that further analyses of these data should be published af-
program may have led to greater improvement in negative ter a simple controlling for age.
symptoms at 12 months is based on a dubious comparison I am concerned that the recent papers by Nash et al. and
of 14 versus 9 subjects from 215 potential patients. They Gorrell et al. will also be used inappropriately to influ-
conclude that this study and their companion case note ence mental health policy. In the UK, resources are being
audit [2] support the introduction of specialized teams diverted from ordinary psychiatric services to highly pro-
for initial treatment of psychotic illnesses. Could I sug- tected early intervention teams. This has caused havoc in
gest that they have, in fact, provided evidence against the some areas for the ongoing treatment of people with se-
overall usefulness of this service innovation? rious mental illnesses. Further comparisons of models of
The authors emphasize the importance of continuity of care are urgently required [4], but with careful presenta-
care one of the specifically audited indicators from the tion and balanced discussion of the results.
Australian Guidelines for Early Psychosis. Their exami-
nation of continuity of care is only based on visits by the
community case manager during inpatient stays. How- References
1. Nash L, Gorrell J, Cornish A, Rosen A, Miller V, Tennant C.
ever, by their very nature, subspecialist teams for early Clinical outcome of an early psychosis intervention program:
psychosis fracture continuity of care. There would have evaluation in a real world context. Australian and New Zealand
to be a massive demonstrable superiority in other areas of Journal of Psychiatry 2004; 38:694701.
treatment to justify transfer of patients with severe and en- 2. Gorrell J, Cornish A, Tennant C et al. Changes in early psychosis
service provision: a file audit. Australian and New Zealand
during mental disorders who are then returned to ordinary Journal of Psychiatry 2004; 38:687693.
services after only 18 months. For 14 out of 24 indicators 3. Yung AR, Organ BA, Harris MG. Management of early psychosis
from the Australian Guidelines there were no clinically or in a generic adult mental health service. Australian and New
Zealand Journal of Psychiatry 2003; 37:429436.
statistically significant differences before and after intro-
4. Fitzgerald PB. Generic services and early psychosis. Australian
duction of the specialized service. Modest improvements and New Zealand Journal of Psychiatry 2003; 37:778.
were found for some relatively trivial indicators (patient
offered group therapy 17% versus 37%; prescription of Reply
new rather than older antipsychotic medicines 62% ver-
sus 87%; as required benzodiazepines instead of antipsy- Alison R. Yung, ORYGEN Youth Health, Parkville,
chotic medicines 17% versus 46%; family offered group Victoria, Australia:
work 6% versus 29%). There were advantages in regard Pelosi is concerned that streamed early psychosis ser-
to more important aspects of care but take-up was disap- vices disrupt the continuity of care of patients. In fact,
pointing with both types of service (psychoeducation re- early psychosis services (EPS) improve engagement and
ceived 36% versus 56%; attendance at group therapy 8% continuity of care in the important early phase after on-
versus 27%; relapse prevention plan prepared 11% versus set [1]. The early psychosis prevention and interven-
26%; attendance at family groups 2% versus 13%). Ordi- tion (EPPIC) service in Melbourne, Australia, guaran-
nary multidisciplinary teams that persevere in attempts to tees continuity of care for a fixed period of 18 months
help mentally ill people and their families will have many and achieves much higher retention rates across this phase
more opportunities to provide these interventions. Sim- of illness than in generic services. Similar services cur-
ilar unexciting advantages for the subspecialist service rently being implemented in Victoria, Australia and in
at the end of the study period may be counterbalanced the UK guarantee a treatment tenure for patients for 3
by lower admission rates for patients under the care of years. This allows adequate attention to be paid to the
generic teams. recovery phase after acute symptom resolution. This is
Gorrell et al. cite a paper by Yung and colleagues pub- the critical period of maximum vulnerability to relapse
lished in this journal claiming to show clear superiority [2]. A special environment and specialized clinical skills
for an elaborate early intervention program compared are required to tackle the psychosocial challenges of this
