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INFLUENTIAL PUBLICATIONS   |    
Evidence-Based Psychotherapy for Schizophrenia 2011 Update
Faith B. Dickerson, Ph.D., M.P.H.; Anthony F. Lehman, M.D., M.S.P.H.
FOCUS 2012;10:217-225. doi:10.1176/appi.focus.10.2.217
Abstract

Many patients with schizophrenia have psychological distress and receive some form of psychotherapy. Several different psychotherapeutic approaches for schizophrenia have been developed and studied. Of these approaches, cognitive behavior therapy (CBT) has the strongest evidence base and has shown benefit for symptom reduction in outpatients with residual symptoms. In addition to CBT, other approaches include compliance therapy, personal therapy, acceptance and commitment therapy, and supportive therapy. Although usually studied as distinct approaches, these therapies overlap with each other in their therapeutic elements. Psychotherapy for schizophrenia continues to evolve with the recent advent of such approaches as meta-cognitive therapy, narrative therapies, and mindfulness therapy. Future research may also consider three different goals of psychotherapy in this patient population: to provide emotional support, to enhance functional recovery, and to alter the underlying illness process.

(Reprinted with permission from The Journal of Nervous and Mental Disease 2011; 199:520-526) 

Abstract Teaser
Figures in this Article

We have decided to revise and update our previous article, published in 2006 (Dickerson and Lehman, 2006) upon an invitation from Dr. Eugene Brody, the esteemed editor-in-chief of this journal for 43 years until his death in March 2010. Gene’s enduring interest in psychotherapy for persons with schizophrenia dated back over half a century, evinced prominently in 1952 with the publication of his groundbreaking book on the topic in the preneuroleptic era (Brody and Redlich, 1952). He later went on to receive psychoanalytic training, as was the ethos of the day, and readily integrated social and psychological perspectives into his views on mental illness. His career spanned several generations of thinking about how psychotherapy could be most helpful to schizophrenia patients, and Gene embraced these developments. He maintained an expansive and global outlook on schizophrenia, always cognizant of the social context in which psychiatric disorders are experienced.

In the 5 years since the publication of our original article, a number of important additions to the evidence base have emerged. In addition, several new approaches to the psychotherapy for schizophrenia have been explored; these are not yet evidence based, but they are interesting and promising new developments and speak to the continued interest in this topic. We refer the reader to recent reviews about psychotherapy for schizophrenia that indicate the ongoing attention to this topic, the recognition of its value, and the motivation to improve and expand psychotherapeutic strategies for persons with schizophrenia (Lysaker et al., 2010b; Tai and Turkington, 2009).

Schizophrenia is a pervasive psychiatric disorder that typically has its onset in early adulthood and persists for the remainder of the lifespan. The etiology of schizophrenia is unknown but is presumed to be genetic with environmental risk factors (Brown and Derkits, 2010; Gejman et al., 2010; Van Winkel et al., 2010). Despite its biological underpinnings, schizophrenia exerts its effects in psychological realms; perceptions, thinking, and emotion are often disrupted. Adding to the impetus for psychotherapeutic treatments is the fact that the experience of schizophrenia is often baffling and frighten-ing to the affected individual. The person with schizophrenia may feel alienated from and shunned by others. Friendships and work roles may be lost. Self-devaluation and despair are not uncommon, and approximately 10% of individuals with schizophrenia ultimately kill themselves (Siris, 2001).

Many patients with schizophrenia have psychological distress and may receive some form of psychotherapy, the models for which continue to evolve. We define psychotherapy as did Strupp (1978): “an interpersonal process designed to bring about modifications of feelings, cognitions, attitudes, and behavior which have proven troublesome to the person seeking help from a trained professional.” During much of the 20th century, psychoanalysis was the dominant paradigm in American psychiatry and was applied to the treatment of schizophrenia (Brody and Redlich, 1952). However, after the introduction of neuroleptic medication in the 1950s and the availability of a clearly effective treatment of schizophrenia, the benefits of psychotherapeutic approaches for the disorder were increasingly challenged. Controlled studies performed in the 1960s indicated that medication treatment was superior to psychodynamic psychotherapy and to milieu therapy, and further research performed in the 1980s also failed to support the specific benefits of psychodynamic therapy for this population (Gunderson et al., 1984; May, 1968).

The study of psychotherapy for schizophrenia declined until the 1990s, when new cognitive-behavioral approaches began to appear in the literature. It is important to note that, even with the availability of second-generation antipsychotic medications starting in the 1990s, significant residual symptoms persist for many patients with schizophrenia Although recovery from schizophrenia is increasingly recognized as a treatment goal, full recovery from the illness is uncommon. Only about a third of patients with schizophrenia have an outcome that is considered favorable, even when adhering to medication treatment (Hegarty et al., 1994). However, more patients with schizophrenia now embrace the goal of personal recovery and seek a life of meaning and purpose even in the face of ongoing illness symptoms (Davidson et al., 2008; Deegan, 1997).

In this article, we review psychotherapeutic approaches that have recently been evaluated with controlled studies and that can be considered to be evidence based. We then comment on other types of psychotherapeutic interventions that may inform further development and refinement of psychotherapy in this population.

Cognitive behavior therapy (CBT) was originally crafted for the treatment of depression and anxiety (Beck, 1976) and has been modified for the treatment of schizophrenia, largely by clinical investigators in the United Kingdom. Several recent reviews are available, including those by Tarrier and Wykes (2004), Tarrier (2005), Gaudiano (2005), Zimmermann et al. (2005), and Wykes et al. (2008). Cognitive behavior therapy is usually conducted in a one-on-one therapy relationship. An empathic and nonthreatening relationship is built, during which the patient elaborates his or her experiences with schizophrenia. Specific symptoms are identified as problematic by the patient and become targeted for special attention. The therapist does not challenge these symptoms as irrational; he or she helps the patient through guided questions to focus on the patient’s own beliefs about the symptoms and the natural coping mechanisms that the patient has elaborated to deal with those symptoms. The therapy also involves supportively guiding the patient to implement coping methods and to develop more rational cognitive perspectives about symptoms. This work may include belief modification (Chadwick et al., 1996), focusing/ reattribution (Bentall et al., 1994), and normalizing psychotic experiences (Kingdon and Turkington, 1994), among other strategies.

