Chapter 12

Schizophrenia

Dale L. Johnson

This lecture will be different from the others. The textbook is quite good, but the topic is enormous. On these pages I will make a few generalizations about schizophrenia and then will ask you to read two papers I have prepared for other purposes. One (Lecture 12A) is about the treatment of serious mental illnesses, and this includes schizophrenia. It includes much more material on the treatment of schizophrenia than the textbook does. The second (Lecture 12B) is a brief account of my family's experience in living with schizophrenia.

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DSM-IV CRITERIA FOR SCHIZOPHRENIA

A. Presence of psychotic symptoms in the active phase for at least one week.

1. Two of the following:

a. delusions

b. prominent hallucinations

c. incoherence or marked loosening of associations

d. catatonic behavior

e. flat or grossly inappropriate affect

2. Bizarre delusions

3. Hallucinations of a voice with content having no apparent relation to depression or elation, or a voice keeping up a running commentary on the person's behavior or thoughts, or two or more voices conversing with one another.

B. Functioning markedly below highest level achieved,

C. Affective disorder ruled out.

D. Continuous signs of disturbance present for at least six months.

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Types of Schizophrenia

Catatonia--alternating immobility and agitation.

Paranoid--delusions of grandeur and persecution.

Disorganized--disruption of speech

Hebephrenic--silly and immature emotionally.

Undifferentiated--

Residual--not grossly disturbed, but still not well.

These are not widely used in thinking about patients and they have not been found to be useful in research. The textbook mentions some tendency for a greater heritability for paranoid forms, but this is quite tentative.

In addition to the symptoms listed above there are other symptoms that are often present, but the committee developing the DSM-IV, for whatever reasons, did not see fit to include. One of these is the feeling that one's thoughts are being drawn from one's brain. A variation on this is that thoughts are being inserted into one's head. People watch TV and feel that they are being given personal instructions by the TV. Thoughts that are not their own are put into their minds.

In general, many researchers believe that schizophrenia may be several disorders, but there is no consensus on what these subtypes or different forms might be.

It is conventional today to think about two sets of symptoms, positive and negative. Positive symptoms are active manifestations of abnormal behavior. These include hallucinations, delusions and thought disorder. Negative symptoms, on the other hand are deficits in normal behavior such as alogia, or less speech, avolition, or less interest, or motivation, affect flat, or less emotional expression, and anhedonia, or less feeling or interest. Anti-psychotic medications tend to subdue positive symptoms, but have little impact on negative symptoms. These respond better to intensive psychosocial treatment.

Some Facts About Schizophrenia

1. Schizophrenia is one of the most disabling illnesses known to humans. People are typically afflicted with schizophrenia when they are in their late teens or early 20s and most continue to be 100% disabled the rest of their lives. Only 10% to 20% of people with this illness are employed.

2. Schizophrenia is a brain disorder. There are now hundreds of studies that have shown this. Several parts of the brain are affected, but evidence is especially strong for involvement of the dorsolateral prefrontal cortex, the amydala/hippocampal complex and the thalamus. Overall brain volume is smaller. Other areas are also involved.

3. Schizophrenia is found everywhere in the world with about 1% of the population affected.

4. Women and men are approximately equally affected, but women seem to develop a less severe form of the disorder.

5. There is no evidence that parental or other family behavior causes schizophrenia. Psychoanalytic theory held that schizophrenia was caused by rejecting behavior by mothers and aloof, non-involved behaviors by fathers. Many studies have failed to find any evidence that this is true.

6. Schizophrenia does not mean "split personality." When sports announcers say things like, "The quarterback had a schizophrenic afternoon; he was good in the first half and fell apart in the second half," they are demonstrating their ignorance about schizophrenia and being stigmatizing toward people with the illness.

7. People with schizophrenia are no more violent than people who do not have the illness. The media tends to play up the dangerousness of schizophrenia, but in fact, most people with the illness are peaceful and quiet. When violence does occur in this condition it is nearly always when the person is not receiving treatment, or is dual-diagnosed with drugs such as crack cocaine. Under the latter condition, the violence rates are like those for people on crack cocaine without schizophrenia.

8. Schizophrenia is said to be a myth by some. Psychiatrist Thomas Szasz and others have argued for years that schizophrenia does not exist as a medical disorder. It is not a myth. People with schizophrenia who are recovering resent this trivialization of their suffering. Their family members have no doubt that their relative has undergone some kind of profound change in functioning.

Genetics of Schizophrenia

The simplest type of genetic study is one based on the common observation that insanity seems to run in families. Comparison is made of the prevalence of the disorder for relatives of the index case with the prevalence for relatives of non-affected controls. If the rate is higher for the former, we infer that a genetic contribution to the disorder is involved.

For first degree relatives, that is parents, children or siblings of the index case, the number of genes in common is approximately 50%. Second degree relatives (grandparents, nieces and nephews, aunts and uncles) have only 25% of their genes in common.

Risk rates are determined by carefully examining family histories and identifying relatives having the same disorder as the index person. Comparisons are made with the risk of developing schizophrenia for the general population, about 1%.

Slater and Courie (1971) estimated the risk factors for various classes of relatives of patients by combining the results of several studies. Their results are summarized below:

Rate of Schizophrenia for Relatives of Patients with Schizophrenia

Relationship Risk

First Degree Crider Range

Siblings 8.5% 8-14%

Children 12.3 9-16

Parents 4.4 5-10

Second Degree

Grandchildren 2.8 2-8

Uncles; Aunts 2.0 2-7

Nephews; Nieces 2.3 1.4

First Cousins 2.9 2-6

It is evident that the risk for first degree relatives is much higher than that for second degree relatives. The risk for the latter is only 2-3 times higher than for individuals in the general population. This is a matter of concern for persons who have a brother or sister and wonder, first, whether they themselves are likely to develop schizophrenia, and second, if their children are likely to develop the disorder. You can see that their risk for developing the disorder is somewhat high at 8.5%, but the risk for their children is quite low, only 2.9%. Genetic counselors would want to know how many relatives in the family have the disorder or other forms of serious mental illness.

Twin Studies

The concordance rates (degree of agreement) for twin studies are shown below for schizophrenia, major depression and manic syndrome. As may be seen there is a significant genetic loading for all three disorders, but it is much higher for manic syndrome.

MZ DZ

Schizophrenia 48% 17 %

Major Depression 40% 11%

Manic Syndrome 72% 14%

A criticism that has often been made of the twin studies is that obviously monozygotic twins (identical) live in more nearly alike environments than even dizygotic (fraternal) twins. This problem has been answered by examining the concordance rates of monozygotic twins who had been reared apart. The concordance rates are about the same as those for twins reared together. This enhances the genetic argument and diminishes the environmental argument.

Molecular Genetic Studies

Contemporary research on the genetics of schizophrenia follows more recently developed methods. These have shown that there is reason to think that there is a linkage of schizophrenia to genes on several chromosomes. Those for which evidence is strongest are 6p, 13 and 8p with less compelling evidence for 5q, 22q and 3p. This range of locations and the strong suggestion that more than one and perhaps several genes are involved makes an understanding of the genetics of schizophrenia very complex.

Markers

Behavioral geneticists are guided in their search for relevant genes by looking at behaviors that are not schizophrenic, but commonly occur with schizophrenia in the patient, and in that person's relatives. These behaviors are called "markers." One such marker was discovered by psychologist, Phil Holzman. This marker is called smooth eye pursuit or eye tracking. The person is told to visually follow a moving target. People with schizophrenia and their near relatives have difficulty with this task. However, for relatives, the effect only appears when the task is made very difficult. A similar kind of behavior occurs with tests of attention.

Non-genetic Basic Causes

It is clear that not all schizophrenia is caused by genetics alone. There is interesting evidence from several other sources.

Weinberger’s (1987) has hypothesized that schizophrenia develops from alterations in the development of the prenatal brain. These might be genetic in origin or from some external source. The commonly replicated finding that season of birth is implicated. People with schizophrenia are slight more often born in the winter months. This has led to the virus hypothesis: mothers who have flu during pregnancy will more often have a child who later develops schizophrenia. In several studies this hypothesis has been supported. The effect is strongest if the flu is during the second trimester of pregnancy.

Flu is not the only potential source of damage. Susser showed that the famine in Holland during the 1940s brought about by the Nazi restriction of food to parts of Holland resulted in more babies in utero during that time later developed schizophrenia..

Other viruses have more recently come under scientific scrutiny and it may be that a virus that affects cats may be involved in the development of schizophrenia.

That the disorder is developmental is shown by research from many points. For example, Barbara Fish found that infants who later develop schizophrenia show intermodal incoordination; in short, on infant tests they are clumsy. ElaineWalker used home movies made during the person's childhood found people who later developed schizophrenia had more unusual emotional reactions. These were apparent to trained raters of the movies. At this time the people showed no symptoms of schizophrenia.

Brain Function

Many psychologists still tend to oppose the idea that schizophrenia has as an essential cause brain dysfunction. Since the time of Kraepelin researchers have believed that there must be some kind of brain dysfunction, but until quite recently there were no good ways to test this hypothesis. Incidently, Freud believed most cases of schizophrenia were caused by brain dysfunction, but he chose to study the psychological implications. Because he believed schizophrenia was a brain disorder he did not think his therapies were appropriate. Many of his followers did not agree with him and used psychodynamic therapy for years, with no evidence of successful outcomes.

Some psychologists, and virtually all psychoanalysts, remain reluctant, in part because they believe that if the cause is biological, the treatment must also be biological. This is not a logical supposition. As we will see, both biological (medical) and psychosocial treatments are essential and necessary for most cases.