with a neighbouring generic service [3]. This study has phase in order to maximize functional recovery. Merely
been used to bolster the unashamed political lobbying of managing risk and reducing acute psychotic symptoms
the early intervention movement even though Fitzger- leaves most of the therapeutic work undone, yet this
ald pointed out a year ago that there were problems due is what typically happens in sparsely resourced generic
to possible confounding factors [4]. The results in regard adult services in Australia. Frequently, first-episode
to duration of untreated psychosis strongly suggest that patients are treated in an acute crisis-based care model
524 CORRESPONDENCE

and in settings populated by much older patients in the My colleagues in first-episode services and I have in-
acute phase of a chronic illness, with follow-up provided deed unashamededly advocated on behalf of our patients
by general practitioners. Real continuity of care is only and their families for better access to high quality phase-
provided to a limited number of the more severely dis- specific care. This advocacy has been evidence-based
abled, once this becomes apparent and entrenched. Until and is well-supported [1,7]. Pelosis claim that resources
the recent reforms, the situation has been similar in the have been diverted from generic services is not sustain-
UK. able. Early intervention services in the UK have been
Pelosi then criticizes the use of our paper [3] by the allocated substantial new resources to fill serious gaps
early intervention movement and cites Fitzgerald [4] in service delivery [8] that are similar to those identified
who previously pointed out problems in our study due in the original audit. Pelosi himself is notorious for his
to the confounding factor of age. Fitzgerald previously own unashamed political lobbying against investment in
claimed that the higher mean age of the first-episode pa- specialized early intervention services, yet he fails to pro-
tients in the generic service (27 years) compared to the duce any scientific evidence for the efficacy of the late
specialist service (EPPIC) (22.6 years) may account for intervention delivered by generic services.
their less favourable outcomes. This argument is not ten-
able for two reasons. First, our paper showed marked dif- References
ferences in clinical practice, pattern of care and outcomes 1. Craig TKJ, Garety PA, Power P et al. The Lambeth Early Onset
between the two groups. Over 80% of the first-episode (LEO) team: randomised controlled trial of the effectiveness of
specialised care for early psychosis. British Medical Journal
patients in the generic service required inpatient admis- 2004; 329:1067.
sion, with police involvement in the admission process in 2. Birchwood M, Todd P, Jackson C. Early intervention in
40% of cases and a mean length of stay of 46.5 days. This psychosis: the critical period hypothesis. British Journal of
compares with data from EPPIC of an admission rate of Psychiatry 1998; 172(Suppl 33):5359.
3. Yung AR, Organ BA, Harris MG. Management of early psychosis
64.1%, with less than 4% requiring police involvement in a generic adult mental health service. Australian and New
and mean length of stay of 12.9 days. Thus, even if age Zealand Journal of Psychiatry 2003; 37:429436.
were a factor and controlled for, it is unlikely to fully ex- 4. Fitzgerald PB. Generic services and early psychosis. Australian
and New Zealand Journal of Psychiatry 2003; 37:778.
plain the magnitude of these differences. Second, younger
5. Linszen D, Lenoir M, De Haan L, Dingemans P, Gersons B. Early
age of onset of first-episode psychosis is actually a pre- intervention, untreated psychosis and the course of recent onset
dictor of poorer not better prognosis, and such patients schizophrenia. British Journal of Psychiatry 1998; 172(Suppl
are much more challenging to manage. Hence, EPPIC is 33):8489.
6. Melle I, Larsen TK, Haahr U et al. Reducing the duration of
more likely to be managing patients at risk of poor out- untreated first-episode psychosis: effects on clinical presentation.
comes than the generic adult service. This is particularly Archives of General Psychiatry 2004; 61:143150.
so as EPPIC takes patients as young as 15, whereas adult 7. Nordentoft M, Jeppesen P, Petersen A et al. The OPUS trial: a
services in Australia have 1618 years as their official randomised multi-centre trial of integrated versus standard
treatment for 547 first-episode psychotic patients. Schizophrenia
lower age range. Research 2004; 70:31.
