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Antipsychotic drugs are still chosen mostly on the basis of side effects. Low potency drugs (e.g., chlorpromazine, thioridazine) are more likely to produce sedation, postural hypotension and anticholinergic side effects, while higher potency drugs (e.g., haloperidol, fluphenazine) tend to cause more extrapyramidal side effects, such as parkinsonism, acute dystonia and akathisia. Some newer drugs (e.g., risperidone) are said to be more benign in their side effect profile; further use and investigation may bear this out. Clozapine seems unique in having marked benefits for about one-third of otherwise "treatment resistant" patients; this drug is subject to stringent controls because of the associated risk of agranulocytosis.

Antipsychotic drugs are only partially effective in controlling psychotic symptoms. Up to 30% of patients on maintenance drug treatment relapse within two years³ -- this is not entirely explained by poor compliance. A third or more of schizophrenic patients taking antipsychotic drugs continue to experience delusions and/or hallucinations, usually in attenuated form.^4,5 Therefore, when psychotic symptoms persist after two or more antipsychotic drugs have been taken (separately), in adequate doses, for a cumulative total of 12 months, measures other than drug treatment are necessary. Firstly, factors that may be contributing to persistent symptoms (e.g., drug or alcohol abuse, relationship problems) should be identified and dealt with if possible, usually by a specialist. Secondly, where appropriate, effective non-pharmacological treatment strategies should be added to a suitable drug regimen. Several individual psychological (e.g., cognitive behaviour therapies) and family-oriented (e.g., training in problem-solving skills) interventions are available. These require specialist expertise, and GPs can be instrumental in locating appropriate providers of these treatments.

With very few exceptions, only one antipsychotic drug should be used at a time. The dose should be the minimum required to maintain remission, and side effects should be absent or minimal. Excessive doses of antipsychotic drugs augment negative symptoms, impair cognitive function, mimic depression, undermine compliance by causing dysphoria and discomfort, produce higher rates of side effects that contribute to stigmatisation by rendering the patient more conspicuous, and can cause irreversible complications (e.g., tardive dyskinesia). Overmedication also interferes with rehabilitation. GPs can monitor antipsychotic drug use to ensure that doses are not unnecessarily high. Doses of haloperidol greater than 10 mg per day (or the equivalent) are not currently justified and approximately half this amount is now recommended, even less for first psychotic episodes.

Adjunctive medication (e.g., lithium, carbamazepine) should only be used on specialist advice. There is no role for long term use of benzodiazepines, although they can be useful adjuncts in acute episodes, particularly when sedating a patient in an emergency. Long term use of anticholinergic drugs for the treatment of drug-induced parkinsonism should be avoided as they may mask the signs of tardive dyskinesia and impair cognitive function.

The relapse signature: Patients and their families should be encouraged to monitor the patient's symptoms in association with GPs and specialist services. Each patient is said to have a unique relapse "signature"⁶ -- a sequential emergence of symptoms and signs which herald an impending relapse. There is often a "window" of 2-4 weeks in which such early warning signs appear,⁶ signalling the need to increase doses of antipsychotic drugs to prevent relapse. GPs should review with patients their typical sequence of warning signs so that they can correctly interpret them and make timely adjustments to the drug regimen.

Non-compliance with medication is inevitable at some stage in most patients' treatment. It is said that 80% of patients are non-compliant with medication 40%-80% of the time.⁷ Reasons for this include medication side effects, complex dosing schedules, stigma, lack of knowledge or false beliefs about medication, and poor insight or denial of illness.^7,8 Some patients reason that stopping medication will signify they are not ill.⁸ Some patients may prefer the psychotic state, either because of certain rewards from being ill (secondary gain) or difficulties in coping with normal expectations and responsibilities.⁸ Non-compliance may occasionally be an attempt to assert control or a manifestation of rebellion.