The reasoning about schizophrenia also included the idea that if the cause was biological, then nothing could be done for the patient. We will see that this is also false. It is well to think of brain function and its adaptive capabilities.

Modern methods of brain imaging have shown that when people with schizophrenia are compared with healthy people the result is typically that there are differences between the two groups in brain structure and function. These differences are not absolute, but they are statistically significant--the criteria nearly always used to demonstrate difference between groups.

Brain areas involved were listed above. Clearly, it not just a matter of the brain area that is implicated it also has to do with the neurotransmitters involved. Among those known to be involved are dopamine (1, 2 and 4), serotonin, GABA, and the endorphins

Diathesis/stress Hypothesis

Brown and Birley, in England, found that people who had much stress in a 3-week period tended to develop more schizophrenic symptoms. They suggested that for schizophrenia to develop there had to be a predisposition, probably genetic, and the presence of stress. What makes this difficult to study is the possibility that the predisposition makes some people unusually sensitive to stress. Therefore, what would be only a little stressful for one person would be of extreme stress to the susceptible person.

Some Problems in the Treatment of Schizophrenia

The treatment of schizophrenia is not easy and calls for highly trained professionals to direct the treatment program. Unfortunately, this is not widely recognized and as a consequence few people with this disorder receive adequate treatment. There are other problems that have to do with the disorder itself.

The course of the illness is life-long for most people.

The course is episodic with relatively symptom-free periods marked by relapses, recurrence of symptoms.

During psychotic episodes there are two symptoms that interfere with treatment: 1) impaired judgment and 2) lack of insight or awareness that one has an illness and needs treatment. The two often lead to rejecting treatment and this in turn makes the illness worse.

When major symptoms are under control the person still has other symptoms that interfere with recovery. One of these is motivational difficulties. People have little interest in doing anything. Unless reminded and assisted they do not show up for appointments or follow through with homework assignments. Secondly, they often have problems in interacting with other people. They do not follow conversations, they make inappropriate comments or they miss the ordinary give and take of social interaction.

Treatment of Schizophrenia

See the paper on serious mental illness below. As you can see it was written for mental health professionals, but I think it is quite clear and is a good presentation of current thinking about the treatment and rehabilitation of schizophrenia.

In Sammons, M. T., & Schmidt, N. B (Eds.).

(2001). Combined treatments for mental disorders:

a guide to psychological and pharmacological

interventions. Washington, DC: American

Psychological Association. (pp.161-190)

Combined Treatments and Rehabilitation of Schizophrenia

William D. Spaulding (University of Nebraska), Dale L. Johnson (University of Houston) and Robert D. Coursey (University of Maryland)

This chapter is for psychologists who work with clients who have schizophrenia or similar disorders, as a member of an interdisciplinary treatment and rehabilitation team. Psychopharmacology usually plays a significant role in the work of such teams. Although a physician member of the team usually has direct responsibility for prescribing the medications, all team members should share responsibility for identifying targets for treatment, monitoring medication effects, and integrating pharmacological and psychosocial approaches. Psychologists are often the team members most knowledgeable and experienced in assessment of cognition and behavior, including changes produced by psychopharmacological treatment. They are also often the most knowledgeable and experienced in conducting treatment and rehabilitation as a sequence of controlled clinical trials, and in analyzing and interpreting the data generated by such trials. Treatment and rehabilitation relies heavily on these skills for optimum outcome. Consequently, the team's overall effectiveness is determined not only by psychologists' expertise in assessment and experimental design, but also by their ability to apply this expertise to issues of psychopharmacology in the comprehensive treatment and rehabilitation of schizophrenia.

In recent years many psychosocial approaches have demonstrated effectiveness for improving the personal and social functioning and quality of life of people with severe and disabling psychiatric disorders. These approaches are increasingly included, along with specialized pharmacotherapeutic approaches, under the umbrella term psychiatric rehabilitation (Anthony, Cohen & Farkas, 1990; Liberman, 1992).[1] The concept of rehabilitation de-emphasizes traditional allopathic treatment goals, such as "cure" or even "resolution of symptoms," and instead emphasizes the importance of acquiring skills necessary to manage the disorder, minimize the impact of disabilities, and get on with life. Achievement of these goals constitutes recovery. This reorientation obviates old debates about whether schizophrenia should be viewed as a medical problem requiring medical treatment, and creates a conceptual environment wherein both biological and psychosocial approaches can work in complementary ways toward common ends. It is in this context that the goal of recovery is now best understood, not as escaping an illness, but as overcoming the consequences of an illness which cannot presently be fully eliminated, using combinations of pharmacological and psychosocial techniques. Psychologists and other non-medical mental health professionals have an essential role in setting the stage for a rehabilitation and recovery agenda, and in making it possible (Johnson, 1990).

New developments in treatment and rehabilitation have appeared, and the clinical armamentarium is growing. In the area of psychosocial treatment, specific intervention modalities are available for an increasing number of the particular functional impairments associated with schizophrenia and similar disorders, including interpersonal functioning, stress management and emotional regulation, and various domains of cognition. Helpful techniques are increasingly available not only to mental health professionals, but also to families, friends, employers, spouses and the affected individuals themselves. Psychopharmacotherapy has reached a new and exciting level with the advent of the atypical antipsychotic drugs. These medications tend to produce more effective relief of major psychotic symptoms, and they may also produce better cognitive functioning as well. Because they cause fewer side effects they are more likely to be taken as prescribed. Medication non-adherence is a major (but not the only) factor in exacerbation of symptoms or relapse. These advances in medical treatment have not made psychosocial treatments less important; on the contrary, they have made them more important. With the new medications and psychosocial interventions it is now possible to expect not only symptom relief but also some degree of recovery in most patients.

Effective Modalities in Treatment and Rehabilitation

The past three decades have seen much systematic research on the efficacy of various treatment approaches for schizophrenia, both pharmacological and psychosocial. Interpretation of this research is difficult and complex, for several reasons. First, schizophrenia is a complex condition that changes over time. Treatment most applicable or efficacious during one phase of the disorder is not necessarily equally so during other phases. Second, the heterogeneity of people with schizophrenia complicates outcome research just as it complicates etiological research. The approach or combination of approaches optimal for one individual is not necessarily optimal for the next. Third, individual circumstances may mediate the effectiveness of any particular approach. This is especially true for psychosocial approaches that emphasize adaptation to certain environments, as opposed to adaptability to environments in general. For example, family-focused interventions are more important for patients who have regular contact with their families, and less important for those who do not. Fourth, treatment trials often combine a number of specific modalities in a single experimental condition. This reflects the multi-modal nature of rehabilitation, and it permits conclusions about overall efficacy, but it does not permit conclusions about the unique contributions of specific modalities.

The complexity and heterogeneity of the schizophrenic syndrome produces a multiplicity of treatment and rehabilitation goals, and this affects outcome research. Different but equally important outcomes include reduction of psychotic symptoms, reduction of other problem behaviors, normalization of affective experience and self-esteem, and improvement of skill performance in many domains of personal and social functioning. Progress on any one of can be quite independent of progress on the others. Different modalities usually target different goals, so experimental comparison of modalities often has limited value. For example, there is little value in showing that a modality designed to improve social skills does so better than a modality designed to improve housekeeping skills. As a result, comparative outcome studies, pitting two contending interventions against each other, are less often of interest in rehabilitation than in other areas. Additive outcome trial designs are more useful, evaluating the unique contribution of a particular modality to some outcome, when used in conjunction with other modalities (see Spaulding, 1992). For example, social skills training would be added to a larger regimen of rehabilitation services to determine whether it uniquely enhances improvement on a measure of social competence. The rehabilitation services are a standard regimen, provided to all subjects, not a separate condition in the study design. In an additive design, control conditions are used to control for placebo and related artifacts, not to determine the differential efficacy of the conditions.

It is important to understand that there has been much simplistic and unhelpful debate about the efficacy of treatments for schizophrenia over the entire 20^th century. Much of this is attributable to unreflective acceptance of a simplistic view of schizophrenia as a unitary, homogeneous disorder. Similarly, parochial attitudes about science have polarized the mental health community. In the 1960s, even as psychoanalysis was losing credibility as the principle paradigm of psychopathology and mental health, the insights of social critics such as Erving Goffman (1961) and the experimental work of social psychologists such as the Braginskys (Braginsky, Braginsky & Ring, 1969), elucidated the pathogenic role of mental hospitals and other social institutions, especially for severe mental illness. Previous views of schizophrenia as a biological disorder yielded to the view that it is a psychosocial phenomenon. Within ten years, with the advent of antipsychotic drugs, opinion swung to the other pole, and views of schizophrenia again became dominated by naive biological reductionism. Psychosocial treatment was viewed by some as a form of welfare (e.g., Klein, 1980). As the limitations of pharmacological treatment became evident in the late 1970s, there was renewed interest in psychosocial treatment.

Throughout these vacillations, research on both pharmacological and psychosocial treatment followed a progression that should be quite familiar to psychologists. As with the history of psychotherapy research, treatment benefits tend to appear first as nonspecific; i.e., people in general benefit from treatment in general. As research progresses, the active components of treatment and their relationships to specific recipient characteristics are gradually identified. It was evident early on that in general any antipsychotic medication tends to be more beneficial than none, and any psychosocial service tends to be more beneficial than the neglect and squalor to which people with severe mental illness have been subjected historically. Today science has reached an intermediate stage of progress in schizophrenia treatment research. The mechanisms and active components of nonspecific treatment effects are just now being identified. No treatment should be devalued simply because its effects are nonspecific, but ultimately the best outcome is achieved with a full understanding of specific and nonspecific treatment effects.