In belief modification, the evidence for a delusional belief is gently challenged; the therapist selects delusions to discuss in the reverse order of the strength with which the delusions are held. Although therapists of previous generations were often cautioned not to dispute a patient’s psychotic beliefs, within CBT delusions may be addressed directly. The therapist may inquire about the evidence for delusional perceptions and may suggest “behavioral experiments” to provide evidence that supports, or does not support, a distressing belief. Carried out in the context of a supportive therapeutic relationship, such challenges have been shown not to have an adverse impact on the therapeutic alliance (Wittorf et al., 2010).

In focusing/reattribution, a strategy that especially targets persistent auditory hallucinations, the therapist encourages the patient to elaborate his or her experience with the hallucination in detail, aiming to have the patient reattribute the hallucination to an internal source. In normalizing psychotic experiences, the therapist helps the patient see that his or her sympt-oms are possibly responses to life stresses, making them seem more normal and less “crazy.”

A variation of individual CBT is a group therapy approach for positive psychotic symptoms. One particular group intervention that has been studied focuses on patients with hallucinations that are distressing and that have persisted despite medication treatment (Wykes et al., 1999). Each of six weekly sessions is focused on a particular topic such as sharing of personal experiences about voices, models of hallucinations, and effective coping strategies for voices.

Another group CBT approach has been developed, this one in the United States, for older persons with chronic schizophrenia (Granholm et al., 2005, 2007) and includes a manualized curriculum entitled “Thought Challenging.” The patients are instructed to use thought records and homework assignments to identify relationships among thoughts, feelings, and behaviors and to identify “mistakes” in thinking. They are also guided to conduct behavioral experiments to gather evidence to evaluate their beliefs. Target symptoms are delusions and beliefs about voices.

Another recent variation of CBT, functional CBT, has been developed in the United States (Cather et al., 2005) and is a 16-session weekly individualized therapy for residual psychotic symptoms. Structured modules cover topics of coping skills, cognitive restructuring, behavioral experiments, and goal sett-ing. Before the start of the therapy, the patient views an introductory videotape which provides simulated therapy vignettes. In the actual therapy, the therap-ist seeks to identify ways in which symptoms are interfering with functioning or causing distress, and only such symptoms are targeted for intervention.

A number of randomized control trials examining the effects of CBT in schizophrenia have been conducted. The largest meta-analysis of CBT trials for psychosis was based on the results of 34 studies, most of which were performed in the United Kingdom, and that included a total of 1964 patients, most of whom are with schizophrenia (Wykes et al., 2008). CBT was compared with either a standard psychiatric practice or another intervention assumed to be inactive for the main outcome. Across all studies, the mean weighted effect size for the reduction of positive symptoms was 0.37 (95% confidence interval [CI], 0.23, 0.52); for the reduction of negative symptoms, 0.44 (95% CI, 0.17, 0.70); for social functioning, 0.38 (95% CI, 0.15, 0.60); and for mood, 0.36 (95% CI, 0.08, 0.65). A nonsignificant effect size was found for hopelessness: −0.19 (95% CI, −0.55, 0.17). However, in studies that were rated to be methodologically rigorous, the significant effects were found only for positive symptoms and not for the other treatment domains.

The gains that accrue from CBT interventions seem to continue in the time after treatment has been completed, based on the results of some studies (Rector et al., 2003; Sensky et al., 2000; Turkington et al., 2008). However, evidence is limited about the benefits on relapse, rehospitalization, or quality of life. The benefits of CBT for patients with recent onset schizophrenia have also not been established, and there is no clear evidence about the benefits of CBT for patients who are not recent onset and who are experiencing an acute exacerbation of psychotic symptoms (Dixon et al., 2010). Another limitation is that many patients are not considered suitable for the therapy and dropout rates are often high, especially among acutely ill patients (e.g.,Startup et al., 2004). Perhaps, this difficulty with engagement occurs because frequent one-on-one meetings amount to therapeutic overload for many patients or because the acute illness phase is often a turbulent one. In contrast, persons with schizophrenia who are most likely to participate in and benefit from cognitive therapy are outpatients who have a long-standing psychotic illness; such patients typically have delusions or hallucinations that are distressing and resistant to medication treatment (Dickerson, 2000). Persons who have less conviction about their delusions may also be more likely to profit from a CBT approach (Brabban et al., 2009). Because CBT interventions are typically complex and because strategies vary somewhat among studies, it is difficult to determine the specific active ingredients.

The CBT interventions that have been studied range in duration from weeks to years. Usually, the therapy is provided in the course of several months, and the intervention is time limited and structured. Cognitive behavior therapy manuals are available (e.g.,Chadwick et al., 1996; Fowler et al., 1995; Kingdon and Turkington, 1994), but application typically requires supervised training.

CBT approaches for schizophrenia continue to be modified, refined, and tested. For example, Beck, Grant, and their colleagues (P Grant, personal communication, March 30, 2011) are completing a trial of CBT for schizophrenia patients with negative symptoms. The therapy is based on a cognitive model in which defeatist beliefs and negative expectancies are conceptualized as interacting with patients’ cognitive deficits and contributing to negative symptoms (Grant and Beck, 2009). The approach is goal oriented and guided by a comprehensive formulation of each patient’s beliefs, motivations, and behavior.

Other new developments in CBT for schizophrenia include the delivery of CBT in combination with another psychosocial intervention with the goal of enhancing the target psychosocial treatment outcome. For example, Lysaker et al. (2009) have developed an enhanced vocational program that includes group and individual sessions that assist persons to learn to recognize the basic cognitive processes that underlie their thoughts about themselves and others and to then identify and correct dysfunctional beliefs relevant to work (Davis et al., 2005). Initial results indicate that the individuals who received the CBT had better work outcomes than did those who received standard work services (Lysaker et al., 2009).

In another adaptation of CBT for schizophrenia, Velligan et al. (2009) have combined CBT with cognitive adaptation training, a home-based psychosocial intervention that provides environmental supports to improve functional outcomes. The combined intervention is designed to address both reasoning and appraisal biases typically addressed in CBT for psychosis and to establish supports that bypass cognitive deficits (Velligan et al., 2009). A clinical trial of this approach is underway.

