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Practice Guideline for the Treatment of Patients With Schizophrenia Second Edition

DOI: 10.1176/appi.books.9780890423363.45859
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Work Group on Schizophrenia

Anthony F. Lehman, M.D., M.S.P.H., Chair

Jeffrey A. Lieberman, M.D., Vice-Chair

Lisa B. Dixon, M.D., M.P.H.

Thomas H. McGlashan, M.D.

Alexander L. Miller, M.D.

Diana O. Perkins, M.D., M.P.H.

Julie Kreyenbuhl, Pharm.D., Ph.D. (Consultant)

Originally published in February 2004. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available.

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Guide to Using This Practice Guideline

The Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition, consists of three parts (Parts A, B, and C) and many sections, not all of which will be equally useful for all readers. The following guide is designed to help readers find the sections that will be most useful to them.

Part A, "Treatment Recommendations for Patients With Schizophrenia," is published as a supplement to the American Journal of Psychiatry and contains general and specific treatment recommendations. Section I summarizes the key recommendations of the guideline and codes each recommendation according to the degree of clinical confidence with which the recommendation is made. Section II is a guide to the formulation and implementation of a treatment plan for the individual patient. Section II.F, "Clinical Features Influencing the Treatment Plan," discusses a range of clinical considerations that could alter the general recommendations discussed in Section II. Section III describes treatment settings and housing options and provides guidance on choice of setting.

Part B, "Background Information and Review of Available Evidence," and Part C, "Future Research Directions," are not included in the American Journal of Psychiatry supplement but are provided with Part A in the complete guideline, which is available in print format from American Psychiatric Publishing, Inc., and online through the American Psychiatric Association (http://www.psych.org). Part B provides an overview of schizophrenia, including general information on its natural history, course, and epidemiology. It also provides a structured review and synthesis of the evidence that underlies the recommendations made in Part A. Part C draws from the previous sections and summarizes areas for which more research data are needed to guide clinical decisions.

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Development Process

This practice guideline was developed under the auspices of the Steering Committee on Practice Guidelines. The development process is detailed in a document available from the APA Department of Quality Improvement and Psychiatric Services: the "APA Guideline Development Process." Key features of this process include the following:

  • A comprehensive literature review.

  • Development of evidence tables.

  • Initial drafting of the guideline by a work group that included psychiatrists with clinical and research expertise in schizophrenia.

  • Production of multiple revised drafts with widespread review; four organizations and 62 individuals submitted significant comments.

  • Approval by the APA Assembly and Board of Trustees.

  • Planned revisions at regular intervals.

Relevant literature was identified through a computerized search of PubMed for the period from 1994 to 2002. Using the keywords schizophrenia OR schizoaffective, a total of 20,009 citations were found. Limiting the search by using the keywords antipsychotic agents, antipsychotic, tranquilizing agents, aripiprazole, olanzapine, ziprasidone, quetiapine, risperidone, clozapine, glycine, beta receptor blockers, antidepressive agents, antidepressant, divalproex, valproic acid, lithium, carbamazepine, benzodiazepines, electroconvulsive therapy, community treatment, psychoeducation, family education, skills training, social support, rehabilitation, case management, community support, supported employment, sheltered workshop, family therapy, family intervention, psychosocial adjustment, cognitive behavior, cognitive training, cognitive therapy, counseling, psychotherapy, group therapy, interpersonal therapy, individual therapy, first break, first episode, new onset, early treatment, and early detection resulted in 8,609 citations. After limiting these references to clinical trials and meta-analyses published in English that included abstracts, 1,272 articles were screened by using title and abstract information. The Cochrane Database of Systematic Reviews was also searched by using the keyword schizophrenia. Additional, less formal literature searches were conducted by APA staff and individual members of the work group on schizophrenia. Sources of funding were considered when the work group reviewed the literature but are not identified in this document. When reading source articles referenced in this guideline, readers are advised to consider the sources of funding for the studies.

This document represents a synthesis of current scientific knowledge and rational clinical practice on the treatment of patients with schizophrenia. It strives to be as free as possible of bias toward any theoretical approach to treatment. In order for the reader to appreciate the evidence base behind the guideline recommendations and the weight that should be given to each recommendation, the summary of treatment recommendations is keyed according to the level of confidence with which each recommendation is made. Each rating of clinical confidence considers the strength of the available evidence and is based on the best available data. When evidence is limited, the level of confidence also incorporates clinical consensus with regard to a particular clinical decision. In the listing of cited references, each reference is followed by a letter code in brackets that indicates the nature of the supporting evidence.

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Part A: Treatment Recommendations for Patients With Schizophrenia

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I. Executive Summary

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A. Coding System

Each recommendation is identified as falling into one of three categories of endorsement, indicated by a bracketed Roman numeral following the statement. The three categories represent varying levels of clinical confidence regarding the recommendation:

  • [I] Recommended with substantial clinical confidence.

  • [II] Recommended with moderate clinical confidence.

  • [III] May be recommended on the basis of individual circumstances.

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B. Formulation and Implementation of a Treatment Plan

Because schizophrenia is a chronic illness that influences virtually all aspects of life of affected persons, treatment planning has three goals: 1) reduce or eliminate symptoms, 2) maximize quality of life and adaptive functioning, and 3) promote and maintain recovery from the debilitating effects of illness to the maximum extent possible. Accurate diagnosis has enormous implications for short- and long-term treatment planning, and it is essential to note that diagnosis is a process rather than a one-time event. As new information becomes available about the patient and his or her symptoms, the patient's diagnosis should be reevaluated, and, if necessary, the treatment plan changed.

Once a diagnosis has been established, it is critical to identify the targets of each treatment, to have outcome measures that gauge the effect of treatment, and to have realistic expectations about the degrees of improvement that constitute successful treatment [I]. Targets of treatment, and hence of assessment, may include positive and negative symptoms, depression, suicidal ideation and behaviors, substance use disorders, medical comorbidities, posttraumatic stress disorder (PTSD), and a range of potential community adjustment problems, including homelessness, social isolation, unemployment, victimization, and involvement in the criminal justice system [I].

After the initial assessment of the patient's diagnosis and clinical and psychosocial circumstances, a treatment plan must be formulated and implemented. This formulation involves the selection of the treatment modalities, the specific type(s) of treatment, and the treatment setting. Periodic reevaluation of the diagnosis and the treatment plan is essential to good clinical practice and should be iterative and evolve over the course of the patient's association with the clinician [I].

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C. Establishing a Therapeutic Alliance

A supportive therapeutic alliance allows the psychiatrist to gain essential information about the patient and allows the patient to develop trust in the psychiatrist and a desire to cooperate with treatment. Identifying the patient's goals and aspirations and relating these to treatment outcomes fosters the therapeutic relationship as well as treatment adherence [II]. The clinician may also identify practical barriers to the patient's ability to participate in treatment, such as cognitive impairments or disorganization and inadequate social resources. Engagement of the family and other significant support persons, with the patient's permission, is recommended to further strengthen the therapeutic effort [I]. The social circumstances of the patient can have profound effects on adherence and response to treatment. Living situation, family involvement, sources and amount of income, legal status, and relationships with significant others (including children) are all areas that may be periodically explored by mental health care clinicians [II]. The psychiatrist can work with team members, the patient, and the family to ensure that such services are coordinated and that referrals for additional services are made when appropriate. The family's needs can be addressed and an alliance with family members can be facilitated by providing families with information about community resources and about patient and family organizations such as the National Alliance for the Mentally Ill (NAMI) [II].

Many patients with schizophrenia require, and should receive, a variety of treatments, often from multiple clinicians. It is therefore incumbent on clinicians to coordinate their work and prioritize their efforts. Because an accurate history of past and current treatments and responses to them is a key ingredient to treatment planning, excellent documentation is paramount [I]. Especially critical, for example, is information about prior treatment efforts and clinical response.

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D. Acute Phase Treatment

The goals of treatment during the acute phase of treatment, defined by an acute psychotic episode, are to prevent harm, control disturbed behavior, reduce the severity of psychosis and associated symptoms (e.g., agitation, aggression, negative symptoms, affective symptoms), determine and address the factors that led to the occurrence of the acute episode, effect a rapid return to the best level of functioning, develop an alliance with the patient and family, formulate short- and long-term treatment plans, and connect the patient with appropriate aftercare in the community. Efforts to engage and collaborate with family members and other natural caregivers are often successful during the crisis of an acute psychotic episode, whether it is the first episode or a relapse, and are strongly recommended [I]. Family members are often under significant stress during this time. Also, family members and other caregivers are often needed to provide support to the patient while he or she is recovering from an acute episode.

It is recommended that every patient have as thorough an initial evaluation as his or her clinical status allows, including complete psychiatric and general medical histories and physical and mental status examinations [I]. Interviews of family members or other persons knowledgeable about the patient may be conducted routinely, unless the patient refuses to grant permission, especially since many patients are unable to provide a reliable history at the first interview [I]. The most common contributors to symptom relapse are antipsychotic medication nonadherence, substance use, and stressful life events, although relapses are not uncommon as a result of the natural course of the illness despite continuing treatment. If nonadherence is suspected, it is recommended that the reasons for it be evaluated and considered in the treatment plan. General medical health as well as medical conditions that could contribute to symptom exacerbation can be evaluated by medical history, physical and neurological examination, and appropriate laboratory, electrophysiological, and radiological assessments [I]. Measurement of body weight and vital signs (heart rate, blood pressure, temperature) is also recommended [II]. Other laboratory tests to be considered to evaluate health status include a CBC; measurements of blood electrolytes, glucose, cholesterol, and triglycerides; tests of liver, renal, and thyroid function; a syphilis test; and when indicated and permissible, determination of HIV status and a test for hepatitis C [II]. Routine evaluation of substance use with a toxicology screen is also recommended as part of the medical evaluation [I]. A pregnancy test should be strongly considered for women with childbearing potential [II]. In patients for whom the clinical picture is unclear or where there are abnormal findings from a routine examination, more detailed studies (e.g., screening for heavy metal toxins, EEG, magnetic resonance imaging [MRI] scan, or computed tomography [CT] scan) may be indicated [II].

