Sbp130 94.103

Schizophrenia Bulletin vol. 36 no. 1 pp. 94–103, 2010doi:10.1093/schbul/sbp130Advance Access publication on December 2, 2009 The Schizophrenia Patient Outcomes Research Team (PORT): Updated TreatmentRecommendations 2009 Julie Kreyenbuhl1–3, Robert W. Buchanan4, tion, representing significant unmet needs in important Faith B. Dickerson5, and Lisa B. Dixon2,3 2Division of Services Research, Department of Psychiatry, Uni-versity of Maryland School of Medicine, 737 West Lombard Street, Key words: evidence-based practices/psychopharmacologic 5th Floor, Baltimore, MD 21201; 3VA Capitol Health care Network (VISN 5) Mental Illness Research, Education, and Clinical Center, Baltimore, MD; 4Maryland Psychiatric Research Center, Depart-ment of Psychiatry, University of Maryland School of Medicine,Baltimore, MD; 5Sheppard Pratt Health System, Baltimore, MD In 1992, the Agency for Health Care Policy and Research http://schizophreniabulletin.oxfordjournals.org/ The Schizophrenia Patient Outcomes Research Team (now the Agency for Healthcare Research and Quality (PORT) project has played a significant role in the devel- [AHRQ]) and the National Institute of Mental Health opment and dissemination of evidence-based practices for (NIMH) funded the Schizophrenia Patient Outcomes Re- schizophrenia. In contrast to other clinical guidelines, the search Team (PORT) Study. The Schizophrenia PORT Schizophrenia PORT Treatment Recommendations, ini- was 1 of 14 Patient Outcomes Research Teams created tially published in 1998 and first revised in 2003, are based in the late 80s and early 90s in response to concerns raised primarily on empirical data. Over the last 5 years, research about the appropriateness of care being delivered for sev- on psychopharmacologic and psychosocial treatments eral common medical and psychiatric conditions, includ- for schizophrenia has continued to evolve, warranting an ing schizophrenia. To improve the quality of medical update of the PORT recommendations. In consultation care for these disorders, the PORT program sought to with expert advisors, 2 Evidence Review Groups (ERGs) reduce variations in care by promoting the adoption identified 41 treatment areas for review and conducted elec- of treatments supported by strong scientific evidence tronic literature searches to identify all clinical studies pub- or ‘‘evidence-based practices.’’ To achieve this goal, lished since the last PORT literature review. The ERGs the various PORTs synthesized the clinical evidence per- also reviewed studies preceding 2002 in areas not covered taining to many common medical conditions and pro- by previous PORT reviews, including smoking cessation, duced treatment recommendations and other types of substance abuse, and weight loss. The ERGs reviewed evidence-based clinical guidelines to be disseminated to over 600 studies and synthesized the research evidence, pro- ducing recommendations for those treatments for which the As a part of the initial Schizophrenia PORT project, evidence was sufficiently strong to merit recommendation investigators conducted systematic reviews of the litera- status. For those treatments lacking empirical support, ture to identify evidence-based practices for the care of the ERGs produced parallel summary statements. An Ex- persons with schizophrenia, from which the first Schizo- pert Panel consisting of 39 schizophrenia researchers, clini- phrenia PORT treatment recommendations were devel- cians, and consumers attended a conference in November oped and published in 19981 and subsequently updated 2008 in which consensus was reached on the state of the ev- in 2003.2 The PORT recommendations are readily distin- idence for each of the treatment areas reviewed. The meth- guishable from other clinical guidelines and algorithms ods and outcomes of the update process are presented for schizophrenia because only those treatments for here and resulted in recommendations for 16 psychophar- which there is substantial scientific evidence achieve rec- macologic and 8 psychosocial treatments for schizophrenia.
ommendation status. Although expert opinion is sought Another 13 psychopharmacologic and 4 psychosocial treat- to reach consensus on the interpretation of the evidence ments had insufficient evidence to support a recommenda- base for a particular treatment, there are no PORT treat-ment recommendations based solely on expert opinion, as is the case with other efforts designed to specify best To whom correspondence should be addressed; tel: 410-605- 7466, fax: 410-605-7739, e-mail: [email protected].
practices for schizophrenia (eg, the American Psychiatric Ó The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: [email protected].