Professional practice guides to treatment of schizophrenia are increasingly available (see Smith and Docherty, 1998). The Guidelines for Treatment of Schizophrenia prepared by the American Psychiatric Association (1997) are intended to provide practical advice for the prescribing physician, including dosing strategies, management of co-morbid conditions and side effects. These guidelines also list the panoply of psychosocial approaches of known effectiveness, but do not describe or give much further information. The Expert Consensus Guideline Series Treatment of Schizophrenia 1999 (McEvoy, Scheifler & Frances, 1999), an update of an earlier set (Frances, Docherty & Kahn, 1996), include detailed protocols for selecting pharmacological and psychosocial treatments and related services. Schizophrenia Treatment Outcomes Research (Lehman, Thompson, Dixon & Scott, 1995) is a thorough review of the efficacy and effectiveness of treatments for schizophrenia. Finally, a special issue of Journal of Consulting and Clinical Psychology, edited by Kendall (1998), is devoted to empirically supported psychological therapies and includes material relevant to the treatment of schizophrenia. Mental health professionals whose practice includes people with schizophrenia should be familiar will all four of these sources.

Despite the existence of guidelines and a robust outcome literature, a cardinal rule in treatment of schizophrenia is to emphasize tailoring of treatment to the individual recipient. Functional assessment and a hypothetico-deductive approach to evaluating treatment response for the individual case are the main tools in the tailoring process. This is a maxim familiar to psychologists in assessment and treatment of all behavior problems, but the complexity and heterogeneity of schizophrenia make it particularly applicable to psychiatric rehabilitation.

An integration of the various guidelines, reviews, meta-analyses and outcome studies in the professional and scientific literature yields the following list of specific modalities of known effectiveness that should be considered essential elements of the service repertoire for people with schizophrenia. Although not all these modalities may be needed for all people with schizophrenia, a service system which serves all people with disabling psychiatric disorders should be expected to have the capability of providing any or all when needed.

1. Enlightened Psychopharmacology

There is some recognition in the psychiatric literature that the complexity of schizophrenia and the unpredictability of its response to treatment demand a somewhat unconventional approach to pharmacotherapy (Falloon & Liberman, 1983. Liberman, Falloon & Wallace, 1984; Liberman, Corrigan & Schade, 1989). There are two key principles: (1) although anti-psychotic drugs are a sine qua non in treating schizophrenia, they are almost never sufficient by themselves, and so special attention must be given to coordinating pharmacological and psychosocial treatment, and (2) nothing can be taken for granted about the effectiveness of any particular drug intervention, and so each intervention must be systematically, comprehensively and objectively evaluated, in a hypothetico-deductive, trial-and-test approach to treatment.

2. Rehabilitation Counseling

Rehabilitation counseling, primarily associated with the work of William Anthony and his colleagues (Anthony, Cohen & Farkas, 1990) represents a fusion of key concepts and principles from traditional physical rehabilitation and traditional client-centered psychotherapy. Rehabilitation counseling typically involves a periodic meeting of the client and at least one other member of the treatment and rehabilitation team. Both directive and nondirective psychotherapy techniques are employed to identify the problems that require treatment and rehabilitation, the client's desires and concerns, and resources to be applied. The initial objective is to reach consensus about the client's needs and what the team can do about them. A subsequent objective is to construct an individualized treatment and rehabilitation plan that integrates the team's goals (remember that the client is a member of the team) and objectives with specific interventions and other services. All the pharmacological and psychosocial modalities to be employed in the client's treatment and rehabilitation are included on this plan, and it thus takes on a key role in consolidating each team member's understanding of the purpose and importance of each modality and service. This is seen as crucial to maximally engaging the client in rehabilitation and ensuring high fidelity implementation of the treatment plan. As the treatment plan is implemented, the focus of counseling turns to appraisal and evaluation of progress, with the ongoing objective of reinforcing the client's experience of success and self-efficacy. Counseling continues until the treatment plan goals have been met and recovery is as complete as possible.

There have been no controlled experimental analyses of the unique contribution of rehabilitation counseling to outcome. It plays such a central role that comprehensive psychiatric rehabilitation would be difficult to provide, if not impossible, without it.

3. Social Skills Training

This modality is familiar to behaviorally oriented psychologists, having been widely applied to a diversity of recipient populations. There are highly developed and manualized versions designed specifically for recipients with severe and persistent schizophrenia. The most widely researched and used are disseminated by Robert Liberman and his colleagues at the UCLA Center for Research on Treatment and Rehabilitation of Psychosis, along with related therapist training materials.[2] Original research studies and a meta-analysis of 27 controlled trials (Benton & Schroeder, 1998) are consistent in showing that formal social skills training improves personal and social functioning and reduces hospital recidivism in participants with schizophrenia.

Social skills training of the type known to be effective for schizophrenia is an energetic, highly structured, highly interactive modality. It involves almost continuous use of role playing exercises, with all group members serving as observers and assistants when not actually role-playing. It is necessary for the therapist to engage the trainees and achieve their active participation throughout treatment. Unfortunately, "social skills" groups in mental health settings are often quite a bit less than this. The availability of therapist training materials and related resources make it possible for most mental health settings to be able to provide high quality services, but only if the training is actually done and high fidelity to training precepts is assured by quality assurance mechanisms.

4. Independent Living Skills Training

This modality is also familiar to behaviorally oriented psychologists. People with schizophrenia and related disorders often lose or fail to develop skills associated with routine daily living, such as keeping a daily schedule, housekeeping, cooking, management of personal funds, and using public resources. Acquisition of these skills contributes importantly to the ability to live safely and comfortably outside institutions.

Trainees receive classroom instruction and in vivo coaching to establish the knowledge base and performance ability necessary to use specific skills. The required therapist skills are often in the professional training of psychiatric nurses, occupational therapists and other mental health professionals besides psychologists.

5. Occupational Skills Training

Occupational functioning incorporates both "work and play." In the "work" domain, occupational skills are generally understood to be those that are important for any work-related activity, e.g., punctuality, proper workplace grooming, staying on task, following instructions, managing relationships with coworkers and supervisors. These should not be confused with vocational skills, which are more specific to particular kinds of work. Leisure and recreational skills, including identifying interests and planning activities, are as important to stable functioning and a decent quality of life as work skills. Occupational skills training should not be confused with occupational therapy, a specific modality provided by certified occupational or recreational therapists

6. Disorder Management Training

This modality has gradually differentiated itself from related social and living skills approaches, reflecting a growing recognition that specialized skills are needed to manage psychiatric disorders, comparable to skills needed to manage severe and persistent physical conditions such as diabetes. Students learn about the episodic and persistent symptoms of their disorder, the relationship between these symptoms and functional impairments, pharmacological and other techniques (e.g., relaxation and stress management) for controlling the symptoms, drug side effects, identification of warning signs of an impending relapse, and various other aspects of their disorder and its management. Behavioral skills indirectly relevant to disorder management are included, for example, the assertive skills necessary for dealing with the doctor and the doctor's receptionist in getting an appointment for a medication review.

Skill training packages have been developed by the UCLA dissemination center, including materials for training therapists. The UCLA medication management and symptom management modalities have proven effective in enhancing medication adherence and preventing relapse (Eckman, Liberman, Phipps and Blair, 1990).

Recently, disorder management training for schizophrenia has begun to benefit from relapse prevention and related techniques (e.g., Bradshaw, 1996; Birchwood, 1995; Kavanagh, 1992; O'Connor, 1991). Well known for application in substance abuse, many of the techniques of relapse prevention are well suited to the episodic nature of schizophrenia and the important role of the identified patient in managing those episodes. The original application of relapse prevention is also of interest, as people with schizophrenia often have substance abuse problems as well. So far there have been no controlled trials of the unique contribution of relapse prevention techniques to disorder management in schizophrenia

7. Family Psychoeducation

A broad spectrum of family processes and therapies have long been of interest in schizophrenia research. In the 1950s many believed that families, and parents in particular, have a causal role in the etiology of the disorder. This view was never empirically supported and today is largely discredited. Nevertheless, family members often experience guilt and/or distress in this regard. Furthermore, they are usually overwhelmed by the burden of living with and trying to help a person with a serious mental illness. Clinicians should always be vigilant for these problems and intervene with corrective information when indicated (Johnson, 1995).

In controlled outcome trials, family services that include psychoeducation, coping skills and problem-solving training, behavioral management and social support have been found to reduce relapse and recidivism rates (e.g., Leff, Kuipers, Berkowitz & Sturgeon, 1985; Falloon, McGill, Boyd & Pederson, 1987; Hogarty, et al., 1991; reviewed by Lam, 1991).

A variant of this approach to family services uses multi-family psychoeducational groups to build supportive social networks and to teach coping and problem-solving skills (McFarlane & Cunningham, 1996). In controlled comparative studies the multi-family format has been superior to a single-family format in reducing relapse (McFarlane et al., 1995; McFarlane, Link, Dushay, Marchal & Crilly, 1995).

Controlled trials of briefer family education and support modalities, ranging from one to eight sessions, have been found to increase family members' sense of support from the treatment team, increase their knowledge about schizophrenia and its treatment and rehabilitation, improve their self-reported coping, reduce distress and self-blame, and increase satisfaction with services (Abramowitz & Coursey, 1989; Posner, Wilson, Kral, Lander, & McIlraith, 1992). However, the briefer modalities have not been shown to reduce relapse or hospital recidivism.

