Symptom Control and Patient Adherence to Treatment

Abstract

A CLINICIAN'S KEY GOALS WHEN TREATING PSYCHOSIS ARE TO control disease symptoms and to ensure patient adherence to treatment. Efficacy as well as side-effect profile are, therefore, the major selection criteria when choosing an antipsychotic medication.

Introduction

Antipsychotic drugs form the mainstay of schizophrenia treatment.¹ Although neuroleptic drugs have been used to control the psychotic symptoms associated with schizophrenia since the 1950s,² the introduction of atypical antipsychotic drugs in recent years has provided several therapeutic advantages. The two most important treatment goals influencing the choice of an antipsychotic drug are establishing symptom control and ensuring patient compliance with treatment.

Symptom Control

In treating patients with schizophrenia, the primary goal of the physician is to control the symptoms of the illness. The efficacy of the medication is a determining factor for the choice of antipsychotic drug that is prescribed.³ The effect of medication on the positive symptoms of schizophrenia is not the only consideration; negative, cognitive, and affective symptoms also should be taken into account. Consequently, atypical antipsychotics have proved advantageous. Atypical antipsychotic drugs are at least as effective as typical antipsychotics at treating the positive symptoms of schizophrenia,⁴ but they are superior at reducing the negative symptoms.⁵ In addition, preliminary reports suggest that atypical antipsychotics, such as olanzapine, may also improve depression and cognitive deficits.⁶

Patient Adherence to Treatment

In the United Kingdom, recently published guidelines from the National Institute for Clinical Excellence state that antipsychotic medication should be part of a comprehensive treatment regimen that also considers the individual's clinical, emotional, and social needs.⁷ If possible, the choice of medication should be made jointly by the patient and the treating physician, after a discussion of the relative benefits of the available drugs and the nature of potential side effects. In addition to dependable symptom control, the manageability of side effects may be an important consideration here. Ultimately, if side effects become too distressing for the patient, it may be appropriate for the physician to consider changing the medication to one that may be better tolerated. From the patient's perspective, atypical antipsychotic drugs significantly increase quality of life in comparison with typical antipsychotics, particularly in combination with nonpharmacological rehabilitative treatment.⁸

Side Effects

The burden of side effects from antipsychotic drugs may also influence patients' adherence to treatment. It is more likely that patients will adhere to treatment if they can tolerate side effects well⁹ and find it easy to comply with the treatment regimen (eg, a simple once-daily dosing). If patients find drug-induced adverse effects distressing, they may discontinue their medication, thereby increasing the risks of relapse¹⁰ and hospitalization.¹¹

Extrapyramidal side effects (EPSs) are more likely to occur when patients are treated with typical antipsychotics than when they receive atypical medication.¹² EPSs limit function, cause distress, may exacerbate the severity of the negative symptoms of schizophrenia,¹³ and are associated with social stigma.¹⁴ Because EPSs have a negative impact on patients' quality of life, it is desirable to avoid their occurrence. Atypical antipsychotics have a lower propensity to induce such side effects, although the different drugs vary in their tendency to do so. EPSs can occur relatively frequently with risperidone¹⁵ but are uncommon with olanzapine and quetiapine and appear to be absent with clozapine.¹³

Other antipsychotic-related side effects also may prove difficult to manage. For instance, early descriptive data from the Schizophrenia Outpatient Health Outcomes (SOHO) Study suggest that the prevalence of EPSs and usage of anticholinergic medication may be similar between typical antipsychotics and the atypical antipsychotic risperidone.¹⁶ In addition, clozapine use can cause agranulocytosis.¹⁷ Hyperprolactinemia can result from treatment with both typical antipsychotics and the atypical antipsychotic agent risperidone, which can cause more hyperprolactinemia than typical antipsychotics.¹⁸ This condition can be associated with amenorrhea, galactorrhea, sexual dysfunction, insulin resistance,^19,20 vascular endothelial damage,²¹ gynecomastia, and osteoporosis.²² Antipsychotic medications also have been associated with QT prolongation; the effects of sertindole (an atypical antipsychotic available in the UK and other European countries) on QT prolongation are well documented.²³

Obesity is becoming a major issue in the general population and is more prevalent in adults with mental illnesses.²⁴ Weight gain is a well recognized side effect of antipsychotic medications.²⁵ However, evidence is emerging that weight gain can be managed through simple intervention strategies. For instance, regular check-ups, lifestyle counseling, and behavioral control programs have all been shown to be effective.²⁶ Weight management clinics are cost-effective and inexpensive.²⁷

The prevalence of type 2 diabetes mellitus is 2 to 4 times higher in patients with schizophrenia and 2 to 3 times higher in bipolar sufferers than in the general population.^28,29 Though it was established well before the introduction of the first antipsychotics that schizophrenia itself is associated with glycemic abnormalities,³⁰ it has been suggested that antipsychotics might have an additional adverse glycemic effect.³¹ Given their greater vulnerability, psychiatric patients need to be regularly screened for diabetes, especially when risk factors such as family history of diabetes, Asian or African-Caribbean origin, and older age are present. To date, diabetes seems to be a class effect of both typical and atypical antipsychotics.

Conclusion

The addition of atypical antipsychotic medication to the therapeutic armamentarium for the treatment of schizophrenia provides clear advantages over therapy with conventional neuroleptic drugs. Symptoms can be targeted more widely (negative and cognitive symptoms may be improved, in addition to positive symptoms), and favorable side-effect profiles are more likely to result in better patient adherence to treatment. Clinical efficacy, along with side effects and their manageability, differs between therapeutic agents, and the final prescribing decision lies in the hands of clinicians who must be both well informed and sensitive to individual patient needs.