Loxapine

The American Psychiatric Association (APA) has issued a practice guideline for the treatment of patients with schizophrenia. The guideline, which covers patients with schizophrenia 18 years of age and older, was published in April 1997 in a supplement to the American Journal of Psychiatry (vol. 154:(Suppl)1-63). It was developed by a six-member work group chaired by Marvin Herz, M.D., University of Rochester.

The guideline is divided into eight main sections. The first section is an executive summary. The other sections cover disease definition, natural history and epidemiology; treatment principles and alternatives; formulation and implementation of a treatment plan; clinical and environmental features influencing treatment; future research directions; names of the individuals and organizations that submitted comments about the guideline, and references.

The section on treatment principles and alternatives covers general issues, psychiatric management, pharmacologic treatments, electroconvulsive therapy, specific psychosocial interventions, other interventions and treatment settings. The section that describes treatment plans covers management of patients in the acute phase, stabilization phase and stable phase of schizophrenia, and addresses special issues in caring for patients with treatment-refractory illness. The discussion of treatment in the acute phase includes a treatment algorithm (see page 1218). The following information has been excerpted from the executive summary:

According to the APA, "schizophrenia is a chronic condition that frequently has devastating effects on many aspects of the patient's life and carries a high risk of suicide and other life-threatening conditions." The guideline outlines three phases of the illness: acute, stabilization and stable. The goals of treatment vary according to the phase and severity of illness.

During the acute phase, the APA recommends that each patient have a thorough initial work-up that includes a complete psychiatric and general medical history, a mental status examination and a physical examination that includes a neurologic evaluation. Basic laboratory tests should be performed. The risk of patients harming themselves or hurting others should be carefully evaluated and appropriate precautions should be taken.

Patients should be cared for in the least restrictive setting that is safe and allows for effective treatment. Hospitalization is required for patients who may harm themselves or others, cannot care for themselves or who have a general medical or psychiatric problem that cannot be treated any other way. If a patient needs to be hospitalized, all possible efforts should be made for the hospitalization to be voluntary.

Antipsychotic medications are indicated for nearly all acute psychotic episodes of schizophrenia, according to the guideline (see algorithm). Because of their known efficacy and safety, conventional antipsychotic medications and risperidone (Risperdal) are all considered reasonable first-line medications. Newer antipsychotics--olanzapine (Zyprexa), sertindole (not yet approved by the U.S. Food and Drug Administration) and quetiapine (not yet approved) also may be indicated for initial therapy. However, these newer drugs have limited safety and efficacy data.

Conventional antipsychotics include all antipsychotic medications except clozapine, risperidone and the three newer medications. The conventional antipsychotics listed in a table in the guideline are fluphenazine (Prolixin), trifluoperazine (Vesprin), perphenazine (Trilafon, Etrafon), mesoridazine (Serentil), chlorpromazine (Thorazine), thioridazine (Mellaril), haloperidol (Haldol), thiothixene (Navane), molindone (Moban) and loxapine (Loxitane). According to the guideline, all of the conventional antipsychotic medications are effective in diminishing most symptoms of schizophrenia, although the drugs differ in potency and side effects.

The APA notes that the choice of drug depends on such factors as past treatments, side effect profile, patient preferences and the preferred route of administration. Side effects and efficacy need to be considered when selecting a dosage of medication. An effective daily dose of a high-potency conventional antipsychotic is in the range of 5 to 20 mg of haloperidol or 300 to 1,000 mg of chlorpromazine equivalents. For risperidone, the daily dose should range from 4 to 6 ma; for olanzapine, it should be 10 to 20 ma. The optimal dose range has not been established yet for quetiapine. Unless side effects are uncomfortable, the initial dose should be monitored for at least three weeks. The guideline recommends that physicians avoid prematurely increasing the dose. If patients fail to respond to an adequate trial of four to six weeks of at least one antipsychotic medication, a trial of clozapine (Clozaril) should be considered except for patients who have specific contraindications to it. A trial of clozapine should last for at least three months, according to the APA.

The executive summary notes that the goals of the stabilization phase should be to minimize stress on the patient and provide support to reduce the likelihood of relapse, enhance the patient's adaptation to life in the community and help alleviate symptoms. The goals of treatment during the stable phase are to ensure that the patient is maintaining or improving his or her level of functioning and quality of life. Symptoms should be effectively treated and patients should be monitored for adverse effects. Ongoing monitoring and assessment are necessary. Review of the need for maintenance antipsychotic medication and the required dose should be done at least annually, according to the guideline.

The guideline also discusses the treatment of patients in demographic and psychosocial variables, including homelessness, cultural factors, gender and pregnancy, psychosocial stressors, older age and correctional settings. Treatment of concurrent medical conditions is also reviewed.

The guideline contains a series of recommendations for future research and new treatment development. In the section on future research, the guideline recognizes that schizophrenia may be a "final common pathway for a group of disorders with a variety of etiologies, courses and outcomes. To provide more-precise diagnosis and prognosis and more-specific treatment approaches, it would be helpful if subgroups of patients with schizophrenia were identified." Other recommended areas for future research include genetic research, improved knowledge of the workings of the brain, optimal dose ranges for patients in the stable phase of schizophrenia, and guidance about when and for which types of patients maintenance medication can be withdrawn. Improved methods of early detection and treatment of childhood schizophrenia are also needed.

Figure 1 reprinted with permission from the American Psychiatric Association Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 1997;154 (April Suppl):37.

COPYRIGHT 1997 American Academy of Family Physicians
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