It is important to pay special attention to the presence of suicidal potential and the presence of command hallucinations and take precautions whenever there is any question about a patient's suicidal intent, since prior suicide attempts, current depressed mood, and suicidal ideation can be predictive of a subsequent suicide attempt in schizophrenia [I]. Similar evaluations are recommended in considering the likelihood of dangerous or aggressive behavior and whether the person will harm someone else or engage in other forms of violence [I].

It is recommended that pharmacological treatment be initiated promptly, provided it will not interfere with diagnostic assessment, because acute psychotic exacerbations are associated with emotional distress, disruption to the patient's life, and a substantial risk of dangerous behaviors to self, others, or property [I]. Before the patient begins treatment with antipsychotic medication, it is suggested that the treating physician, as is feasible, discuss the potential risks and benefits of the medication with the patient [I]. The selection of an antipsychotic medication is frequently guided by the patient's previous experience with antipsychotics, including the degree of symptom response, past experience of side effects, and preferred route of medication administration. In choosing among these medications, the psychiatrist may consider the patient's past responses to treatment, the medication's side effect profile (including subjective responses, such as a dysphoric response to a medication), the patient's preferences for a particular medication based on past experience, the intended route of administration, the presence of comorbid medical conditions, and potential interactions with other prescribed medications [I]. Finally, while most patients prefer oral medication, patients with recurrent relapses related to nonadherence are candidates for a long-acting injectable antipsychotic medication, as are patients who prefer this mode of administration [II].

The recommended dose is that which is both effective and not likely to cause side effects that are subjectively difficult to tolerate, since the experience of unpleasant side effects may affect long-term adherence [I]. The dose may be titrated as quickly as tolerated to the target therapeutic dose of the antipsychotic medication, and unless there is evidence that the patient is having uncomfortable side effects, monitoring of the patient's clinical status for 2–4 weeks is warranted to evaluate the patient's response to the treatment [II]. During these weeks it is often important for physicians to be patient and avoid the temptation to prematurely escalate the dose for patients who are responding slowly [I]. If the patient is not improving, it may be helpful to establish whether the lack of response can be explained by medication nonadherence, rapid medication metabolism, or poor absorption [II].

Adjunctive medications are also commonly prescribed for comorbid conditions in the acute phase. Benzodiazepines may be used to treat catatonia as well as to manage both anxiety and agitation until the antipsychotic has had time to be therapeutically effective [II]. Antidepressants can be considered for treating comorbid major depression or obsessive-compulsive disorder, although vigilance to protect against the risk of exacerbation of psychosis with some antidepressants is important [II]. Mood stabilizers and beta-blockers may be considered for reducing the severity of recurrent hostility and aggression [II]. Careful attention must be paid to potential drug-drug interactions, especially those related to metabolism by cytochrome P450 enzymes [I].

Psychosocial interventions in the acute phase are aimed at reducing overstimulating or stressful relationships, environments, or life events and at promoting relaxation or reduced arousal through simple, clear, coherent communications and expectations; a structured and predictable environment; low performance requirements; and tolerant, nondemanding, supportive relationships with the psychiatrist and other members of the treatment team. Providing information to the patient and the family on the nature and management of the illness that is appropriate to the patient's capacity to assimilate information is recommended [II]. Patients can be encouraged to collaborate with the psychiatrist in selecting and adjusting the medication and other treatments provided [II].

The acute phase is also the best time for the psychiatrist to initiate a relationship with family members, who tend to be particularly concerned about the patient's disorder, disability, and prognosis during the acute phase and during hospitalization [I]. Educational meetings, "survival workshops" that teach the family how to cope with schizophrenia, and referrals to local chapters of patient and family organizations such as NAMI may be helpful and are recommended [III]. Family members may be under considerable stress, particularly if the patient has been exhibiting dangerous or unstable behavior.

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E. Stabilization Phase

During the stabilization phase, the goals of treatment are to reduce stress on the patient and provide support to minimize the likelihood of relapse, enhance the patient's adaptation to life in the community, facilitate continued reduction in symptoms and consolidation of remission, and promote the process of recovery. If the patient has improved with a particular medication regimen, continuation of that regimen and monitoring are recommended for at least 6 months [I]. Premature lowering of dose or discontinuation of medication during this phase may lead to a recurrence of symptoms and possible relapse. It is also critical to assess continuing side effects that may have been present in the acute phase and to adjust pharmacotherapy accordingly to minimize adverse side effects that may otherwise lead to medication nonadherence and relapse [I].

Psychosocial interventions remain supportive but may be less structured and directive than in the acute phase [III]. Education about the course and outcome of the illness and about factors that influence the course and outcome, including treatment adherence, can begin in this phase for patients and continue for family members [II].

It is important that there be no gaps in service delivery, because patients are particularly vulnerable to relapse after an acute episode and need support in resuming their normal life and activities in the community [I]. For hospitalized patients, it is frequently beneficial to arrange an appointment with an outpatient psychiatrist and, for patients who will reside in a community residence, to arrange a visit before discharge [II]. Adjustment to life in the community for patients can be facilitated through realistic goal setting without undue pressure to perform at high levels vocationally and socially, since unduly ambitious expectations can be stressful and can increase the risk of relapse [I]. While it is critical not to place premature demands on the patient regarding engagement in community-based activities and rehabilitation services, it is equally critical to maintain a level of momentum aimed at improving community functioning in order to instill a sense of hope and progress for the patient and family [I].

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F. Stable Phase

The goals of treatment during the stable phase are to ensure that symptom remission or control is sustained, that the patient is maintaining or improving his or her level of functioning and quality of life, that increases in symptoms or relapses are effectively treated, and that monitoring for adverse treatment effects continues. Regular monitoring for adverse effects is recommended [I]. If the patient agrees, it is helpful to maintain strong ties with persons who interact with the patient frequently and would therefore be most likely to notice any resurgence of symptoms and the occurrence of life stresses and events that may increase the risk of relapse or impede continuing functional recovery [II]. For most persons with schizophrenia in the stable phase, psychosocial interventions are recommended as a useful adjunctive treatment to pharmacological treatment and may improve outcomes [I].

Antipsychotic medications substantially reduce the risk of relapse in the stable phase of illness and are strongly recommended [I]. Deciding on the dose of an antipsychotic medication during the stable phase is complicated by the fact that there is no reliable strategy available to identify the minimum effective dose to prevent relapse. For most patients treated with first-generation antipsychotics, a dose is recommended that is around the "extrapyramidal symptom (EPS) threshold" (i.e., the dose that will induce extrapyramidal side effects with minimal rigidity detectable on physical examination), since studies indicate that higher doses are usually not more efficacious and increase the risk of subjectively intolerable side effects [II]. Lower doses of first-generation antipsychotic medications may be associated with improved adherence and better subjective state and perhaps ultimately better functioning. Second-generation antipsychotics can generally be administered at doses that are therapeutic yet well below the "EPS threshold." The advantages of decreasing antipsychotic doses to minimize side effects can be weighed against the disadvantage of a somewhat greater risk of relapse and more frequent exacerbations of schizophrenic symptoms. In general, it is more important to prevent relapse and maintain the stability of the patient [III].

The available antipsychotic medications are associated with differential risk of a variety of side effects, including neurological, metabolic, sexual, endocrine, sedative, and cardiovascular side effects. Monitoring of side effects based on the side effect profile of the prescribed antipsychotic is warranted. During the stable phase of treatment it is important to routinely monitor all patients treated with antipsychotics for extrapyramidal side effects and the development of tardive dyskinesia [I]. Because of the risk of weight gain associated with many antipsychotics, regular measurement of weight and body mass index (BMI) is recommended [I]. Routine monitoring for obesity-related health problems (e.g., high blood pressure, lipid abnormalities, and clinical symptoms of diabetes) and consideration of appropriate interventions are recommended particularly for patients with BMI in the overweight and obese ranges [II]. Clinicians may consider regular monitoring of fasting glucose or hemoglobin A1c levels to detect emerging diabetes, since patients often have multiple risk factors for diabetes, especially patients with obesity [I].

Antipsychotic treatment often results in substantial improvement or even remission of positive symptoms. However, most patients remain functionally impaired because of negative symptoms, cognitive deficits, and limited social function. It is important to evaluate whether residual negative symptoms are in fact secondary to a parkinsonian syndrome or untreated major depression, since interventions are available to address these causes of negative symptoms [II].

Most patients who develop schizophrenia and related psychotic disorders are at very high risk of relapse in the absence of antipsychotic treatment. Unfortunately, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. It is important to discuss with the patient the risks of relapse versus the long-term potential risks of maintenance treatment with the prescribed antipsychotic [I]. If a decision is made to discontinue antipsychotic medication, additional precautions to minimize the risk of a psychotic relapse are warranted. Educating the patient and family members about early signs of relapse, advising them to develop plans for action should these signs appear, and encouraging the patient to attend outpatient visits on a regular basis are warranted [I]. Indefinite maintenance antipsychotic medication is recommended for patients who have had multiple prior episodes or two episodes within 5 years [I]. In patients for whom antipsychotic medications have been prescribed, monitoring for signs and symptoms of impending or actual relapse is recommended [I].

