Substance misuse in patients with schizophrenia: a primary care guide
THE VAST MAJORITY of people with schizophrenia misuse substances, but this comorbidity is frequently under-recog-
nised and poorly addressed. Between 60% and 90% of
■ Smoking presents a substantial health and economic burden
people with schizophrenia smoke cigarettes,1 which has a
■ Comorbid use of other substances is common, under-
2 In addition, between 40% and 60% misuse
recognised, and associated with a number of serious
r substances,3 related in part to the general increase in
ilit y and accessibility of drugs, and the change from
adverse consequences, such as psychotic relapse and
ional care of the severely mentally ill to their manage-
■ All patients with schizophrenia need to be screened for
psychoactive substances are alcohol, cannabis and ampheta-mine,5 and less commonly opioids, hallucinogens, inhalants
■ Effective interventions involve integrated, modified
(eg, petrol, glue and paint) and anticholinergics.
pharmacological and psychosocial strategies.
People with schizophrenia and concurrent psychoactive
substance misuse present unique challenges to thoseinvolved in their care, but often the disjunction betweenpsychiatric services and specialist drug and alcohol servicesresults in these patients being rejected or shuttled between
a difficult diagnostic challenge. Of most value is the tempo-
services. This failure of cooperation and coordination
ral association between using psychoactive substances and
between specialist services lays a greater responsibility for
the onset and resolution of psychotic symptoms. Guidelines
the care of these patients onto GPs, despite the fact that
exist to help differentiate between a primary psychotic
many feel under-resourced and inadequately trained to meet
disorder and a substance-induced disorder (Box 1). How-
the complex needs of people with schizophrenia.
ever, in cases of chronic and unremitting substance misuse,
GPs may play a variety of roles in managing this comorbid
with gradual onset of psychotic symptoms and marked
group. They may be the sole clinician, or provide shared
functional decline, diagnosis may be extremely difficult. In
care with mental health or addiction services. This may
such situations, treatment should be initiated regardless,
involve monitoring the physical wellbeing of patients in
with the diagnosis deferred until a perspective over time can
psychiatric services, or the mental health needs of patients
linked only with drug and alcohol services. Both these rolesrequire close collaboration and communication between alltreatment providers. For patients with complex needs or
severe symptoms, it is important to seek specialist advice
A number of hypotheses exist on the relationship between
early. However, cigarette smoking is rarely addressed in
substance misuse and established schizophrenia, and rea-
either setting for this population, and the GP is in a key
sons why such psychotic patients may use substances. One
position to motivate patients for change.
hypothesis is that both the choice and use of substances is amethod of “self-medication”, to treat adverse states inducedby either the schizophrenia or its treatment.8 These may
include primary positive symptoms (eg, hallucinations and
Understanding the basis of psychotic symptoms in the
delusions) and primary negative symptoms (eg, amotiva-
substance-using individual often presents the clinician with
tion, anhedonia) of schizophrenia, negative symptoms sec-ondary to neuroleptic treatment, depressive mood states,
Orygen Research Centre and Cognitive Neuropsychiatry
and neuroleptic-induced extrapyramidal movement disor-
Research and Academic Unit, University of Melbourne,
ders. (For definitions of “positive” and “negative” symp-
toms, see Lambert and Castle, page S57 9.) Despite the
Dan I Lubman, PhD, FRANZCP, FAChAM, Senior Lecturer; Consultant
intrinsic appeal of this hypothesis, there is conflicting evi-
Psychiatrist, Orygen Youth Health; and Senior Research Fellow, Mental
dence, and it seems that factors associated with substance
Health Research Institute, Melbourne, VIC.
use in people with schizophrenia are similar to those in the
Mental Health Research Institute, Melbourne, VIC.
general community (ie, availability, cost, peer-group use and
Suresh Sundram, PhD, FRANZCP, Senior Research Scientist;
acceptance, facilitation of social interaction, intoxication
and Clinical Director, Northern Area Mental Health Service, VIC.