2009 Schizophrenia PORT Treatment Recommendations Association [APA] Practice Guideline for the Treatment determine whether the evidence was sufficient to support of Patients with Schizophrenia,3 the Texas Medication the development of new treatment recommendations. To Algorithm Project [TMAP4]). By remaining silent on identify critical new evidence, we adopted a comprehen- a number of aspects of care for schizophrenia for which sive approach that involved conducting systematic empirical support is currently lacking, the PORT is reviews of the schizophrenia treatment literature in con- known for being relatively conservative. However, unlike sultation with experts from relevant disciplines. The lit- TMAP, the PORT includes recommendations for ad- erature reviews were performed by 2 Evidence Review junctive psychopharmacologic treatments as well as for Groups (ERGs), one focusing on psychopharmacologic antipsychotic medications, and also includes recommen- treatments and the other focusing on psychosocial treat- dations for psychosocial interventions, which are impor- ments for schizophrenia. The ERGs were comprised of 16 tant treatments that augment gains from medication faculty members from the University of Maryland therapies. Also, in contrast to the APA Practice Guide- Schools of Medicine and Pharmacy who have both clin- line and the algorithms developed by TMAP, the PORT ical expertise and experience in conducting research on provides clear-cut and concise statements of recommen- treatments for schizophrenia. Four residents in psychia- dations for best practices. As such, PORT recommenda- try and 2 postdoctoral fellows in psychology also partic- tions have been applied to evaluate the quality of care ipated on the ERGs as a component of their training.
provided to people with schizophrenia in a variety of The work of both ERGs was accomplished in consul- tation with Advisory Boards of recognized experts in the Since the previous PORT update 5 years ago, research fields of psychopharmacologic and psychosocial inter- on technologies for treating persons with schizophrenia ventions for schizophrenia. The Advisory Boards served http://schizophreniabulletin.oxfordjournals.org/ has continued to quickly evolve. Most notably, the find- a number of purposes, including helping to determine the ings of 2 large pragmatic clinical trials on the comparative treatment areas to be reviewed and participating in the effectiveness of first-generation and second-generation debate over whether the evidence was sufficient for a rec- antipsychotic medications, the Clinical Antipsychotic ommendation, and if so, what the recommendation Trials of Intervention Effectiveness (CATIE)10 and the should entail. Together the ERGs and their respective Cost Utility of the Latest Antipsychotic Drugs in Schizo- Advisory Boards selected 41 treatment areas for review, phrenia Study (CUtLASS),11 have been published. In ad- which included areas of treatment addressed in the extant dition, the literature on both psychopharmacologic and PORT recommendations as well as areas reviewed in pre- psychosocial interventions for neurocognitive impair- vious PORT updates that had insufficient evidence at ments, co-occurring psychiatric and medical conditions, that time to support a recommendation but for which ev- and treatments for individuals experiencing a recent on- idence had continued to accumulate (eg, interventions for set of psychosis has expanded considerably. As new treat- negative symptoms and cognitive impairments). Also ments for schizophrenia become available, new studies reviewed were several emerging treatment areas, includ- are completed, and new outcomes (eg, remission and re- ing peer-delivered services, psychosocial treatments for covery) are identified, it is imperative to update treatment recent-onset schizophrenia, cognitive remediation, and recommendations to accommodate the ever growing and repetitive transcranial magnetic stimulation (rTMS).
shifting evidence base. Treatment recommendations for Whereas previous PORT reviews focused on treatment schizophrenia must also be regularly updated to ensure domains directly related to the symptoms and outcomes that efforts to improve quality of care reflect current em- of schizophrenia, a new addition to this PORT effort in- pirical knowledge. This article presents the methods used cluded reviews of the literature on treatments for several to produce the second update of the Schizophrenia PORT co-occurring medical and psychiatric conditions that are Psychopharmacological and Psychosocial Treatment highly prevalent and considered to be vital components Recommendations, which are included together here.