Adjunctive medications are commonly prescribed for comorbid conditions of patients in the stable phase. Comorbid major depression and obsessive-compulsive disorder may respond to antidepressant medications [II]. Mood stabilizers may also address prominent mood lability [II]. Benzodiazepines may be helpful for managing anxiety and insomnia during the stable phase of treatment [II].

In assessing treatment resistance or partial response, it is important to carefully evaluate whether the patient has had an adequate trial of an antipsychotic medication, including whether the dose is adequate and whether the patient has been taking the medication as prescribed. An initial trial of 4–6 weeks generally is needed to determine if the patient will have any symptomatic response, and symptoms can continue to improve over 6 months or even longer periods of antipsychotic treatment [II]. Given clozapine's superior efficacy, a clozapine trial should be considered for a patient who has had no response or partial and suboptimal response to two trials of antipsychotic medication (at least one second-generation agent) or for a patient with persistent suicidal ideation or behavior that has not responded to other treatments [I].

A number of psychosocial treatments have demonstrated effectiveness during the stable phase. They include family intervention [I], supported employment [I], assertive community treatment [I], skills training [II], and cognitive behaviorally oriented psychotherapy [II]. In the same way that psychopharmacological management must be individually tailored to the needs and preferences of the patient, so too should the selection of psychosocial treatments [I]. The selection of appropriate psychosocial treatments is guided by the circumstances of the individual patient's needs and social context [II].

Interventions that educate family members about schizophrenia are needed to provide support and offer training in effective problem solving and communication, reduce symptom relapse, and contribute to improved patient functioning and family well-being [I]. The Program for Assertive Community Treatment (PACT) is a specific model of community-based care that is needed to treat patients who are at high risk for hospital readmission and who cannot be maintained by more usual community-based treatment [I]. Persons with schizophrenia who have residual psychotic symptoms while receiving adequate pharmacotherapy also may be offered cognitive behaviorally oriented psychotherapy [II].

Supported employment is an approach to improve vocational functioning among persons with various types of disabilities, including schizophrenia, and should be made available [I]. The evidence-based supported employment programs that have been found effective include the key elements of services focused on competitive employment, eligibility based on the consumer's choice, rapid job search, integration of rehabilitation and mental health care, attention to the consumer's preferences, and time-unlimited and individualized support.

Social skills training may be helpful in addressing functional impairments with social skills or activities of daily living [II]. The key elements of this intervention include behaviorally based instruction, modeling, corrective feedback, and contingent social reinforcement.

Treatment programs need to combine medications with a range of psychosocial services to reduce the need for crisis-oriented hospitalizations and emergency department visits and enable greater recovery [I].

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G. Other Specific Treatment Issues

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1. First episode

It is important to treat schizophrenia in its initial episode as soon as possible [II]. When a patient presents with a first-episode psychosis, close observation and documentation of the signs and symptoms over time are important because first episodes of psychosis can be polymorphic and evolve into a variety of specific disorders (e.g., schizophreniform disorder, bipolar disorder, schizoaffective disorder) [I]. Furthermore, in persons who meet the criteria for being prodromally symptomatic and at risk for psychosis in the near future, careful assessment and frequent monitoring are recommended until symptoms remit spontaneously, evolve into schizophrenia, or evolve into another diagnosable and treatable mental disorder [III]. The majority of first-episode patients are responsive to treatment, with more than 70% achieving remission of psychotic signs and symptoms within 3–4 months and 83% achieving stable remission at the end of 1 year. First-episode patients are generally more sensitive to the therapeutic effects and side effects of medications and often require lower doses than patients with chronic schizophrenia. Minimizing risk of relapse in a remitted patient is a high priority, given the potential clinical, social, and vocational costs of relapse [I]. Family members are especially in need of education and support at the time of the patient's first episode [I].

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2. Negative symptoms

Treatment of negative symptoms begins with assessing the patient for syndromes that can cause the appearance of secondary negative symptoms [I]. The treatment of such secondary negative symptoms consists of treating their cause, e.g., antipsychotics for primary positive symptoms, antidepressants for depression, anxiolytics for anxiety disorders, or antiparkinsonian agents or antipsychotic dose reduction for extrapyramidal side effects [III]. If negative symptoms persist, they are presumed to be primary negative symptoms of the deficit state. There are no treatments with proven efficacy for primary negative symptoms.

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3. Substance use disorders

Nearly one-half of patients with schizophrenia have comorbid substance use disorders, excluding nicotine abuse/dependence, which itself exceeds 50% in prevalence in this group. The goals of treatment for patients with schizophrenia who also have a substance use disorder are the same as those for treatment of patients with schizophrenia without comorbidity but with the addition of the goals for the treatment of substance use disorders, e.g., harm reduction, abstinence, relapse prevention, and rehabilitation. A comprehensive integrated treatment model is recommended in which the same clinicians or team of clinicians provide treatment for schizophrenia as well as treatment of substance use disorders [III]. This form of treatment features assertive outreach, case management, family interventions, housing, rehabilitation, and pharmacotherapy. It also includes behavioral interventions for those who are trying to attain or maintain abstinence and a stage-wise motivational approach for patients who do not recognize the need for treatment of a substance use disorder.

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4. Depression

Depressive symptoms are common at all phases of schizophrenia. A careful differential diagnosis that considers the contributions of side effects of antipsychotic medications, demoralization, the negative symptoms of schizophrenia, and substance intoxication or withdrawal is recommended [I]. Depressive symptoms that occur during the acute psychotic phase usually improve as patients recover from the psychosis. There is also evidence to suggest that depressive symptoms are reduced by antipsychotic treatment, with comparison trials finding that second-generation antipsychotics may have greater efficacy for depressive symptoms than first-generation antipsychotics [II]. Antidepressants may be added as an adjunct to antipsychotics when the depressive symptoms meet the syndromal criteria for major depressive disorder or are severe, causing significant distress or interfering with function [II].

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5. Suicidal and aggressive behaviors

Suicide is the leading cause of premature death among patients with schizophrenia. Some risk factors for suicide among patients with schizophrenia are the same as those for the general population: male gender, white race, single marital status, social isolation, unemployment, a family history of suicide, previous suicide attempts, substance use disorders, depression or hopelessness, and a significant recent adverse life event. Specific demographic risk factors for suicide among persons with schizophrenia are young age, high socioeconomic status background, high IQ with a high level of premorbid scholastic achievement, high aspirations and expectations, early age at onset/first hospitalization, a chronic and deteriorating course with many relapses, and greater insight into the illness.

Despite identification of these risk factors, it is not possible to predict whether an individual patient will attempt suicide or die by suicide. It is important to consider suicide risk at all stages of the illness and to perform an initial suicide risk assessment and regular evaluation of suicide risk as part of each patient's psychiatric evaluation [I]. There is evidence to suggest that both first- and second-generation antipsychotic medications may reduce the risk of suicide. However, clozapine is the most extensively studied and has been shown to reduce the rates of suicide [II] and persistent suicidal behavior [I].

During a hospitalization, use of suicide precautions and careful monitoring over time for suicidal patients are essential [I]. Upon discharge, the patient and the family members may be advised to look for warning signs and to initiate specific contingency plans if suicidal ideation recurs [I]. After a recent discharge from the hospital, a higher frequency of outpatient visits is recommended, and the number of visits may need to be increased during times of personal crisis, significant environmental changes, heightened distress, or deepening depression during the course of illness [III].

A minority of patients with schizophrenia have an increased risk for aggressive behavior. The risk for aggressive behavior increases with comorbid alcohol abuse, substance abuse, antisocial personality, or neurological impairment. Identifying risk factors for aggressive behavior and assessment of dangerousness are part of a standard psychiatric evaluation [I].

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H. Treatment Settings and Housing Options

Patients with schizophrenia may receive care in a variety of settings. In general, patients should be cared for in the least restrictive setting that is likely to be safe and to allow for effective treatment [I]. Indications for hospitalization usually include the patient's being considered to pose a serious threat of harm to self or others or being unable to care for self and needing constant supervision or support [I]. Other possible indications for hospitalization include general medical or psychiatric problems that make outpatient treatment unsafe or ineffective [III] or new onset of psychosis [III]. Efforts should be made to hospitalize such patients voluntarily [I].

Treatment programs that emphasize highly structured behavioral techniques, including a token economy, point systems, and skills training that can improve patients' functioning, are recommended for patients with treatment-resistant schizophrenia who require long-term hospitalization [I].

When it is uncertain whether the patient needs to be hospitalized, alternative treatment in the community, such as day hospitalization, home care, family crisis therapy, crisis residential care, or assertive community treatment, should be considered [III]. Day hospitalization can be used as an immediate alternative to inpatient care for acutely psychotic patients or used to continue stabilization after a brief hospital stay [III].

Day treatment programs can be used to provide ongoing supportive care for marginally adjusted patients with schizophrenia in the later part of the stabilization phase and the stable phase of illness, and such programs are usually not time-limited [III]. The goals are to provide structure, support, and treatment to help prevent relapse and to maintain and gradually improve the patient's social functioning [III].