Dealing with non-compliance requires a good working relationship, incorporating sound education about the illness and its management. Keeping dosing schedules simple and eliminating side effects are important strategies. Asking about medication and reasons for non-compliance in a non-judgemental way will encourage disclosure. One useful strategy is to assume episodic non-compliance and openly regard each occasion as a learning opportunity for the patient. Involving the patient in drug management, including allowing limited self-regulation of doses,⁸ together with self-monitoring of symptoms, will benefit the patient. Simply resorting to depot medications undermines the patient's collaborative role in health care. Arranging for medication to be taken under supervision, which is fraught with potential conflict, or seeking legal means of enforcing drug administration (e.g., community treatment orders), should only be a last resort.

GPs should supplement self-monitoring of symptoms by examining patients' mental state at each appointment. This includes assessment of the status of psychotic symptoms and, although it is important not to dwell excessively on these, GPs should not avoid asking such questions as:

Do your beliefs about . . . continue to trouble you?; or

Have you been hearing voices in the past few weeks? Are you able to ignore them? What have you found helpful when they occur?

Patients with schizophrenia learn three kinds of palliative coping techniques to deal with psychotic and other symptoms:¹⁰

• cognitive control (e.g., reappraisal, self-instruction, acceptance, manipulation of attention);

• behavioural control or the generation and implementation of action alternatives (e.g., increased or decreased activity, diversion, withdrawal from stimulation, altered arousal); and

• social support recruitment.

They can be helped to identify their usual coping techniques, modify and extend them. GPs can encourage patients to practise these by imagining they have a particular symptom and then implementing an identified coping strategy. Such rehearsal of coping skills may facilitate their successful transfer to everyday settings.

Families of schizophrenic patients need support and GPs can provide education, aided by various leaflets and other publications on schizophrenia which are now readily available. GPs can also provide explanation, reassurance, advice and the opportunity to air emotional distress (especially anger, shame, sadness and guilt). Specialist services can provide various forms of more specific family counselling and education on schizophrenia.

Schizophrenia is usually a prolonged illness of relapses and remissions, but the eventual outcome is better than was previously thought -- most patients make a good long-term social recovery (i.e., improved social relationships and self-care abilities).¹¹ The early years are crucial in determining the patient's ultimate level of function and substantial gains may take years to become apparent.

Depressive disorders in schizophrenic patients can be treated as for similar conditions in other patients, including the use of antidepressant medication. The risk of such drugs triggering relapse of schizophrenic symptoms is small. Major risks include the risk of suicide by overdose, and appropriate precautions should be taken to guard against this. A course of antidepressant drugs at recommended daily doses can be added to the antipsychotic drug regimen for 6-12 months, together with whatever psychotherapeutic assistance is indicated.

Between 10% and 13% of schizophrenic patients commit suicide,¹² mostly during the first 10 years of the illness. There are no reliable guidelines for predicting and preventing suicide in these patients. The schizophrenic patient more likely to commit suicide is a young, single, unemployed, socially isolated man whose illness is marked by numerous exacerbations and hospital admissions for psychosis.¹² He often has a past history of depression and/or attempted suicide, and perhaps a non-delusional, demoralising awareness of his deterioration, which is particularly acute if he has previously had some higher education and realises that his family's expectations and his own ambitions are unlikely to be fulfilled. Sensitive enquiry may reveal considerable underlying emotional distress with depressive symptoms, accompanied by feelings of hopelessness and inadequacy. If a GP recognises something like this pattern in a patient, then a thorough assessment should be undertaken and an urgent specialist referral should be made if the GP is concerned about the patient's risk of suicide.

Detecting substance abuse in schizophrenia is the first priority. GPs should use non-judgemental enquiry to become thoroughly familiar with the patient's current and past pattern of drug use, including tobacco, caffeine and alcohol, gauging the quantity, frequency and context of use. An undetected alcohol or drug problem should be suspected in patients who respond poorly to treatment. If necessary, a referral can be made to mental health services with special therapeutic programs for psychiatric and substance abuse comorbidity. If alcohol or drug abuse is detected in patients during remission, even when no immediate adverse consequences are apparent, the GP should first attempt to determine the patient's reasons for using those substances. The patient can then be informed in a matter-of-fact way about their detrimental effects on schizophrenia and general health, highlighting the extent to which alcohol, cannabis and amphetamines worsen psychotic symptoms and lead to relapse.