Other psychotherapy approaches have received some empirical support but not to the extent that they can be considered fully evidence based for the treatment of schizophrenia, as is CBT (Lehman et al., 2004). Such approaches include personal therapy, compliance therapy, acceptance and commitment therapy, and supportive therapy. The therapeutic elements of these approaches overlap with those of CBT for schizophrenia as shown in Table 1.

 
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Table 1.

Therapeutic Elements in Psychotherapies for Schizophrenia

Table Footer Notea

These approaches are still under development, so the definition of therapeutic elements is preliminary at this time.

Table Footer Noteb

Phase of illness in which the psychotherapy has been studied.

Table Footer Note

CBT indicates cognitive behavior therapy.

Developed by Hogarty et al. (1995), personal therapy is a disorder specific and intensive psychotherapy for individuals with schizophrenia that is provided within a larger treatment program (Hogarty et al., 1995). The psychotherapy focuses primarily on the patient’s affective dysregulation, which is conceptualized as a core deficit in schizophrenia. A major goal of the therapy is to develop an understanding of the patient’s mood states, especially negative affects, and to promote the patient’s more adaptive response to emotional stresses. Personal therapy includes formal illness educational workshops and also incorporates traditional social skills train-ing techniques of modeling, practice, feedback, and homework assignments. Behavioral exercises are focused on the awareness of self and others. Although personal therapy and cognitive behavior therapy for schizophrenia were developed independently, they share some common elements as shown in Table 1.

Unlike some other psychotherapy approaches, personal therapy is staged to the patient’s degree of recovery from an acute psychotic episode. Patients graduate to the next phase only if they have been managed and stabilized during the previous phase. An operational principle is that recovery requires time- and disorder-appropriate treatment. Therefore, personal therapy is a long-term endeavor. This very ambitious therapy approach was tested in a trial in which personal therapy was compared with family therapy and supportive psychotherapy and was delivered over a 3-year period to patients who were recently discharged from the hospital (Hogarty et al., 1997a, 1997b). Despite careful attention to the development of this specialized therapy, the results did not show any significant difference in relapse rates among the treatment groups; the overall relapse rate was 29%, which is considered low by some standards. Patients receiving personal therapy did have more improvements in psychosocial functioning during the course of the study than did patients in other treatment conditions. This improvement underscores the importance of replicating this study in another treatment setting.

Compliance therapy differs from the personal therapy described previously in that this approach is a relatively short intervention that is applied during the acute illness phase. Unlike broader-based CBT approaches and personal therapy, the content of intervention is focused on medication adherence, and the goal of the therapy is to increase the patient’s adherence to medication after hospital discharge (Kemp et al., 1996). The patient’s affect and symptom status are not the primary focus of the therapy. Patients receive four to six individual sessions in the hospital setting and then several booster sessions. Compliance therapy borrows extensively from motivational interviewing, a technique that fosters the patient’s consideration of behavior through the therapist’s questioning and reflective listening. As in personal therapy, compliance therapy also occurs in phases. In the first phase, the therapist reviews the patient’s illness history. In the next phase, ambivalence toward treatment is explored. During the third phase, the therapy focuses on medication as a strategy to enhance the patient’s quality of life. Psychiatric medications are presented as a kind of “insurance policy” to staying well. Compliance therapy was studied in a clinical trial with acutely ill hospital patients with schizophrenia in the United Kingdom. Compared with a nonspecific counseling approach, compliance therapy was more effective in terms of the patients’ illness insight, attitudes about medication, medication compliance, and global functioning with gains that persisted during an 18-month follow-up period (Kemp et al., 1998). However, two replication studies did not find a benefit for compliance therapy in terms of adherence to medication and other outcomes measured 1 year after hospital discharge (O’Donnell et al., 2003) or psychiatric symptoms at the end of treatment (Anderson et al., 2010). Of note, there is an overlap between aspects of compliance therapy and CBT approaches (Table 1). For example, motivational interviewing is explicitly included in CBT trials with patients who have both schizophrenia and substance abuse (Barrowclough et al., 2001).

Acceptance and commitment therapy (ACT) is a variation on CBT and was also originally developed for the treatment of non-psychotic conditions (Hayes et al., 1999). In contrast to CBT, which aims to change the individual’s cognitions and to facilitate the development of a more rational perspective, the goal in ACT is to modify the individual’s relationship to his or her thinking more broadly. ACT is based on the premise that attempting to suppress or control mental events is not helpful. Instead, ACT encourages persons to accept and to experience thoughts and feelings nonjudgmentally, that is, mindfully. In the case of psychotic symptoms and negative thoughts, the individual is counseled to “just notice” these mental events without struggling with them, taking them to be literally true, or acting on them. Such a stance is encouraged through experiential exercises including meditation. ACT also encourages persons to define and pursue their personal goals and to adopt coping strategies for symptoms that will help attain those goals. Two pilot studies of ACT have been performed with psychotic inpatients, most of them with schizophrenia; in comparing those who received ACT vs. the usual treatments, one study found significantly reduced distress related to hallucinations at posttreatment, and the other found a significantly lower rate of rehospitalization 4 months later (Bach and Hayes, 2002; Gaudiano and Herbert, 2006, respectively).

Supportive psychotherapy is not a standardized approach but includes an assortment of therapeutic strategies and was originally conceived as an alternative to psychoanalytically based psychotherapy. What is called supportive therapy is frequently provided to persons with schizophrenia, but no standard supportive therapy has been used in psychotherapy trials.

The elements of supportive therapy may overlap with informal sources of support and with other therapeutic approaches (Kates and Rockland, 1994; Penn et al., 2004). For example, supportive therapy is focused on the “here and now” of the patient’s life and, like some models of CBT, aims to help the patient define reality more clearly and to solve practical problems. Therapeutic issues may include the human concerns raised by having a persistent psychiatric illness, problems in managing the disorder, and problems of living that may take on added difficulty because of the schizophrenia illness. The specific strategies that comprise supportive counseling may include providing reassurance, offering explanations and clarification, and giving guidance and suggestions. Supportive therapy differs from cognitive-behavioral therapies in that, typically, CBT is focused more explicitly on illness symptoms and more systematically facilitates the patients’ changing of their thinking and behavior patterns.