Mueser and Gingrich (1995) provided a book that serves as a manual for family members undergoing psychoeducation. In addition to didactically presented information, it included "workbook" materials for learning and practicing behavioral analysis and problem-solving, making it ideally suited as a resource for education and support groups. Similar, more comprehensive, materials are available for professionals (Mueser & Glynn, 2000).

8. Contingency Management

Contingency management is a genre of techniques that evolved from learning and social-learning theories in the 1960s They are especially important in psychiatric inpatient settings (see Corrigan & Liberman, 1994). Nevertheless, contingency management is one of the most underutilized technologies in adult mental health services. Implementation is complicated by the need for administrative mechanisms to review and approve individual treatment plans, because of the potentially restrictive nature of the approach and the fact that it is often used to address problems with people who are involuntary patients.

The earliest applications of contingency management for schizophrenia, in the form of token economies in psychiatric hospitals, provided strong empirical evidence of effectiveness in promoting adaptive behavior (Ayllon & Azrin, 1968). An accumulation of case studies and institutional experience continues to support its effectiveness in suppressing inappropriate behavior (including "symptoms"), increasing adaptive behavior and increasing participation in treatment and rehabilitation (e.g., Wong, Massel, Mosk & Liberman, 1986; Paul & Menditto, 1992). There are no controlled trials that specifically demonstrate the unique contribution of contingency management, within a broader social-learning based rehabilitation program, to outcome. In addition to general effects on maladaptive and adaptive behavior, when combined with other social-learning modalities, contingency management has been shown to be effective with two of the most troublesome and drug-resistant problems encountered in inpatient settings, aggression (Beck, Menditto, Baldwin, Angelone & Maddox, 1991) and polydipsia (Baldwin, Beck, Menditto, Arms & Cormier, 1992).

A contingency management program or contract can be a vehicle for operationalizing and implementing the resolutions that derive from the new approach of therapeutic jurisprudence (Elbogin & Tomkins, in press). So far there have been no controlled outcome trials of this approach to contingency management. However, the approach should be expected to get considerable attention in the near future, as issues of voluntary and involuntary treatment are increasingly discussed and debated in national mental health forums.

9. Cognitive-Behavioral Therapy (CBT)

Some patients who take anti-psychotic medications still have troublesome symptoms such as hallucinations or delusions. A controlled trial (Drury, Birchwood, Cochrane & MacMillan, 1996) has shown that people with acute psychosis in acute inpatient settings, receiving standard pharmacological and psychosocial treatment, experienced a faster and more complete remission if they received a specialized version of CBT in addition to pharmacotherapy. Similar results were obtained by Sensky et al., (2000), Kuipers et al. (1997), Tarrier et al. (1998) and by Buchremer, Klingberg, Holle, Schulze and Hornung (1997) with patients who had been ill for a longer time. In these studies CBT has also been shown efficacious in the residual phase of schizophrenia for improving psychophysiological self-regulation and stress-tolerance, reducing drug-resistant symptoms (positive and negative), improving problem solving skills, increasing medication adherence and reducing relapse. Wykes, Parr and Landau (1999) obtained positive results with a group form of CBT. In addition, Lecompte and Pelc (1996) found CBT effective in enlisting patients into the treatment process and improving medication adherence.

Hogarty's Personal Therapy (Hogarty et al., 1997a, 1997b) includes CBT elements, but focuses on helping the patient identify and manage affective dysregulation. For patients who had supportive living arrangements Personal Therapy reduced relapse, eased symptoms and improved social adjustment.

10. Neurocognitive treatment and environmental engineering

Pharmacotherapy can reduce the cognitive disorganization of acute psychosis, but stabilized and optimally medicated individuals often have significant residual neuropsychological impairment. As previously mentioned, such impairment is a strong limiting factor in rehabilitation success. There is mounting evidence that some neurocognitive impairments in schizophrenia can be reduced by specialized therapy techniques which apply principles of experimental psychopathology, neuropsychology and CBT (Brenner, 1987; Spaulding, et al 1986; Flesher, 1990).

Two large scale controlled trials have established that such techniques contribute uniquely to overall rehabilitation outcome (Spaulding, Reed, Sullivan, Richardson & Weiler, 1999) ;Hogarty & Flesher, 1999) In both studies, the subjects were clinically stable and optimally medicated with antipsychotics. Both studies showed the neurocognitive modalities made unique contributions to functional improvement, in the context of comprehensive rehabilitation.A third controlled trial of neurocognitive treatment (Wykes, Reeder, Corner, Williams & Everitt, 1999) showed improvements in cognitive flexibility and memory. This study found that subjects who received the neurocognitive treatment showed differential improvement in self-esteem, suggesting it has subjective as well as objective benefits.

A similar approach, but based on operant learning principles, has proven effective in helping people with severe impairments achieve a level of functioning which allows them to participate in conventional skill training (Menditto, Baldwin, O'Neal & Beck, 1991). In this approach, individuals are systematically reinforced with tokens as they successively approximate motor behaviors prerequisite to group participation, such as appropriate motor orientation, disregard of ambient distraction, and performance of elemental group-related tasks.

11. Acute Treatment, Crisis Intervention and Related Milieu-Based Services

There is general agreement that the availability of acute inpatient and/or crisis/respite services is a necessary component of a mental health service system for people with schizophrenia. However, there is some room for debate about the precise nature of crisis intervention services.

One view that has been dominant since the 1960s is that crises in schizophrenia are predominantly the result of psychotic relapse, and the best setting in which to evaluate and treat psychotic relapse is in an inpatient psychiatric unit. Psychiatric inpatient units do provide necessary safety and medical care, but they are not always necessarily the most cost-effective alternative. Crises in schizophrenia may be driven by a host of factors other than psychotic relapse, and in such cases addressing those factors in a timely way may be more important than removing the person to a protected environment and administering drugs. As a result, alternative crisis services and 24-hour respite facilities are increasingly included in mental health systems. Often, these are incorporated in a comprehensive case management system.

Another predominant view has been that however useful psychosocial treatment may be in the residual phase, pharmacotherapy is the sole treatment of choice for acute psychosis. This presumption is challenged by a twelve year study of drug-free treatment, the Soteria Project (Mosher, 1999). In a series of controlled studies, the drug-free condition proved comparable to conventional hospital-and-medication treatment, for a large majority of recipients. The drug-free treatment was considerably less expensive. Interestingly, the interpersonal therapeutic community model of the Soteria Project is similar to one of the psychosocial treatment conditions previously validated by Paul & Lentz (1977). Although the social-learning condition produced the best outcome in the Paul & Lentz (1977) trial, the therapeutic community condition was superior to conventional "medical model" treatment, and both social-learning and therapeutic community treatments produced dramatic reductions in use of antipsychotic drugs. Strauss and Carpenter (1977) also report successful treatment of acute schizophrenia without drugs.

Despite these findings, drug-free treatment of schizophrenia, especially in the acute phase, remains outside generally accepted standards of practice. While caution about drug-free treatment is clearly indicated, the available data exacerbate suspicions that treatment of schizophrenia has become overly dependent on psychopharmacology, even in the acute phase.

12. Case Management

The diversity and complexity of the rehabilitation technology requires systematic coordination for cost-effective delivery. Multidisciplinary treatment teams operating within a case management model are typically used for this purpose (Holloway, Oliver, Collins & Carson, 1995; Mueser, Bond, Drake & Resnick, 1998).

Case management is closely associated with Programs for Assertive Community Treatment (PACT, also known as ACT). PACT is a comprehensive approach to services for people with severe and disabling psychiatric disorders. In addition to case management, PACT programs include conventional psychiatric services and varying amounts of rehabilitative services, delivered in an outreach mode that takes the services to the recipient when necessary. PACT has been manualized (Allness & Knoedler, 1998), to the degree that most relevant therapist skills, including case management, can be acquired by following the manual under experienced supervision. There has been much research on the efficacy and cost-effectiveness of PACT programs, but the results have been inconsistent (reviewed by Mueser, Bond, Drake & Resnick, 1998; and Latimer, 1999). PACT programs that include more living skills training and higher staff-client ratios appear to be more effective. Similarly, the transition from institution to community is enhanced by inclusion of focused skill training with case management (MacKain, Smith, Wallace & Kopelowicz, 1998),

The Role of Pharmacotherapy in the Treatment and Rehabilitation of People with Schizophrenia

The pharmacological agents most primarily associated with treatment of schizophrenia are grouped in a large and heterogeneous family, the antipsychotics. Recently, this family has been subdivided into the typicals, or neuroleptics, and the atypicals (see Table 1). The neuroleptics are so named because they all produce side effects suggestive of neurotoxicity. Until the late 1980's there was only one known antipsychotic which was not a neuroleptic, clozapine. In early trials, clozapine was observed to cause a potentially lethal side effect, agranulocytosis, a suppression of white blood cell (WBC) production, in an unacceptably high proportion of individuals. For that reason, clozapine was not approved for use in the U.S. until 1990. However, clinical use in Europe increasingly suggested that clozapine has important advantages over neuroleptics, and it was eventually made available in the U.S., under a strict regimen of continuous monitoring. Shortly thereafter, additional atypical antipsychotics began to appear, and they continue to proliferate. They have little in common, except that whereas the neuroleptics all appear to work through strong blockade effects on the D₂ receptor of the neurotransmitter dopamine, the new ones affect other neurotransmitter systems and some show little or no D₂ blockade (See Table 2). This inspired the categorical distinction between the "typical" neuroleptic D₂ blockers, and the atypicals. Today the development and marketing of ever safer and more effective atypical anti-psychotic agents has become a major activity in the pharmaceutical industry.