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II. Formulation and Implementation of a Treatment Plan

Because schizophrenia is a chronic illness that affects virtually all aspects of life of affected persons, treatment planning has three goals: 1) reduce or eliminate symptoms, 2) maximize quality of life and adaptive functioning, and 3) enable recovery by assisting patients in attaining personal life goals (e.g., in work, housing, and relationships). For purposes of presentation throughout this guideline, the course of treatment for persons with schizophrenia is divided into three phases: acute, stabilization, and stable. The acute phase begins with a new onset or acute exacerbation of symptoms and spans the period until these symptoms are reduced to a level considered to be the patient's expected "baseline." The stabilization period follows the acute phase and constitutes a time-limited transition to continuing treatment in the stable phase. Combined, the acute and stabilization phases generally span approximately 6 months. The stable phase represents a prolonged period of treatment and rehabilitation during which symptoms are under adequate control and the focus is on improving functioning and recovery. While these distinctions may be somewhat arbitrary, they provide a useful framework for discussion of treatment.

Many of the advances in the treatment of schizophrenia over the past two decades have come from recognition of the complexities of the manifestations and the different stages of the illness. These insights into the multiple components of psychopathology in schizophrenia and into the role of family, social, and other environmental factors in influencing both psychopathology and adaptation have resulted in development of a wide range of treatments that target specific aspects of the illness. Recognition of the different stages of the illness has led to various approaches in treatment planning, treatment selection, and drug dosing. Fragmentation of services and treatments has long been a problem in delivering comprehensive care to persons with schizophrenia. This fragmentation is determined by several factors, including the use of many different treatment settings, the necessary involvement of several professional disciplines, and the use of multiple funding streams, coupled with inadequate insurance coverage and the decline in funding for public and private mental health services, to mention just a few. It is critical, under these circumstances, that there be an overarching treatment plan that serves the short- and long-term needs of the patient and that is periodically modified as clinical circumstances change and new knowledge about treatments becomes available.

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A. Psychiatric Management

This section is an overview of key issues in the psychiatric management of patients with schizophrenia. It highlights areas that research has shown to be important in affecting the course of illness and success of treatment. These issues arise in the management of all psychiatric illnesses. This section notes the particular ways in which they occur in the treatment of patients with schizophrenia.

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1. Assessing symptoms and establishing a diagnosis

Effective and appropriate treatments are based on accurate, relevant diagnostic and clinical assessments. In the case of schizophrenia, the diagnosis has major implications for short- and long-term treatment planning. (See Part B, Section IV.A, "Clinical Features," for a description of the characteristic symptoms of schizophrenia and the DSM-IV-TR criteria for diagnosis of the illness.) It is beyond the scope of this guideline to discuss the differential diagnosis of psychotic disorders and their evaluation. However, it is important to note that diagnosis is a process rather than a one-time event. As new information becomes available about the patient and his or her symptoms, the patient's diagnosis should be reevaluated and, if necessary, the treatment plan changed.

Proper diagnosis, while essential, is insufficient to adequately guide treatment of schizophrenia. Treatments are directed at the manifestations and sequelae of schizophrenia. It is critical to identify the targets of each treatment, to have outcome measures that gauge the effect of treatment, and to have realistic expectations about the degrees of improvement that constitute successful treatment. Depression, suicide, homelessness, substance use disorders, medical comorbidities, social isolation, joblessness, criminal victimization, past sexual or physical abuse, and involvement in the criminal justice system are all far more common among persons with schizophrenia, particularly in the chronic stages of the illness, than in the general population. In addition to the core symptoms of schizophrenia, these areas need careful assessment and, as warranted, appropriate interventions.

A number of objective, quantitative rating scales to monitor clinical status in schizophrenia are available, as described in the American Psychiatric Association's (APA's) Handbook of Psychiatric Measures (1). They include the Structured Clinical Interview for DSM-IV (2) for establishing diagnosis, the Abnormal Involuntary Movement Scale (3) for monitoring tardive dyskinesia and other abnormal movements, and the Brief Psychiatric Rating Scale (BPRS) (4–6) and the Positive and Negative Syndrome Scale (PANSS) (7) for monitoring psychopathology. Other brief structured assessments are also available (8, 9). There are several reasons that use of rating scales is important. First, rating scales provide a record that documents the patient's response to treatment. This record is of particular value when the treatment is nonstandard (e.g., combination of antipsychotics) or expensive. Second, the ratings can be compared with the patient's, family members', and clinician's impressions of treatment effects and over time can clarify the longitudinal course of the patient's illness. This process can help temper excessive optimism when new treatments are begun and can provide useful information about the actual effects of prior treatments. Third, use of anchored scales with criteria to assess the severity and frequency of symptoms helps patients become more informed self-observers. Finally, use of the rating scales over time ensures that information about the same areas is collected at each administration and helps avoid omission of key elements of information needed to guide treatment.

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2. Developing a plan of treatment

After the assessment of the patient's diagnosis and clinical and psychosocial circumstances, a treatment plan must be formulated and implemented. This process involves the selection of the treatment modalities, specific type(s) of treatment, and treatment setting. Depending on the acuity of the clinical situation and because information about the patient's history and from the clinical evaluation may only gradually become available, this process can be iterative and evolve over the course of the patient's association with the clinician. Indeed, formulation and periodic reevaluation of the treatment plan at different phases of implementation and stages of illness are essential to good clinical practice. This process is described in greater detail in the subsequent sections on the various phases of illness, treatment settings, and types of treatments.

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3. Developing a therapeutic alliance and promoting treatment adherence

It is essential for the psychiatrist who is treating the patient to establish and maintain a supportive therapeutic alliance, which forms the foundation on which treatment is conducted (10). Such an alliance allows the psychiatrist to gain essential information about the patient and allows the patient to develop trust in the psychiatrist and a desire to collaborate in treatment. To facilitate this process, continuity of care with the same psychiatrist over time is recommended, allowing the psychiatrist to learn more about the patient as a person and the individual vicissitudes of the disorder over time. However, while continuity is desirable, it does not ensure quality, and continuity of inadequate treatment can be highly problematic.

Research indicates that specific attention in the therapeutic relationship to identifying the patient's goals and aspirations and relating them to treatment outcomes increases treatment adherence (11). Moreover, evidence supports the conclusion that the most effective medication adherence strategies focus on the patient's attitudes and behaviors with respect to medication rather than taking a general psychoeducational approach (12).

Not uncommonly, patients with schizophrenia stop taking medications, miss clinic appointments, fail to report essential information to their psychiatrists, and otherwise choose to not participate in recommended treatments. To address partial or full treatment nonadherence, the clinician should first assess contributing factors. Potential factors can be broadly conceptualized under the health belief model, which assumes adherence behavior is dynamic and influenced by a patient's beliefs about need for treatment, the potential risks and benefits of treatment, barriers to treatment, and social support for adhering to treatment (13). Frequent causes of poor adherence are lack of insight (14), breakdown of the therapeutic alliance, discrimination associated with the illness, cultural beliefs, failure to understand the need to take daily medication even in the stable phase, cognitive impairment (15, 16), and experience of unpleasant medication side effects such as akathisia (17, 18). Most patients have some ambivalence about taking antipsychotic medications, all of which can be associated with unpleasant and, rarely, dangerous side effects. Even patients with good insight into their symptoms or illness may not perceive their prescribed medication as potentially or actually helpful. Patients who do experience troublesome or serious side effects may decide that these effects outweigh the benefits of medication. Finally, people important to the patient, including family and friends, may discourage the patient from taking medication or participating in other aspects of treatment.

Once the reasons for incomplete adherence are understood, clinical interventions can be implemented to address them. For example, encouraging the patient to report side effects and attempting to diminish or eliminate them can significantly improve medication adherence. Also, it is important for patients who are relatively asymptomatic in the stable phase to understand that medication may be prophylactic in preventing relapse (19, 20). If a patient stops taking medication during the stable phase, he or she may feel better, with less sedation or other side effects. As a result, the patient may come to the false conclusion that the medication is not necessary or does not have benefits. As will be described in later sections, psychotherapeutic techniques based on motivational interviewing and cognitive behavior techniques may enhance insight and treatment adherence. In situations in which patients choose not to adhere to prescribed psychosocial interventions, a careful review of the patient's perceptions of the goals of the treatment and its likelihood for success is recommended.

The clinician may also help to identify practical barriers to adherence, such as cognitive impairments or disorganization that interferes with a willing patient's regular taking of medication or participation in treatment. Use of simple aids, such as a pillbox placed in a prominent location in the home and a watch with an alarm, can enhance adherence. Family members and significant others can also be involved, for example, by helping the patient fill the pillbox and by regularly monitoring adherence. Patients without health care insurance may have difficulty affording even generic antipsychotics or basic psychosocial services. The clinician may help with access to medications by suggesting and completing the physician's sections of the application for patients' assistance programs offered by most pharmaceutical companies. Some patients may not have transportation to the pharmacy or to physician appointments and other treatment services. For patients who are parents, lack of child care may also pose a barrier to attending appointments.

For some patients, medication with a longer elimination half-life or long-acting injectable medications are options that may improve treatment adherence or minimize nonadherence. It is also important to note that the half-lives of oral antipsychotic medications vary widely. For patients who are prone to forget doses or are intermittently nonadherent to treatment, drugs with slower rates of metabolism may be used preferentially.

