European Neuropsychopharmacology 15 (2005) 399 – 409
www.elsevier.com/locate/euroneuro
Size of burden of schizophrenia and psychotic disordersB
Wulf Rösslera,*, Hans Joachim Salizeb, Jim van Osc, Anita Riecher-Rösslerd
a
Psychiatric University Hospital, Militärstrasse 8, CH-8021 Zurich, Switzerland
b
Central Institute of Mental Health, Mannheim, D, Switzerland
c
Department of Psychiatry and Neuropsychology, Maastricht University, NL, Switzerland
d
University Psychiatric Outpatient Department, University Hospital Basel, CH, Switzerland
Abstract
Schizophrenia is a severe mental disorder characterised by fundamental disturbances in thinking, perception and emotions. More than 100
years of research have not been able to fully resolve the puzzle that schizophrenia represents. Even if schizophrenia is not a very frequent
disease, it is among the most burdensome and costly illnesses worldwide. It usually starts in young adulthood. Life expectancy is reduced by
approximately 10 years, mostly as a consequence of suicide. Even if the course of the illness today is considered more favourable than it was
originally described, it is still only a minority of those affected, who fully recover. The cumulative lifetime risk for men and women is similar,
although it is higher for men in the age group younger than 40 years. According to the Global Burden of Disease Study, schizophrenia causes
a high degree of disability, which accounts for 1.1% of the total DALYs (disability-adjusted life years) and 2.8% of YLDs (years lived with
disability). In the World Health Report [The WHO World Health Report: new understanding, new hope, 2001. Geneva], schizophrenia is
listed as the 8th leading cause of DALYs worldwide in the age group 15 – 44 years. In addition to the direct burden, there is considerable
burden on the relatives who care for the sufferers. The treatment goals for the moment are to identify the illness as early as possible, treat the
symptoms, provide skills to patients and their families, maintain the improvement over a period of time, prevent relapses and reintegrate the
ill persons into the community so that they can lead as normal a life as possible.
D 2005 Elsevier B.V. and ECNP. All rights reserved.
Keywords: Psychosis; Schizophrenia; Epidemiology; Burden; Costs; Gender differences; Early detection
1. Introduction
Schizophrenia and psychotic disorders are combined in
the chapter F2 of the International Classification of Diseases
(ICD-10). It is a heterogeneous category, mainly merged for
practical reasons. The most frequent and most important
illness group is schizophrenia. This illness entity was first
described by Emil Kraepelin (1896). He separated schizophrenia from manic-depressive illness, initially naming the
B
This paper was prepared in the framework of the European College of
Neuropsychopharmacology (ECNP) Task Force project on ‘‘Size and
Burden of Mental Disorders in Europe’’ (PI: Hans-Ulrich Wittchen)
supported by funds of the ECNP Council and the European Brain Council
(EBC; http://www.ebc-eurobrain.net) Initiative ‘‘Cost of Disorders of the
Brain in Europe’’ (CDBE; steering committee: Jes Olesen, Bengt Jönnson,
Hans-Ulrich Wittchen).
* Corresponding author. Tel.: +41 1 296 74 00; fax: +41 1 296 74 00.
E-mail address: [email protected] (W. Rössler).
syndrome ‘‘Dementia praecox’’. The term schizophrenia,
not introduced until 1911, was coined by Eugen Bleuler
(1911).
More than 100 years of research have not been able to fully
resolve the puzzle that schizophrenia represents, but much
progress has been booked over the last two decades.
Schizophrenia behaves epidemiologically like other complex
disease phenotypes, such as diabetes and cardiovascular
disease, in that the disease tends to cluster in families; yet
genetic factors appear to be neither necessary nor sufficient to
produce illness onset (Murray et al., 2003). Thus, the
causation of schizophrenia involves multiple interactions
between genes and environment over the life course (van Os
and Marcelis, 1998) –probably often starting as early as fetal
life (Susser et al., 1999) –and leaving traces in the early
social, motor and cognitive development of children later
destined to develop schizophrenia (Jones et al., 1994). Fourfifths of the differences in liability to schizophrenia are
0924-977X/$ - see front matter D 2005 Elsevier B.V. and ECNP. All rights reserved.
doi:10.1016/j.euroneuro.2005.04.009
400
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
attributable to genes and the first probable risk genes have
been identified, although their function remains unclear
(Harrison and Owen, 2003). Their effects are small and
many may be involved. They are likely to interact with
environmental exposures that impact on the individual over
the life course, such as fetal hypoxia (Cannon et al., 2002), the
proxy environmental risk factor: season of birth (Mortensen
et al., 1999), adverse rearing environments (Tienari et al.,
2004), the stresses of urban life during upbringing (van Os et
al., 2003, Spauwen et al., 2004), cannabis use (Verdoux et al.,
2003), stress in daily life (Myin-Germeys et al., 2001) and a
minority position (Hutchinson et al., 1996). The causes of
schizophrenia impact on brain development, as evidenced by
a small reduction in the volume of grey matter (Wright et al.,
2000) that appears to progress over time, and may be linked to
social deterioration, use of medication or factors intrinsic to
the disease itself (Cahn et al., 2002, Ho et al., 2003a,b).
