Summary

Psychoses affect up to 4% of the population.These conditions usually require long-term treatment with antipsychotic drugs, mood stabilisers or both. The availability of effective treatment means that most people with psychoses can live in the community. Psychosocial treatments and the provision of community services are critical, but are often inadequate. Long-term adverse effects can be a problem and adherence to treatment can be difficult for almost all patients. Depot antipsychotics have been widely used to improve adherence to maintenance treatment, but extrapyramidal adverse effects have been a major problem.

Introduction

Psychoses include schizophrenia, schizoaffective disorder, psychotic depression and bipolar mania. The diagnostic boundaries between these disorders can be unclear, but together they have a lifetime prevalence in the population of about 4%. Antipsychotic drugs treat positive symptoms (delusions, hallucinations and thought disorder) across the diagnostic spectrum. Atypical antipsychotics are also helpful for mania and psychotic depression. Mood stabilisers are also used in psychoses to treat mania and depression, usually in addition to antipsychotic drugs.1

While up to 30% of patients do not experience any relapse after their first psychotic episode, the remainder will develop long-term problems. Some patients will manifest a remitting-relapsing pattern of illness, while others will develop chronic illness, including negative symptoms (flat affect, poverty of thought, amotivation, social withdrawal and poor concentration). Negative symptoms tend to be associated with poor insight into the presence of illness and the need for treatment. Adherence to treatment can therefore be particularly problematic.

Chronic or relapsing illness is associated with impaired function and lower quality of life. These patients require active rehabilitation and integration into the community.

Long-term management in the community

Although many people with psychoses have a favourable outcome, others suffer unemployment, social and family dislocation and housing problems. Many patients with psychosis may require a comprehensive mix of services, which can be challenging to co-ordinate. Community psychiatric services may offer case management to assist with management planning and organisation. Specialist services provide specific psychological interventions (such as cognitive behavioural therapy for refractory psychoses) and vocational rehabilitation aimed toward functional recovery. Assertive community management (which involves proactive home visits, medication support and personal assistance) is recommended.

Almost all patients with psychoses living in the community will see a general practitioner; 81% do so in any given year. Often working together with specialist psychiatric services and social agencies, general practitioners can provide a number of key interventions.2

The physical care of patients with psychoses is a central role for general practitioners. These patients are at greater risk of physical illness, particularly cardiorespiratory and metabolic disorders. General practitioners can regularly monitor patients' physical state, undertaking a number of relevant investigations every 6–12 months depending on individual requirements (Table 1).

In addition to monitoring the mental state for evidence of deterioration or relapse, general practitioners can provide supportive psychotherapy and counselling, monitor and encourage adherence to treatment, check for adverse effects and adjust the dose and type of medication in collaboration with a psychiatrist. They also liaise with family and carers, provide education about the illness, and recognise and address problems associated with substance abuse. Good communication between the general practitioner and specialists is imperative.

Antipsychotic medications

Following the first psychotic episode, antipsychotic medication is usually stopped by the patient after 1-2 years, although long-term therapy is the rule for patients with recurrent illness. Antipsychotics prevent relapse in patients with remitted positive and mood symptoms, and maintenance treatment helps to reduce symptoms in patients with chronic illness. These drugs enable many patients who previously would have been institutionalised to live in the community.

The most commonly used conventional antipsychotics in the long-term treatment of psychoses are high-potency oral antipsychotics, such as haloperidol and trifluoperazine or depot formulations, such as flupenthixol. The major drawback with conventional antipsychotics is their tendency to produce extrapyramidal adverse effects at effective doses. These include dystonias, parkinsonism, akathisia and tardive dyskinesia, a disfiguring, stigmatising and often irreversible neurological disorder.