When a patient does not appear for appointments or is nonadherent in other ways, assertive outreach, including telephone calls and home visits, when appropriate, may be very helpful in reengaging the patient in treatment. This outreach can be carried out by the psychiatrist or other designated team member (e.g., of an assertive community treatment team), when available, in consultation with the psychiatrist. For some patients, nonadherence with care is frequent and is associated with repeated cycles of decompensation and rehospitalization. Particularly for patients who pose ongoing risks to self or others as a result of nonadherence, many states now have programs available for mandatory outpatient treatment (sometimes referred to as outpatient commitment). Although some have questioned whether mandatory outpatient treatment increases patients' reluctance to seek help voluntarily (21–23), a growing body of evidence suggests that a number of benefits may occur with mandatory outpatient treatment for appropriately selected patients when it incorporates intensive individualized outpatient services for an extended period of time. In addition to enhanced adherence, most (24–27) but not all (28) studies show mandatory outpatient treatment to be associated with benefits, including reductions in substance use and abuse, decreases in violent incidents, reductions in the likelihood of being criminally victimized, and improvements in quality of life in appropriately targeted patients. Thus, for a small subgroup of patients with repeated relapses and rehospitalizations associated with nonadherence, mandatory outpatient treatment can be a useful approach to improved adherence and enhanced outcomes (29).

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4. Providing patient and family education and therapies

Working with patients to recognize early symptoms of relapse can result in preventing full-blown illness exacerbations (30). Family education about the nature of the illness and coping strategies can markedly diminish relapses and improve quality of life for patients (31). For general educational purposes, a variety of useful written materials about schizophrenia is available. The interventions that have been shown to be effective, however, involve face-to-face interactions in individual or group sessions for a total of at least 9–12 months, with the availability of crisis intervention and problem-solving tasks as a central element of the therapy.

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5. Treating comorbid conditions

As already noted, a number of psychiatric, social, and other medical conditions occur far more frequently in persons with schizophrenia than in the general population. Periodic assessment of these conditions by the treatment team is important. Commonly co-occurring major depression, substance use disorders, and PTSD are usually identifiable through clinical examinations and discussions with the patient and significant others, combined with longitudinal observation of the patient's behavior patterns. Each of these conditions deserves attention and possibly treatment in its own right, with such treatment concurrent with that for schizophrenia. Substance use disorders, in particular, complicate assessment and treatment of schizophrenia, but delaying treatment of the psychotic disorder until the substance use disorder is under control is not recommended, as untreated psychosis is likely to be associated with increased substance use (32).

Section II.F.3, "Concurrent General Medical Conditions", discusses nonpsychiatric medical conditions that are commonly comorbid with schizophrenia. Certain illnesses, such as diabetes, are more common in persons with schizophrenia and have also been associated with some second-generation antipsychotic medications. Nicotine dependence is also common among persons with schizophrenia and contributes to the increased risk of physical illnesses (33, 34). It is important that patients have access to primary care clinicians who can work with the psychiatrist to diagnose and treat concurrent general medical conditions and that the psychiatrist maintain competence in screening for common medical conditions and for providing ongoing monitoring and treatment of common medical conditions in conjunction with primary care clinicians.

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6. Attending to the patient's social circumstances and functioning

The social circumstances and functioning of the patient can have profound effects on adherence and response to treatment. The patient's living situation, family involvement, sources and amount of income, legal status, and relationships with significant others (including children) can both produce stress and be protective; thus, all are areas where periodic exploration by mental health care clinicians is warranted. A frequently neglected aspect of social assessment is the parenting role of patients with children (35, 36). The patient's sexuality is also often not adequately assessed, not only from the standpoint of adverse medication effects, but in terms of sexual relations and practices.

Depending on the nature of the problem in the patient's social circumstances, other mental health professionals may need to be involved in achieving its resolution. The psychiatrist can work with team members, the patient, and the family to ensure that such services are coordinated and that referrals for additional services are made when appropriate. It is important that disability income support is secured when indicated.

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7. Integrating treatments from multiple clinicians

Many patients with schizophrenia require a variety of treatments, often from multiple clinicians. This requirement creates the potential for fragmentation of treatment efforts for patients who frequently have problems with planning and organizing. In many settings integration of treatments is best accomplished through designation of treatment teams, led by a psychiatrist or other skilled mental health professional, that meet periodically to review progress and goals and to identify obstacles to improvement. So-called case management, which provides the patient assistance in gaining access to community services and resources, is often useful to facilitate integration of treatments. Either several members of a team or one person can be assigned to be the case manager, ensuring that the patient receives coordinated, continuous, and comprehensive services. For example, the case manager may accompany the patient to a welfare agency, visit the patient's home if a clinical appointment is missed, or convene a meeting of workers from different agencies serving the patient to formulate an overall treatment plan in conjunction with the psychiatrist. There are a variety of educational and organizational approaches to building teams and programs that facilitate the goal of integrated treatment (37, 38).

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8. Documenting treatment

Whether treated in the private or public sector, most persons with schizophrenia will have many different practitioners over the course of their illness. These transitions result from changes in treatment venues (inpatient, outpatient, assertive community treatment, etc.), program availability, insurance, the patient's locale, and clinic personnel. Because an accurate history of past and current treatments and responses to them is a key ingredient to treatment planning, excellent documentation is paramount. Especially critical, for example, is information about prior medication trials, including doses, length of time at specific doses, side effects, and clinical response. Despite the importance of an accurate history, studies of the adequacy of documentation (39) and clinical experience illustrate the extraordinary difficulty encountered in efforts to piece together a coherent story from the medical records of most patients with schizophrenia. Although actual chart documentation is the responsibility of the individual practitioner, it is typically the employing or contracting organization that is in the best position to facilitate good documentation and to effect periodic overviews of treatment. Appropriate documentation of assessment of competency, informed consent for treatment, and release of information also deserve careful attention by the clinician and the treatment organization.

Within the organization there are at least two major issues in information management. From the standpoint of information collection, the organization and its practitioners need to agree on the critical elements of information to obtain and the frequency with which they should be obtained. Recording of information may occur contemporaneously with collection or immediately thereafter. Labor-saving forms (paper or computer-based) may help in prompting data collection and easing its recording. Once information is collected, the ability to gain access to the information is essential. Thus, the organization will want to develop plans so that medical records will be available whenever and wherever the patient is seen. In addition, if the patient's care is transferred from one practitioner to another (e.g., outpatient to inpatient), necessary information will need to be transferred to the new practitioner ahead of or along with the patient. Release of a patient's information will generally require the patient's consent and should conform to applicable regulations and policies (e.g., state law, the Health Insurance Portability and Accountability Act, and Principles of Medical Ethics: With Annotations Especially Applicable to Psychiatry[40]).

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B. Acute Phase

The goals of treatment during the acute phase of a psychotic exacerbation are to prevent harm, control disturbed behavior, reduce the severity of psychosis and associated symptoms (e.g., agitation, aggression, negative symptoms, affective symptoms), determine and address the factors that led to the occurrence of the acute episode, effect a rapid return to the best level of functioning, develop an alliance with the patient and family, formulate short- and long-term treatment plans, and connect the patient with appropriate aftercare in the community. It is especially important to address the anxiety, fear, and dysphoria commonly associated with an acute episode. Efforts to engage and collaborate with family members and other natural caregivers are often successful during the crisis of an acute psychotic episode, whether it is the first episode or a relapse. Also, family members and other caregivers are often needed to provide support to the patient while he or she is recovering from an acute episode. The main therapeutic challenge for the clinician is to select and "titrate" the doses of both pharmacological and psychosocial interventions in accordance with the symptoms and sociobehavioral functioning of the patient (41). It is important to emphasize that acute-phase treatment is often but no longer necessarily associated with hospitalization. With the growth of managed care restricting the use of hospitalization and the development of alternative community-based programs, acute-phase treatment frequently occurs outside of the hospital.

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1. Assessment in the acute phase

A thorough initial workup, including complete psychiatric and general medical histories and physical and mental status examinations, is recommended for all patients, as allowed by the patient's clinical status. Interviews of family members or other persons knowledgeable about the patient should be conducted routinely unless the patient refuses to grant permission, especially since many patients are unable to provide a reliable history at the first interview. In emergency circumstances, as when a patient's safety is at risk, it may be necessary and permissible to speak with others without the patient's consent.

When a patient is in an acute psychotic state, acutely agitated, or both, it may be impossible to perform an adequate evaluation at the time of the initial contact. With the patient's consent, the psychiatrist may begin treatment with an appropriate medication and perform the necessary evaluations as the patient's condition improves and permits. For acutely psychotic or agitated patients who lack the capacity or are unwilling to agree to receive medication, state regulations on involuntary treatment should be followed.

Some of the most common contributors to symptom relapse are antipsychotic medication nonadherence, substance use, and stressful life events (42–47). Medication adherence may be assessed by the patient's report, the reports of family members or other caregivers, pill counts, prescription refill counts, and, for some medications, antipsychotic blood levels. Attention needs to be given to potential drug-drug interactions that may affect blood levels and hence toxicity and adherence. Useful guides for determining potential adverse drug interactions related to the cytochrome P450 enzyme system are now available (48, 49). The reason for nonadherence should also be evaluated and considered in the treatment plan.

General medical health as well as medical conditions that could contribute to symptom exacerbation can be evaluated by medical history; physical and neurological examination; and appropriate laboratory, electrophysiological, and radiological assessments. Substance use should be routinely evaluated as part of the medical history and with a urine toxicology screen. It is important to realize that many drugs of abuse, including most designer drugs and hallucinogens, are not detected by urine toxicology screens; if use of such substances is suspected, a blood toxicology screen can detect some of them. Withdrawal from alcohol or some other substances can present as worsening psychosis, and the possibility of withdrawal should be evaluated by medical history and vital sign monitoring in all patients with acute exacerbation of symptoms. (The results of toxicology screens will usually be negative, since risk of withdrawal is often highest several days after abstinence from chronic abuse.) Body weight and vital signs (heart rate, blood pressure, temperature) should be measured. A CT or MRI scan may provide helpful information, particularly in assessing patients with a new onset of psychosis or with an atypical clinical presentation. Although imaging studies cannot establish a diagnosis of schizophrenia, specific findings from a CT or MRI scan (e.g., ventricular enlargement, diminished cortical volume) may enhance the confidence of the diagnosis and provide information that is relevant to treatment planning and prognosis. Given the subtle nature of the neuropathological findings in schizophrenia, MRI is preferred over CT.