2. Incidence and prevalence of schizophrenia
Schizophrenia occurs worldwide. Incidence seems to be
very similar worldwide, at least if schizophrenia is narrowly
defined, i.e. with a nuclear schizophrenic syndrome consisting mainly of first-rank systems at onset (Sartorius et al.,
1986; Jablensky et al., 1992). With a wider disease concept,
reported rates vary between and within countries. From the
lowest (0.3 per 1000) to the highest (22 per 1000) (Torrey,
1987; Hovatta et al., 1997) prevalence rates, there are more
than 50-fold variations, with differences being due partly to
differing observation times and methodology, and partly to
true differences (see Wittchen and Jacobi, 2005). Lifetime
prevalence has been reported in the range of 0.5% to 1.6%;
i.e. out of 100 individuals, about one will experience a
schizophrenic episode in his lifetime (Jablensky, 1995).
Concerning European prevalence rates, a recent German
survey (Wittchen et al., 2000; Jacobi et al., 2004) names a
12-month prevalence rate of 26 cases and a lifetime
prevalence of 45 cases for having any psychotic syndrome
per 1000 population of 18 –65 years. Psychotic syndromes
as defined in this study include schizophrenia, schizoaffective, delusional disorders as well as psychotic syndromes
occurring in the course of depressive and bipolar disorders.
The Munich Follow-up Study (Wittchen et al., 1992) found
a lifetime prevalence rate of 7 per 1000 for schizophrenia
and schizophreniform disorder. In a Dutch survey, the
lifetime prevalence rate for schizophrenia was 4 and the 12month prevalence rate 2 per 1000 (Bijl et al., 1998). Jenkins
et al. (1997) found in a household survey in Great Britain a
1-year prevalence of 4 per 1000 (including psychotic
disorders according to ICD-10 chapters F20 and F30).
As regards incidence rates, the ‘‘Determinants of Outcome
of Severe Mental Disorders’’, DOS Study by the WHO was
one of the first methodologically sound, representative
studies on worldwide incidence rates for schizophrenia
(Jablensky et al., 1992; Sartorius et al., 1986). Departing
from a narrow schizophrenia concept, between 0.7 and 1.4
cases per 10,000 population were found to arise in 1 year.
Based on a wider concept, the incidence was 1.6 to 4.2 cases
per 10,000 population and per year. These figures correspond
well to those found in the German ABC Study, which was one
of the first representative European studies on all firstadmitted patients from a defined catchment area. It found
incidence rates of 1.7 per 10,000 and year for ICDschizophrenia only and 1.9 per 10,000 and year using a
wider disease concept that also included paranoid disorders
(Riecher-Rössler et al., 1997).
Independent of variations in incidence rates, recent
research suggests that the incidence of schizophrenia may
be declining. Such a decline, for example, was reported by
Suvisaari et al. (1999). Based on the Finnish population
register between 1954 and to 1965, they found for each
successive cohort a decline from 0.79 to 0.53 per thousand
among males and from 0.58 to 0.41 per 1000 among females.
One of the reasons might be the conceptual narrowing of
schizophrenia, evidence for which was provided in a recent
study (Allardyce et al., 2000).
On the other hand, epidemiological surveys report
prevalence rates of hallucinatory and delusional experiences
in the general population of between 10% and 15% (Johns
and van Os, 2001). These symptoms, although not yet of
clinical relevance or associated with substance abuse,
obviously do have strong predictive power for the onset of
clinical psychotic disorders later in life (Poulton et al., 2000).
3. Course
In his first descriptions, Kraepelin expressed a very
pessimistic view of the course of the illness. He was of the
opinion that the illness follows a path of continuous
progression with persistent and serious symptoms in over
70% of the cases. Today, we know that this poor course was
mainly due to Kraepelin’s selected samples of long-term
hospitalised patients living in the deprived environment of
isolated asylums. Since then, numerous studies have shown
a better course. Hegarty et al. (1994) identified a total of 821
studies on the course of schizophrenia that were carried out
between 1895 and 1992: Of these, 320 satisfied methodological standards. In this meta-analysis, 40.2% of the
patients were considered to have improved after followups averaging 5.6 years. The proportion of patients who
improved increased significantly after mid-century. In the
1980s, the outcome seemed to deteriorate again. However,
this finding was probably mainly an artefact, reflecting the
re-emergence of narrow diagnostic concepts.