Reprints will not be available from the authors. Correspondence:
and relaxation).4,10 Nevertheless, exploring individual rea-
Dr Dan I Lubman, Orygen Research Centre, Locked Bag 10, Parkville,
sons for substance misuse may uncover symptoms that are
readily alleviated by pharmacological strategies, such as
optimising antipsychotic treatment or initiating antidepres-
interventions have been shown to be beneficial,14 and
clinicians should remain optimistic with realistic expecta-
Alternative hypotheses for the high rates of comorbidity
include the possibility of a common underlying neurobio-
For comorbid patients, the most appropriate management
logical vulnerability toward both disorders, or traits (eg,
combines effective pharmacological treatment of the psy-
antisocial personality) that increase the likelihood of comor-
chotic illness with modified psychosocial strategies to reduce
substance misuse.14 As improved medication complianceincreases the effectiveness of psychosocial interventions,14the initial goal is to effectively treat patients’ psychotic
symptoms and ensure minimal side effects. Ideally, the
People with schizophrenia have a mortality rate three times
mental state of patients with established substance depend-
higher than people in the general population, with most of
ence should be relatively stable before attempting detoxifica-
this excess attributable to cigarette smoking.2 Typically,
tion in a community setting. Chaotic patients with frank
these patients are heavily nicotine dependent and inhalemore deeply.11 Smoking also places a heavy financial burdenon individuals, who spend a sizeable proportion of their
1: Guidelines to assist in differentiating between
income on cigarettes.11 Importantly, the majority of patients
a primary psychotic and a substance-induced disorder
admit smoking is a problem, and about half want to quit.11However, although effective treatments exist,1,12 the prevail-
Substance-induced psychotic symptoms can result from intoxication,
ing view of most clinicians is that treatment of this group is
futile, and interventions are not routinely offered to this
■ Intoxication with cannabis can induce a transient, self-limiting
psychotic disorder characterised by hallucinations and agitation;
■ Prolonged heavy use of psychostimulants (eg, amphetamine,
Misuse of other substances has a significant impact on
methylenedioxymethamphetamine [MDMA]) can produce a
both the course of illness and the outcome of treatment
psychotic picture similar to schizophrenia;
(Box 2), and patients do poorly in standard treatment
■ Hallucinogen-induced psychosis is usually transient, but may
settings.14 On a positive note, comorbid patients may have a
better prognosis than non-using patients if they cease
■ Heavy alcohol use has been associated with alcoholic
using,8 owing to their generally higher level of premorbid
functioning. Further, even limited, brief interventions have
■ Psychotic symptoms can also occur during withdrawal
(eg, delirium tremens) and delirious states.
been shown to improve outcomes for previously refractorypatients.14
A non-substance-induced psychotic disorder should be considered when:*■ Psychosis precedes the onset of substance use;
■ Psychosis persists for longer than one month after acute
The key principles of assessment and treatment are summa-
■ Psychotic symptoms are not consistent with the substance used;
rised in Box 3. Developing a collaborative therapeutic
■ There is a history of psychotic symptoms during periods (> one
alliance is essential for a successful outcome, and requires
the clinician to adopt an empathic, non-judgemental
■ There is a personal or family history of a non-substance-induced
approach. This may be especially difficult when working
with patients with schizophrenia given their poor interper-
sonal skills, and the engagement phase may be protracted. Screening for substance misuse is an important first step,although patients with schizophrenia often deny and mini-mise their substance use.13,14 It is therefore useful to
2: Possible consequences of psychoactive substance
monitor progress using urine testing and/or breath analysis
misuse in patients with schizophrenia4,13
for alcohol. These patients are often unusually sensitive to
the effects of psychoactive substances, experiencing adverse
effects with dosages that produce no difficulties in people
■ Frequent use of healthcare services and increased rates of
“Dual diagnosed” patients (ie, those with combined diag-
noses of schizophrenia and substance misuse) commonly
■ Increased rates of tardive dyskinesia;
evoke powerful, unpleasant feelings in health profession-
als.16 Clinicians may feel unskilled to handle, and over-
whelmed by, the multitude of presenting problems, and
■ Housing instability and homelessness;
unclear which issue to tackle first. Moreover, practitioners
are often pessimistic regarding outcomes and believe that
■ Criminal behaviour and incarceration;
intensive time and effort will produce minimal gains. Hence,
it is not uncommon for the clinician to want to avoid
involvement with these patients. However, appropriate
psychosis, intractable substance misuse and non-compli-
3: Principles of management of patients with
ance are difficult to manage in the community, and require
schizophrenia and comorbid substance misuse
referral to mental health services for inpatient detoxificationand stabilisation of their psychotic illness. Standard commu-
nity-based detoxification units can be used with more stable
■ Screen all patients with psychosis for substance misuse and other
psychiatric disorders (eg, social phobia);
patients, but patients may still relapse in the sometimes
■ Determine severity of use and associated risk-taking behaviours
confrontational environment of these units. Thus, these
(eg, injecting practices, “unsafe sex”);
patients require a tailored detoxification regimen incorpo-