Evidence on the possible effectiveness of supportive therapy for schizophrenia comes indirectly from the results of recent clinical trials in which it was provided as a control or comparison condition to CBT (Penn et al., 2004). In studies of CBT performed by Pinto et al. (1999), Haddock et al. (1999), Tarrier et al. (1998, 2000), Penn et al. (2009), and Sensky et al. (2000), the supportive therapy condition performed favorably compared with a treatment as usual, no psychotherapy condition, or with a therapy performed at a level that was similar or close to that of the CBT intervention.

Since our review 5 years ago, some new psychotherapeutic approaches are being explored for the treatment of persons with schizophrenia. Although none of these approaches have accumulated sufficient data to be considered “evidence based,” the approaches represent interesting and promising next directions.

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Metacognitive training

Metacognitive training (MCT) represents a natural evolution, building upon the promising results achieved with CBT, psychoeducation, and cognitive remediation (Moritz et al., 2010). Whereas CBT, as previously discussed, focuses on specific thoughts and behaviors of the individual, MCT targets more general cognitive biases that are especially prevalent among persons with schizophrenia. In effect, CBT targets “what” a person thinks, and MCT targets “how” a person thinks. The range of problematic cognitive processes addressed by MCT include attributional biases (tendency to attribute causality to single external events or persons rather than to consider alternatives or the complexity of causality, including internal events), jumping to conclusions (arriving at conclusions with scant evidence and overconfidence), bias against disconfirmatory evidence (difficulty incorporating new evidence that refutes a belief), deficits in theory of mind (failure to incorporate multiple cues in the interpretation of the perspective or behavior of another), overconfidence in memory errors, and depressive cognition (Moritz et al., 2010, 2011; Tai and Turkington, 2009). MCT uses a psychoeducational approach, typically in small groups and individually, to present the concepts of these impairing cognitive processes, to provide examples, and to stimulate discussion among group participants. In one of the more developed programs, eight structured modules are presented by trained clinicians to small groups of patients. Each session includes a PowerPoint presentation on the cognitive process, followed by discussion that lasts from 45 to 60 minutes. These group sessions are augmented by individual sessions. These modules are available online in multiple languages (www.uke.de/mkt; Moritz et al., 2010). Initial small trials suggest good feasibility and acceptability to patients, improvement in positive symptoms, some improvement in cognitive biases, and improvement in self-efficacy (Aghotor et al., 2010; Moritz et al., 2011).

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Narrative psychotherapies

Psychotic experiences and disruptions in cognition, coupled with the typical therapeutic focus on symptoms, contribute to disorganized, impoverished, and negative internal experiences of persons with schizophrenia. As a result, they may lack coherent, well-informed personal narratives about their lives that are essential to a strong and positive sense of self. This runs counter to recent concepts of recovery, emphasizing competence and a sense of control over one’s life. Recognizing this, some emerging psychotherapeutic approaches promote the development of positive personal narratives among persons with schizophrenia (Lysaker et al., 2010a, 2010b; Perez-Alvarez et al., 2010). Perez-Alvarez et al. (2010) state that narrative psychotherapies “all (seek) recovery of self-experience, sense of self and personal identity through the narrative” (Perez-Alvarez et al., 2010, p.723). Three types of narrative psychotherapy are identified. First, as articulated by Lysaker and Lysaker (2008), “dialogical therapy” focuses on the development of the capacity for interpersonal and intrapersonal dialogues that organize self-experience, the relative lack of which often leads to a fragmented sense of self in persons with schizophrenia (Lysaker and Lysaker, 2008). Second, “narrative cognitive-behavioral therapy” uses techniques of CBT but emphasizes biographic information as well. In short, “making changes” through CBT is augmented with “making sense” of things through a narrative (Perez-Alvarez et al., 2010; Rhodes and Jakes, 2009). Third, “cognitive-interpersonal narrative therapy” emphasizes emotional recovery from psychotic experiences and the development of a narrative that enables the person to make sense of what happened and to frame the experience in a manner that integrates it with their life narrative. The emphasis is on normalizing the experience and increasing compassion toward oneself. Work is underway to develop methods to reliably study and evaluate such approaches (Lysaker et al., 2010b).

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Mindfulness therapy

Mindfulness therapy builds upon the Buddhist notion of mindfulness and is also incorporated in ACT, discussed previously. Mindfulness emphasizes “being in the present” with acceptance and compassion. Such receptivity to the present is enhanced through meditative and relaxation techniques and promotes compassion toward oneself and others. As applied more specifically to the experience of schizophrenia, the works of Abba et al. (2008) and Chadwick (2006) seek to help persons change their experience of psychosis from one of trying to expunge or overcome the experience to one of learning to live with it, consistent with the concept of recovery. This process involves “(1) learning to center on awareness of psychosis, (2) allowing psychosis to come and go without reacting or struggle, and (3) reclaiming power by acceptance of psychosis and the self” (Perez-Alvarez et al., 2010, p. 11). It is important to emphasize that this approach is not counter to traditional therapies but, rather, seeks to enable persons to accept their illness experiences nonjudgmentally in the context of more traditional therapeutic approaches.

In considering the next steps in research on psychotherapy for persons with schizophrenia, it is essential to reconsider briefly the current state of practice and the broader context of our evolving understanding of schizophrenia etiology, treatment, and the process of coping and recovery from chronic disease. As stated at the beginning, our current understanding is that schizophrenia is a brain disorder with significant genetic and environmental risk factors. The latter most likely occur in the prenatal, perinatal, and/or early childhood periods. Our current understanding is also that persons with schizophrenia are capable of personal growth and of achieving meaningful life goals in the face of ongoing illness symptoms.

Projecting forward, what is the likely future of psychological interventions for such a disorder, and where should research focus? At least three potential goals for psychotherapy for persons with schizophrenia are identified: (1) emotional support in dealing with an ongoing illness which may be disabling, (2) enhancement of coping strategies to promote recovery, and (3) alteration of underlying pathophysiology and processes of illness. Research needs to address each of these potential benefits. The potential benefits need to be considered in terms of the dimensions of outcomes (symptoms, functioning, quality of life) as well as of phases of the illness (initial onset, acute episode, continuing treatment).