[Tables 1&2 about here]

Changing Views of Schizophrenia and Anti-psychotic Agents

In the years following the introduction of the first anti-psychotic drugs (the mid-1950's), their most clinically salient effect was suppression of the symptoms of acute psychosis, including delusions, hallucinations, thought disorder, agitation and gross disorganization (Davis & Casper, 1977). The last several years of research on the outcome of pharmacotherapy for schizophrenia have seen an emphasis on those domains of functioning where the neuroleptics fall short, most particularly, negative symptoms, deficit states and cognitive and neuropsychological impairments. In addition, there has been much study of response to atypicals by people who are known to be unresponsive to typicals. As of this writing, most of the published studies contrast clozapine (Clozaril), the first widely available atypical, with haloperidol (Haldol), a first-generation typical. There is a considerable amount of information on risperidone (Risperidal), the second widely available atypical, and on olanzapine (Zyprexa). Data on the remaining approved atypicals, quetiapine (Seroquel) and ziprasidone (Zeldox) are just beginning to appear.

There is broad agreement that about half of the people diagnosed with schizophrenia who are unresponsive to typicals show a fair to good response to clozapine, and that clozapine produces substantially fewer side effects at standard therapeutic dose levels (Lieberman, Safferman, Pollack, Szymanski, Johns, Howard, Kronig, Bookstein & Kane, 1994; Meltzer, 1995; Buchanan, 1995; Skelton, Pepe & Pineo, 1995;). There is controversy as to whether clozapine has differentially greater effects on negative symptoms (Meltzer, 1992; Breier, Buchanan, Kirkpatrick, Davis et al, 1994; Miller, Perry, Cadoret & Andreasen, 1994; Carpenter, Conley, Buchanan, Breier et al, 1995; Kane, 1996; Rosenheck, Dunn, Peszke, Cramer, Xu, Thomas & Charney, 1999). The problem appears to be that "negative symptoms" represent a heterogeneous category of clinical expressions, probably linked to different neurophysiological and developmental mechanisms. Some may be primary, directly linked to the etiology of the disorder, while others are secondary, arising from incidental factors such as drug side effects or individuals' responses to the primary expressions. For example, some of the differential effectiveness of atypicals for negative symptoms (lack of motivation or feeling) may be attributable to their lower levels of extrapyramidal side effects (Kane et al., 1994). There is some evidence that secondary negative symptoms show more differential response than primary negative symptoms (Buchanan, 1995).

Both clozapine and risperidone are superior to typicals in reducing the degree of neurocognitive impairment that remains in the severe and persistent, residual phase of the disorder, after the recipient has been determined to be medicated optimally (Meltzer & McGurk, 1999, Kern, Green, Marshal, Wirshing, Wirshing, McGurk, Marder & Mintz, 1999; Keefe, Silva, Perkins & Liebermann, 1999). There is some preliminary evidence that olanzapine also improves cognitive functioning (Meltzer & McGurk, 1999). However, no atypical returns cognition to premorbid or normal levels, and the impact of the atypicals' superior cognitive effects on overall outcome is not established clearly.

It is not obvious why atypicals benefit neurocognition. One possibility is that they are simply more effective at resolving acute psychosis and the severe cognitive impairments attendant to that condition. Another possibility is that typical antipsychotics have detrimental effects on cognition during the residual phase, while atypicals lack these effects. Residual phase impairments could be partly caused by the typicals' anticholinergic (interference with the action of acetylcholine in the brain) properties, as is suspected for some negative symptoms (it is noteworthy in this regard that, as discussed above, neurocognitive impairments are associated with negative symptoms). A third possibility is that in addition to their antipsychotic action, atypicals affect other neurochemical systems that produce cognitive impairments in the residual phase of the disorder. In this regard, candidate mechanisms include selective acetylcholine agonism, down-regulation of 5-hydroxytryptamine type 2a (5HT_2a) receptors, and enhanced glycine modulation of the N-methyl-D-aspartate (NMDA) receptor, a component of the glutamate transmitter system (Meltzer & McGurk, 1999; Goff & Evins, 1998; Goff, Henderson, Evins & Amico, 1999). It is entirely possible that different atypicals affect neurocognition in different ways.

Clozapine appears to moderate some dimensions of affective dysregulation, in the domains of hostility and irritability (Buchanan, 1995). This may prove an important advantage for managing aggression, mania and depression when they co-occur with the more pathognomic characteristics of schizophrenia. Clozapine has been found to reduce aggression in particularly violent and treatment-resistant individuals (Menditto et al., 1996). Risperidone was found to be no more effective than typicals (Beck, Greenfield, Gotham, Menditto, Stuve & Hemme, 1997) in this regard.

The atypicals are considerably more expensive than the typicals. However, cost-effectiveness analyses indicate that the greater cost is more than offset by the reduced costs consequent to atypicals' greater clinical efficacy (Davies, Adena, Keks, Catts, Lanber & Schweitzer, 1998; Rivicki, 1999).

Strategies for Optimal Use of Antipsychotics

As awareness of the phasic nature of schizophrenia has increased, tactical principles for use of antipsychotics have evolved. For example, it was recognized early in the history of antipsychotic pharmacotherapy that dosages can be reduced to maintenance levels after resolution of the acute episode. Lower doses incur fewer side effects, thus enhancing regimen adherence. Lower doses are also thought to incur less risk for tardive dyskinesia. ,However, titration to the lowest necessary dose is not without risks. Ironically, the development of high-intensity rehabilitation programs may increase stress levels, necessitating a higher dose than would otherwise be necessary, at least temporarily. Since rehabilitation tends to increase in intensity as acute psychosis is resolved, premature titration could promote relapse (Schooler & Spohn, 1982).

Systematic protocols for optimizing maintenance have been developed, and are part of the aforementioned practice guidelines. However, there is very little in any of those guidelines concerning integrating pharmacological and psychosocial treatment in the context of comprehensive psychiatric rehabilitation. This appears to be an important issue for current research. Collaboration between pharmacotherapists, neuropsychologists, behavior analysts and rehabilitation therapists appears to be a key part of the solution.

The issue of polypharmacy (a regimen of more than one antipsychotic) has been hotly debated. For a long time, experimental studies showed no differences between specific typicals, other than differences in potency (dosage required for an antipsychotic effect). Nevertheless, clinicians were compelled by their experience to suspect that in some individuals combinations of antipsychotics can achieve better results than any single antipsychotic. As neuropharmacological knowledge and technology progressed, it became apparent that in fact each antipsychotic, typical and atypical, has a unique profile of histochemical activity. This converged with a growing realization that the D₂ receptor, and dopamine activity in general, is probably just one component of a complex biochemical system involved with psychosis (Weinberger, 1994; Weinberger & Lipska, 1995). As a result, pronouncements about polypharmacy have grown more circumspect (e.g., see Goff & Evins, 1998). In the end, these developments converge on the general principle that pharmacotherapy of schizophrenia should be driven by systematic trials, evaluated with cognitive and behavioral data, whether the intervention is a single drug or a combination.

The question of when to stop a medication trial can be as important as the choice of agent. Too often, regimens are continued long after they have demonstrated ineffectiveness. This is often because the targets for treatment are vaguely or incompletely specified. In the risk management decisions involved in controlling potentially dangerous behavior, discontinuing an agent intended to prevent harmful consequences is difficult to justify without clear and quantitative clinical data. The result is sometimes an accumulation of improbably complex regimens which don't contribute to stability or rehabilitation progress. This can be prevented by identifying targets precisely and inclusively before a medication trial begins, collecting reliable measurements over the course of the trial, and systematically analyzing the data before making the next treatment decisions.

For example, if a pharmacological intervention is chosen to eliminate assaultive behavior in a person with severe and persistent psychosis, the intervention should be preceded by a thorough functional behavioral analysis (FBA) of the assaultive behavior. The FBA should precisely and reliably identify the target behavior. It should reveal no antecedents or consequences associated with the behavior which could be easily controlled (control of such stimuli would be a compelling first choice treatment option). If the selection of the pharmacological option is based on hypothesized relations between the target behavior and other typical targets for antipsychotic medication (e.g., the assaults are hypothesized to be associated with paranoid hallucinations and/or delusions) then that hypothesis should be supported, or at least not disconfirmed, by FBA data. No other interventions potentially affecting assaultive behavior should be introduced during the period required to exert an effect. Restraint and seclusion are not typically expected to reduce assaultive behavior over time, but a properly executed Time Out from Reinforcement program may have such an effect, while also managing the risk of injury. For this reason, such behavioral interventions should often be tested for effectiveness before a pharmacological option is exercised.

If after 6 weeks the continuing FBA shows no decrease in assaultive behavior, the intervention should be stopped, the FBA data reanalyzed, and new hypotheses and interventions entertained. If the FBA data shows some, but not sufficient, effect, further decisions must be made to try a different pharmacological intervention, continue the present medication but add additional interventions (e.g., a contingency management program selectively reinforcing assault-free periods), or abandon the pharmacological option altogether. In any case, the FBA must be continued until effective controlling factors are identified, pharmacological or otherwise

An absolute minimum time frame for determining antipsychotic pharmacotherapy to be ineffective is about two weeks. Full evaluation of antipsychotic effects on personal and social functioning may require more than a year, especially for the atypicals.

Considerations in the choice of an anti-psychotic agent

Ultimately, the best choice of anti-psychotic agent must be determined empirically for each individual. Little is currently known about factors that may facilitate the choice of a candidate before the empirical trial. The choice of drug is influenced by side effects considerations and circumstantial factors, as much as by anti-psychotic efficacy. Generally, the lower-potency antipsychotics have more sedating action, so these get earlier consideration when agitation is part of the clinical picture. Sedation is often aversive, especially to individuals who do not need it, so the higher-potency antipsychotics are preferred when sedation is not needed. However, the higher-potency antipsychotics are more likely to produce extrapyramidal side effects (the high-potency atypicals are an exception to this). Two agents, haloperidol (Haldol) and fluphenazine (Prolixin), are available in an injectable slow-release medium, which eliminates the need for daily dosing (see Glazer & Kane, 1992). This is advantageous when psychoeducation and skill training are insufficient to establish adherence to a regimen (or until those modalities have time to work).