of recovery-oriented treatment. These important treat- The syntheses of the evidence for the 29 psychopharmacol- ment areas included psychopharmacologic and psycho- ogy and 12 psychosocial treatment areas reviewed for social interventions for alcohol and substance abuse, this update are included in separate papers12–13 and in weight management, and smoking cessation. As with past PORT reviews, the ERGs did not evaluate aspectsof care that meet basic human needs (eg, housing) orthe benefits of having the mutual support of peers or establishing trusting relationships with providers. Each A primary goal of this update was to review the results of of these areas is vitally important to recovery-oriented new studies of schizophrenia treatments published since care but is generally not amenable to randomized experi- the last literature survey in 2002 to determine if modifi- ments and, thus, does not meet PORT criteria for review.
cations in the extant PORT treatment recommendations Also, because the Schizophrenia PORT identifies evi- were warranted. We also sought to evaluate the research dence-based practices for the treatment of schizophrenia, evidence for a number of promising areas of treatment to we did not review interventions for treating prodromal symptoms or for treating persons at high risk for an initial ducing suicidal behaviors). In the case of pharmacologic treatments, only those treatments with at least one non– To identify candidate studies for review, the ERGs first industry-sponsored investigation were considered for rec- conducted extensive electronic literature searches of ommendation status because of the potential biases in- MEDLINE, Psychlit, and the Cochrane Library using herent in studies in which a company’s financial as search terms the names of treatments or treatment interests are linked to study outcomes. Recommendation methods and schizophrenia. To augment this approach, statements include a description of the treatment, the the ERGs also identified relevant primary studies by population for which the treatment is indicated, and reviewing the bibliographies of systematic review articles the outcomes of the treatment. The ERGs also produced and through consultation with the Advisory Boards. For accompanying syntheses of the evidence base supporting treatment areas considered in previous PORT efforts, the time period of review was January 2002 through March Alternatively, the evidence could be judged to be not 2008; studies published prior to January 2002 were only sufficient to merit a treatment recommendation, in which reviewed if they had not been included in previous PORT case a summary statement was written that described the reviews. For newly reviewed areas of treatment, we treatment and its indication along with a summary of the searched the literature as far back as required to capture evidence and the important gaps in knowledge that pre- all studies that met review criteria. For all areas, we cluded treatment recommendation status. The ERGs also only reviewed studies published after March 2008 that produced evidence syntheses explaining the ways in were likely to significantly alter the evaluation of the ev- which the research fell short of permitting a recommenda- idence. We restricted our reviews to English language tion. It should be noted that treatment areas for which the http://schizophreniabulletin.oxfordjournals.org/ evidence is judged to be insufficient to support a treat- After reviewing abstracts of candidate studies, the ment recommendation are not proscriptions against us- ERGs then selected for more in-depth review and ab- ing a particular treatment, ie, they are not ‘‘negative straction all randomized controlled trials for which at recommendations.’’ The PORT simply remains silent least 50% of participants had a schizophrenia spectrum with respect to these areas of treatment for schizophrenia, disorder diagnosis, ie, schizophrenia, schizoaffective dis- many of which hold future promise but for which empir- order, or schizophreniform disorder. The few exceptions to these criteria were case reports or case series that were Next, the ERGs posted on a dedicated Web site draft reviewed for outcomes of psychopharmacologic treat- versions of the updated treatment recommendations, ments that constitute rare adverse events, eg, neuroleptic summary statements, and accompanying evidence sum- malignant syndrome (NMS). Also, the majority of con- maries for review by the Schizophrenia PORT Expert trolled studies of psychosocial interventions for sub- Panel. Along with the aforementioned members of the stance use disorders and peer-delivered services include Advisory Boards, the Expert Panel consisted of 39 schizo- populations reflective of those who receive the treatments phrenia researchers, clinicians, and consumers, including in clinical practice. Therefore, the Psychosocial ERG 23 psychiatrists, 15 PhDs in psychology or related fields, reviewed studies of these services that included samples and 1 individual with an MPP degree. For those treat- comprised of less than half of individuals with schizo- ment areas in which Expert Panel members indicated phrenia spectrum disorders. In all, the ERGs reviewed they had sufficient expertise, they provided feedback and abstracted 424 studies of psychopharmacologic on the content and wording of the draft recommenda- and other somatic treatments and 175 studies of psycho- tions and summary statements via the Web site. Also, social interventions for schizophrenia.