First, as for other persistent and potentially disabling medical disorders, some psychological assistance to deal with the impact of the disease on self-esteem and psychological well-being may be helpful. Psychological assistance may also be helpful in identifying the person’s personal goals, which likely extend beyond the reduction of illness symptoms, and in developing a collaboration between the patient and the treatment provider around these goals. The importance of research about such interventions arises from findings that most patients with schizophrenia receive little or no such counseling (Lehman and Steinwachs, 1998). Research on the impacts of adding such counseling to routine medication management, the modal treatment today, would inform this situation. Shared decision making, a structured process that encourages full participation by patient and provider within medication management visits, is one method that has been developed (Deegan, 2010; Drake et al., 2009). A related approach, personal medicine, involves incorporating discussion within medication management visits of nonpharmaceutical activities that the patient has found to be beneficial (Deegan, 2005).

Second, the enhancement of coping strategies to promote functional recovery has been a particular focus of research, especially for CBT, as discussed previously. This can be viewed as a tertiary prevention of disability. The imperative for a search for treatments to improve functional recovery aris-es from the fact that current pharmacologic treatments succeed in ameliorating symptoms but have, at best, modest effects on functioning. Schizophre-nia research must continue to vigorously tackle this problem, searching for treatments that promote functional recovery from disability. In the absence of a breakthrough in the realm of psychopharmacology or other biological treatments, it seems clear that psychosocial interventions will be an important component. This line of research should, in particular, examine the impacts of combination pharmacologic and psychosocial treatments. It is possible that specific forms of psychotherapy, such as CBT, will prove effective in this tertiary prevention, although it would be expected that rehabilitation approaches, such as supported employment, will play a more prominent role.

An important shortcoming of psychotherapy research in schizophrenia to date concerns the only limited focus on patient-centered outcomes and on patients’ definitions of their own recovery goals. Although some studies have measured patient self-esteem and satisfaction with treatment, psychotherapy trials have not been organized around definitions of recovery generated by patients themselves. Recovery in this context is focused less on the reduction of illness symptoms and more on an increase in psychological adaptation to the illness. Adaptation may be measured by the degree to which the individual experiences hope, personal confidence, and a willingness to ask for help and assumes personal responsibility for the recovery process (Corrigan et al., 2004; Deegan, 1997).

Finally, the long-term therapeutic goal must be treatments that prevent the illness (primary prevention) or alter its course in the early stages (secondary prevention). The role that psychotherapeutic approaches may play in these early stages of prevention and treatment remains quite unclear. It is difficult to imagine a psychotherapy that prevents the illness, but psychotherapeutic techniques, combined with other treatments that target underlying brain processes, are not entirely farfetched, especially when monitored by evolving neuroimaging technologies as have recently been shown to predict responsiveness to CBT in individuals with schizophrenia (Kumari et al., 2009; Premkumar et al., 2009). Psychotherapy that changes behaviors to manage disease risks, analogous to medical counseling to enhance treatment compliance and to thwart negative health habits in persons such as those at risk for diabetes, would fall within this realm of inquiry.

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Dixon  LB;  Dickerson  F;  Bellack  AS;  Bennett  M;  Dickinson  D;  Goldberg  RW;  Lehman  A;  Tenhula  WN;  Calmes  C;  Pasillas  RM;  Peer  J;  Kreyenbuhl  J (2010)  Schizophrenia Patient Outcomes Research Team (PORT).The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements.  Schizophr Bull. 36:48–70.
[PubMed]
[CrossRef]
 
Drake  RE;  Cimpean  D;  Torrey  WC (2009)  Shared decision making in mental health: Prospects for personalized medicine.  Dialogues Clin Neurosci. 11:455–463.
[PubMed]
 
Fowler  D;  Garety  P;  Kuipers  E (1995)  Cognitive behaviour therapy for psychosis.   West Sussex, UK:  John Wiley & Sons.
 
Gaudiano  BA (2005)  Cognitive behavior therapies for psychotic disorders: current empirical status and future directions.  Clin Psychol Sci Pract. 12:33–50.
[CrossRef]
 
Gaudiano  BA;  Herbert  JD (2006)  Acute treatment of inpatients with psychotic symptoms using Acceptance and Commitment Therapy: Pilot results.  Behav Res Ther. 44:415–437.
[PubMed]
[CrossRef]
 
Gejman  PV;  Sanders  AR;  Duan  J (2010)  The role of genetics in the etiology of schizophrenia.  Psychiatr Clin North Am. 33:35–66.
[PubMed]
[CrossRef]
 
Granholm  E;  McQuaid  JR;  McClure  FS;  Auslander  LA;  Perivoliotis  D;  Pedrelli  P;  Patterson  T;  Jeste  DV (2005)  A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia.  Am J Psychiatry. 162:520–529.
[PubMed]
[CrossRef]
 
Granholm  E;  McQuaid  JR;  McClure  FS;  Link  PC;  Perivoliotis  D;  Gottlieb  JD;  Patterson  TL;  Jeste  DV (2007)  Randomized controlled trial of cognitive behavioral social skills training for older people with schizophrenia: 12-month follow-up.  J Clin Psychiatry. 68:730–737.
[PubMed]
[CrossRef]
 
Grant  PM;  Beck  AT (2009)  Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia.  Schizophr Bull. 35: 798–806.
[PubMed]
[CrossRef]
 
Gunderson  JG;  Frank  AF;  Katz  HM;  Vannicelli  M.L;  Frosch  JP;  Knapp  PH (1984)  Effects of psychotherapy in schizophrenia: II. Comparative outcome of two forms of treatment.  Schizophr Bull. 10:564–598.
[PubMed]
 
Haddock  G;  Tarrier  N;  Morrison  AP;  Hopkins  R;  Drake  R;  Lewis  S (1999)  A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis.  Soc Psychiatry Psychiatr Epidemiol. 34:254–258.
[PubMed]
[CrossRef]
 
Hayes  SC;  Strosahl  KD;  Wilson  KG (1999)  Acceptance and commitment therapy: An experiential approach to behavior change.   New York:  Guilford.
 