The difficulty is that this information may not match the selective recollection of patients, who may even report certain benefits from using drugs. It is preferable not to argue, but to point out that all substances, including therapeutic agents, have a certain "margin of safety" between desired effects and adverse consequences, but that the "margin of safety" for some drugs is much narrower than others.

Having indicated that complete abstinence is the safest course of action, a harm minimisation approach can be negotiated as a satisfactory compromise. A series of short-term achievable goals can be identified in sequence, including aiming to control levels of consumption (including issues of safe needle use, where relevant), then moving on to goals for reducing consumption, incorporating strategies for preventing relapse and parting from the alcohol and drug culture. Simultaneously, the GP can attend to factors that may be contributing to the patient's substance use, including resolution of interpersonal and practical problems (e.g., money, accommodation), with the help of other agencies if necessary, and encourage the development of additional coping skills and the pursuit of other interests.

GPs should enquire about patients' relationships, sexual behaviours, sexual orientation, knowledge of sexuality and reproduction, need for contraception, and understanding of safe-sex practices. It can also be helpful to ascertain whether the patient experiences any sexual dysfunction, which is common,¹⁸ but not always due to medication, and ensure that the patient is informed about sexually transmitted diseases where necessary. Specific interventions may be appropriate.

Schizophrenic patients should be examined six-monthly for side effects and complications of antipsychotic drug use. Akathisia can be detected by observing the patient at rest, both seated and standing, and asking whether there are any subjective feelings of restlessness (especially in the legs)²² which may be present in the absence of objective signs. Observations of gait and posture will enable the characteristic tremor and bradykinesia of parkinsonism to be detected, while passive flexion and extension of the upper limbs will reveal cog-wheel rigidity.²³ Examination for tardive dyskinesia can be conducted using the readily available Abnormal Involuntary Movement Scale (AIMS), which facilitates detection and quantification of the variety of orobuccal and choreoathetoid limb movements possible in this condition.²⁴

Parkinsonism and akathisia should be dealt with by a reduction in the dose of antipsychotic drugs or by changing to a lower-potency drug. Anticholinergic agents should only be used in the short term for parkinsonism and are ineffective for akathisia; the latter can sometimes be controlled with propranolol. There is no effective treatment for tardive dyskinesia and decisions about its management should be made in consultation with a psychiatrist or other specialist.

Patients over the age of 40 require an annual physical (and dental) examination, including measurement of blood pressure, examination of the cardiovascular and respiratory systems and skin, assessment of drug side effects, and urinalysis.²⁵ This can also provide an opportunity for a systems review to help detect symptoms which patients may not report spontaneously. Thyroid function, full blood count and erythrocyte sedimentation rate should be determined. Vision and hearing can be checked, and a chest x-ray and electrocardiogram ordered²⁵ if there is any indication of cardiovascular or respiratory disease. Breast examination and Pap smear in women should be performed as indicated for the general female population.