for this update, we implemented a new method by which In the case of the extant PORT treatment recommen- Expert Panel members rated the strength of the body of dations, the selected articles were reviewed for their po- evidence for each treatment area reviewed. However, be- tential to importantly modify these recommendations. In cause we experienced considerable difficulty in using and the case of new treatments or outcomes, there were 2 pos- interpreting the new ratings, we are not reporting them sible review results. First, the reviewed evidence could here. Instead, we provide a full description of the expert meet criteria for sufficient evidence to merit a treatment rating process we attempted to implement and the chal- recommendation by ERG consensus. In general, the ERGs considered sufficient evidence to be at least 3 well-designed randomized controlled studies performed At a 1-day conference held in Baltimore, MD, in by independent investigator groups that concluded that November 2008, the feedback provided by the Expert the treatment is effective in promoting a desired outcome.
Panel was aggregated and used to stimulate discussion We only deviated from this criterion in one instance, in in order to achieve consensus about the interpretation which the conduct of multiple randomized controlled tri- of the evidence base and treatment recommendation sta- als is logistically and ethically infeasible and involves an tus for each treatment area reviewed by the ERGs. This uncommon treatment outcome (use of clozapine for re- contrasts with other guideline efforts in which the Expert 2009 Schizophrenia PORT Treatment Recommendations Panel suggests what should be recommended in treat- exacerbation of their illness, the daily dosage of first-gen- ment areas where the evidence is lacking. During the con- eration antipsychotic medications should be in the range ference, the Expert Panel provided suggestions regarding of 300–1000 chlorpromazine (CPZ) equivalents. The daily the addition of studies to the evidence syntheses as well as dosage of second-generation antipsychotic medications suggestions for editing of the text of the recommenda- for an acute symptom episode should be: aripiprazole: tions and summary statements. With regard to potential 10–30mg*; olanzapine: 10–20 mg*; paliperidone: 3–15 conflicts of interest, prior to the conference we asked all mg; quetiapine: 300–750 mg*; risperidone: 2–8 mg; and members of the ERGs and Expert Panel to disclose any ziprasidone: 80–160 mg*. Treatment trials should be at financial interests they had during the prior 24 months in least 2 weeks, with an upper limit of 6 weeks to observe commercial interests producing health care goods or serv- optimal response. (*, There is insufficient evidence to de- ices. Dr Anthony Lehman, principal investigator of the termine the upper effective dose limit. The quoted upper first PORT project and the last update, reviewed all par- ticipants’ disclosures in detail, and a summary of all dis-closures was provided to conference participants. Using Treatment of Acute Positive Symptoms in People With the extensive feedback from the expert consensus confer- First-Episode Schizophrenia: Antipsychotic Medication ence, the ERGs revised the treatment recommendations and summary statements and distributed the revisions to the Expert Panel for a final round of comments in clozapine and olanzapine, are recommended as first-line treatment for persons with schizophrenia experiencing The resulting final versions of the 16 Psychopharmaco- their first acute positive symptom episode.
