Psychiatric Hospital, University of Munich, Nußbaumstrasse 7, 80336 Munich, Germany
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See editorial pp.
307311, this issue.
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ABSTRACT |
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Aims The literature was evaluated to assess whether people with schizophrenia who use substances have an increased risk for violence and disturbed behaviour.
Method A detailed Medline analysis was performed and relevant studies were reviewed.
Results A large number of studies have linked substance misuse in schizophrenia with male gender, high incidence of homelessness, more pronounced psychotic symptoms, non-adherence with medication, poor prognosis, violence and aggression. The latter has been proved by clinical, epidemiological and longitudinal prospective studies of unselected birth cohorts. The increased risk for aggression and violent acts cannot be interpreted only as a result of poor social integration. Male gender, more severe psychopathology, a primary antisocial personality, repeated intoxications and non-adherence with treatment are important confounding variables.
Conclusion Substance misuse has been shown consistently to be a significant risk factor for violence and disturbed behaviour. Future research should try to evaluate possible pharmacological and psychosocial treatment approaches.
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INTRODUCTION |
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SUBSTANCE MISUSE IN SCHIZOPHRENIA |
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Is substance misuse in schizophrenia increasing?
It is a matter of debate whether substance abuse in schizophrenia is really
increasing over time (Cuffel,
1992). A recent study of Boutros et al
(1998) has linked a rapid
increase in new admissions with schizophrenia to Connecticut State Hospitals
to an increase in drug-related admissions. For first-episode psychosis,
prevalence rates for substance use were 20-30%
(Strakowski et al,
1993; Hambrecht &
Häfner, 1996). A more recent study
on 168 patients with first-episode psychosis showed that 37% of the sample met
the diagnosis of substance or alcohol misuse. One-year prevalence rates for
drug and alcohol misuse were 19.5 and 11.7%, respectively
(Cantwell et al,
1999). The study also gave evidence for an increase in diagnosis
of substance-related psychotic disorders over time.
Epidemiological findings
Owing to Berkson's fallacy (Berkson,
1949), prevalence estimates of substance misuse in schizophrenia
or other major mental disorders drawn from clinical samples of inpatients may
overestimate the real amount of comorbidity of the two disorders. Prevalence
estimates for substance misuse in more chronic samples of patients with
schizophrenia were higher than those studied in psychiatric university
hospitals (Soyka et al,
1993). Epidemiological studies also indicate substance misuse as
being a major problem in schizophrenia. Data from the Epidemiologic Catchment
Area study (Regier et al,
1990) suggest a four-fold increased risk of substance misuse in
schizophrenia and a six-fold increased risk in mania. Apart from antisocial
personality disorder these two disorders had the highest comorbidity with
substance misuse; this comorbidity was also higher than with anxiety or
depressive disorders. Other epidemiological studies also confirm a significant
comorbidity of substance use and schizophrenia
(Lindquist & Allebeck,
1989).
Studies in first-episode psychosis and follow-up studies
Cantwell et al
(1999) examined 168 subjects
with first-episode psychosis and reported that criteria for drug use, drug
misuse or alcohol misuse were met by 37% of the sample; 8.4% of the subjects
received a primary diagnosis of substance-related psychotic disorder, which is
a significant increase compared with an earlier cohort from the same catchment
area. Risk for substance use was highest in young males. Hambrecht &
Häfner
(1996) conducted a careful
longitudinal study on the chronology of onset of alcohol dependency in
schizophrenia and found that alcohol misuse typically preceded the first signs
of schizophrenia, but followed the appearance of the first positive symptom.
For cannabis, but no other drugs, Andréasson
et al (1987), in a
follow-up study on 45 570 young men, reported a strong association between
cannabis use at conscription to the Swedish Army and later diagnosis of
schizophrenia. The relative risk ratio was 6.0 for heavy users and 2.9 when
controlled for other psychiatric diagnoses at conscription. Patients had a
more rapid onset of schizophrenia and positive symptoms
(Andréasson et al,
1987,
1989;
Allebeck et al,
1993).