Furthermore, differences in duration of untreated psy- 8. Garety PA, Rigg A. Early psychosis in the inner city: a survey to
chosis (DUP) may well explain some of the differences inform service planning. Social Psychiatry and Psychiatric
in age between the samples. Several of the generic pa- Epidemiology 2001; 36:537544.
tients had very long DUPs, so it is likely that they would Maintenance treatment of bipolar disorder: con-
present and receive treatment at a later age than the cerning results from a nationwide questionnaire
EPPIC cohort. The low DUP in the EPPIC cohort com- survey in Finland
pared to the generic cohort is an important finding. Re-
duction in DUP has been a major focus of the EPPIC Marko Sorvaniemi, Department of Psychiatry, Univer-
service for the last decade. Strategies that have been put sity of Turku, Rauma, Finland, Tuomo Lahti, Adolescent
in place to achieve this (described in the original article Psychiatric Clinic of Pori, Rauma, Finland:
[3]) are not funded in generic services. Indeed, it is dif- Bipolar disorder often goes undetected and under-
ficult for first-episode patients to gain entry into generic treated in clinical practice. Recently, consensus guide-
services in most settings, as reflected in the long DUPs lines have been published in many countries for the better
seen across the developed world in the absence of Early recognition and management of the illness [1,2]. Expert
Psychosis Service (EPS). These DUPs are reduced when opinions are hoped to compensate for the gaps in the
EPS are set up [5,6]. empirical database.
Finally, Pelosi expresses his concern about the In Finland, a national consensus guideline for bipolar
unashamed political lobbying for early intervention re- disorder is in preparation. Earlier, a nationwide question-
sources at the expense of ordinary psychiatric services. naire survey on treatment practices of bipolar disorder
CORRESPONDENCE 525

was carried out. In the questionnaire, 41 items focused on Re: Clinical outcome of an early psychosis intervention
maintenance treatment. The questionnaires were mailed program: evaluation in a real world context (Nash L et al.)
to all clinicians employed in adult psychiatry in Finnish [2].
psychiatric hospitals. A 3-month response time was set, In these two articles, we aimed to evaluate the extent
and two reminders were sent during this period. to which a mental health service was able to implement
The effective response rate was 62% (139/225). Of the optimal treatment strategies for young people with first-
responders, 77 (55%) were female, 59 (43%) were psy- episode psychosis and to measure any change in patient
chiatric residents, 56 (40%) psychiatrists and 24 (17%) outcome. Our first article is about change in service de-
general practitioners. The mean (SD, range) length of livery measured by file audit over two time periods. The
experience in clinical practice was 12 (7.8, 030) years second article attempts to measure patient outcomes dur-
and in psychiatry 7.7 (6.9, 030) years. The mean age ing 12 months of treatment for patients entering our ser-
(SD, range) was 39.5 years (7.9, 2460) for the respon- vice between 1997 and 2000. The intervention provided
ders and 42.6 years (8.9, 2263) for the non-responders was a training program for all staff, and from this, there
(p = 0.007). No statistically significant gender difference was a groundswell of support to reorient the service to
between the two groups was found. Both the responders develop three early psychosis (EP) teams. The study was
and the non-responders were evenly distributed over the not a comparison of generic mental health services versus
different hospital districts in Finland. specialized EP teams, as Dr Pelosi appears to believe.
Twenty-one per cent of clinicians recommended a The baseline mental health service in 1997 was, and still
mood stabilizer after one manic episode (54%, if the is, a high-functioning service with integrated crisis and
patient had positive family history), 67% after two manic case management, integrated inpatient, outpatient and as-
episodes and 2% after three manic episodes. In bipolar II sertive community treatment systems. Perhaps Dr Pelosi
disorder, only 31% of clinicians suggested that a mood misunderstands the extent of continuity of care that our
stabilizer should be used almost always with an illness baseline generic service provides, which is replicated
history of several hypomanias and bipolar depressions. and intensified by our early intervention in psychosis
If the patient had a positive family history and rapid cy- subteams.
cling or induction of hypomania/mania associated with In the file audit article, the first period of the audit in
the use of an antidepressant, 26, 42 and 24% of clinicians 1997, no patients received treatment from an EP team. In
favoured a mood stabilizer, respectively. the second period, 2 years later, 51% of patients received
Finnish psychiatrists seem to have a moderate formal at least some of their treatment from a specialized EP
knowledge of the contemporary guideline recommenda- team. We will address some specific issues raised by Dr
tions, which is a reason for concern. Our bipolar patients Pelosi.
seem to be at risk of a low level of adequate pharmacother- Dr Pelosi highlights a lack of change in 14 out of 24
apy. The continuous education of clinicians is needed clinical indicators found in the file audit. However, there
to narrow the gap between guideline recommendations, was a statistically significant improvement in 10 mea-
research evidence and clinical practices. sures, no indicator showed adverse change and five indi-
cators performed well at both time points. Additionally,
as mentioned in the paper, the file audit could only rely
References on what was documented in the file. A subsequent audit
1. American Psychiatric Association Practice Guideline for the
treatment of patients with bipolar disorder. American Journal of using the file and an interview with the clinician found a
Psychiatry 2002; 159:150. much higher degree of change in some items; for exam-
2. Australian and New Zealand Clinical Practice Guidelines for the ple, attendance at groups was often not documented in
treatment of bipolar disorder. Australian and New Zealand the medical records.