http://schizophreniabulletin.oxfordjournals.org/ logical and 8 Psychosocial Treatment Recommendationsare presented below and in the 2 companion papers12–13,which also include the detailed summaries of the evidence Treatment of Acute Positive Symptoms in Treatment- for each recommendation. The summary statements and Responsive People With Schizophrenia: Antipsychotic associated evidence summaries for the 13 psychopharma- cological treatments and 4 psychosocial treatments for which the evidence is currently insufficient to support nia exhibit increased treatment responsiveness and an in- a treatment recommendation are included in the creased sensitivity to adverse effects compared with people with multiepisode schizophrenia. Therefore, antipsy- chotic treatment should be started with doses lowerthan those recommended for multiepisode patients (first-generation antipsychotics: 300–500 mg CPZ equiv- Recommendations: Psychopharmacological Treatment alents; risperidone and olanzapine: lower half of recom- mended dosage range for multiepisode patients). Animportant exception is with quetiapine, which often Treatment of Acute Positive Symptoms in Treatment- requires titration to 500–600 mg/day. The therapeutic Responsive People With Schizophrenia: Acute efficacy of low-dose aripiprazole or ziprasidone has not been evaluated in people with first-episode schizophrenia.
multiepisode schizophrenia who are experiencing an Maintenance Pharmacotherapy in Treatment-Responsive acute exacerbation of their illness, antipsychotic medica- People With Schizophrenia: Maintenance Antipsychotic tions, other than clozapine, should be used as the first line of treatment to reduce positive psychotic symptoms. The initial choice of antipsychotic medication or the decision multiepisode schizophrenia who experience acute and to switch to a new antipsychotic should be made on the sustained symptom relief with an antipsychotic medica- basis of individual preference, prior treatment response, tion should be offered continued antipsychotic treatment and side effect experience; adherence history; relevant in order to maintain symptom relief and to reduce the risk medical history, and risk factors; individual medication of relapse or worsening of positive symptoms.
side effect profile; and long-term treatment planning.
Maintenance Pharmacotherapy in Treatment-Responsive Treatment of Acute Positive Symptoms in Treatment- People With Schizophrenia: Maintenance Antipsychotic Responsive People With Schizophrenia: Acute multiepisode schizophrenia who experience acute and multiepisode schizophrenia who are experiencing an acute medication, the maintenance dosage for first-generation Clozapine for the Treatment of Residual Symptoms: antipsychotics should be in the range of 300–600 CPZ equivalents per day. The maintenance dosage for aripi- prazole, olanzapine, paliperidone, quetiapine, risperi- to people with schizophrenia who present with persistent done, and ziprasidone should be the dose found to be symptoms of hostility and/or display persistent violent effective for reducing positive psychotic symptoms in Clozapine for the Treatment of Residual Symptoms:Clozapine for Suicidality Maintenance Pharmacotherapy in Treatment-ResponsivePeople With Schizophrenia: Long-Acting Antipsychotic ered for people with schizophrenia who exhibit markedand persistent suicidal thoughts or behaviors.
psychotic medication should be offered as an alternative Other Psychopharmacological Recommendations: to oral antipsychotic medication for the maintenance treatment of schizophrenia when the LAI formulationis preferred to oral preparations. The recommended dos- age range for fluphenazine decanoate is 6.25–25 mg ad- tion antipsychotics, prophylactic use of antiparkinson ministered every 2 weeks and for haloperidol decanoate is agents to reduce the incidence of extrapyramidal side 50–200 mg administered every 4 weeks, although alterna- effects should be determined on a case by case basis, tak- http://schizophreniabulletin.oxfordjournals.org/ tive dosages and administration intervals equivalent to ing into account individual preferences, prior history of the recommended dosage ranges may also be used.
extrapyramidal side effects, characteristics of the antipsy- The recommended dosage range for risperidone long- chotic medication prescribed, and other risk factors for acting injection is 25–75 mg administered every 2 weeks.
both extrapyramidal side effects and anticholinergicside effects. The use of prophylactic antiparkinson agentsin people treated with second-generation antipsychotics Maintenance Pharmacotherapy in Treatment-Responsive People With Schizophrenia: Targeted, IntermittentAntipsychotic Medication Maintenance Strategies Other Psychopharmacological Recommendations:Medication for the Treatment of Acute Agitation in maintenance strategies should not be used routinely inlieu of continuous maintenance treatment regimens due to the increased risk of symptom worsening and relapse.