1. Keks NA, Kulkarni J, Copolov DL. Treatment of schizophrenia. Med J Aust 1989; 151: 462-467.
2. Kane JM. Schizophrenia. N Engl J Med 1996; 334: 34-41.
3. Davis J. Overview: maintenance therapy in psychiatry: I. Schizophrenia. Am J Psychiatry 1975; 132: 1237-1245.
4. Silverstein ML, Harrow M. First-rank symptoms in the postacute schizophrenic: a follow-up study. Am J Psychiatry 1978; 135: 1481-1486.
5. Johnstone EC, Owens DGC, Gold A, et al. Schizophrenic patients discharged from hospital: a follow-up study. Br J Psychiatry 1984; 145: 586-590.
6. Birchwood M, Macmillan F, Smith J. Early intervention. In: Birchwood M, Tarrier N, editors. Innovations in the psychological management of schizophrenia. Assessment, treatment and services. Chichester: John Wiley & Sons, 1992: 115-145.
7. Van Kammen DP, Marder SR. Dopamine receptor antagonists. In: Kaplan HI, Sadock BJ, editors. Comprehensive textbook of psychiatry. 6th ed. Baltimore: Williams & Wilkins, 1995: 1987-2022.
8. Fenton WS, McGlashan TH. Schizophrenia: individual psychotherapy. In: Kaplan HI, Sadock BJ, editors. Comprehensive textbook of psychiatry. 6th ed. Baltimore: Williams & Wilkins, 1995: 1007-1018.
9. Frank AF, Gunderson JG. The role of the therapeutic alliance in the treatment of schizophrenia: relationship to course and outcome. Arch Gen Psychiatry 1990; 47: 228-236.
10. Carr V. Patients' techniques for coping with schizophrenia: an exploratory study. Br J Med Psychol 1988; 61: 339-352.
11. Harding CM, Zubin J, Strauss JS. Chronicity in schizophrenia: fact, partial fact, or artifact? Hosp Community Psychiatry 1987; 38: 477-485.
12. Caldwell CB, Gottesman II. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophr Bull 1990; 16: 571-589.
13. Cuffel BJ. Prevalence estimates of substance abuse in schizophrenia and their correlates. J Nerv Ment Dis 1992; 180: 589-592.
14. Duke PJ, Pantelis C, Barnes TRE. South Westminster Schizophrenia Survey: alcohol use and its relation to symptoms, tardive dyskinesia and illness onset. Br J Psychiatry 1994; 164: 630-636.
15. Linszen DH, Dingemans PM, Lentor ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry 1994; 51: 273-279.
16. Lane A, Byrne M, Mulvany F, et al. Reproductive behaviour in schizophrenia relative to other mental disorders: evidence for increased fertility in men despite decreased marital rate. Acta Psychiatr Scand 1995; 91: 222-228.
17. Darves-Bornoz JM, Lemperiere T, Degiovanni A, Gaillard P. Sexual victimization in women with schizophrenia and bipolar disorder. Soc Psychiatry Psychiatr Epidemiol 1995; 30: 78-84.
18. Bhui K, Puffet A, Herriot P. A survey of sexual problems amongst psychiatric inpatients. Soc Psychiatry Psychiatr Epidemiol 1995; 30: 73-77.
19. Brugha TS, Wing JK, Smith BL. Physical health of the long-term mentally ill in the community. Is there unmet need? Br J Psychiatry 1989; 155: 777-781.
20. Honig A, Pop P, Tan ES, et al. Physical illness in chronic psychiatric patients from a community psychiatric unit. The implications for daily practice. Br J Psychiatry 1989; 155: 58-64.
21. Vieweg V, Pandurangi A, Levenson J, Silverman J. Medical disorders in the schizophrenic patient. Int J Psychiatry Med 1995; 25: 137-172.
22. Barnes TRE. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154: 672-676.
23. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 1970; 212 Suppl: 11-19.
24. Kaplan HI, Sadock BJ, Grebb JA, editors. Kaplan and Sadock's synopsis of psychiatry: behavioural science, clinical psychiatry. 7th ed. Baltimore: Williams & Wilkins, 1994: 952.
25. Burns T, Kendrick T. Schizophrenia. In: Pullen I, Wilkinson G, Gray DP, editors. Psychiatry in general practice today. London: The Royal College of Psychiatrists and the Royal College of General Practitioners, 1994: 194-208.

Reprints: Professor V J Carr, Discipline of Psychiatry, Faculty of Medicine and Health Sciences, The University of Newcastle, Callaghan, NSW 2308.

©MJA 1999

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