Journal of Psychiatry 2004; 38:280305.
We agree with Dr Pelosi that the visit of a community
case manager to an inpatient unit is a limited indicator of
continuity. However, involving the community case man-
Reply to letter of Anthony J. Pelosi regarding the ager at this stage provides the beginning of continuous
following two articles service provision from hospital to community. We also
attempted to measure general practitioner (GP) contact
Louise Nash, Jo Gorrell, Chris Tennant, Viv Miller, but this was unreliable, therefore we looked at whether
Alan Rosen, University of Sydney, Royal North Shore the GP name was at least recorded in the file and this
Hospital, New South Wales, Australia: increased significantly.
Re: Changes in early psychosis service provision: a file Dr Pelosi appears to regard group therapy as an im-
audit (Gorrell J et al.) [1] portant aspect of care, and our early intervention teams
526 CORRESPONDENCE

were more likely to provide this aspect of care. Forty-five Dr Pelosis central concern is that in the UK resources
per cent of patients who received at least some treat- are being diverted from general psychiatric services to
ment from an EP team versus 12% of those who did not, early intervention teams. Our subteams were formed
participated in a group program. In our service, it would without additional financial resources and are seen as an
be more difficult to run appropriate group programs enhancement to our service, not a diversion. We would
for these patients in the generic teams than in the spe- certainly advocate that any subteam be resourced as we
cialist teams. This is clearly different from Dr Pelosis understand has been planned in the UK. It is not a mat-
experience. ter of generic service versus functional subteam, it is a
With regard to admission rates, Dr Pelosi appears to matter of both [3].
have misunderstood our results as he thought that there
was a lower admission rate for patients under the care of
generic teams. Our paper states that patients for EP teams References
1. Gorrell J, Cornish A, Rosen A, Tennant C, McKay D, Nash L.
were more likely to have had an admission before their What are we doing differently? Changes in early psychosis
referral to the EP team. We believe that the method and service provision: a file audit. Australian and New Zealand
the results of the file audit study are robust. Journal of Psychiatry 2004; 38:687693.
Dr Pelosis point of subspecialist teams fracturing con- 2. Nash L, Gorrell J, Cornish A, Tennant C, Rosen A. Clinical
outcome of an early psychosis intervention programme:
tinuity of care is an important concern, and one that evaluation in a real-world context. Australian and New Zealand
echoes concerns of our staff in our staff surveys of at- Journal of Psychiatry 2004; 38:694701.
titude to the changes. However, as the changes were 3. Rosen A. Australia from colonial rivalries to a national mental
health strategy. In: Thornicroft G, Tansella M, eds. Mental health
implemented and as the education program continued
matrix. Cambridge: Cambridge Univerity Press, 2000.
(available to all staff), this level of concern diminished
[Gorrell J, Cornish A, Tennant C, Rosen A, Miller V,
Nash L: unpublished data]. The smaller caseloads al- Potential risks associated with high-dose val-
low for good integration of services of crisis, inpatient proate in pregnancy in psychiatric patients
and continuity of care phases. The teams do not detract
from our service but add to it. Despite this, we have in- F.J.E. Vajda, Monash University and Medical Cen-
creased the period of time from 18 months to 3 years tre, Australian Centre for Clinical Neuropharmacology,
that patients spend in the early psychosis teams. At the Raoul Wallenberg Centre, University of Melbourne; Aus-
end of 3 years patients are referred either to their GP, tralian Registry of Pregnancies on Antiepileptic Drugs;
the community mental health teams or private psychi- Epilepsy Society of Australian, Carlo Solinas, Neuro-
atrists, or in one of the EP teams the person may stay sciences, St. Vincents Hospital, Melbourne, Australia:
in treatment with the EP team while they need intensive We summarize information presented at recent inter-
care. national meetings, of the Australian Pregnancy Registry
The final question is: did these service changes transmit for Women on Antiepileptic Medications, based at Mel-
to better patient outcomes? Throughout the study period bourne University [14].