psychotic medication, alone or in combination with a rapid acting benzodiazepine, should be used in thepharmacological treatment of acute agitation in people Clozapine for the Treatment of Residual Symptoms: with schizophrenia. If possible, the route of antipsychotic Clozapine for Positive Symptoms in Treatment-Resistant administration should correspond to the preference of Other Psychopharmacological Recommendations: ple with schizophrenia who continue to experience persis- Intervention for Smoking Cessation in Schizophrenia tent and clinically significant positive symptoms after 2adequate trials of other antipsychotic agents. A trial of clozapine should last at least 8 weeks at a dosage from to quit or reduce cigarette smoking should be offered treatment with bupropion SR 150 mg twice daily for10–12 weeks, with or without nicotine replacement ther-apy, to achieve short-term abstinence. This pharmaco- Clozapine for the Treatment of Residual Symptoms: logical treatment should be accompanied by a smoking cessation education or support group, although the cur- rent evidence base is insufficient to recommend a partic- failed to demonstrate an adequate response, then a cloza- pine level should be obtained to ascertain whether the clo-zapine level is above 350 ng/ml. If the blood level is less Other Psychopharmacological Recommendations: rTMS than 350 ng/ml, then the dosage should be increased, to the extent that side effects are tolerated, to achieve the left temporoparietal cortex, is recommended for 2009 Schizophrenia PORT Treatment Recommendations the acute treatment of auditory hallucinations that have approximately 4–9 months in duration. The key elements not responded to adequate antipsychotic therapy.
of this intervention include the collaborative identifica-tion of target problems or symptoms and the develop-ment of specific cognitive and behavioral strategies to cope with these problems or symptoms.
Recommendations: Psychosocial TreatmentRecommendations term inpatient or residential care should provide a behav- schizophrenia should include a program of assertive com- ioral intervention based on social learning principles for munity treatment. This intervention should be provided patients in these settings in order to improve their per- to individuals who are at risk for repeated hospitaliza- sonal hygiene, social interactions, and other adaptive tions or have recent homelessness. The key elements of behaviors. The key elements of this intervention, often assertive community treatment include a multidisciplin- referred to as a token economy, are contingent positive ary team including a medication prescriber, a shared reinforcement for clearly defined target behaviors, an in- caseload among team members, direct service provision dividualized treatment approach, and the avoidance of by team members, a high frequency of patient contact, punishing consequences. The intervention should be de- low patient to staff ratios, and outreach to patients in livered in the context of a safe treatment environment the community. Assertive Community Treatment has that provides patient access to basic amenities, evi- been found to significantly reduce hospitalizations and http://schizophreniabulletin.oxfordjournals.org/ dence-based pharmacological treatment, and the full homelessness among individuals with schizophrenia.
range of other recommended psychosocial interventions.
has the goal of employment should be offered supported employment to assist them in both obtaining and main- have ongoing contact with their families, including rela- taining competitive employment. The key elements of tives and significant others, should be offered a family supported employment include individually tailored job intervention that lasts at least 6–9 months. Interventions development, rapid job search, the availability of ongoing that last 6–9 months have been found to significantly re- job supports, and the integration of vocational and mental duce rates of relapse and rehospitalization. Though not as consistently observed, research has found other bene-fits for patients and families, such as increased medica- tion adherence, reduced psychiatric symptoms, andreduced levels of perceived stress for patients. Family members have also been found to have lower levels of have deficits in skills that are needed for everyday activ- burden and distress and improved family relationships.
ities should be offered skills training in order to improve Key elements of effective family interventions include ill- social interactions, independent living, and other out- ness education, crisis intervention, emotional support, comes that have clear relevance to community function- and training in how to cope with illness symptoms and ing. Skills training programs vary widely in content but related problems. The selection of a family intervention typically include a focus on interpersonal skills and share should be guided by collaborative decision making several key elements, including behaviorally based in- among the patient, family, and clinician. In addition, struction, role modeling, rehearsal, corrective feedback, a family intervention that is shorter than 6 months, and positive reinforcement. Skills training provided in but that is at least 4 sessions in length, should be offered clinic-based settings should be supplemented with strat- to persons with schizophrenia who have ongoing contact egies for ensuring adequate practice in applying skills in with their families, including relatives and significant an individual’s day-to-day environment.