Clinical characteristics of patients with dual-diagnosis
schizophrenia
Patients with schizophrenia and comorbid substance use disorder differ from
patients with schizophrenia alone and from other patients with substance use
in a number of ways. Patients with dual-diagnosis schizophrenia tend to
consume lower quantities of drugs than other psychiatric patients and show
less physical symptoms compared with others (for a review, see
Mueser et al, 1998).
There is overwhelming evidence for these patients to have a very high
re-hospitalisation rate. Prognosis is usually poor
(Cuffel et al, 1994;
DeQuardo et al, 1994;
Linszen et al, 1994).
Some studies suggest that dual-diagnosis patients have a better premorbid
function and less severe negative symptoms compared with other patients
(Dixon et al, 1991;
Arndt et al, 1992;
Serper et al, 1995;
Kirkpatrick et al,
1996). Mueser et al
(1990) felt that this
phenomenon may reflect selection factors whereby more socially oriented
patients with schizophrenia are more likely to come into contact with drugs
and subsequently develop substance use, but other studies failed to
demonstrate clinical differences between dual-diagnosis patients and patients
with simple schizophrenia (for a review, see
Mueser et al, 1998).
Interestingly, Scheller-Gilkey et al
(1999), in a recent magnetic
resonance imaging study of 176 patients with schizophrenia, reported that in
patients with schizophrenia and alcohol or drug misuse the rate of gross brain
abnormalities was slightly less than the rate found in patients with
schizophrenia alone. These results failed to reach statistical significance,
but the authors felt that these findings reflect a trend that is comparable
with previous findings suggesting a better premorbid adjustment and less
impairment in certain areas in dual-diagnosis patients. Furthermore,
Scheller-Gilkey et al
(1999) could not demonstrate
more severe symptoms and a poorer outcome in these patients.
Apart from premorbid functioning, there are some demographic and clinical characteristics of dual-diagnosis schizophrenia that have been more or less consistently reported in the literature. The typical features of dual-diagnosis patients are: male, younger, high incidence of homelessness, more positive and less negative symptoms, more affective disturbance, increased suicide rate, more often treatment refractory, non-adherence with medication, higher rates of tardive dyskinesia, higher doses of neuroleptic, higher rates of hospital admission, higher rates of discharge against advice, higher rates of violence (see below), younger age at time of first hospitalisation (for a review, see Scheller-Gilkey et al, 1999). Even so, apart from gender and age these are only general trends and different studies have shown very mixed results. With regard to psychopathological features, higher levels of hallucinations and delusions and less severe symptoms, no differences at all were reported (for a review, see Mueser et al, 1998).
Aetiological models
A broad number of theories and findings, as reviewed by Mueser et
al (1998), have been put
forward to explain the comparatively high comorbidity of substance misuse and
schizophrenia, including genetic factors, a shared vulnerability to both
disorders, the role of antisocial personality disorder, socio-economic status
and cognitive functioning, psychosocial risk factors, selfmedication
(alleviation of dysphoria, etc.), and others. Mueser et al
(1998) concluded that most of
the models have not been proved, and stated that antisocial personality
disorder may account for some increased comorbidity but otherwise favoured the
supersensitivity model, which posits that biological vulnerability of
psychiatric disorders results in sensitivity to small amounts of alcohol and
drugs, leading to substance use disorders. This supersensitivity model is an
elaboration of the stressvulnerability models proposed for
schizophrenia (Liberman et al,
1986). Mueser et al
(1998) also indicated
pharmacological studies showing that very low doses of amphetamine produced
psychotic symptoms in schizophrenia
(Janowsky et al,
1973; Lieberman et
al, 1987) and proposed two aetiological-based subtypes of
dual-diagnosis patients. The first type would be linked to antisocial
personality and the second to supersensitivity or increased vulnerability. For
aggression and violence, the antisocial personality disorder-related type
would be of special relevance.
