The Causes of Schizophrenia- Part One > Part 2



The treatment of schizophrenia has advanced considerably in recent years. A battery of treatments has become available to reduce symptoms, to improve quality of life, and to restore productive lives. Treatment and other service interventions often are linked to the clinical phases of schizophrenia: acute phase, stabilizing phase, stable (or maintenance) phase, and recovery phase. Where possible, this report ties available data to these treatment phases.

Optimal treatment across all phases of treatment includes some form of pharmacotherapy with antipsychotic medication, usually combined with a variety of psychosocial interventions. Psychosocial interventions include supportive psychotherapy, and family psychoeducational interventions, as well as psychosocial and vocational rehabilitation. The treatment of individuals with schizophrenia who are high service users should be orchestrated by an interdisciplinary treatment team to ensure continuity of services (i.e., assertive community treatment, which is discussed below). Others may benefit from less intensive forms of case management and various self-help and consumer-operated services, described later. It is also important to assist individuals with schizophrenia in meeting their many related needs, such as for supported housing, transportation, and general medical care. These are among the 30 pivotal treatment recommendations of the Agency for Healthcare Research and Quality (AHRQ)- and NIMH-sponsored Schizophrenia Patient Outcomes Research Team (PORT), which developed its recommendations on the basis of a comprehensive review of the treatment outcomes literature. Table 4-8 contains a distillation of key recommendations.

Although the Schizophrenia PORT study recommendations are grounded in research such as that reviewed in the following paragraphs, it is noteworthy that treatment practices fail to adhere to these recommendations, with conformance generally falling below 50 percent . The disturbing gap between knowledge and practice is discussed later in this chapter. Many barriers exist in the transfer of information about treatment and evidence-based practice to clinicians, family members, and service users.

Pharmacotherapies are the most extensively evaluated intervention for schizophrenia. The conventional or older antipsychotic medications (e.g., chlorpromazine, haloperidol, fluphenazine, molindone) and the more recently developed medications (e.g., clozapine, risperidone, olanzapine, quetiapine, sertindole) are used to reduce the positive symptoms of schizophrenia. The newer medications, often called atypical because they have a different mechanism action than their predecessors, also appear in preliminary studies to be more effective against negative symptoms, display fewer side effects, and show promise for treating people for whom older medications are ineffective . Their introduction has created more treatment options for people with schizophrenia and other serious mental illnesses. Although the newer, more broadly effective medications have increased hopes for recovery, they also have resulted in greater treatment complexity for patients and providers alike (Fenton & Kane, 1997).

Conventional antipsychotics have been shown to be highly effective both in treating acute symptom episodes and in long-term maintenance and prevention of relapse. Across many studies, positive symptoms improved in about 70 percent of patients, compared with only 25 percent improvement in placebo groups. Their common mechanism of action is by blocking dopamine D2 receptors, and their therapeutic effects are presumably due to D2 blockade in the mesolimbic system.

For acute symptom episodes, treatment recommendations call for dosages of antipsychotic medication in the range of 300 to 1,000 “chlorpromazine equivalents”14 per day (Lehman & Steinwachs, 1998b). Among patients discharged from inpatient units whose dosage fell outside of this range, minority patients often are much more likely than Caucasian patients to be on a higher dose (> 1,000 chlorpromazine equivalents). Such dosing patterns run counter to evidence that a higher proportion of minority patients, because of lower rates of drug metabolism, may require lower doses of antipsychotics.

Dosage studies have found that moderate levels (300 to 750 chlorpromazine equivalents daily for acute episodes, 300 to 600 for maintenance, although many people require less than 300) are more effective for positive symptom reduction over the long run than very high (“loading”), intermittent, or very low doses . Very low and intermittent dosing substantially increases the risk of relapse, while rapid loading and very high doses greatly increase adverse effects , although medication programs must be tailored to individual needs. On conventional neuroleptics, patients experience symptom reduction over the first 5 to 10 weeks of treatment, with more gradual improvement sometimes continuing for more than double that time (Baldessarini et al., 1990). The older medications are occasionally found to reduce some negative symptoms as well, although it is impossible to tell from existing research if this is a primary or secondary effect of reduced positive symptoms.