Also, new understanding about subtypes of schizophrenia may influence medication choices. For example, it may be that the hypothesized neurodevelopmental subtype of schizophrenia (Knoll et al., 1999) responds best to atypicals because the multiple actions of the atypicals address the pervasive dysregulation of brain systems that inspired the neurodevelopmental model. In other subtypes, symptoms and other impairments may be more focally influenced by dopamine systems, and consequently more responsive to specific dopamine blockade.

As the atypicals have proliferated, there has been increasing discussion of whether there is now an antipsychotic drug of first recourse. Clozapine would not be a candidate, despite its superior antipsychotic properties, because of the problems associated with agranulocytosis (discussed below). Based on lower risk of side effects and greater antipsychotic efficacy, any of the three recently introduced atypicals, olanzapine, quetiapine and risperidone, should be given priority over any typical. Within the next few years, one atypical may emerge as the first choice, or perhaps more than one, for different subtypes or clinical pictures. Of course, even after a first recourse agent is identified on safety and efficacy grounds, cost and other factors could further influence its use.

Adjunctive Pharmacotherapy and Related Issues

a. Managing antipsychotic side effects

Antipsychotic drugs produce problematic side effects in many individuals (See Table 3). A major category of side effects results from neurotransmitter dysregulation of the extrapyramidal motor system. It is thought that these side effects are the result of an imbalance of dopaminergic and acetylcholinergic activity in subcortical motor control systems, brought about by the selective blockade of dopamine. Simultaneous blockade of acetylcholine can relieve these symptoms in most cases. The anticholinergic agents trihexyphenidyl (Artane) and benztropine (Cogentin) are most commonly used for this purpose.

[Table 3 about here]

A subcategory of side effects are Parkinsonian, so named because they mimic the symptoms of Parkinson's disease. These include suppression of facial motility (fixed facies), disruption of postural reflexes resulting in a shuffling gait and loss of balance, tremor and muscle stiffness.

Other extrapyramidal side effects of neuroleptics include torticollis and oculogyrus, spasm-like contractions of the neck- and eye-muscles respectively. These can be particularly frightening, but are readily observable and usually respond quickly to anticholinergic treatment or change of anti-psychotic. A related side effect is akathisia. Unlike the motor side effects, akathisia is primarily a subjective experience of agitation and restlessness, sometimes observable as motor restlessness or persistent irritability. It is often difficult to detect, partly because it is primarily subjective (and people with schizophrenia may have particular difficulty in reporting a purely subjective experience), and partly because it tends to appear several days to 2 weeks after initiating neuroleptics, after clinical vigilance for side effects has dissipated. Akathisia is extremely aversive, and thought to be a major cause of medication nonadherence. It can usually be controlled adequately with anticholinergics. Its incidence with atypicals appears to be low, but this is not a reason for relaxing vigilance.

There is substantial evidence that anticholinergic agents can themselves produce cognitive impairments, especially in memory (Blanchard & Neale, 1992). For this reason, it is considered desirable to keep anticholinergic treatment to a minimum (and antipsychotics themselves have anticholinergic properties, to varying degrees). An alternative to anticholinergic treatment of side effects is the selective dopamine agonist amantadine (Symmetril). Amantadine increases dopamine activity in motor systems without necessarily affecting the other dopamine systems, allowing effective control of Parkinsonian symptoms in some individuals. However, it is considerably more costly than anticholinergics, and in many individuals its dopamine agonism is not selective enough to avoid exacerbation of psychotic symptoms. Most of the atypical antipsychotics produce fewer side effects, requiring little or no adjunctive treatment

The D₂ blocking properties of neuroleptics cause an increase in blood prolactin levels, by way of a hypothalamic dopaminergic pathway that normally inhibits lactation. This sometimes produces gynecomastia (swelling of breast tissue, predominantly in males) and galactorrhea (expression of breast milk, predominantly in females). This is usually managed by switching to another antipsychotic. The atypicals, with less D₂ blocking activity, are less likely to cause this problem (see Drug and Therapy Perspectives, 1999).

Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal side effect involving the disruption of hypothalamic mechanisms that regulate body temperature. Symptoms include fever, diaphoresis, autonomic instability (fluctuations in blood pressure and heart rate), elevated white blood cell count (WBC) and compromised kidney function (indicated by elevated blood levels of serum creatinine). There is some evidence that as many as 12% of people on neuroleptics experience a mild, sub-clinical form of this syndrome. The malignant form is associated with high doses, high potency agents and intra-muscular administration. It usually appears within 2 weeks of starting treatment, but it can appear at any time. It is managed by carefully observing recipients when they are started on a new antipsychotic, and discontinuing it immediately if the symptoms occur. Dopamine blockade is thought to be a proximal cause of NMS, and dopamine agonists such as bromocriptine are sometimes recommended for acute treatment. NMS is a medical emergency, and is generally managed in intensive care settings.

Side effects that are encountered with both typicals and atypicals, include significant weight gain and a lowered seizure threshold. Management of these side effects must be based on case-by-case assessment of the relative advantages of switching antipsychotic versus adjunctive treatment. Weight gain is less likely when administering clozapine when quetiapine is also taken (Reinstein, Sirotvskaya, Jones, Hohan & Chasanov, 1999).

Tardive dyskinesia (TD) is a serious, potentially irreversible side effect of protracted use of antipsychotics. Its symptoms are spasmodic contraction of muscle groups, mostly oral, facial and lingual muscles in the early stages, and the entire torso in later stages. It can be reliably detected in its early stages by physical examination. Dangerously common for typicals, it is thought to be rare for atypicals, and thought not to occur at all with clozapine. The American Psychiatric Association has acknowledged that TD is an iatrogenic condition caused by antipsychotic drug treatment, and has published a detailed protocol for early detection and response to tardive dyskinesia (Tardive Dyskinesia Task Force, 1980). Management of TD may involve a difficult choice between control of psychosis and TD symptoms, but early detection preserves some degrees of freedom in the decision process. As with all such decisions, the involvement of the identified patient and/or family is of paramount importance.

As previously mentioned, agranulocytosis is a potentially lethal side effect, extremely rare but thought to be less rare for clozapine, at 1-2% of the recipients of that drug (Krupp & Barnes, 1992).[3] This risk has been a major factor in weighing the advantages of clozapine's superior antipsychotic capabilities and lack of risk for TD. Use of clozapine requires strict adherence to a regimen of white blood cell counts, weekly at first and biweekly after 6 months (80% of cases occur within the first 18 weeks). A sudden drop in the white blood cell counts demands immediate discontinuation of the drug.[4]

b. Adjunctive treatment of affective and psychophysiological dysregulation

There is some evidence that agents normally used to enhance affective regulation and control seizures, including clonazepam (Klonopin), carbamazepine (Tegretol) and valproic acid (divalproex sodium, Depakote), among others, can enhance the effects of antipsychotics (Meltzer, 1992; Schulz, Kahn & Baker, 1990). It would be logical to expect that this enhancement is best when the clinical picture includes affective dysregulation closely associated with psychotic symptomatology, as in schizoaffective disorder and borderline personality disorder co-occurring with schizophrenia. However, there is insufficient experimental evidence to allow a confident conclusion about this. For an individual case, there may be sufficient evidence to justify a controlled clinical trial of an adjunctive affective regulation agent when satisfactory symptom control and stabilization cannot be achieved with antipsychotics alone. However, psychosocial interventions may also contribute to affective stabilization, and this should be weighed against the disadvantages of a more complex medication regimen. The implicit message to the recipient often is that drugs are preferable to skills as a means of managing one's emotional life. It is necessary to provide an educational intervention that will counteract this message.

Extreme caution is indicated in using anticonvulsants with antipsychotics. Carbamazapine and possibly also clonazepam may suppress bone marrow function, exacerbating the potential effects of neuroleptics and clozapine. Lithium is sometimes used in conjunction with neuroleptics (the evidence that lithium enhances antipsychotic effects on schizophrenic symptoms is weak, but it may be used for co-occurring manic symptoms) and this may increase risk for neuroleptic malignant syndrome.

c. Adjunctive treatment of negative and deficit symptoms

Negative and deficit symptoms are still a persistent problem in treatment and rehabilitation of schizophrenia, even though the atypicals may be more effective in this regard. The discovery that D₂ blockade is not the sole mechanism of the anti-psychotic effect, and the realization that people with schizophrenia may also have other psychiatric problems such as depression, has spurred exploration of alternative pharmacological approaches.

Non-tricyclic antidepressants appear to have some efficacy in reducing negative symptoms (Goff, Midha, Brotman, 1991; Silver & Nassar, 1992), not surprisingly, considering the similarity between negative symptoms and depressive symptoms. The efficacy of atypicals for negative symptoms is probably related to their efficacy for neurocognitive impairments. Logically, the same might be expected of antidepressants, but that has not been experimentally demonstrated. Research in this domain has only just begun, and the next few years may see some significant advances.

d. Treatment of depression co-occuring with schizophrenia.