The largest studies on the course of schizophrenia have
been coordinated by the WHO. Within the framework of the
so-called ‘‘Disability Study’’, An der Heiden et al. (1995)
conducted a 14-year follow-up assessment of the German
sample in Mannheim. About one third of the patients still
showed delusions or hallucinations. Almost the same
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
number suffered from psychological impairments and two
thirds were socially disabled.
The Nottingham sub-sample of the WHO-‘‘DOS Study’’
(see above) has been followed-up over 14 years. Of that
sample, 18% never relapsed and 25% were never readmitted. However, 33% of the cohort experienced psychotic
symptoms almost continuously. At the 13-year follow-up, as
many as 44% of the patients were found to have recovered
or be only mildly impaired (Mason et al., 1996).
Apart from some well-known American studies, e.g. the
‘‘Iowa 500 Study’’ (Tsuang et al., 1979), the ‘‘Chestnut Lodge
Study’’ (McGlashan, 1984a,b) or the ‘‘Vermont Study’’
(Harding et al., 1987a,b), there are only a few European
studies that have provided prospective and standardised data
on representative samples of first-admitted patients.
One of these is the ‘‘Buckinghamshire Study’’ by
Shepherd et al. (1989). Twenty-two percent of his patients
remained symptom-free over 5 years following the first
admission. Thirty-five percent developed further discrete
episodes, but were free of psychotic symptoms between
episodes. Eight percent had persistent florid symptoms with
one or more exacerbations, and suffered from stable residual
psychopathology between episodes. Thirty-five percent
showed the same florid picture, with increasing impairment
after each episode.
It has been repeatedly demonstrated that schizophrenia
follows a more severe course in industrialised countries like
Europe, as opposed to developing countries (Thara and
Eaton, 1996). For example, in the WHO-DOS Study, the
proportion of patients showing full remission at 2 years was
63% in developing countries, compared to 37% in developed
countries (Jablensky et al., 1992). Though attempts have
been made to explain this better outcome on the basis of
stronger family support and fewer demands on the patients,
the exact reasons for these differences are not clear.
Social functioning is another indicator of the course of
illness. With respect to that indicator, more than one third
of the patients of the ‘‘Determinants of Outcome Study’’
showed no sign of disability during at least three quarters
of the observation period and only less than one third
suffered more or less severe impairments during the entire
2 years. Shepherd et al. (1989) rated social impairment
after 5 years. Of their patients, 45% showed only minimal
impairment, 43% mild to moderate and 12% severe
impairment. In their ability to work, 24% of patients were
mildly to moderately impaired and 16% impaired. Almost
half of the patients were mildly to moderately disturbed in
their leisure and social skills, and 15% severely disturbed.
Finally, in family relationships, there were mild to
moderate problems for 36% and severe problems for
14% of the patients. In the ‘‘ABC Study’’ (Häfner et al.,
1995, 1998), it was shown that these impairments often
already occur in the early preclinical course of the disease.
As compared with their peers, these often very young
patients frequently lag behind in their social development
from the start.
401
The course of the illness has been found to be better in
women (also see below), in patients who had an acute,
stress-related onset of their illness, low levels of negative
symptoms, higher social class, better premorbid social
development and no evidence of cannabis use (Kelly et
al., 2001).
4. Burden
The burden of schizophrenia is large and multifaceted.
Headmost, there are the direct costs of providing care for
individuals with schizophrenia. The indirect costs encompass the loss of productivity through impairments, disability
and premature death, burden on caregivers, as well as some
legal problems—including violence.
One specific aspect of burden is the health burden, which
has preferably been measured in national and international
health statistics in terms of incidence/prevalence and
mortality. While these indicators are well suited for acute
diseases that either cause death or result in full recovery, their
use for chronic and disabling diseases, like schizophrenia is
limited. One way to account for the chronicity of disorders
and the disability they cause is the Global Burden of Disease
(GBD) methodology. GBD introduced a new metric called
disability-adjusted life year (DALY) to quantify the burden
of diseases. DALY combines information on the impact of
mortality (years of life lost because of premature death = YLL) and disability (years lived with disability = YLD). One
DALY can be thought as one lost year of ‘‘healthy’’ life.
According to the Global Burden of Disease Study (Murray
and Lopez, 1996, 1997), schizophrenia causes a high degree
of disability that accounts for 1.1% of the total DALYs and
2.8% of YLDs. In the World Health Report (2001),
schizophrenia is listed as 8th leading causes of disabilityadjusted life years worldwide in the age group 15– 44.