Table 1 delineates suggested laboratory tests for evaluating health status, including studies that may be indicated when the clinical picture is unclear or when there are abnormal findings on routine examination, as well as suggested methods to monitor for side effects of treatment.

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Table Reference Number
Table 1. Suggested Physical and Laboratory Assessments for Patients With Schizophrenia 

These tests may detect occult disease that is contributing to psychosis and also determine if there are comorbid medical conditions that might affect medication selection, such as impaired liver or renal function. Tests to assess other general medical needs of patients should also be considered (e.g., gynecological examination, mammogram, and rectal examination) (54). The U.S. Preventive Services Task Force has reviewed the evidence of effectiveness and developed recommendations for clinical preventive services (http://www.ahcpr.gov/clinic/uspstfix.htm).

It is also important that special precautions be taken in the presence of suicidal ideation or intent or a suicide plan, including an assessment of risk factors such as prior attempts, depressed mood, and suicidal ideation, which are the best predictors of a subsequent suicide attempt in schizophrenia (55, 56). Other predictors of suicide that also warrant close attention include the presence of command hallucinations, hopelessness, anxiety, extrapyramidal side effects, and an alcohol or other substance use disorder. Similar evaluations are necessary in considering the likelihood of dangerous or aggressive behavior and whether the person will harm someone else or engage in other forms of violence (57). The coexistence of substance use (58) significantly increases the risk of violent behavior. Because past behavior best predicts future behavior, family members and friends are often helpful in determining the risk of a patient's harming self or others and in assessing the patient's ability for self-care.

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2. Psychiatric management in the acute phase

Psychosocial interventions in the acute phase are aimed at reducing overstimulating or stressful relationships, environments, or life events and at promoting relaxation or reduced arousal through simple, clear, coherent communication and expectations; a structured and predictable environment; low performance requirements; and tolerant, nondemanding, supportive relationships with the psychiatrist and other members of the treatment team.

The patient should be provided information on the nature and management of the illness that is appropriate to his or her ability to assimilate information. The patient should also be encouraged to collaborate with the psychiatrist in selecting and adjusting the medication and other treatments provided. Ordinarily, a hospitalized patient should be provided with some information about the disorder and the medications being used to treat it, including their benefits and side effects. As described in Section II.A.3, "Developing a Therapeutic Alliance and Promoting Treatment Adherence", the psychiatrist must realize that the degree of acceptance of medication and information about it will vary according to the patient's cognitive capacity, the extent of the patient's insight, and efforts made by the psychiatrist to engage the patient and the patient's family members in a collaborative treatment relationship.

The acute phase is also the best time for the psychiatrist to initiate a relationship with family members, who tend to be particularly concerned about the patient's disorder, disability, and prognosis during this phase and during hospitalization. Educational meetings, "survival workshops" that teach the family how to cope with schizophrenia, and referrals to the local chapter of NAMI may be helpful. The NAMI web site (http://www.nami.org) offers a wealth of useful information. Manuals, workbooks, and videotapes are also available to aid families in this process (59–64). Active efforts to involve relatives in treatment planning and implementation are often a critical component of treatment.

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3. Use of antipsychotic medications in the acute phase

Treatment with antipsychotic medication is indicated for nearly all episodes of acute psychosis in patients with schizophrenia. In this guideline the term "antipsychotic" refers to several classes of medications (Table 2). These include the first-generation antipsychotic medications and the second-generation (sometimes referred to as "atypical") agents clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole.

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Table Reference Number
Table 2. Commonly Used Antipsychotic Medications

Pharmacological treatment should be initiated as soon as is clinically feasible, because acute psychotic exacerbations are associated with emotional distress, disruption to the patient's life, and a substantial risk of behaviors that are dangerous to self, others, or property (57, 68, 69). There are limited circumstances where it may be appropriate to delay treatment, for example, for patients who require more extensive or prolonged diagnostic evaluation, who refuse medications, or who may experience a rapid recovery because substance use or acute stress reactions are thought to be the potential cause of the symptom exacerbation.

Before treatment with antipsychotic medication is begun, baseline laboratory studies may be indicated, if they have not already been obtained as a part of the initial assessment (Table 1). In addition, the treating physician should, as is feasible, discuss the potential risks and benefits of the medication with the patient. The depth of this discussion will, of course, be determined by the patient's condition. Even with agitated patients and patients with thought disorder, however, the therapeutic alliance will be enhanced if the patient and physician can identify target symptoms (e.g., anxiety, poor sleep, and, for patients with insight, hallucinations and delusions) that are subjectively distressing and that antipsychotics can ameliorate. Acute side effects such as orthostatic hypotension, dizziness, and extrapyramidal side effects, including dystonic reactions, insomnia, or sedation, should be discussed at this stage, leaving discussion of long-term side effects to when the acute episode is resolving. Mentioning the possibility of acute side effects helps patients to identify and report their occurrence and also may help maintain a therapeutic alliance. To the extent possible, it is important to minimize acute side effects of antipsychotic medications, such as dystonia, that can significantly influence a patient's willingness to accept and continue pharmacological treatment. Patients with schizophrenia often have attentional and other cognitive impairments that may be more severe during an acute illness exacerbation, and so it is often helpful to return to the topic of identifying target symptoms and risk of acute side effects multiple times during the course of hospitalization.

Rapid initiation of emergency treatment is needed when an acutely psychotic patient is exhibiting aggressive behaviors toward self, others, or objects. When the patient is in an emergency department, inpatient unit, or other acute treatment facility, existing therapeutic protocols usually define the appropriate response. Most of these protocols recognize that the patient is usually frightened and confused and that the first intervention involves staff members talking to the patient in an attempt to calm him or her. Attempts to restrain the patient should be done only by a team trained in safe restraint procedures to minimize risk of harm to patients or staff (70). Antipsychotics and benzodiazepines are often helpful in reducing the patient's level of agitation (71). If the patient will take oral medication, rapidly dissolving forms of olanzapine and risperidone can be used for quicker effect and to reduce nonadherence. If a patient refuses oral medication, most states allow for emergency administration despite the patient's objection. Short-acting parenteral formulations of first- and second-generation antipsychotic agents (e.g., haloperidol, ziprasidone, and olanzapine), with or without a parenteral benzodiazepine (e.g., lorazepam), are available for emergency administration in acutely agitated patients (72–79). Use of rapidly dissolving oral formulations of second-generation agents (e.g., olanzapine, risperidone) or oral concentrate formulations (e.g., risperidone, haloperidol) may also be useful for acute agitation. Other medications, such as droperidol, can be used in selected clinical situations of extreme emergency or in highly agitated patients (80). However, if droperidol is used, its potential for cardiac rhythm disturbances must be considered, as indicated in its labeling by a black-box warning for QTc prolongation.

In nonemergency circumstances in which the patient is refusing medication, the physician may have limited options. When a patient refuses medication, it is often helpful to enlist family members as allies in helping the patient to accept medication. Often, patients can be helped to accept pharmacological treatment over time and with psychotherapeutic interactions that are aimed toward identifying subjectively distressing symptoms that have previously responded to treatment (12). Clinicians are encouraged to make greater use of the option of advance directives by patients in states where this option is available. Advance directives allow competent patients to state their preferences about treatment choices in the event of future decompensation and acute incapacity to make decisions. Depending on prevailing state laws, when treatment measures instituted on the basis of an advance directive fail, pharmacological treatment may be administered involuntarily even in the absence of acute dangerousness (81). In other instances, depending on state laws, a judicial hearing may need to be sought for permission to treat a patient who lacks capacity.

The process for determining pharmacological treatment in the acute phase is shown in Table 3 and Figure 1.

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Table Reference Number
Table 3. Choice of Medication in the Acute Phase of Schizophrenia
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FIGURE 1. Somatic Treatment of Schizophrenia.

The selection of an antipsychotic medication is frequently guided by the patient's previous experience with antipsychotics, including the degree of symptom response, the side effect profile (including past experience of side effects such as dysphoria), and the patient's preferences for a particular medication, including the route of administration. The second-generation antipsychotics should be considered as first-line medications for patients in the acute phase of schizophrenia, mainly because of the decreased risk of extrapyramidal side effects and tardive dyskinesia (82–85), with the understanding that there continues to be debate over the relative advantages, disadvantages, and cost-effectiveness of first- and second-generation agents (86–89). For patients who have been treated successfully in the past or who prefer first-generation agents, these medications are clinically useful and for specific patients may be the first choice. With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating the positive symptoms of schizophrenia, although there is emerging evidence and ongoing debate that second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative, and mood symptoms. To date, there is no definitive evidence that one second-generation antipsychotic will have superior efficacy compared with another, although in an individual patient there may be clinically meaningful differences in response (89). A patient's past history of side effects can guide antipsychotic drug selection, since there is considerable difference in side effect profiles among the available antipsychotics. Table 4 lists the relative frequency of some adverse effects associated with selected antipsychotic medications. Strategies for the monitoring and clinical management of selected side effects of antipsychotic medications are outlined in Table 1 and discussed in detail in Part B, Section V.A.1, "Antipsychotic Medications."