Apart from their minimal effects on negative symptoms, the greatest problem with conventional neuroleptic medications is their pervasive, uncomfortable, and sometimes disabling and dangerous side effects. The spectrum of side effects is broad, yet the most common and troubling are extrapyramidal effects such as acute dystonia, parkinsonism, and tardive dyskinesia and akathisia.15 Side effects are evident in an estimated 40 percent of patients, but pinpointing their prevalence is complicated by the vagaries of diagnosis, length of prescription and observation, and variability across individuals and medications. Rare side effects (seizures, paradoxical exacerbation of psychotic symptoms, neuroleptic malignant syndrome) also can be devastating.

Acute dystonia, parkinsonism, dyskinesias, and akathisia are usually treated by lowering the doses of neuroleptics and/or using adjunctive anticholinergic, antiparkinsonian medications (e.g., benztropine). Because these side effects can be mistaken for core psychotic symptoms, the neuroleptic dose is often increased, rather than decreased, exacerbating the side effects. Many other side effects such as attention and vigilance problems, sleepiness, blurry vision, dry mouth, and constipation are worse in the initial weeks of treatment and usually taper off as a person adjusts to the medication. However, the discomfort and disability of the initial weeks are intolerably disruptive to some individuals. Dosages can be individualized to minimize side effects while maximizing benefit.

Efficacy data on the newer antipsychotics indicate that they are as efficacious as the older agents at reducing positive symptoms and carry fewer side effects. They also offer important additional advantages for some who have had treatment-resistant schizophrenia.

The prototype of the newer medications, clozapine, has been found effective for about 30 to 50 percent of treatment-resistant patients, as well as for patients who have responded to previous medications. Clozapine also seems to help secondary depression and anxiety, and perhaps the negative symptoms of schizophrenia . Clozapine not only has a very low incidence of tardive dyskinesia but may also show some promise as its treatment . However, the use of clozapine was constrained for many years in the United States because of findings that in about 1 percent of patients it causes a potentially fatal blood condition: agranulocytosis, a loss of white blood cells that fight infection. Because agranulocytosis is reversible if detected early, frequent (weekly) blood monitoring is critical . Although effective safeguards exist, use of clozapine tends to be limited to those who are unresponsive to, or cannot tolerate, other antipsychotics. The Veterans’ Administration sponsored the largest cost-effectiveness study to date of clozapine, comparing it to haloperidol. Studies by Rosenheck and his collaborators (1997, 1998b, 1999) replicated previous findings that clozapine was more effective than haloperidol in treating positive and negative symptoms and had fewer extrapyramidal side effects. In addition to its direct pharmacologic effect, the investigators found that clozapine enhances participation in psychosocial treatments, which augments its overall clinical effectiveness (Rosenheck et al., 1998b). Savings associated with use of clozapine were particularly significant among study participants who had averaged 215 inpatient hospital days in the year prior to the study (Rosenheck et al., 1998b).

Increasing numbers of patients with schizophrenia receive newer agents like risperidone, olanzapine, and quetiapine. They have replaced the older antipsychotics in many cases because they cause fewer side effects at therapeutic levels and do not require clozapine’s close monitoring. Their effects on negative schizophrenia symptoms are currently being evaluated and hold some promise, as do their effects on some cognitive dysfunctions. Furthermore, current cost analyses find these newer medications at least cost-neutral and sometimes more cost-effective in the long run than older agents, despite being more expensive per pill .

Thus, as a whole, there is evidence that the newer antipsychotics are more clinically advantageous than the older ones due to the combination of their effective treatment of positive (and perhaps negative) symptoms, their treatment of ancillary symptoms such as anxiety and depression, and their more favorable side effect profile . Having fewer side effects generally results in better compliance with the medication, although atypical side effects can include sedation, weight gain, sexual dysfunction, and other dose-related discomforts . Although the newer agents have less adverse impact on fecundity, so that more women with schizophrenia can conceive, there are very little data to address the impact of treatment on pregnancy and lactation. While it is not clear whether the newer medications directly lessen the functional disabilities that usually accompany schizophrenia, they may improve a person’s quality of life and responsiveness to psychosocial, rehabilitation, and therapeutic interventions. Effectiveness in real-world settings may be substantially lower than efficacy in clinical trials, possibly due to patient heterogeneity, prescribing practices, and noncompliance.

Growing awareness that ethnicity and culture influence patients’ response to medications has catapulted to prominence the field of ethnopharmacology. In the past decade, studies have demonstrated that psychiatric medications interact with patient ethnicity in multiple ways, with response to the same medication and dose varying by patient ethnicity . For example, due to racial and ethnic variation in pharmacokinetics, Asians and Hispanics with schizophrenia may require lower doses of antipsychotics than Caucasians to achieve the same blood levels . Pharmacokinetics and pharmacodynamics also vary across other ethnic groups.16 Racial and ethnic variation likely stem from a combination of genetic and psychosocial factors, such as diet and health behaviors.