However, there are concerns about the universality of the
disability weights used. Therefore, Üstün et al. (1999)
undertook a study to investigate the stability of such
weighting in different countries and informant groups. In
their 14-country study on disability associated with physical
and mental conditions, active psychosis was ranked the third
most disabling condition, higher than paraplegia and
blindness, by the general population (Üstün et al., 1999).
A further study, based on the Global Burden of Disease
Study, assessed the degree of dependency, i.e. the need for
daily assistance from another person in carrying out health,
domestic or personal tasks. Again, active psychosis was
ranked in the highest disability class, requiring daily care
(Harwood et al., 2004).
5. Mortality
Globally, schizophrenia reduces an affected individual’s
life span by on average 10 years (World Health Report, 2001).
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
Mortensen and Juel (1993) analysed case-register data of
9156 patients with schizophrenia. They found that, compared
to the age-standardised general population, the relative
mortality risk of male schizophrenia patients was increased
4.7-fold and that of female patients 2.3-fold. This increased
mortality seems to be due mainly to suicide. A recent study
showed that 30% of patients diagnosed with schizophrenia
had attempted suicide at least once during their lifetime
(Radomsky et al., 1999). About 10% of the patients die by
suicide (Caldwell and Gottesman, 1990).
Hiroeh et al. (2001) also recorded an increased risk of
dying by homicide in men with schizophrenia. Furthermore,
individuals with schizophrenia show an increased morbidity
due to natural causes (Hewer et al., 1995, Hewer and
Rössler, 1997), which certainly also contributes to their
increased mortality.
6. Burden on patients, families and communities
Schizophrenia has a large impact, not only on
individuals, but also on families and communities.
Individuals suffer primarily from the distressing symptoms
of disorders. They also lack self-esteem because they are
unable to participate in work and leisure activities, often
not only as a result of disability, but also because of the
stigma and discrimination. Not quite unjustified, they
additionally worry about being a burden for others.
The burden on families ranges from emotional reactions
to the illness, the stress of coping with disturbed behaviour,
the disruption of household routine, the stigma they too are
confronted with and the restriction of social activities, to
economic difficulties. Restriction of involuntary hospital
admission and reduced lengths of hospital stay can further
increase the burden on relatives. In a study by Lauber et al.
(2003), the most important predictor of the burden on
relatives was the distress and changes in the relationship
between caregiver and the affected individual that occur
during acute illness. Threats, nuisances, time spent with the
affected one and restricted social life and leisure activities
were additional predictors. Despite their burden, relatives
do not complain much, although they sometimes receive
little support, advice or information from the professionals
engaged in treating the respective patient (Fadden et al.,
1987).
If one converts relatives’ time and effort of caring for
their affected ones during acute illness into euro, the sum
of money amounts roughly to the expenses of inpatient
treatment (Lauber et al., in press). In a study conducted by
Magliano et al. (2002), (reduced) family burden was
associated with professional and social network support
received by the family. Thus, professional and social
network support represents a crucial resource to reduce
family burden in schizophrenia. Mental-health services
should therefore aim to assist key caregivers for people
with chronic schizophrenia to manage stress, whether or
No family intervention
Family intervention
60
Patients relapsing (%)
402
50
40
30
20
10
0
A
B
C
D
E
Fig. 1. Effect of family intervention on relapse rate. A= Goldstein et al.
(1978); B = Leff and Vaughn (1981); C = Falloon et al. (1982); D = Hogarty
et al. (1986); E = Tarrier et al. (1988).
not the patient lives in the same household as the caregiver
(Laidlaw et al., 2002).
In addition to the direct burden, hidden burdens have to
be taken into account. Based on data from the U.S.
National Health Survey, Gallagher and Mechanic (1996)
compared respondents living with the mentally ill with
randomly selected respondents not living with anyone
mentally ill concerning health outcomes. They found that
sharing a household with someone who is mentally ill is
associated with poorer self-reported physical health,
increased reporting of activity limitation, increased service
utilisation and other negative consequences.
The social and emotional environment within the family
has been found to correlate with relapses in schizophrenia.
This led to research on the cause of this phenomenon.
Most studies have used the concept of ‘‘expressed
emotions’’. It describes the attitude and behaviour of
family members towards the individuals with schizophrenia, especially critical comments, hostility, lack of warmth
or emotional over-involvement. A large number of studies
have demonstrated in the meantime that expressed emotions can predict the course of schizophrenia, including
relapses (Butzlaff and Hooley, 1998). Some studies have
shown that a combination of regular medication, family
education and family support can reduce the rate of
relapses from 50% to less than 10% (Fig. 1).