■ Exclude organic illness or physical complications of substance
rating slower withdrawal and close monitoring of their
■ Seek collateral history — families or close supports should be
The newer atypical antipsychotics (eg, olanzapine, risperi-
done, quetiapine, amisulpride)9 are recommended first-line
agents for this population in view of their efficacy, tolerabil-
■ First engage patient, adopting a non-judgemental attitude;
ity and reduced risk of extrapyramidal symptoms. There are,
however, associated side effects, such as postural hypoten-
Give general advice about harmful effects of substance
sion, sedation, and corrected QT (QTc) prolongation,
➤ Advise about safe and responsible levels of substance use
which may be more problematic in a substance-using popu-
(eg, National Health and Medical Research Council guidelines
lation. Although there are limited published data on the
effect of clozapine in dual-diagnosed patients, it has been
➤ Make individual links between substance misuse and patient's
reported to reduce substance misuse in psychotic patients
problems (eg, cannabis use and worsening paranoia);
➤ Inform patient about safer practices (eg, using clean needles,
when switched from typical antipsychotics.15 In addition,
not injecting alone, practising “safe sex”);
compared with typical antipsychotics, clozapine and other
■ Treat psychotic illness and monitor patient for potential side
atypical agents enhance smoking cessation rates when used
in combination with nicotine-replacement therapy.1 Patients
■ Help patient establish advantages and disadvantages of current
who are non-compliant or chaotic may benefit from a switch
use, and motivate patient for change (see Box 5);
■ Evaluate need for concurrent substance-use medications
to the longer-acting depot antipsychotics. Daily pick-up of
(eg, methadone, acamprosate, nicotine-replacement therapy);
antipsychotics from a local pharmacy, especially if combined
■ Refer patient to relevant clinical and community services, as
with appropriate substance-misuse medications, may also be
■ Devise relapse prevention strategies that address both psychosis
There is little published research on the use of medica-
tions to treat substance misuse in schizophrenia, but most
■ Identify triggers for relapse (eg, meeting other drug users, being
paid, family conflict) and explore alternative coping strategies
appear to be safe and effective in combination with antipsy-
chotics.15 Naltrexone and acamprosate, both effective treat-ments for alcohol dependence, may also be useful in thecomorbid patient. However, disulfiram at high doses
4: Selected psychosocial interventions for addiction,
(1000 mg) has been associated with psychotic symptoms in
specially modified for patients with schizophrenia
people without schizophrenia,15 and should be used withcaution in dual-diagnosed patients. Nicotine replacement
■ Explore reasons for substance misuse, including relationship to
psychiatric symptoms, antipsychotic treatment and feelings of
therapies and bupropion have both been successfully and
safely used in patients with schizophrenia.1,11,12,17 Although
■ Address patient’s motives and degree of commitment towards
bupropion is contraindicated in patients with a history of
treatment of both their psychotic illness and their substance
seizures or mania, it has rarely been reported to exacerbate
■ Adopt concrete problem-solving approach with patient, where
Medications with misuse potential (eg, benzodiazepines,
anticholinergics) should be prescribed only for brief periods.
■ Set tasks that are simple and readily achievable (eg, keeping a
diary of substance use or psychotic symptoms; regularly taking
There should be a clear indication for their use (eg, alcohol
withdrawal), and their continued prescription should be
■ Focus on specific skills to deal with high-risk situations, and
frequently reassessed. Comorbid patients stabilised on
consider use of role play (eg, learning how to say "no" to a dealer
methadone should have their dose reduced gradually, as
rapid withdrawal may precipitate a psychotic relapse in some
■ Suggest alternatives to substance use for coping with stressful
individuals. Although acute nicotine withdrawal has not
situations (eg, exercise, contacting a support person);
■ Treat comorbid anxiety with behavioural techniques (eg,
been clearly linked to an increase in psychotic symptoms,
breathing exercises, progressive muscular relaxation);
tapered nicotine replacement therapy is better tolerated.11
■ Remain supportive and emphasise any gains made;
Smoking induces hepatic metabolism of psychotropic
■ Recommend group support (eg, refer patient to SANE SmokeFree
drugs through the cytochrome P450 system. Thus,
program (<http://www.sane.org/ourworksmoking.html>);
increased antipsychotic dosages are often required to
■ Encourage participation in alternative activities and contact with
control psychotic symptoms in patients who smoke.17 In
non-substance-using peer group (discuss available resources with local community health centre or mental health service);
view of this, patients should be monitored closely for the
■ Adopt a long-term perspective, with ongoing intervention.
emergence of dose-dependent side effects or toxicity
Families can play an important role in supporting and
monitoring treatment, and should be included in the man-
Motivational interviewing18 is a useful therapeutic approach, based
agement plan, with the patient’s consent. However, carers
on a model conceptualising stages through which behavioural
themselves often require additional support, and should be
change occurs. It emphasises the role of both ambivalence and
advised about local support networks (eg, Al-Anon, SANE).
relapse within the process of change.19 Thus, it is normal for patients to cycle several times through the various stages before making long-lasting changes.