Hegarty  JD;  Baldessarini  RJ;  Tohen  M;  Waternaux  C;  Oepen  G (1994)  One hundred years of schizophrenia: A meta-analysis of the outcome literature.  Am J Psychiatry. 151:1409–1416.
[PubMed]
 
Hogarty  GE;  Greenwald  D;  Ulrich  RL;  Kornblith  SJ;  DiBarry  AL;  Cooley  S;  Carter  M;  Flesher  S (1997a)  Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.  Am J Psychiatry. 154:1514–1524.
 
Hogarty  GE;  Kornblith  SJ;  Greenwald  D;  DiBarry  AL;  Cooley  S;  Flesher  S;  Reiss  D;  Carter  M;  Ulrich  RL (1995)  Personal therapy: A disorder-relevant psychotherapy for schizophrenia.  Schizophr Bull. 21:379–393.
[PubMed]
 
Hogarty  GE;  Kornblith  SJ;  Greenwald  D;  DiBarry  AL;  Cooley  S;  Ulrich  RL;  Carter  M;  Flesher  S (1997b)  Personal therapy: Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.  Am J Psychiatry. 154: 1504–1513.
 
Kates  J;  Rockland  LH (1994)  Supportive psychotherapy of the schizophrenic patient.  Am J Psychother. 4:543–561.
 
Kemp  R;  Hayward  P;  Applewhaite  P;  Everitt  B;  Anthony  B (1996)  Compliance therapy in psychotic patients: Randomised controlled trial.  BMJ. 312:345–349.
[PubMed]
[CrossRef]
 
Kemp  R;  Kirov  G;  Everitt  B;  Hayward  P;  David  A (1998)  Randomized controlled trial of compliance therapy, 18-month follow-up.  Br J Psychiatry. 172:413–419.
[PubMed]
[CrossRef]
 
Kingdon  DG;  Turkington  D (1994)  Cognitive-behavioral therapy of schizophrenia.   New York:  Guilford.
 
Kumari  V;  Peters  ER;  Fannon  D;  Antonova  E;  Premkumar  P;  Anilkumar  AP;  Williams  SC;  Kuipers  E (2009)  Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive-behavioral therapy in schizophrenia.  Biol Psychiatry. 66:594–602.
[PubMed]
[CrossRef]
 
Lehman  AF;  Kreyenbuhl  J;  Buchanan  RW;  Dickerson  FB;  Dixon  LB;  Goldberg  R;  Green-Paden  LD;  Tenhula  WN;  Boerescu  D;  Tek  C;  Sandson  N;  Steinwachs  DM (2004)  The Schizophrenia Patient Outcomes Research Team (PORT): Updated Treatment Recommendations 2003.  Schizophr Bull. 30:193–217.
[PubMed]
[CrossRef]
 
Lehman  AF;  Steinwachs  DM (1998)  Patterns of usual care for schizophrenia: Initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey.  Schizophr Bull. 24:11–20.
[PubMed]
[CrossRef]
 
Lysaker  PH;  Buck  KD;  Carcione  A;  Procacci  M;  Salvatore  G;  Nicolo  G;  Dimaggio  G (2010a)  Addressing metacognitive capacity for self reflection in the psychotherapy for schizophrenia: a conceptual model of the key tasks and processes.  Psychol Psychother. 84:58–69.
 
Lysaker  PH;  Davis  LW;  Bryson  GJ;  Bell  MD (2009)  Effects of cognitive behavioral therapy on work outcomes in vocational rehabilitation for participants with schizophrenia spectrum disorders.  Schizophr Res. 107:186–191.
[PubMed]
[CrossRef]
 
Lysaker  PH;  Glynn  SM;  Wilkniss  SM;  Silverstein  SM (2010b)  Psychotherapy and recovery from schizophrenia: A review of potential applications and need for future study.  Psychol Serv. 7:75–91.
[CrossRef]
 
Lysaker  P;  Lysaker  J (2008)  Schizophrenia and the fate of the self.   Oxford, UK:  Oxford University Press.
 
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Moritz  S;  Veckenstedt  R;  Randjbar  S;  Vitzthum  F;  Woodward  TS (2011)  Antipsychotic treatment beyond antipsychotics: metacogntive intervention for schizophrenia patients improves delusional symptoms.  Psychol Med.  Jan 28: 1–10. [Epub ahead of print].
 
Moritz  S;  Vitzthum  F;  Randjbar  S;  Veckenstedt  R;  Woodward  TS (2010)  Detecting and defusing cognitive traps: Metacognitive intervention in schizophrenia.  Curr Opin Psychiatry. 23:561–569.
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[CrossRef]
 
O’Donnell  C;  Donohoe  G;  Sharkey  L;  Owens  N;  Migone  M;  Harries  R;  Kinsella  A;  Larkin  C;  O’Callaghan  E (2003)  Compliance therapy: A randomised controlled trial in schizophrenia.  BMJ. 327:834.
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Penn  DL;  Meyer  PS;  Evans  E;  Wirth  RJ;  Cai  K;  Burchinal  M (2009)  A randomized controlled trial of group cognitive-behavioral therapy vs. enhanced supportive therapy for auditory hallucinations.  Schizophr Res. 109:52–59.
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Penn  DL;  Mueser  KT;  Tarrier  N;  Gloege  A;  Cather  C;  Serrano  D;  Otto  MW (2004)  Supportive therapy for schizophrenia: Possible mechanisms and implications for adjunctive psychosocial treatments.  Schizophr Bull. 30:101–112.
[PubMed]
[CrossRef]
 
Perez-Alvarez  M;  Garcia-Montes  JM;  Vallina-Fernandez  O;  Perona-Garcelan  S;  Cuevas-Yust  C (2011)  New life for schizophrenia psychotherapy in the light of phenomenology.  Clin Psychol Psychother. 18:187–200.
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Pinto  A;  La Pia  S;  Menella  R;  Giorgio  D;  DeSimone  L (1999)  Cognitive-behavioral therapy and clozapine for clients with treatment-refractory schizophrenia.  Psychiatr Serv. 50:901–904.
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Premkumar  P;  Fannon  D;  Kuipers  E;  Peters  ER;  Anilkumar  AP;  Simmons  A;  Kumari  V (2009)  Structural magnetic resonance imaging predictors of responsiveness to cognitive behaviour therapy in psychosis.  Schizophr Res. 115:146–155.
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Rhodes  J;  Jakes  S (2009)  Narrative CBT for psychosis.  New York:  Routledge. Sensky  T;  Turkington  D;  Kingdon  D;  Scott  JL;  Scott  J;  Siddle  R;  O’Carroll  M;  Barnes  TRE, (2000) A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Arch Gen Psychiatry. 57:165–272.
 