(i.e. at the early phase of change in 1997, up to the end The relevance of psychiatrists arises because anti-
of the study with greater change occurring in 2000), all epileptic drugs (AEDs) are increasingly employed in
young people receiving treatment for first-episode psy- treating bipolar disorder and depression. A few psychi-
chosis gained significant improvement in their symptoms atric patients are enrolled in the Registry and they may
during the first 3 months of treatment and the gains were not be aware of the risks associated with a high dose of
maintained at 12 months on all measures. A compari- valproate (VPA) (doses above 1100 mg day1 ).
son of 12-month data between people treated early in the Over 800 women are represented in the Registry, of
project compared with those treated late in the project which 565 have completed their pregnancy. The fetal
found a lower level of negative symptoms. Dr Pelosi high- malformations (FMs) rate for infants was significantly
lights our small sample size for this part of the study. We, higher for the VPA than for any other AEDs.
too, are aware of this limitation and discuss these includ- It has been suggested that polytherapy was more detri-
ing the small return of all questionnaires, the complex mental in causing FMs than monotherapy. It may be that
consent process and the fact that we were reliant on the the VPA component of polytherapy is the main factor
case managers to coordinate the questionnaires on top of causing FMs, rather than polytherapy itself.
their other work. Were our method and results limited Lamotrigine (LTG) monotherapy (n = 62) was not as-
in the outcome paper? Undoubtedly. Was our experience sociated with a single FM compared to those patients
worthy of discussion and publication for other services taking VPA monotherapy (n = 115, FMs = 19). Even in
to consider? We think so. LTG polytherapy only four patients had outcomes with
CORRESPONDENCE 527

FMs. In these cases, a high-dose VPA component could that in bipolar disorder, efficacy of LTG in pregnancy
be identified. may be less than that of VPA.
Lamotrigine has been approved for treating bipolar dis- Lamotrigine plasma levels may need to be monitored.
orders and from the fetal safety point of view, it may Lamotrigine takes 6 weeks after introduction to reach
represent a suitable option. recommended doses and plasma concentrations.
The relative safety of the four most commonly used At present the use of these two drugs pose a dilemma
drugs in pregnancy indicates the risks of high dose VPA. for doctors using VPA and LTG.
Monotherapy figures show a risk with carbamazepine If a change was to be made on the grounds of fetal
(3.8%), phenytoin (5.9%) not significantly different from safety, the replacement of VPA with LTG may require
untreated women (2.5%), no malformations noted at this individual planning before conception, to get the best
stage with LTG- and VPA-related risks, all doses were results in bipolar disorder.
16.5.% (p < 0.04).
With doses of VPA of 1100 mg day1 , there was a sta-
tistically high significant increase in the risk of a fetal
outcome with a malformation (15/39, 30.5%), compared References
1. Vajda FJE, Lander CM, Cook M et al. Report of the Australian
to that in untreated women (1/40) (p < 0.0002). This was
Pregnancy Registry of women on antiepileptic drugs after 52
not noted at doses below 1100 mg day1 . months. European Journal of Neurology 2004; 11(Suppl 2):21.
In terms of efficacy against seizures, the safety of LTG 2. Vajda F, Lander C, OBrien T et al. Australian Pregnancy
is not matched by effectiveness in pregnancy. Although Registry of women on antiepileptic drugs. Epilepsia 2004;
45:1.
the Registry is not a formal randomized trial, seizures 3. Vajda FJ, Lander CM, Cook M et al. Australian Registry of
were statistically significantly more frequent in patients Pregnancy of women on antiepileptic drugs [Abstract]. Journal of
treated with LTG monotherapy than with VPA. A selec- Neurology 2004; 251(Suppl 3):48.
tion bias and small numbers may affect this result. Under- 4. Vajda FJE, OBrien TJ, Hitchcock A et al. Critical relationship
between sodium valproate dose and human teratogenicity: results
dosing due to a fall in LTG plasma levels in each trimester of the Australian register of antiepileptic drugs in pregnancy.
and induction to LTG metabolism by hormones associ- Journal of Clinical Neuroscience 2004 (in press) (available on
ated with pregnancy are likely. It is possible, however, line).

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