7. Legal problems
It is a longstanding public belief that schizophrenia is
associated with an increased risk of violence. In fact,
Angermeyer (2000), in a meta-analysis of studies from the
1990s, found that there is an increased risk of violence in
terms of odds ratios between 4 and 8 predominantly for men
with schizophrenia. This risk is even more elevated if there
is comorbid substance abuse. Nevertheless, there is only a
negligible – but possibly growing– proportion (Munk-Jörgensen, 1999) of community violence that could be
attributed to schizophrenia. Nearly all victims of schizo-
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
Table 1
Rates of involuntary placements for mental disorder in European Union
countries per 100,000 population
Austria
Belgium
Denmark
Finland
Germany
Ireland
Luxemburg
The Netherlands
Portugal
Sweden
United Kingdom
175
47
34
218
175
74
93
44
6
114
48
(1999)
(1998)
(2000)
(2000)
(2000)
(1999)
(2000)
(1999)
(2000)
(1998)
(1999)
Data source: Salize and Dressing (2004).
phrenic offenders can be found among the closest relatives.
It therefore does not surprise that, among all psychiatric
patients, it is especially single males with schizophrenia
who are compulsorily admitted (Riecher et al., 1991). In a
representative survey in Switzerland, we could show that
this is in line with the general public’s attitude: about 70%
of the respondents agreed to compulsory admissions in case
of serious mental illness (Lauber et al., 2000). Nevertheless,
there are considerable differences in rates of compulsory
admission between different European countries (RiecherRössler and Rössler, 1993; Salize and Dressing, 2004),
which is by no means justified by objective reasons, but due
more to differing legislation (Table 1).
8. Stigma
Negative attitudes towards the mentally ill, especially
towards persons with schizophrenia, are widespread (Stuart
and Arboleda-Florez, 2001). Individuals with schizophrenia
are looked at frequently as being dangerous and unpredictable (Angermeyer and Matschinger, 2003). Many media
reports reflect this fear; even if, in reality, a potential risk is
mainly directed to the closest relatives (see above). This,
and other stigmata attached to schizophrenia, creates a
vicious cycle of discrimination leading to social isolation,
unemployment, drug abuse, long-lasting institutionalisation
or even homelessness—all factors that further decrease the
chances of recovery and reintegration into normal life, in
addition to the often-deleterious consequences of the illness
itself.
On the basis of comprehensive research in this area
during the last decade, several strategies were developed to
fight stigma and discrimination because of schizophrenia.
Within the framework of the global anti-stigma program
‘‘Open the Doors’’ of the World Psychiatric Association,
different research centres developed interventions directed
to specific target groups relevant for de-stigmatisation—e.g.
students (Meise et al., 2000) or police officers (Pinfold et al.,
2003). Interestingly, contact with the mentally ill seems to
reduce social distance (Lauber et al., 2004) and predict a
403
more positive attitude, which is a strong argument in favour
of community psychiatry.
9. Cost
Although the financial aspects of schizophrenia only
became an issue of psychiatric research within the general
discussion concerning cost containment in health care, there
is meanwhile enough evidence that schizophrenia has
serious financial consequences for the patients, their
relatives and the national economy (Rössler et al., 1998).
Psychotic disorders are considered to be the most expensive
mental illnesses in terms of costs of care per patient,
accounting for 1.5% (UK), 2% (the Netherlands, France) or
2.5% (USA) of national health expenditures during the
1980s or 1990s (Knapp, 1997; Evers and Ament, 1995;
Rouillon et al., 1994; Rupp and Keith, 1993). A most recent
calculation estimated 1.3% health expenditures for schizophrenic patients in Germany in 2002 (Statistisches Bundesamt, 2004). Among all psychiatric disorders, only
treatment and care for patients suffering from alcoholism
or dementia might claim a greater proportion of the health
care budgets of industrialised societies, but only due to a
higher prevalence of these illnesses.
However, most cost-figures represent only expenditures
for treated schizophrenic patients within the national health
care systems. Although there are considerable efforts by the
WHO and others to estimate the coverage and efficacy of
mental health care worldwide, the proportions of schizophrenic patients who are treated in the national primary care
or mental health care sectors, and how many remain
untreated, is widely unknown. Only few studies assessed
service use by schizophrenic patients. Estimates from the
Epidemiological Catchment Area Program in the US show a
1-year service-use rate of about 60% of individuals with
schizophrenia (Regier et al., 1993). Most probably, these
proportions may vary with the specific conditions of the
national health care systems.