Siris  SG (2001)  Suicide and schizophrenia.  J Psychopharmacol. 15:127–135.
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Startup  M;  Jackson  MC;  Bendix  S (2004)  North Wales randomized controlled trial of cognitive behaviour therapy for acute schizophrenia spectrum disorders: Outcomes at 6 and 12 months.  Psychol Med. 34:413–422.
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Strupp  H (1978)  Psychotherapy research and practice: An overview. InGarfield  SL;  Bergin  AE(Eds),  Handbook of psychotherapy and behavior change  (2nd ed, p 3).  New York:  John Wiley & Sons.
 
Tai  S;  Turkington  D (2009)  The evolution of cognitive behavior therapy for schizophrenia: Current practice and recent developments.  Schizophr Bull. 35:865–873.
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[CrossRef]
 
Tarrier  N (2005)  Cognitive behaviour therapy for schizophrenia—a review of development, evidence and implementation.  Psychother Psychosom. 74:136–144.
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Tarrier  N;  Kinney  C;  McCarthy  E;  Humphreys  L;  Wittkowski  A;  Morris  J (2000)  Two-year follow-up of cognitive-behavioral therapy and supportive counseling in the treatment of persistent symptoms in chronic schizophrenia.  J Consult Clin Psychol. 68:917–922.
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Tarrier  N;  Wykes  T (2004)  Is there evidence that cognitive behaviour therapy is an effective treatment for schizophrenia? A cautious or cautionary tale? Behav Res Ther. 42:1377–1401.
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Tarrier  N;  Yusupoff  L;  Kinney  C;  McCarthy  E;  Gledhill  A;  Haddock  G;  Morris  J (1998)  Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia.  BMJ. 317:303–307.
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[CrossRef]
 
Turkington  D;  Sensky  T;  Scott  J;  Barnes  TR;  Nur  U;  Siddle  R;  Hammond  K;  Samarasekara  N;  Kingdon  D (2008)  A randomized controlled trial of cognitive-behavior therapy for persistent symptoms in schizophrenia: A five-year follow-up.  Schizophr Res. 98:1–7.
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[CrossRef]
 
Van Winkel  R;  Esquivel  G;  Kenis  G;  Wichers  M;  Collip  D;  Peerbooms  O;  Rutten  B;  Myin-Germeys  I;  Van Os  J (2010)  Genome-wide findings in schizophrenia and the role of gene-environment interplay [review].  CNS Neurosci Ther.  16:e185–e192.
 
Velligan  DI;  Draper  M;  Stutes  D;  Maples  N;  Mintz  J;  Tai  S;  Turkington  D (2009)  Multimodal cognitive therapy: Combining treatments that bypass cognitive deficits and deal with reasoning and appraisal biases [published online ahead of print July 20, 2009].  Schizophr Bull. 35:884–893.
[PubMed]
[CrossRef]
 
Wittorf  A;  Jakobi  UE;  Bannert  KK;  Bechdolf  A;  Müller  BW;  Sartory  G;  Wagner  M;  Wiedemann  G;  Wölwer  W;  Herrlich  J;  Buchkremer  G;  Klingberg  S (2010)  Does the cognitive dispute of psychotic symptoms do harm to the therapeutic alliance? J Nerv Ment Dis. 198:478–485.
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Wykes  T;  Parr  AM;  Landau  S (1999)  Group treatment of auditory hallucinations: Exploratory study of effectiveness.  Br J Psychiatry. 175:180–185.
[PubMed]
[CrossRef]
 
Wykes  T;  Steel  C;  Everitt  B;  Tarrier  N (2008)  Cognitive behavior therapy for schizophrenia: Effect sizes, clinical models, and methodological rigor.  Schizophr Bull. 34:523–537.
[PubMed]
[CrossRef]
 
Zimmermann  G;  Favrod  J;  Trieu  VH;  Pomini  V (2005)  The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: A meta-analysis.  Schizophr Res. 77:1–9.
[PubMed]
[CrossRef]
 
References Container
Anchor for Jump
Table 1.

Therapeutic Elements in Psychotherapies for Schizophrenia

Table Footer Notea

These approaches are still under development, so the definition of therapeutic elements is preliminary at this time.

Table Footer Noteb

Phase of illness in which the psychotherapy has been studied.

Table Footer Note

CBT indicates cognitive behavior therapy.

+

References

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Barrowclough  C;  Haddock  G;  Tarrier  N;  Lewis  SW;  Moring  J;  O’Brien  R;  Schofield  N;  McGovern  J (2001)  Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders.  Am J Psychiatry. 158: 1706–1713.
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Davis  LW;  Lysaker  PH;  Lancaster  RS;  Bryson  GJ;  Bell  MD (2005)  The Indianapolis Vocational Intervention Program: A cognitive behavioral approach to addressing rehabilitation issues in schizophrenia.  J Rehabil Res Dev. 42:35–45.
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Dickerson  FB (2000)  Cognitive behavioral psychotherapy for schizophrenia: A review of recent empirical studies.  Schizophr Res. 43:71–90.
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Dickerson  FB;  Lehman  AF (2006)  Evidence-based psychotherapy for schizophrenia.  J Nerv Ment Dis. 194:3–9.
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[CrossRef]
 
Dixon  LB;  Dickerson  F;  Bellack  AS;  Bennett  M;  Dickinson  D;  Goldberg  RW;  Lehman  A;  Tenhula  WN;  Calmes  C;  Pasillas  RM;  Peer  J;  Kreyenbuhl  J (2010)  Schizophrenia Patient Outcomes Research Team (PORT).The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements.  Schizophr Bull. 36:48–70.
[PubMed]
[CrossRef]
 
Drake  RE;  Cimpean  D;  Torrey  WC (2009)  Shared decision making in mental health: Prospects for personalized medicine.  Dialogues Clin Neurosci. 11:455–463.
[PubMed]
 
Fowler  D;  Garety  P;  Kuipers  E (1995)  Cognitive behaviour therapy for psychosis.   West Sussex, UK:  John Wiley & Sons.
 