Depressive signs sometimes occur with schizophrenia and can be effectively treated with antidepressant medications (Siris, 1994). Cognitive-behavioral or interpersonal psychotherapy are logical alternatives, but there has not been systematic study of this possibility. Considering the greater safety of the non-tricyclic antidepressants and their efficacy for reducing negative symptoms, they are probably the best first choice for treating depression in schizophrenia pharmacologically. One of the newer atypical antipsychotics, olanzapine, appears to be effective in treating depressive symptoms (Tollefson, Sanger, Lu & Thieme, 1998).

e. Adjunctive treatment of anxiety and agitation

Anxiety often accompanies schizophrenic symptomatology, and this causes an understandable desire among many clinicians to treat the anxiety directly with pharmacotherapy. In addition, psychotic relapses are usually preceded by increases in anxious and depressive symptoms, before the appearance of acute schizophrenic symptoms (Jorgensen, 1998). Anxiolytics have been recommended as an adjunct to antipsychotics for emergency treatment of extreme agitation in schizophrenia, although the potential disinhibiting effects of anxiolytics demands caution (Wolkowitz & Pickar, 1991; Corrigan, Yudofsky & Silver, 1993). The efficacy of chronic anxiolytic treatment has never been supported. As with affective regulation, the value of pharmacological treatment of problems which may be more effectively addressed with psychosocial treatment, should be carefully weighed.

Coordinated Use of Pharmacotherapy and Psychosocial Therapy in the Treatment and Rehabilitation of People with Schizophrenia

All the foregoing considerations reduce to a fairly straightforward algorithm for coordinating pharmacotherapy and psychosocial treatment. While simple in concept, implementation is, of course, much more complex.

The steps in the algorithm reflect a logical sequence of assessments and decisions. Refinement and further specification of algorithms such as this will be a primary focus in research and development of rehabilitation technology in the coming years.

An algorithm for treatment and rehabilitation of schizophrenia

Preliminary differential diagnosis: rule out presence of other conditions as possible causes of psychotic behavior:

-- intoxication -- febrile delerium

-- acute neuropathy -- known chronic or progressive neurological conditions

-- bipolar disorder -- psychotic depression

-- factitious report of symptoms -- malingering

-- transient periods of psychotic-like behavior associated with extreme stress, anxiety, depression or severe personality disorder

-- psychotic-like behavior associated with cultural or sociological circumstances (e.g. spiritual, religious or political beliefs, associated with identifiable groups or ideologies, which appear bizarre to other groups).

Proceed with algorithm if, after ruling out or resolving these causes, a clinical picture of "schizophrenia" or other severe, adult-onset psychiatric condition persists, including continuous or episodic psychotic symptoms when untreated, and significant compromise of personal and social functioning (the functional deficits need not be attributable to the psychotic symptoms).

1. Begin functional assessment and rehabilitation counseling to identify problems and treatment goals.

2. Does historical or current behavioral-observational data indicate problems in adherence to treatment and rehabilitation regimens, and/or inability to give informed consent to treatment?

If yes, assess thoroughly and take action as indicated to protect those at risk and engage treatment (these actions must be continuously re-evaluated as recovery permits greater participation and less restriction, and restores legal competence):

-- establish means of appropriate substitute decision-making (e.g. appointment of guardian, civil commitment, judicial supervision of treatment, etc.) when necessary;

-- provide environmental structure sufficient to ensure safety at lowest possible level of restriction (e.g. hospitalization, crisis respite, supervised residential services, etc.);

-- negotiate contingency management programs sufficient to establish engagement in treatment and rehabilitation at the lowest possible level of restriction.

3. (Under most circumstances, this step is conducted simultaneously with the previous step) Does history and presentation suggest the affected individual is currently experiencing an acute psychotic episode?

If yes, take action to resolve acute episode:

-- provide crisis intervention as circumstances demand;

-- begin clinical trial of antipsychotic medication, beginning with first recourse selection; titrate dose upward or select alternative as indicated by treatment response;

-- administer adjunctive medication to control side effects as necessary;

-- provide psychosocial interventions to enhance resolution of acute psychosis (e.g. specialized CBT) and suppress dangerous or unacceptable behaviors (e.g. Time Out From Reinforcement contingency management programs).

4. (When the antipsychotic used in resolving acute psychosis is a neuroleptic:) Is there evidence of residual negative symptoms, deficit states, side effects, or psychophysiological or affective dysregulation, for which an atypical antipsychotic would be more beneficial?

If yes, begin controlled trial of an atypical antipsychotic (under most circumstances, the switch should be gradual and staggered).

Proceed to next step when data indicates acute episode is stabilized as much as possible, i.e. psychotic symptoms, related behaviors and acute cognitive impairments are not expected to respond to further adjustments in medication and/or more time in the therapeutic milieu.

5. Is there evidence of residual negative symptoms, deficit states, or psychophysiological or affective dysregulation for which adjunctive pharmacotherapy may be beneficial?

If yes, begin controlled trial of adjunctive pharmacotherapy targeting specific residual problems (e.g. antidepressant medication if residual state is suspected to be depression-related, anticonvulsant for agitation or aggression).

6. Does assessment reveal residual neurocognitive impairments sufficient to compromise personal or social functioning or response to rehabilitation?

If yes, provide neuropsychological intervention:

-- begin trial of cognitive-rehabilitative intervention (e.g. IPT, CET);

-- provide supportive and prosthetic environmental conditions for residual impairments that limit functioning and are not eliminated by treatment.

7. Is there evidence of residual symptoms, affective dysregulation or other persistent condition for which psychosocial treatment may be effective?

If yes, begin trial of psychosocial treatment targeting specific problem (e.g. CBT for symptom control or depression, relapse prevention for substance abuse).

8. (This step is usually conducted simultaneously with the previous step:) Does functional assessment reveal deficits in key skill areas needed to achieve the affected individual's full potential, live in the least restrictive possible environment and enjoy a satisfactory quality of life?

If yes, begin psychosocial rehabilitation targeting specific skill deficits.

9. Does progress in rehabilitation allow titration of antipsychotic dose to maintenance level, discontinuation of adjunctive pharmacotherapy, reduction or discontinuation of restrictive environmental supports or contingency management programs?

If yes, adjust regimen accordingly.

10. Is recovery proceeding as expected, toward measurable goals identified by the entire treatment team (including identified patient and relevant family)?

If no, identify barriers to progress, reformulate the treatment and rehabilitation plan, and recycle the entire algorithm.

Conclusions: The Role of the Psychologist in Treatment and Rehabilitation

The complexity and variety of the assessment and treatment technologies needed for effective rehabilitation make it clear why people with severe and disabling disorders usually receive services from an interdisciplinary team. Team members usually have overlapping, as well as unique, areas of expertise and clinical skills. Particular areas of expertise vary, even within disciplines, including psychology. The role of a particular psychologist may vary across different teams, complementing the other resources among the team members. Nevertheless, the background and perspective of psychologists usually gives them a unique and especially useful role in identifying and resolving the key decisions to be made in the course of providing services. The algorithm for treatment and rehabilitation described in this chapter identifies those key decisions. Psychological assessment and functional behavioral analysis often emerge as the technologies most important in informing the key decisions. Whatever other resources the psychologist may bring; e.g. special knowledge in social skills training, cognitive therapy or psychopharmacology, systematic application of behavioral and psychological assessment data to key clinical decisions is their sine qua non. Inevitably, such a central function in selecting and guiding treatment constitutes a leadership role. Psychologists who provide services to people with severe and disabling disorders should accept and prepare themselves for such a role.

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Table 1

Selected Antipsychotic Medications and Their Characteristics

____________________________________________________________________________

Chemical Name Trade Name Dose(mg.) Half-Potency

Usual Range Life

__________________________________________________________________________________________

Typical Antipsychotics

Phenothiazines

Aliphatic

Chlorpromazine Thorazine 400-800 100

Piperazine

Fluphenazine Prolixin 4-20

Triffluoperazine Stelazine 6-20 5

Thioridazine Mellaril 200-600 100

Butyrophenone

Haloperidol Haldol 8-32 2

Thioxanthene

Thiothixene Navane 15-30 5

Dihydroindolone

Molindone Moban 40-200 10

Dibenzoxazepine

Loxapine Loxitane 20-250 15
Table 1 Continued

Atypical Antipsychotics: Relative potencies and side-effect

___________________________________________________________________________

Antipsychotic Potency Side Effects Relative Clinical Dose

(mg/day) Sedation Autonomic EPS (CPZ Equivalent) ___________________________________________________________________________

Clozapine 200-600 +++ +++ (+) 1

Quetiapine 300-900 ++ ++ + 1

Risperidone 2-8 + ++ ++ 80

Olanzapine 10-25 ++ + (+) 20

Ziprasidone* 80-200 ++ ++ ++ 2

____________________________________________________________________________

Plus signs represent semiquantitative estimates of the degree of side effects of the antipsychotics based on the available, relatively limited literature.

*ziprasidone is not yet approved for clinical use

From Wirshing et al., (1997). Adapted with permission from Essential Psychopharmacology (1996; 1:5-26) Copyright 1996 the Hatherleigh Company, Ltd.

Parentheses mean very minimal.

CPZ = chlorpromazine; EPS = extrapyramidal symptoms.

____________________________________________________________________________

Table 2

Atypical Antipsychotic Receptor-Binding Profiles

________________________________________________________________________

Antipsychotic D1 D2 5-HT2 alpha1 Chol Hist
______________________________________________________________________________

Clozapine ++ + +++ +++ +++ ++

Quetiapine (+) + + ++ - ++

Risperidone - +++ +++ +++ - -

Olanzapine ++ ++ +++ ++ +++ ++

Sertindole - + +++ ++ - -

Ziprasidone + +++ +++ ++ - -

________________________________________________________________________

D = dopamine; 5-HT = hydroxytryptamine; Chol= cholinergic; Hist = histaminergic. (Adapted by Wirshing et al., 1997, from Essential Psychopharmacol. (1996);1:5-26), Coyright 1996, The Hatherleigh Company, Ltd.