This therapeutic approach aims to match appropriate treatment options with the patient’s motivational level, based on the patient’s
Given the excess morbidity and mortality associated with
current stage within the cycle (see below).
cigarette smoking, helping patients with schizophrenia toreduce and stop smoking should be a key goal for clinicians. Intervention
In addition, patients with comorbid psychoactive substance
Educate patient about substance misuse and
misuse need an integrated treatment program that addresses
allow patient to examine problems with current
both disorders. Such programs, incorporating assertive out-
reach with intensive case management, boast better engage-
ment and retention of patients and improved treatment
acknowledge patient’s ambivalence and resistance to change
outcomes.14 Currently, few such programs exist in Australia,but, encouragingly, in response to the identified need, a
Help patient to determine most appropriate strategies for change
number of innovative approaches have been introduced thatawait further evaluation. Given the high prevalence of
Assist patient to instigate planned changes
comorbidity in people with schizophrenia, primary and
Encourage new skills and rehearse relapse-
secondary prevention strategies for substance misuse are
urgently required. Even with adequately resourced, targeted
Support patient and assist in renewing process of change
interventions, the GP remains a key treatment provider forthis population.
following prolonged periods of cigarette reduction or
S S has received honoraria from Eli Lilly and AstraZeneca. D I L has received
Psychosocial interventions for addiction need to be modi-
conference support from Pfizer, Eli Lilly and AstraZeneca.
fied for people with schizophrenia (Box 4) in view of thecognitive deficits and poor self-belief of these patients.15Techniques to enhance motivation remain an important
component of treatment.15 Enhancing motivation reduces
Dr Lubman is supported by the Norma Licht Trust.
substance use and can be applied by the GP as a brief,ongoing intervention (Box 5). Relapse prevention,20 based
on a cognitive behavioural approach, helps patients toidentify triggers to relapse, both to psychosis and substance
1. George TP, Ziedonis DM, Feingold A, et al. Nicotine transdermal patch and
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Psychiatry 2000; 157: 1835-1842.
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2. Brown S, Inskip H, Barraclough B. Causes of the excess mortality of schizophre-
“Lapses” should be expected and seen as opportunities to
nia. Br J Psychiatry 2000; 177: 212-217.
3. Cantor-Graae E, Nordstrom LG, McNeil TF. Substance abuse in schizophrenia: a
modify and develop patient coping strategies rather than
review of the literature and a study of correlates in Sweden. Schizophr Res 2001;
viewed as failures. At these times, patients often feel demor-
alised, and it is important to remind them of their previous
4. Dixon L. Dual diagnosis of substance abuse in schizophrenia: prevalence and
impact on outcomes. Schizophr Res 1999; 35 Suppl: S93-S100.
5. Fowler IL, Carr VJ, Carter NT, Lewin TJ. Patterns of current and lifetime
Twelve-step peer-support groups (eg, Alcoholics Anony-
substance use in schizophrenia. Schizophr Bull 1998; 24: 443-455.
mous or Narcotics Anonymous) and smoking-cessation
6. Chick J, Cantwell R, editors. Seminars in alcohol and drug misuse. London:
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7. Woody G, Schuckit M, Weinrieb R, Yu E. A review of the substance use disorders
tings, are often not appropriate for patients with psychosis,
section of the DSM-IV. Psychiatr Clin North Am 1993; 16: 21-32.
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8. Krystal JH, D’Souza DC, Madonick S, Petrakis IL. Toward a rational pharmaco-
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London Programme, December 2001. Available at: http://www.ash.org.uk/html/
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nature publishing group Bronchodilatory Effect of the PPAR-γ Agonist Rosiglitazone in Smokers With Asthma M Spears1, I Donnelly2, L Jolly2, M Brannigan1, K Ito3, C McSharry2, J Lafferty1, R Chaudhuri1, G Braganza1, P Bareille4, L Sweeney4, IM Adcock3, PJ Barnes3, S Wood5 and NC Thomson1 Smokers with asthma show a reduced response to inhaled subtypes in vitro and reduce inflammation
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