The economic impact of schizophrenia is caused by the
specific symptoms and characteristics of the disease as
described above (e.g. early onset, frequently chronic course,
early retirement, excess mortality, frequent readmissions to
hospital treatment, high rate of disability, comprehensive
rehabilitative needs). Although these characteristics imply
enormous productivity losses, family financial burden and
overall societal costs, little empirical data is available on
secondary expenditures for schizophrenia. Its share of
indirect costs is considered considerably higher than that
for all other mental illnesses, which is estimated to be
between 40% and 50% of the total financial burden for the
economy.
Due to methodological problems, cross-national or panEuropean studies aiming at standardised cost estimates are
scarce, with only one study published during recent years
(Knapp et al., 2002). Results from this study revealed
404
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
UK pounds
10000
7460
7500
6771
5730
5000
5038
4112
2500
1444
0
Amsterdam
(n=61)
Copenhagen
(n=52)
London (n=84)
Santander
(n=100)
Verona (n=107)
all sites
(n=404)
Fig. 2. Service cost comparisons for schizophrenic patients in five European
countries—average direct cost of mental health care per annum and patient.
1998 prices, UK currency (English pounds). Costs were adjusted for centre,
gender, marital status, ethnicity, language, employment, age, education,
GAF and BPRS. Data source: The Epsilon Study (Knapp et al., 2002).
considerable differences in the annual cost of care per
patient (Fig. 2) between and within different countries
(ranging from 2215 euros in Santander, Spain to 14,127
euros in Copenhagen, Denmark (unadjusted means, in 1998
prices)). Several national studies report a comparable (Salize
and Rössler, 1996), even higher average annual cost of care
(e.g. 18,038 euros for Germany, Salize and Stamm, 2004).
These large differences are caused by several factors, mainly
varying mental health care systems and quality standards of
care (Salize et al., 1999).
Along with problems in evaluating the direct or indirect
costs of schizophrenia, the cost-effectiveness analysis of
essential aspects of care for schizophrenia patients is even
more underdeveloped. There is a wide field of special
treatments or care strategies in schizophrenia that whose
cost impacts are worth analysis, i.e. quality of life in
different treatments settings (Rössler et al., 1999). Nonetheless, cost-effectiveness research in schizophrenia has
focused almost exclusively on pharmacological treatments,
largely triggered by an ongoing international debate on the
efficacy of so-called atypical neuroleptics, which are much
more expensive than conventional drugs (Knapp, 2000).
10. Treatment
The treatment of schizophrenia rests on three main
pillars. Firstly, there are medications to relieve symptoms
and prevent relapse. Secondly, psychosocial interventions
help patients and families to cope with the illness, and aim
at preventing relapses. Thirdly, rehabilitation helps to
reintegrate patients into the community and helps them to
regain occupational functioning. The challenge in the care
of people suffering from schizophrenia is the need to
coordinate services, from early identification to regular
treatment and rehabilitation. Currently, few patients with
schizophrenia need long-term hospitalisation.
Antipsychotic medication has proved useful in reducing,
and often eliminating, acute symptoms of schizophrenia,
such as hallucinations and delusions. Medication status is
the strongest predictor for relapse. Discontinuation of
medication seems to increase the relapse risk about fivefold
(Robinson et al., 1999).
Psychosocial intervention and rehabilitation for people
with schizophrenia encompass a variety of measures from
skills training or family interventions, to supported employment. The interactions between medication and psychosocial treatments appear to be more than merely additive, since
each can enhance the effects of the other. Recent studies
using newer antipsychotics suggest that these agents
improve the participation of patients in psychosocial
treatments (Marder, 2000). Four cognitive-behavioural
approaches have emerged as being especially effective as
adjuncts to pharmacotherapy, i.e. the training of social skills,
cognitive training programs for the remediation of neurocognitive deficits, psychoeducative, coping-orientated interventions with patients and their families, and cognitivebehavioural therapy of residual symptoms (Brenner and
Pfammatter, 2000).
With respect to the delivery of treatment and care, the
process of deinstitutionalisation has led to fragmentation of
services in the community. Lack of coordination and
cooperation between services is the result and is one of
the main reasons for the revolving-door phenomenon. Better
coordination and cooperation are the major objectives of
case management. However, research on case management
is not conclusive. This might be due among others to the
evident significant influence of national culture, both in the
acceptability of case management and in approaches to
researching it (Burns et al., 2001).
11. Early detection
Early detection and therapy of schizophrenic psychoses
has become widely accepted goal in psychiatry. For
example, the UK Government has decided to invest
systematically in early detection and intervention, as ‘‘the
rationale for early intervention is overwhelming’’ (Pelosi
and Birchwood, 2003).