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Table Reference Number
Table 4. Selected Side Effects of Commonly Used Antipsychotic Medicationsa

While many patients prefer oral medication, patients with recurrent relapses related to partial or full nonadherence are candidates for a long-acting injectable antipsychotic medication, as are patients who prefer the injectable formulation (91). If a long-acting injectable medication is indicated, the oral form of the same medication (i.e., fluphenazine, haloperidol, and risperidone in the United States) is the logical choice for initial treatment during the acute phase. The transition from oral to long-acting injectable medication can begin during the acute phase; however, the long-acting injectable agents are not usually prescribed for acute psychotic episodes because these medications can take months to reach a stable steady state and are eliminated very slowly (92). As a result, the psychiatrist has relatively little control over the amount of medication the patient is receiving, and it is difficult to titrate the dose to control side effects and therapeutic effects. There may, however, be circumstances when it is useful to prescribe long-acting medications during acute treatment. For example, if a patient experiences an exacerbation of psychotic symptoms while receiving long-acting injectable medications, it may be useful to continue the long-acting injectable medication while temporarily supplementing it with oral medication (92).

Determining the optimal dose of antipsychotic medication in the acute phase is complicated by the fact that there is usually a delay between initiation of treatment and full therapeutic response. Patients may take between 2 and 4 weeks to show an initial response (93) and up to 6 months or longer to show full or optimal response. It is important to select a dose that is both effective and not likely to cause side effects that are subjectively difficult to tolerate, since the experience of unpleasant side effects may affect long-term adherence (see Section II.A.3, "Developing a Therapeutic Alliance and Promoting Treatment Adherence"). Some common early side effects such as sedation, postural hypotension, acute dystonia, or nausea will typically improve or resolve after the first several days or weeks of treatment, and patients can be encouraged to tolerate or temporarily manage these short-term effects. Other side effects, notably akathisia and parkinsonism, are likely to persist with long-term treatment. In general, the optimal dose (range) of medication is that which produces maximal therapeutic effects and minimal side effects. The optimal dose of first-generation antipsychotics (Table 2) is, for most patients, at the "EPS threshold," the dose that will induce extrapyramidal side effects and where a physical examination of the patient shows minimal rigidity (94). Evidence suggests that doses above this threshold increase risk of extrapyramidal and other side effects without enhancing efficacy (95–97). Second-generation antipsychotics can generally be administered at doses that are therapeutic yet well below the "EPS threshold." The target dose (Table 2) usually falls within the therapeutic dose range specified by the manufacturer and in the package labeling approved by the U.S. Food and Drug Administration (FDA). In clinical practice, however, doses of several second-generation drugs, including olanzapine, quetiapine, and ziprasidone, have extended above their recommended ranges. In determining the target dose, the psychiatrist should consider the patient's past history of response and dose needs, clinical condition, and severity of symptoms. Doses should be titrated as quickly as tolerated to the target therapeutic dose (generally sedation, orthostatic hypotension, and tachycardia are the side effects that limit the rate of increase), and unless there is evidence that the patient is having uncomfortable side effects, the patient's clinical status ideally should then be monitored for 2–4 weeks before increasing the dose or changing medications. During these weeks it is often important for the physician to be patient and avoid the temptation to prematurely escalate the dose for patients who are responding slowly. Rapid escalation can create the false impression of enhanced efficacy when time is often an important factor, and higher doses may actually be detrimental.

If the patient is not improving, consider whether the lack of response can be explained by medication nonadherence, rapid medication metabolism, or poor absorption. If the patient has been treated with one of the medications for which there are adequate data on blood level relationships with clinical response (e.g., clozapine, haloperidol), determination of the plasma concentration may be helpful. If nonadherence is a problem, behavioral tailoring (i.e., fitting taking medication into one's daily routine) (30), motivational interviewing, and other psychotherapeutic techniques may be useful in helping the patient develop an understanding of the potential benefits of medication (12, 98). In addition, surreptitious nonadherence (i.e., "cheeking") may be addressed by use of a liquid (e.g., risperidone, haloperidol), a quick-dissolving tablet (e.g., olanzapine, risperidone), or a short-acting intramuscular form (e.g., ziprasidone, haloperidol).

If the patient is adhering to treatment and has an adequate plasma concentration of medication but is not responding to the treatment, alternative treatments should be considered. If the patient is able to tolerate a higher dose of antipsychotic medication without significant side effects, raising the dose for a finite period, such as 2–4 weeks, can be tried, although the incremental efficacy of higher doses has not been well established. If dose adjustment does not result in an adequate response, a different antipsychotic medication should be considered.

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4. Use of adjunctive medications in the acute phase

Other psychoactive medications are commonly added to antipsychotic medications in the acute phase to treat comorbid conditions or associated symptoms (e.g., agitation, aggression, affective symptoms), to address sleep disturbances, and to treat antipsychotic drug side effects. Therapeutic approaches to treatment resistance and residual symptoms are discussed in Section II.E, "Special Issues in Caring for Patients With Treatment-Resistant Illness".

Adjunctive medications are also commonly prescribed for residual symptoms and comorbid conditions during the acute phase. For example, benzodiazepines may be helpful in treating catatonia as well as in managing both anxiety and agitation. The most agitated patients may benefit from addition of an oral or a parenteral benzodiazepine to the antipsychotic medication. Lorazepam has the advantage of reliable absorption when it is administered either orally or parenterally (99). There is some evidence that mood stabilizers and beta-blockers may be effective in reducing the severity of recurrent hostility and aggression (100–102). Major depression and obsessive-compulsive disorder are common comorbid conditions in patients with schizophrenia and may respond to an antidepressant. However, some antidepressants (those that inhibit catecholamine reuptake) can potentially sustain or exacerbate psychotic symptoms in some patients (103). Careful attention must be paid to potential drug-drug interactions, especially those related to the cytochrome P450 enzymes (48, 49).

Sleep disturbances are common in the acute phase, and while controlled studies are lacking, there is anecdotal evidence that a sedating antidepressant (e.g., trazodone, mirtazapine) or a benzodiazepine sedative-hypnotic may be helpful.

Medications can be used to treat extrapyramidal side effects (Table 5) and other side effects of antipsychotic medications that are described in detail in Part B, Section V.A.1, "Antipsychotic Medications." Decisions to use medications to treat side effects are driven by the severity and degree of distress associated with the side effect and by consideration of other potential strategies, including lowering the dose of the antipsychotic medication or switching to a different antipsychotic medication. The following factors should be considered in decisions regarding the prophylactic use of antiparkinsonian medications in acute-phase treatment: the propensity of the antipsychotic medication to cause extrapyramidal side effects, the patient's preferences, the patient's prior history of extrapyramidal side effects, other risk factors for extrapyramidal side effects (especially dystonia), and risk factors for and potential consequences of anticholinergic side effects.

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Table Reference Number
Table 5. Selected Medications for Treating Extrapyramidal Side Effects
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5. Use of ECT and other somatic therapies in the acute phase

ECT in combination with antipsychotic medications may be considered for patients with schizophrenia or schizoaffective disorder with severe psychotic symptoms that have not responded to treatment with antipsychotic agents. The efficacy of acute treatment with ECT in patients with schizophrenia has been described in a number of controlled trials as well as in multiple case series and uncontrolled studies (106–108). The greatest therapeutic benefits appear to occur when ECT is administered concomitantly with antipsychotic medications. The majority of studies, including several randomized studies, have shown benefit from ECT combined with first-generation antipsychotic agents (109–126). More recent findings also suggest benefit from combined treatment with ECT and second-generation antipsychotic medications (127–135). However, given the clear benefits of clozapine in patients with treatment-resistant psychotic symptoms, a trial of clozapine will generally be indicated before acute treatment with ECT.

Clinical experience, as well as evidence from case series and open prospective trials, suggests that ECT should also be considered for patients with prominent catatonic features that have not responded to an acute trial of lorazepam (136–143). For patients with schizophrenia and comorbid depression, ECT may also be beneficial if depressive symptoms are resistant to treatment or if features such as suicidal ideation and behaviors or inanition, which necessitate a rapid therapeutic response, are present.

For additional details on the assessment of patients before ECT, the informed consent process, the technical aspects of ECT administration, and the side effects associated with treatment, the reader is referred to APA's The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging: A Task Force Report of the American Psychiatric Association (107).

Although it has been suggested that repetitive transcranial magnetic stimulation (rTMS) may share beneficial features of ECT (144, 145) and several recent studies with rTMS have shown promising results in decreasing auditory hallucinations (146–148), rTMS does not have an FDA indication for the treatment of psychosis, and additional research is needed before recommending its use in clinical practice.

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C. Stabilization Phase

During the stabilization phase, the aims of treatment are to sustain symptom remission or control, minimize stress on the patient, provide support to minimize the likelihood of relapse, enhance the patient's adaptation to life in the community, facilitate the continued reduction in symptoms and consolidation of remission, and promote the process of recovery.

Controlled trials provide relatively little guidance for medication treatment during this phase. If the patient has achieved an adequate therapeutic response with minimal side effects or toxicity with a particular medication regimen, he or she should be monitored while taking the same medication and dose for the next 6 months. Premature lowering of dose or discontinuation of medication during this phase may lead to a relatively rapid relapse. However, it is also critical to assess continuing side effects that may have been present in the acute phase and to adjust pharmacotherapy accordingly to minimize adverse side effects that may otherwise lead to medication nonadherence and relapse. Moreover, any adjunctive medications that have been used in the acute phase should be evaluated for continuation.