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AGGRESSION AND VIOLENCE IN DUAL-DIAGNOSIS PATIENTS |
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In a recent study Scott et al (1998) reported results of a follow-up study in a community sample of patients with psychosis: 27 people met the criteria for both psychotic illness and a substance use disorder; 65 were psychotic only. Although the severity of aggression and offending among this community sample was low, individuals with a dual diagnosis were significantly more likely to report a history of committing an offence or recent hostile behaviour. Keyworkers were also more likely to report recent aggression in dual-diagnosis patients. Surprisingly, a relatively large proportion of patients in the psychosis-only group reported substance-related offences. This finding might suggest that either the number of dual-diagnosis patients may be underestimated when basically relying on self-reports, or the substance-related offences themselves may not in any case suggest a substance use disorder. This methodological problem deserves more attention in the future.
Swartz et al (1998) examined 331 involuntarily admitted in-patients with severe mental illness (predominantly schizophrenia and other psychotic disorders, 26.9% bipolar patients and 5.1% major depression) who were awaiting a period of out-patient commitment: 33.8% had problems related to alcohol or drugs and 17.8% of the study group (n=59) had engaged in serious violent acts before admission. In a multivariable model the authors examined a number of risk factors for violent behaviour and found that the combination of substance misuse and problems and medication non-adherence was found to be associated significantly with serious violent behaviour that occurred in the four-month period before hospitalisation after key socio-economic and clinical characteristics were controlled. Other factors were of minor or no importance. Surprisingly, Swartz et al (1998) were unable to find a relationship between serious violent acts and clinical characteristics of diagnosis and score on the Global Assessment of Functioning Scale (Endicott et al, 1976).
An interesting study on violence in 1136 patients with mental disorders discharged from acute psychiatric in-patient facilities (Steadman et al, 1998) showed that there was no significant difference between the prevalence of violence as detected by self-reports and by reports of collateral informants and by police and hospital records by patients without symptoms of substance misuse and by others living in the same neighbourhood. Substance misuse symptoms significantly raised the rate of violence in both the patients and the comparison groups. The study confirmed the finding of substance misuse being a major risk factor for violence in patients with a major mental disorder, especially schizophrenia. However, a possible methodological problem of the Steadman et al study should be mentioned: due to Berkson's bias there might be a tendency for this material to include a preponderance of comorbid patients (37.6%), which may account for the high prevalence rates for violence.
Epidemiological studies
The most robust findings come from epidemiological and case register
studies. Lindquist & Allebeck
(1989) in a study on 644
patients with schizophrenia reported a four times higher rate of violent
offences among males with schizophrenia compared with the general population.
Prevalence rates for substance misuse in violent offenders (38%) were
significantly higher compared with patients with simple schizophrenia
(16%).
Wallace et al (1998) examined the psychiatric history of those convicted in Victoria (Australia) between 1993 and 1995 by case linkage to a register listing nearly all contacts with the public psychiatric service, and found that 25% of offenders had prior psychiatric contact. Personality disorder and substance misuse accounted for much of this relationship, and schizophrenia and affective disorder were also over-represented, particularly those with coexisting substance misuse. Wallace et al (1998) concluded that the increased offending in schizophrenia and affective disorder is modest and often mediated by coexisting substance misuse.
Longitudinal prospective studies of unselected birth cohorts
Data from longitudinal prospective studies of an unselected birth cohort in
Sweden (n=15117; Hodgins,
1992) and Denmark (Hodgins
et al, 1996) also suggest substance use to be a major
covariable in the violence of patients with schizophrenia. In the Swedish
cohort, men with major mental disorders (schizophrenia, major affective
disorders, paranoid states, other psychoses) were 2.5 times more likely to
commit a crime than other men and four times more likely to commit a violent
offence. The relative risk for violence was even higher in women with major
mental disorders. Those people with alcohol dependency were also at a greater
risk for such acts. In the Danish cohort, men with major mental disorders had
a 2.4-4.5 times increased risk and men who also misused alcohol a 4.2-6.7
times increased risk of committing a violent crime compared with healthy
individuals.