Whereas until some time ago early diagnosis and
intervention in schizophrenia concentrated on clear-cut,
frank schizophrenia, during recent years some centres have
also started to treat patients, even before a clear diagnosis
has been established. However, reliable methods for an early
detection already in this phase of beginning schizophrenia
do not yet exist, and the evidence base for treatment on the
basis of psychosis-like experiences in the general population
is thin (Hanssen et al., 2003).
Thus, one of the key questions for now is whether, and at
what stage, early intervention, such as treatment with lowdose atypical neuroleptics, is indicated. This question
confronts researchers and clinicians with the ethical
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
dilemma of diagnosing/treating this disorder either too early
or too late. On the one hand, the disease process can be very
devastating already in the early prodromal stages (Häfner et
al., 1991a,b; Riecher-Rössler et al., in press). On the other
hand, it is important not to diagnose/treat too early because
of the potential identification of ‘‘false positives’’, the stigma
associated with the diagnosis or the potential side effects of
treatment (Larsen et al., 2001; Malla and Norman, 2002;
McGorry, 2002; Verdoux and Cougnard, 2003; RiecherRössler et al., in press).
The rationale for early detection of schizophrenia is
based on several observations:
& Diagnosis and treatment of schizophrenia are often
seriously delayed. Thus, patients on average suffer from
productive psychotic symptoms such as delusions or
hallucinations for an average of 1– 3 years before this
disorder is diagnosed and treated for the first time
(duration of untreated psychosis, DUP). In addition, even
before then, patients suffer from an ‘‘unspecific prodromal phase’’ for an average of 2 –5 years (duration of
untreated illness, DUI) (for reviews, see e.g. Norman and
Malla, 2001; Bottlender and Möller, 2003; RiecherRössler et al., in press).
& Consequences of the disease are very severe already in
the early preclinical, undiagnosed phase of the disorder.
Even before first admission, most patients already suffer
from serious impairments and losses in various social
domains, such as education, work, partnership or
independent living (Häfner et al., 1995). Recent studies
have also shown that the quality of life is seriously
impaired already at first admission and is associated with
DUP (Browne et al., 2000).
& Early treatment seems to improve the course of the
disease. There is a large body of evidence that the early
treatment of psychosis can substantially improve the
course and outcome of the disease (for reviews, see e.g.
Norman and Malla, 2001; McGorry, 2002; Harrigan et
al., 2003; Riecher-Rössler et al., in press). Thus, the
majority of studies found a statistically significant
correlation between a long duration of untreated psychosis (DUP) and a poor outcome.
The mechanisms by which DUP influences outcome
could be manifold. Thus, ongoing psychosis could have
direct ‘‘neurotoxic’’ effects, including neurodegeneration
with symptomatic progression (Lieberman et al., 2001,
Stahl, 2002) and cognitive deterioration (Amminger et al.,
2002), although there are also studies that do not support
this theory (e.g. Ho et al., 2003a,b). In any case, it is quite
clear that the early treatment of frank psychosis can
substantially ameliorate symptoms and shorten psychotic
episodes (for review, e.g. Norman and Malla, 2001), and
thereby avoid, or at least ameliorate, the immediate negative
psychological and social consequences. Therefore, it can be
stated quite safely that patients should be treated as early as
405
possible as soon as frank psychosis has occurred. However,
detection and treatment of the disorder even before that
raises a number of questions that have not been sufficiently
addressed as yet.
12. Gender issues
Gender differences in schizophrenia are well known. In
particular, differences in age at onset have been confirmed
in many studies. Less consistent are the findings
concerning differences in symptomatology and the course
of the disease, which might be due partly to methodological problems in earlier studies (for review, see RiecherRössler and Häfner, 2000; Riecher-Rössler and Rössler,
1998).
Methodologically sound studies (e.g. Sartorius et al.,
1986; Jablensky et al., 1992; Salokangas and Stengård,
1990; Häfner et al., 1989, 1993a,b) consistently showed a
higher age of onset in women than in men. The average
difference of 3.5 –6 years was already evident at the first
onset of early symptoms of the disease and was found in
almost all cultures investigated.
The cumulative lifetime risk for men and women seems
to be identical (Häfner et al., 1991a,b), although this has
been questioned by a recent meta-analysis that, however,
was based mainly on studies excluding older age groups
(Aleman et al., 2003). In fact, men seem to show their peak
of onsets in their early twenties and women theirs only in
their late twenties; and there is a second, smaller peak of
onsets in women after age 45 (Häfner et al., 1989, 1993a).
Gender thus has no stable influence on the outbreak of the
disease, but this influence is modulated by age—a finding
that could be explained by a presumably protective effect of
estrogens (Riecher-Rössler and Häfner, 1993; RiecherRössler, 2003).