Psychotherapeutic interventions remain supportive but may be less structured and directive than in the acute phase. Education about the course and outcome of the illness and about factors that influence the course and outcome, including treatment adherence, can begin in this phase for patients and continue for family members. Educational programs during this phase have been effective in teaching a wide range of patients with schizophrenia the skills of medication self-management (e.g., the benefits of maintenance antipsychotic medication, how to cope with side effects) and symptom self-management (e.g., how to identify early warning signs of relapse, develop a relapse prevention plan, and refuse illicit drugs and alcohol), as well as strategies for interacting with health care providers (149–152).

It is important that there be no gaps in service delivery, because patients are vulnerable to relapse and need support in adjusting to community life. Not uncommonly, problems in continuity of care arise when patients are discharged from hospitals to community care. It is imperative to arrange for linkage of services between hospital and community treatment before the patient is discharged from the hospital. Short lengths of hospital stay create challenges for adequately linking inpatient to outpatient care, but to the extent possible, patients should have input into selecting their postdischarge follow-up residential and treatment plans. It is frequently beneficial to arrange an appointment with an outpatient psychiatrist and, for patients who will reside in a community residence, to arrange a visit before discharge (153, 154). After discharge, patients should be helped to adjust to life in the community through realistic goal setting without undue pressure to perform at high levels vocationally and socially, since unduly ambitious expectations on the part of therapists (20), family members (155), or others, as well as an overly stimulating treatment environment (156), can be stressful to patients and can increase the risk of relapse. These principles also apply in the stable phase. Efforts should be made to actively involve family members in the treatment process. Other psychosocial treatments, discussed in Section II.D, "Stable Phase"), may be initiated during this phase depending on the patient's level of recovery and motivation. While it is critical not to place premature demands on the patient regarding engagement in community-based activities and rehabilitation services, it is equally critical to maintain a level of momentum aimed at improving community functioning in order to instill a sense of hope and progress for the patient and family. These efforts set the stage for continuing treatments during the stable phase.

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D. Stable Phase

Treatment during the stable phase is designed to sustain symptom remission or control, minimize the risk and consequences of relapse, and optimize functioning and the process of recovery.

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1. Assessment in the stable phase

Ongoing monitoring and assessment during the stable phase are necessary to determine whether the patient might benefit from alterations in the treatment program. Ongoing assessment allows patients and those who interact with them to describe any changes in symptoms or functioning and raise questions about specific symptoms and side effects.

Monitoring for adverse effects should be done regularly (Table 1). Clinicians should inquire about the course of any side effects that developed in the acute or stabilization phases (e.g., sexual side effects, sedation). Monitoring for other potential adverse effects should be guided by the particular medications chosen (see Part B, Section V.A.1, "Antipsychotic Medications,"

If the patient agrees, it is helpful to maintain strong ties with persons who interact with the patient frequently and would therefore be most likely to notice any resurgence of symptoms and the occurrence of life stresses and events that may increase the risk of relapse or impede continuing functional recovery. However, the frequency of assessments by the psychiatrist or other members of the treatment team depends on the specific nature of the treatment and expected fluctuations of the illness. Frequency of contacts may range from every few weeks for patients who are doing well and are stabilized to as often as every day for those who are going through highly stressful changes in their lives.

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2. Psychosocial treatments in the stable phase

For most persons with schizophrenia in the stable phase, treatment programs that combine medications with a range of psychosocial services are associated with improved outcomes. Knowledge and research regarding how best to combine treatments to optimize outcome are scarce. Nonetheless, provision of such packages of services likely reduces the need for crisis-oriented care hospitalizations and emergency department visits and enables greater recovery.

A number of psychosocial treatments have demonstrated effectiveness. These treatments include family interventions (31, 157, 158), supported employment (159–162), assertive community treatment (163–166), social skills training (167–169), and cognitive behaviorally oriented psychotherapy (158, 170). An evidence-based practices project sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA) is developing resource kits on family interventions, assertive community treatment, and supported employment (draft versions available at http://mentalhealth.samhsa.gov/cmhs/communitysupport/toolkits/family/; http://mentalhealth.samhsa.gov/cmhs/communitysupport/toolkits/community/; http://mentalhealth.samhsa.gov/cmhs/communitysupport/toolkits/employment/).

In the same way that psychopharmacological management must be individually tailored to the needs and preferences of the patient, so too should the selection of psychosocial treatments. The selection of appropriate and effective psychosocial treatments needs to be driven by the circumstances of the individual patient's needs and his or her social context. At the very least, all persons with schizophrenia should be provided with education about their illness. Beyond needing illness education, most patients will also benefit from at least some of the recommended psychosocial interventions. However, since patients' clinical and social needs will vary at different points in their illness course and since some psychosocial treatments share treatment components, it would be rare for all of these psychosocial interventions to be utilized during any one phase of illness for an individual patient.

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a) Prevention of relapse and reduction of symptom severity

A major goal during the stable phase is to prevent relapse and reduce the severity of residual symptoms. Certain psychosocial interventions have demonstrated effectiveness in this regard. They include family education and support, assertive community treatment, and cognitive therapy.

Interventions that educate families about schizophrenia, provide support, and offer training in effective problem solving and communication have been subjected to numerous randomized clinical trials (171, 172). The data strongly and consistently support the value of such interventions in reducing symptom relapse, and there is some evidence that these interventions contribute to improved patient functioning and family well-being. Randomized clinical trials have reported 2-year relapse rates for patients receiving family "psychoeducation" programs in combination with medication that are 50% lower than those for patients receiving medication alone (173–180). Further, a recent study found psychoeducational programs using multiple family groups to be more effective and less expensive than individual family psychoeducational interventions for Caucasians, though not for African Americans (178). On the basis of the evidence, persons with schizophrenia and their families who have ongoing contact with each other should be offered a family intervention, the key elements of which include a duration of at least 9 months, illness education, crisis intervention, emotional support, and training in how to cope with illness symptoms and related problems.

PACT is a specific model of community-based care. Its origin is an experiment in Madison, Wisconsin, in the 1970s in which the multidisciplinary inpatient team of the state hospital was moved into the community (181, 182). The team took with it all of the functions of an inpatient team: interdisciplinary teamwork, 24-hour/7-days-per-week coverage, comprehensive treatment planning, ongoing responsibility, staff continuity, and small caseloads. PACT is designed to treat patients who are at high risk for hospital readmission and who cannot be maintained by more usual community-based treatment as well as for patients with severe psychosocial impairment who need extensive assistance to live in the community. Randomized trials comparing PACT to other community-based care have consistently shown that PACT substantially reduces utilization of inpatient services and promotes continuity of outpatient care (183, 184). Patients' satisfaction with this model is generally high, and family advocacy groups, such as NAMI in the United States, strongly support its use and dissemination.

Results are less consistent regarding the effect of PACT on other outcomes, although at least some studies have shown enhancement of clinical status, functioning, and quality of life. Cost-effectiveness studies support its value in the treatment of high-risk patients. Studies also indicate that a particular PACT program's effectiveness is related to the fidelity with which it is implemented, that is, the degree to which the program adheres to the original PACT model.

Controlled studies of cognitive behavior psychotherapy have reported benefits in reducing the severity of persistent psychotic symptoms (170). Most of the studies have been performed with individual cognitive behavior therapy of at least several months' duration; in some studies, group cognitive behavior therapy and/or therapy of a shorter duration has been used. In all of the studies clinicians who provided cognitive behavior therapy received specialized training in the approach. In addition, the key elements of this intervention include a shared understanding of the illness between the patient and therapist, identification of target symptoms, and the development of specific cognitive and behavioral strategies to cope with these symptoms. Therefore, based on the available evidence, persons with schizophrenia who have residual psychotic symptoms while receiving adequate pharmacotherapy may benefit from cognitive behaviorally oriented psychotherapy.

A variety of other approaches to counseling individual patients to help them cope better with their illness are used, although research in this area remains limited. In general, counseling that emphasizes illness education, support, and problem solving is most appropriate. A notable prototype of this approach is personal therapy, as developed by Hogarty and colleagues (185–187). Personal therapy is an individualized long-term psychosocial intervention provided to patients on a weekly to biweekly frequency within the larger framework of a treatment program that provides pharmacotherapy, family work (when a family is available), and multiple levels of support, both material and psychological. The approach is carefully tailored to the patient's phase of recovery from an acute episode and the patient's residual level of severity, disability, and vulnerability to relapse.

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b) Negative symptoms

During the stable phase, negative symptoms (e.g., affective flattening, alogia, avolition) may be primary and represent a core feature of schizophrenia, or they may be secondary to psychotic symptoms, a depressive syndrome, medication side effects (e.g., dysphoria), or environmental deprivation. The effectiveness of psychosocial treatments for reducing negative symptoms is not well studied. Furthermore, most research (for both psychosocial and pharmacological treatments) does not distinguish between primary and secondary negative symptoms. Thus, the generic term "negative symptoms" is used to summarize these findings. Some studies of cognitive behavior therapy report improvements in residual negative symptoms. In a review of three studies, Rector and Beck (188) reported a large aggregated effect size favoring cognitive behavior therapy over supportive therapy for reducing negative symptoms. Also, one study of family psychoeducation reported an improvement in negative symptoms with this intervention (189).

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c) Improving functional status and quality of life

A primary treatment goal during the stable phase is to enable the patient to continue the recovery process and to achieve the goals of improved functioning and quality of life. To the degree to which active positive symptoms impair functional capacity, medications that reduce positive symptoms may improve functioning. However, research indicates consistently that positive symptoms show a low correspondence with functional impairments among patients with schizophrenia (190). Rather, it is the negative symptoms and cognitive impairments that are more predictive of function