Atypical antipsychotics are a diverse group of drugs with a lower risk of extrapyramidal adverse effects at therapeutically effective doses. Some atypicals may be more effective than conventional antipsychotics in long-term treatment. Clozapine is particularly effective for treatment resistant cases. While its toxicity restricts initiation of treatment to specialist centres, increasingly general practitioners are involved in long-term care and monitoring of patients on clozapine therapy. Risperidone has shown superior efficacy to haloperidol in long-term prevention of relapse.3Recently, high-dose olanzapine was shown to have greater effectiveness than conventional and other atypical antipsychotics (apart from clozapine) in terms of discontinuation rates over an 18-month period.4

While reducing problems with extrapyramidal adverse effects, atypicals have caused other problems such as postural hypotension, weight gain and hyperglycaemia. Each drug seems to have adverse effects which are particular problems, for example, clozapine can cause neutropenia, agranulocytosis and myocarditis. Olanzapine frequently causes considerable weight gain and increases glucose and lipids which can lead to hyperlipidaemia and diabetes.4Although weight gain is less of a problem with risperidone, it may cause sexual dysfunction and amenorrhoea due to hyperprolactinaemia. Quetiapine may cause mild weight gain, while amisulpride and aripiprazole are generally well tolerated in long-term treatment (although aripiprazole can initially cause troubling nausea and restlessness).

Table 1
Monitoring the physical health of patients with psychosis *

Assessment Checks for:

History and examination, including:
- cardiovascular - evidence of arrhythmias and ischaemic heart disease
- neurological - tardive dyskinesia, akathisia and tremor
- funduscopic exam through undilated pupils - lens opacities and retinal pigmentation
Weight: calculate body mass index (weight/height2) changes in weight
Random blood glucose diabetes (increased risk with some atypical antipsychotics)
Cholesterol and triglycerides cardiovascular disorders (increased risk)
Vitamin B12 and folate nutritional deficiency
Calcium, phosphate drug effects
Full blood exam, erythrocyte sedimentation rate infection, nutritional deficiency, anaemia
Liver function alcohol and other drug effects
ECG drug effects, cardiovascular disease
Drug screen illicit drug use
Other investigations as appropriate, e.g.
- thyroid function - effects of lithium
- therapeutic drug monitoring - effects of lithium
- echocardiography - cardiomyopathy (clozapine)
- cervical smear

* suggested monitoring at initial examination and repeated at 6–12 month intervals depending on risk

Addressing adherence to treatment

Education, cognitive behaviour therapy, social skills training, treatment of substance abuse, personal assistance and assertive community support are probably the most important measures in aiding adherence when medication is not fully effective in re-establishing the patient's insight.5Depot formulations are widely used when psychosocial measures have been inadequate to ensure adherence to daily oral doses.

Depot antipsychotics take a long time to reach steady state, so oral supplementation is usually required in the first few months of treatment. Depending on the drug, the interval between injections can be extended to four weeks. Many patients receiving conventional depot antipsychotics experience extrapyramidal adverse effects, including a high prevalence of tardive dyskinesia.6

Risperidone is available in a long-acting injectable formulation. Initial findings and clinical experience suggest that injectable risperidone is effective for maintenance treatment of schizophrenia-related psychoses and causes relatively few adverse effects. The incidence of new cases of tardive dyskinesia has been low to date, but weight gain, amenorrhoea and sexual dysfunction do occur.

Conclusion

The long-term treatment of psychosis is challenging. General practitioners have a key role, particularly in the ongoing physical care of patients and in monitoring medication and the patient's mental state. Adherence to treatment is a frequent problem, which can be addressed with intensive psychosocial assistance. More often than not, services are less than adequate, and other measures such as long-acting injectable antipsychotic drugs may be required to ensure that patients continue their medication.

Self-test questions

The following statements are either true or false.

1. Atypical antipsychotics do not cause tardive dyskinesia.
2. Up to 30% of patients have no relapses after their first psychotic episode.

Answers to self-help questions

1. False
2. True

References

  1. Freedman R. Drug therapy: schizophrenia. N Engl J Med 2003;349:1738-49.
  2. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346:16-22.
  3. Charles J, Miller G, Ng A. Management of psychosis in Australian general practice. Aust Fam Physician 2006;35:88-9.
  4. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins Do, et al; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23.
  5. Mueser KT, McGurk SR. Schizophrenia. Lancet 2004;363:2063-72.
  6. Hope JD, Keks NA, Sacks TL, Freer T. Abnormal involuntary movements in people with schizophrenia in the community. Med J Aust 1999;171:111-12.