The most robust findings probably come from a 26-year follow-up study of an unselected birth cohort (n=11017) in Finland (Räsänen et al, 1998). Men who misused alcohol and were diagnosed with schizophrenia were 25.2 times more likely to commit violent crimes than other mentally healthy men. The risk for patients with schizophrenia without alcohol dependency was 3.6 and for other psychoses it was 7.7. None of the patients with schizophrenia who did not misuse alcohol was recidivist (>2 offences), but the risk of committing more crimes among subjects with schizophrenia and alcohol dependency was 9.5-fold. One-fifth of male subjects with schizophrenia were already dependent on alcohol (n=11) before the age of 27 years and they were seven times more likely to commit a violent crime than other patients with schizophrenia. The authors pointed out that these findings greatly exceed other figures reported in the literature (Lindquist & Allebeck, 1989; Swanson et al, 1990; Eronen et al, 1996a).
Reasons for violence
The reasons for violence and aggression, especially among dual-diagnosis
patients, are a matter of debate because male gender, more severe
psychopathology, early onset of psychosis, a primary antisocial personality,
social class, employment status, poor insight and non-adherence to treatment
are possible important confounding variables, among others. Also, Swartz
et al (1998), Smith
(1989) and Bartels et
al (1991) had already
demonstrated a significant relationship between medication nonadherence and
violent acts. Interestingly, demographic factors have not been found to be
reliable in identifying high-risk individuals in clinical practice
(Taylor & Monahan, 1996).
Persecutory delusions seem to be of special relevance for violence in
schizophrenia (Nestor et al,
1995). Psychostimulants and cocaine especially were found to
provoke or worsen psychotic symptomatology
(Dixon et al, 1991). Also, a poor neuroleptic response in patients with a history of psychogenetic
drug use has been postulated. Junginger et al
(1998) stated that although
delusional motivation of violence is rare, a moderate risk exists that
delusions will motivate violence at some time during the course of a violent
patient's illness. The role of intoxication should also be emphasised
(Häfner
& Böker, 1992).
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DISCUSSION |
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The next step will be the development of risk management strategies and the evaluation of treatment in people with dual-diagnosis schizophrenia and violent offenders. As stated above, most authors agree that substance misuse in schizophrenia is associated not only with violence, but also with a number of other problems, including poor treatment adherence, an increased suicide risk and increased rates of hospital admissions and HIV infection.
Treatment perspectives
Pharmacological interventions
Possible pharmacotherapeutic approaches in dual-diagnosis schizophrenia
have been discussed in detail elsewhere
(Soyka, 1996). Key problems
are choice of neuroleptic agent and dosage, drug interactions, management of
side-effects, possible role of atypical neuroleptics, antidepressant treatment
and relapse prevention. Although few studies have been conducted on this
topic, any strategy to reduce psychotic relapse and minimise the risk for
side-effects of antipsychotic treatment, including the use of atypical
neuroleptics, should be advocated. Alcohol dependency in particular, but also
cannabis, were linked to increased rates of tardive dyskinesia. Some authors
feel that substance misuse may be explained as a form of self-medication to
improve psychopathology (depression, anhedonia, negative symptoms) or to
ameliorate the side-effects of neuroleptic treatment. Pharmacological
interactions may also be of importance. Serum levels of neuroleptics
(fluphenazine) were found to be decreased in those suffering from
schizophrenia and alcohol misuse. A relative neuroleptic refractoriness and a
cannabisneuroleptic antagonism were postulated. Although the
antipsychotic dose given to dual-diagnosis patients did not differ from that
used for patients with simple schizophrenia, the topic deserves specific
attention (for a review, see Soyka,
1996). Little is known about the effect of new anticraving drugs
such as acamprosate or naltrexone in dual-diagnosis schizophrenia but they
should be looked at in more detail.
Psychosocial interventions
In which facilities should patients with dual-diagnosis schizophrenia be
treated more in the psychiatry or the addiction section of psychiatry,
or both? Scott et al
(1998) suggested strengthening
links between general adult and addiction services, or introducing special
services for dual-diagnosis patients
(Johnson, 1997) may be a
possible strategy. A number of both in-patient and and out-patient treatment
models for dual-diagnosis schizophrenia have been proposed
(Evans & Sullivan, 1990)
but there is little catamnestic evidence for the efficacy of special treatment
models. Even so, this is where the future for these patients lies.
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Clinical Implications and Limitations |
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LIMITATIONS
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Received for publication May 19, 1999. Revision received November 29, 1999. Accepted for publication December 7, 1999.