Gaudiano  BA (2005)  Cognitive behavior therapies for psychotic disorders: current empirical status and future directions.  Clin Psychol Sci Pract. 12:33–50.
[CrossRef]
 
Gaudiano  BA;  Herbert  JD (2006)  Acute treatment of inpatients with psychotic symptoms using Acceptance and Commitment Therapy: Pilot results.  Behav Res Ther. 44:415–437.
[PubMed]
[CrossRef]
 
Gejman  PV;  Sanders  AR;  Duan  J (2010)  The role of genetics in the etiology of schizophrenia.  Psychiatr Clin North Am. 33:35–66.
[PubMed]
[CrossRef]
 
Granholm  E;  McQuaid  JR;  McClure  FS;  Auslander  LA;  Perivoliotis  D;  Pedrelli  P;  Patterson  T;  Jeste  DV (2005)  A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia.  Am J Psychiatry. 162:520–529.
[PubMed]
[CrossRef]
 
Granholm  E;  McQuaid  JR;  McClure  FS;  Link  PC;  Perivoliotis  D;  Gottlieb  JD;  Patterson  TL;  Jeste  DV (2007)  Randomized controlled trial of cognitive behavioral social skills training for older people with schizophrenia: 12-month follow-up.  J Clin Psychiatry. 68:730–737.
[PubMed]
[CrossRef]
 
Grant  PM;  Beck  AT (2009)  Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia.  Schizophr Bull. 35: 798–806.
[PubMed]
[CrossRef]
 
Gunderson  JG;  Frank  AF;  Katz  HM;  Vannicelli  M.L;  Frosch  JP;  Knapp  PH (1984)  Effects of psychotherapy in schizophrenia: II. Comparative outcome of two forms of treatment.  Schizophr Bull. 10:564–598.
[PubMed]
 
Haddock  G;  Tarrier  N;  Morrison  AP;  Hopkins  R;  Drake  R;  Lewis  S (1999)  A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis.  Soc Psychiatry Psychiatr Epidemiol. 34:254–258.
[PubMed]
[CrossRef]
 
Hayes  SC;  Strosahl  KD;  Wilson  KG (1999)  Acceptance and commitment therapy: An experiential approach to behavior change.   New York:  Guilford.
 
Hegarty  JD;  Baldessarini  RJ;  Tohen  M;  Waternaux  C;  Oepen  G (1994)  One hundred years of schizophrenia: A meta-analysis of the outcome literature.  Am J Psychiatry. 151:1409–1416.
[PubMed]
 
Hogarty  GE;  Greenwald  D;  Ulrich  RL;  Kornblith  SJ;  DiBarry  AL;  Cooley  S;  Carter  M;  Flesher  S (1997a)  Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.  Am J Psychiatry. 154:1514–1524.
 
Hogarty  GE;  Kornblith  SJ;  Greenwald  D;  DiBarry  AL;  Cooley  S;  Flesher  S;  Reiss  D;  Carter  M;  Ulrich  RL (1995)  Personal therapy: A disorder-relevant psychotherapy for schizophrenia.  Schizophr Bull. 21:379–393.
[PubMed]
 
Hogarty  GE;  Kornblith  SJ;  Greenwald  D;  DiBarry  AL;  Cooley  S;  Ulrich  RL;  Carter  M;  Flesher  S (1997b)  Personal therapy: Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.  Am J Psychiatry. 154: 1504–1513.
 
Kates  J;  Rockland  LH (1994)  Supportive psychotherapy of the schizophrenic patient.  Am J Psychother. 4:543–561.
 
Kemp  R;  Hayward  P;  Applewhaite  P;  Everitt  B;  Anthony  B (1996)  Compliance therapy in psychotic patients: Randomised controlled trial.  BMJ. 312:345–349.
[PubMed]
[CrossRef]
 
Kemp  R;  Kirov  G;  Everitt  B;  Hayward  P;  David  A (1998)  Randomized controlled trial of compliance therapy, 18-month follow-up.  Br J Psychiatry. 172:413–419.
[PubMed]
[CrossRef]
 
Kingdon  DG;  Turkington  D (1994)  Cognitive-behavioral therapy of schizophrenia.   New York:  Guilford.
 
Kumari  V;  Peters  ER;  Fannon  D;  Antonova  E;  Premkumar  P;  Anilkumar  AP;  Williams  SC;  Kuipers  E (2009)  Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive-behavioral therapy in schizophrenia.  Biol Psychiatry. 66:594–602.
[PubMed]
[CrossRef]
 
Lehman  AF;  Kreyenbuhl  J;  Buchanan  RW;  Dickerson  FB;  Dixon  LB;  Goldberg  R;  Green-Paden  LD;  Tenhula  WN;  Boerescu  D;  Tek  C;  Sandson  N;  Steinwachs  DM (2004)  The Schizophrenia Patient Outcomes Research Team (PORT): Updated Treatment Recommendations 2003.  Schizophr Bull. 30:193–217.
[PubMed]
[CrossRef]
 
Lehman  AF;  Steinwachs  DM (1998)  Patterns of usual care for schizophrenia: Initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey.  Schizophr Bull. 24:11–20.
[PubMed]
[CrossRef]
 
Lysaker  PH;  Buck  KD;  Carcione  A;  Procacci  M;  Salvatore  G;  Nicolo  G;  Dimaggio  G (2010a)  Addressing metacognitive capacity for self reflection in the psychotherapy for schizophrenia: a conceptual model of the key tasks and processes.  Psychol Psychother. 84:58–69.
 
Lysaker  PH;  Davis  LW;  Bryson  GJ;  Bell  MD (2009)  Effects of cognitive behavioral therapy on work outcomes in vocational rehabilitation for participants with schizophrenia spectrum disorders.  Schizophr Res. 107:186–191.
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