______________________________________________________________________________
Table 3

Antipsychotic Medications Side Effects

________________________________________________________________________

Drug Sedation Autonomic Extrapyramidal

________________________________________________________________________

Typical Antipsychotics

Fluphenazine + + +++

Perphenazine ++ + ++/+++

Triffluoperazine ++ + +++

Mosoridazine +++ ++ +

Thioridazine +++ +++ +

Acetophenazine ++ + ++/+++

Chlorpromazine +++ +++ ++

Triflupromazine +++ ++/+++ ++

Haloperidol + + +++

Thiothixene + + +++

Chlorprothixene +++ +++ +/+++

Molindone ++ + +

Loxapine ++ +/++ ++/+++

__________________________________________________________________

The Social Learning Program developed by Gordon Paul of UH Department of Psychology requires a bit more information. Here is a summary of his results.

SOCIAL LEARNING PROGRAM RESULTS

N = 84

N = 28 N = 28 N = 28

GROUP CONTROL MILIEU SOCIAL LEARNING

HOSPITAL

RELEASE

RATE 46.4% 67.9% 96.4%

Medication USE HIGH HIGH VERY LOW

STAFF CONTACT LOW MEDIUM HIGH

AVERAGE DAYS

IN COMMUNITY 230 449 591

WEEKS IN

PROGRAM 260 215 213

A Family's Experience with Schizophrenia

Although it was not something we would have expected, our first-born, a son, developed symptoms of schizophrenia when he was 19 in 1972. Below is one brief account of our experience.

Johnson, D. L. (2000). The family's role in recovery.

Journal of NAMI-California, 11, 75-76.

The Family's Role in Recovery

Dale L. Johnson

Our son is now 46 years old. When he was 19, he was hospitalized for the first time for treatment of schizophrenia. His psychosis could hardly have been predicted. He was a happy child, with many friends, an excellent student, and a good big brother to his younger sister and brother. He was a leader in high school and active in drama and sports. He was accepted at Harvard, but stayed only one semester. His counselor advised that he take a leave of absence because he was obviously so preoccupied with the Viet Nam war (It was 1971) that he was unable to focus on his studies. He has never been able to return to the university.

Prevention

I think that if my wife and I knew then what we know now we would have been more alarmed about the early signs of schizophrenia. Early treatment, as is being done in Australia, might have averted the full symptoms and minimized his disability. Of course, we did not know this then, nor did the various professionals who saw him. But our experience tells us that early identification and preventive intervention should now have high priority for researchers and practitioners.

Terrible Times

The ten years after the first appearance of psychotic symptoms were years of turmoil, certainly for parents and siblings, and much more for our son who became ill. A full account of this dreadful period would take the pages of a book. All I can do here is list some of the most memorable events.

He switched from near normality to terrible psychosis repeatedly. He did well while taking medication, and was psychotic when not.

He was homeless and on the streets many times. He would leave a hospital against advice and disappear, sometimes for months. We searched for him, but with no success. Eventually, we would get a call, typically from police, asking us to come and get him.

He attempted suicide several times and failed only because his psychosis disrupted his planning.

He was in jail several times, not for committing crimes, but for his own protection. In nearly every instance, the police behaved admirably.

There were episodes of violence against family members when he was not taking medication and when he was psychotic. This violence was shocking to us because he had always been a gentle person. Perhaps because he is so large he has never had to prove anything with aggression.

He sometimes accepted hospitalization, but at other times he refused and we had to seek involuntary commitment.

Although always concerned with maintaining good health, he began smoking while in a hospital that passed out free cigarettes and provided nothing to do for eight months.

Although we were not told until later, he was engaged in psychodynamic therapy twice. Both times this resulted in terrible psychotic episodes.

Mistakes Made

Although I am a clinical psychologist with much experience in working with schizophrenia and my wife is a medical sociologist, we were not prepared to cope with our son's psychosis. We did things that we should not have not have done. One was that when we learned there were no private hospital beds available when we needed one we chose to assist in his early treatment and have him live at home. We could have had him hospitalized at some remote place. Home treatment was not good for him and was devastating for his younger siblings. I think it delayed his course of recovery.

We were also somewhat casual about his medication adherence. No one told us, or our son, why medication was so important. Even the professionals seemed rather indifferent about adherence.

We should have spent more time with his siblings and told them more about what was happening. It was not easy to talk with them. They blamed us and insisted he was not ill, just having a hard time discovering himself, or having a religious experience.

We relied too much on private psychiatric hospitals. The staff in these hospitals were simply not trained to work well with psychotic patients. Our son did much better in the state hospital where staff were well-trained.

Things We Did Right

We did some things right, and I am convinced it was these things that are responsible for the level of recovery he has achieved to date. It was these things and his own struggle for recovery that made a difference.

Insisting on hospitalization, even when involuntary, was essential and eventually contributed to his acceptance of his illness and willingness to accept treatment.

We were so angry about the lack of services, incompetence of staff, and inappropriateness of some services that we assembled other parents in the living room of our home and began an advocacy group. We organized to change the mental health system. Later we learned about NAMI and joined. Our group was the first AMI group in Texas and my wife, Carmen, was a founder, and second president, of TEXAMI. I served on the NAMI board for seven years and was president one year. We marched on the state capitol, picketed stigmatizing movies, visited jails and prisons, helped locate missing family members, posted our home telephone number publicly in Houston and invited calls at any hour. We did the work of NAMI members, for ourselves, but mostly, we did it for our son.

It was through NAMI contacts that we discovered a board and care home that was just right for our son. He had been in places that could not have passed any kind of public health screening. He has been a resident of this one in Southern California for about 15 years.

I learned of clozapine while on the NAMI board and obtained information about its pros and cons from such experts as Dave Pickar and Dan Weinberger at NIMH. Even with their advice I still was not sure about using it. His mother simply went ahead, contacted our son's doctor who agreed to prescribe it, and we paid for the medication the first year. Soon, with her persistence, the state agreed to cover the cost. The drug worked slowly for him, but after many months his delusions and hallucinations disappeared. He was left with negative symptoms, but was much better able to function in the community. Furthermore, side effects that gave him so much discomfort with other drugs were not present.

We helped to involve the whole family in his recovery. His grandmothers have been highly supportive and now his siblings are also supportive, kind, and understanding.

Perhaps most important is that we were there for him whenever he needed help. We ignored doctors who said he was very ill, nothing can be done for him, we should hospitalize him and forget him. We did not accept the statements of some professionals that because of confidentiality they could not provide us with information about his treatment. We told them they should find ways around confidentiality limitations and that if they expected us to assist in the treatment, and they did, they would have to give us information. They all found ways to provide us with needed information.

Ten Years of Recovery

Although he is still quite disabled with negative symptoms, difficulty in maintaining concentration, and lacking initiative, he has made great strides toward recovery. He does not appear ill to people he meets casually, he enjoys social occasions, likes movies, likes to eat out, and delights in taking part in the normal world.

Much of the credit for this goes to clozapine which has removed the most disabling symptoms. Living in good residence with safety, assurance that he will not be kicked out, some sociability, decent food and care and a generally low stress, benign environment have also contributed to his recovery.

Another important part of his recovery are his visits to us in New Mexico. The emphasis is on living in normal situations--eating out, seeing some movies, doing a little work in the garden, attending the anthropology lectures series at the Southern Methodist University summer school, and field trips with the Taos Archeological Society, including rafting on the upper Chama River in search of yet undiscovered petroglyphs. He was one of the best of the rafters. Another part of this life is his membership in a health club where works out, entirely on his own volition, for three hours a day and lost 30 pounds last summer.

We have also taken steps to see that he will be cared for in the long-run, after we are gone.

Could We Do More?

The question any parent might ask is, "Could we do more to promote his recover?" We can see that it would be good to counter the negative symptoms; he sleeps fifteen hours a day and rarely initiates any activity. Perhaps his medication level is too high? Should he be involved in a psychosocial program? He did well in one, but was told he could no longer attend because he was doing too well, and because his trips to New Mexico placed a burden of paperwork on the staff. Perhaps another could be found.

Perhaps he should receive cognitive retraining? Or, maybe Falloon's Optimal Treatment Program would be helpful? In any case, the plan would have to be with his willing participation. The days of coercive treatments are past. There is also the problem of finding these recovery enhancers. They are not available where he lives in Southern California, nor can they be found in Northern New Mexico. The search continues.

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[1] The term psychiatric rehabilitation may be confused with psychosocial rehabilitation, and the two are sometimes used interchangeably. In practice, both are sometimes used as a contraction of biopsychosocial rehabilitation. However, psychosocial rehabilitation sometimes specifically refers to a particular type of program, associated with specific prototypes such as Fountain House in New York and Thresholds in Chicago. For example, a recent set of practice guidelines (McEvoy, Scheifler & Frances, 1999) explicitly distinguishes between psychiatric and psychosocial rehabilitation in this way.

[2] Materials developed by the UCLA Center for Research On Treatment and Rehabilitation of Psychosis can be obtained by request to Psychiatric Rehabilitation Consultants, P.O Box 2867, Camarillo, CA 93011-2867.

[4] Agranulocytosis is not to be confused with benign leukopenia, a milder suppression of WBC that is occasionally related to use of low potency agents like chlorpromazine.. Clozapine also may also produce benign leukopenia, so WBCs must be carefully interpreted.