At the same time, it is possible that the documented medication differences are the result of underlying biological mechanisms of mental illness related to ethnicity, culture, and gender variations. Additionally, the effects of psychotropic medications may be interpreted differently by culture. Although knowledge in these areas is incomplete, it is important to consider cultural patterns in dosing decisions and medication management, as well as risks of side effects and tardive dyskinesia. Furthermore, studies suggest that medication differences among African American people diagnosed with schizophrenia may reflect clinician biases in diagnosis and prescription practices more than differences in medication metabolism or health behaviors alone.

Psychosocial Treatments
Psychosocial treatments are vital complements to medication for individuals with schizophrenia. They help patients maximize functioning and recovery. The PORT treatment recommendations, as noted earlier, stipulate that patients should receive pharmacotherapy in conjunction with supportive psychotherapy, family treatment, psychosocial rehabilitation and skill development, and vocational rehabilitation. In the active phase of illness, medication enables patients to be more receptive to psychosocial treatments. During periods of remission, when maintenance medication is still recommended, psychosocial treatments continue to help patients to improve quality of life. Psychosocial treatments assume even greater importance for patients who do not respond to, cannot tolerate, or refuse to take medications. Several decades ago, psychosocial programs were developed that used little or no medication . For a highly selected group of patients at the beginning of their first acute episode of schizophrenia, these programs were reported effective . Most patients, however, do not meet the selection criteria employed in this study. Few such programs are currently operating , and treatment with antipsychotic medication is recommended in conjunction with psychosocial treatments .

Outcomes of individual and group therapies have been studied for people with schizophrenia, although not extensively and not in relation to current managed care practices. Overall, it is clear that individual and group therapies that focus on practical life problems associated with schizophrenia (e.g., life skills training) are superior to psychodynamically oriented therapies . Psychodynamically oriented therapies are considered to be potentially harmful; therefore, their use is not recommended (Lehman, 1997). Individual, group, or family therapies that combine support, education, and behavioral and cognitive skills, and that address specific challenges, can help clients cope with their illness and improve their functioning, quality of life, and degree of social integration. However, the optimum length of therapy seems to be longer than that afforded by “brief therapy” . Additionally, certain targeted therapeutic interventions may be useful in addressing specific symptoms . Certain subgroups of clients appear to find different types of therapy more or less useful than others.

Family Interventions
Several professionally operated family intervention programs have been developed to help the family member with severe mental illness. Randomized trials have been conducted for interventions that educate families about schizophrenia, provide support and crisis intervention, and offer training in effective problem solving and communication. These interventions have strongly and consistently demonstrated their value in preventing or delaying symptom relapse and appear to improve the patient’s overall functioning and family well-being. Research has suggested that groups of multiple families are more effective and less expensive than individual family interventions. Incorporating family religious and ethnic background may prove useful in family interventions ]. Family self-help groups are discussed subsequently in this chapter.

Psychosocial Rehabilitation and Skills Development
Psychosocial skills training strives to teach clients verbal and nonverbal interpersonal skills and competencies to live successfully in community settings. Skills or tasks are divided into small, simple behavioral elements that the client then learns, practices, and puts together. Currently, there is a growing addition of cognitive skill remediation to rehabilitation programs that have focused on social skills training. As one example of the scope of such programs, the program examined by Liberman and co-workers (1998) focused on four skill areas: medication management, symptom management, recreation for leisure, and basic conversation skills. Each area was addressed through concrete topics, with the basic conversation skills module, for example, consisting of active listening skills, initiating conversations, maintaining conversations, terminating conversations, and putting it all together.

The evolution of psychosocial skills training is important yet incomplete. A review in the mid-1990s concluded that its overall impact on social, cognitive, or vocational functioning is modest, and it remains unclear whether these gains are maintained after the training is over and can be used in real-life situations. However, a more recent study found greater independent living skills among clients who had received skills training during a 2-year followup of everyday community functioning. Several others agree that skills training is effective for specific behavioral outcomes. Specific symptom profiles may also influence how effective skills training is for a given person (Kopelowicz et al., 1997). Furthermore, Medalia and coworkers (1998) report recent success adapting cognitive rehabilitation techniques, originally developed for survivors of serious head injuries, for people with schizophrenia, but long-term effects and generalizability have not been determined. This exemplifies both the progress and the need for further refinement of this intervention.