As to symptomatology, it has often been reported that
negative symptoms occur more frequently in men and
affective symptoms more often in women. More recent
studies have not consistently confirmed these findings (for
review, see Riecher-Rössler and Häfner, 2000). Thus,
gender differences in negative and affective symptoms seem
to disappear if the sample is restricted to narrowly defined
schizophrenia or to higher age groups. The few differences
still found obviously have more to do with illness behaviour
than with core symptomatology.
Women seem to have a more favourable course and a
better psychosocial ‘‘outcome’’ than men (for review, see
Riecher-Rössler and Rössler, 1998; Riecher-Rössler and
Häfner, 2000). Their hospital stays were fewer and shorter,
and their social adjustment and living situation better than
those of men, whereas the symptom-related course seems to
be similar for both genders. Women’s mortality is also
lower, due mainly to their significantly lower suicide rate.
Here again, more recent and reliable studies show that
course does not differ between genders anymore if analyses
406
W. Rössler et al. / European Neuropsychopharmacology 15 (2005) 399 – 409
are restricted to narrowly defined schizophrenia with a
nuclear schizophrenic syndrome at onset. Furthermore, the
better course of the disease was observed mainly in women
up to menopause. The tendency for the better course in
women could have to do with their later age of onset, which
is associated with a better social integration, and with the
protective effect of estrogens in young women (Navarro et
al., 1996; Riecher-Rössler and Rössler, 1998).
The burden of the disease can be very different for men
and women. Thus, e.g. the later age of onset in women
means that they frequently have to cope with losses, e.g. in
relationships or in the professional sphere. Men, due to their
younger age, typically have not established themselves in
these respects to the same extent at the onset of the
condition. This means that for women the focus in therapy
has to be the maintenance or reestablishment of certain
roles, whereas for men the goal is often to attain certain
roles for the very first time. In addition, gender-specific
social roles, social status, social stress or social support can
influence the course of the disease. For example, significantly more women than men with schizophrenia care for
children (Seeman, 2004). The care for these children can be
an enormous burden, with which these women so far get far
too little help. In most European countries, there is a severe
lack of assessment and treatment facilities for these mothers
with their children, although the need for such facilities is
well documented (Seeman, 2004; Mowbray et al., 2001;
Oyserman et al., 1994).
There are times of an enhanced risk for an exacerbation
of psychosis in women, dramatically so after parturition
(Kendell et al., 1987), but also in perimenopause (see
above) or perimenstrually (for review, see Riecher-Rössler,
2003). This puts a specific burden on women and needs a
gender-sensitive therapeutic approach.
Consideration also needs to be given to the large field of
gender-specific pharmacotherapy, e.g. the sex-specific treatment and side effects of neuroleptics (Goldstein et al.,
2002). Hyperprolactinaemia-inducing neuroleptics, for example, can have severe short- and long-term consequences
in women, such as premature menopause, osteopenia, etc.
(Riecher-Rössler, 2003). It is not clear yet to which extent
men are also affected by hyperprolactinaemia-inducted side
effects.
Men, on the other hand, not only need higher doses of
neuroleptics (Goldstein et al., 2002), they also have specific
needs in terms of psychosocial care. We have to be aware of
their higher comorbidity—especially with respect to drugs
and alcohol, and their higher risk of self-neglecting
behaviour or suicide (Häfner et al., 1993a; Riecher-Rössler
and Rössler, 1998).
13. Discussion
Although schizophrenia does not show a high incidence,
due to the early age of onset and the often-chronic recurrent
course, it shows a relatively high prevalence. This, and the
fact that it often leads to mental and social disability, makes
it one of the most burdensome and costly illnesses
worldwide.
In addition to the direct burden, the affected persons are
confronted with prejudice and discrimination. The stigma
attached to schizophrenia creates a vicious cycle of
discrimination leading to social isolation, unemployment,
drug abuse, long-lasting institutionalisation or even homelessness, which further decreases the chances for recovery
and reintegration into normal life.
The burden of schizophrenia can be very different in men
and women, and the consequences of these differences for
treatment and the provision of care have only begun to
impact on professionals. Over the last decades, there has
been considerable progress in treatment and care, with most
efforts directed towards severely ill and chronic patients.
Only recently has interest also been directed to early
intervention, which might offer an opportunity to make a
further major step towards positive changes in psychiatric
practice. Yet it has to be stated that there are still many open
research questions in this area.
A decrease in costs could be achieved mainly by a
reduction in incidence; moderately, given an improvement
in prognosis, and relatively minor, given the economies in
direct treatment costs likely to follow a transfer to
community treatment (Andrews, 1991). Current interventions avert some 13% of the burden, whereas 22% could be
averted by optimal treatment (Andrews et al., 2003).
Improvement in community treatment might also be
associated with a further improvement of prognosis.
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