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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 (<>); 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.
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 atypical antipsychotic medications for smoking cessation in schizophrenia. Am J misuse (eg, social stressors), and to develop alternative Psychiatry 2000; 157: 1835-1842.
strategies when confronted with high-risk situations.
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: groups, which are invaluable in traditional addiction set- 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.
who may feel stigmatised and misunderstood. In response, 8. Krystal JH, D’Souza DC, Madonick S, Petrakis IL. Toward a rational pharmaco- therapy of comorbid substance abuse in schizophrenic patients. Schizophr Res programs in the United States have been modified to support this population,14 but few such programs exist in 9. Lambert T, Castle DJ. Pharmacological approaches to the management of schizophrenia. Med J Aust 2003; 178 Suppl May 5: S57-S61.
Australia. There are, however, publicly available smoking- 10. Spencer C, Castle D, Michie PT. Motivations that maintain substance use among cessation programs, such as Quitline, which offer specialised individuals with psychotic disorders. Schizophr Bull 2002; 28: 233-247.
packages incorporating telephone advice and supporting 11. McNeill A. Smoking and mental health: a review of the literature. SmokeFree London Programme, December 2001. Available at: materials for people with mental illness. In addition, smok- policy/menlitrev.html (accessed Jan 2003).
ing-reduction management guidelines for GPs, and associ- 12. Peters MJ, Morgan LC. The pharmacotherapy of smoking cessation. Med J Aust ated resources, are available from the SANE Australia 13. Smith J, Hucker S. Schizophrenia and substance abuse. Br J Psychiatry 1994; 14. Drake RE, Mueser KT. Psychosocial approaches to dual diagnosis. Schizophr 17. George TP, Vessicchio JC, Termine A, et al. A placebo controlled trial of bupropion for smoking cessation in schizophrenia. Biol Psychiatry 2002; 52: 53-61.
15. Ziedonis DM, D’Avanzo K. Schizophrenia and substance abuse. In: Kranzler HR, Rounsaville BJ, editors. Dual diagnosis and treatment: substance abuse and 18. Miller W, Rollnick S. Motivational interviewing: preparing people to change comorbid medical and psychiatric disorders. New York: Marcel Dekker, 1998: addictive behaviours. New York: Guildford, 1991.
19. Prochaksa JO, DiClemente CC, Norcross JC. In search of how people change: 16. O’Neill MM. Countertransference and attitudes in the context of clinical work with applications to addictive disorders. Am Psychol 1992; 47: 1102-1114.
dually diagnosed patients. In: Solomon J, Zimberg S, Shollar E, editors. Dualdiagnosis: evaluation, treatment, training, and program development. New York: 20. Marlatt G, Gordon J. Relapse prevention: maintenance strategies in the treatment of addictive behaviours. New York: Guildford Press, 1985.


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