In a recent review article, a team of researchers concluded that the most potent rehabilitation programs (1) establish direct, behavioral goals; (2) are oriented to specific effects on related outcomes; (3) focus on long-term interventions; (4) occur within or close to clients’ naturally preferred settings; and (5) combine skills training with an array of social and environmental supports. They also note that most programs do not contain all of these elements, but most are much improved over previous eras.

There are a host of multi-component psychosocial rehabilitation services that combine pharmacologic treatment, independent living and social skills training, psychological support to clients and their families, housing, vocational rehabilitation, social support and network enhancement, and access to leisure activities (World Health Organization [WHO], 1997). These are discussed in the later section on service delivery.

Coping and Self-Monitoring
An important goal of recovery and the consumer movement is to enable patients themselves to participate more actively in their own treatment. While complete remission of all symptoms is unlikely for the majority, most can and do learn skills and techniques over time that they can use to manage distressing symptoms and the effects of the illness. Often, better skills in coping and monitoring one’s own health status occurs simply through experience. However, the growth of self-help and the development of recovery models for serious mental illnesses has spawned interventions that purposefully teach and encourage active coping on the part of clients and their families. Controlled research is sparse (Penn & Mueser, 1996), except in the area of relapse prevention.

For example, some people find it very useful to pay attention to their own warning signs of relapse or symptom exacerbation, so that additional coping practices, supports, or interventions can be put into place. Norman and Malla (1995) conclude that there is not a standardized set of signs that predict relapse, but that some individuals have and get to know their own reasonably consistent patterns. Herz and Lamberti (1995) agree that many people experience predictable signs, although whether a relapse occurs depends on many factors besides the signs themselves. Therefore, the risk and magnitude of relapse can be reduced by monitoring early symptoms and intervening when they emerge. Watching for such signs is recommended for consumers, family members, and clinicians. Specific training programs for teaching individuals with schizophrenia to identify the warning signs of relapse and to develop relapse prevention plans have been shown to be effective.

Vocational Rehabilitation
Unemployment is pervasive among people with serious and persistent mental illness. Employment is valued highly by the general public and by people with schizophrenia alike because it generates financial independence, social status, contact with other people, structured time and goals, and opportunities for personal achievement and community contribution (Mowbray et al., 1997). These attributes of employment, combined with the self-esteem and personal purpose that it engenders, make vocational rehabilitation a prominent facet of treatment for serious mental illnesses. Vocational rehabilitation is especially important because early adult onset often disrupts education and employment history.

Controlled studies of vocational rehabilitation interventions have shown mixed results . Although such programs do seem to increase work-related activities while people are engaged in them, the gains do not seem to be translated into more independent employment once services cease. This has led to the conclusion that ongoing support is needed for many individuals with schizophrenia who wish to work in competitive employment (Wehman, 1988). Recent controlled studies have shown the effectiveness of this newer type of so-called supported employment models, which emphasize rapid placement in a real job setting and strong support from a job coach to learn, adapt, and maintain the position . These models, which are growing in use, strike a dynamic balance between being supportive yet challenging in order to avoid clients’ dependency and maximize their growth.

As vocational rehabilitation has moved away from sheltered workshops and toward supported employment models, the Americans With Disabilities Act of 1990 has helped to open jobs and educate employers about reasonable accommodations for people with psychiatric disabilities. Additionally, innovations like client-run and client-owned vocational programs and independent businesses have begun to be developed on a larger scale . These innovations are part of a larger movement of consumer involvement in the provision of services for people with mental illness (see Chapter 2).

(The prior text is an excerpt from Chapter 4 of the Surgeon General's Report on Mental Health, 2002) See the previous link for the full report - with full reference listings.)

14 A chlorpromazine equivalent is a measure in milligrams of antipsychotic medication doses indexed to the potency of a standard dosage of chlorpromazine, one of the earliest, most widely used antipsychotic medications.

15 Acute dystonia is involuntary muscle spasms resulting in abnormal and usually painful body positions. Parkinsonism is defined by tremors, muscle rigidity, and stuporous appearance. Dyskinesias are involuntary repetitive movements, often of the mouth, face, or hands, and akathisia is painful muscular restlessness requiring the person to move constantly.

16 For Caucasian, Hispanic, Asian, Africian-Americans variations, see Frackiewicz et al., 1997; Chinese-Jann et al., 1992; black, white, Chinese, Mexican American-Lam et al., 1995; Lin et al., 1995).




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