others, and for whom a longer intervention is not feasibleor acceptable. Characteristics of the briefer interventions include education, training, and support. Possible benefits for patients include reduced psychiatric symp- have persistent psychotic symptoms while receiving ade- toms, improved treatment adherence, improved func- quate pharmacotherapy should be offered adjunctive tional and vocational status, and greater satisfaction cognitive behaviorally oriented psychotherapy to reduce with treatment. Positive family outcomes include reduced the severity of symptoms. The therapy may be provided family burden and increased satisfaction with family in either a group or an individual format and should be Psychosocial Interventions for Alcohol and Substance Use In evaluating the validity of evidence-based guidelines over time, Shekelle and colleagues15 found that after 5 years, half of the guidelines published by the AHRQ a comorbid alcohol or drug use disorder should be of- needed to be updated, and thus, we undertook this, fered substance abuse treatment. The key elements of the second PORT update, 5 years following the first up- treatment for alcohol or drug use disorders for persons date. Our searches of the treatment literature yielded al- with schizophrenia include motivational enhancement most 600 studies that required in-depth review, the and behavioral strategies that focus on engagement in majority of which substantiated the evidence base for treatment, coping skills training, relapse prevention train- the extant PORT recommendations. It is encouraging ing, and its delivery in a service model that is integrated that new research continues to support the effectiveness with mental health care. The duration of the recommen- of several well-established evidence-based practices for ded substance abuse treatment cannot be specified at this schizophrenia, including antipsychotic medications (and time; both brief (1–6 meetings) and more extended (10 or clozapine in particular), assertive community treatment, more meetings) interventions have been found to be help- and interventions for families, which primarily target ful in reducing substance use and improving psychiatric Although treatments that address the key psychiatric symptoms of schizophrenia are vital components ofcare, in recent years, considerable attention has been di-rected toward the overall poor health status of individu- Psychosocial Interventions for Weight Management als with schizophrenia. Concerns have been raised about http://schizophreniabulletin.oxfordjournals.org/ the disproportionately high rates of obesity, diabetes, and are overweight (body mass index 25.0–29.9) or obese cardiovascular disease as well as significantly reduced life (body mass index greater than or equal to 30.0) should expectancy in individuals with schizophrenia.16 Because be offered a psychosocial weight loss intervention that of the deleterious effects of cigarette smoking and over- is at least 3 months in duration to promote weight weight, in particular, on the health status of these loss. The key elements of psychosocial interventions patients, research on interventions for smoking cessation for weight loss include psychoeducation focused on nu- and antipsychotic-induced weight gain has expanded tritional counseling, caloric expenditure, and portion considerably over the past 5 years and were, thus, in- control; behavioral self-management including motiva- cluded in this review. The ERGs and Expert Panel found tional enhancement; goal setting; regular weigh-ins; that the evidence was sufficient to support new treatment self-monitoring of daily food and activity levels; and di- recommendations in both these areas, representing a sig- etary and physical activity modifications.
nificant contribution of this latest PORT update. Al-though clinicians and patients should be justifiably optimistic about the potential benefits of these treat-ments, such enthusiasm must also be tempered by clinical realities. Sustained abstinence from cigarette smoking Evidence-based medicine involves the integration of the and maintenance of clinically significant weight loss best available evidence for the treatment of a health con- have been notoriously difficult for individuals with dition with clinical expertise and patient values.14 Over schizophrenia to achieve. This is borne out in the research the past 15 years, the Schizophrenia PORT has played we reviewed, which shows replicated findings with statis- a vital role in promoting evidence-based care for schizo- tically significant, but relatively modest, smoking quit phrenia by synthesizing the treatment research literature rates and amounts of weight lost. As most of the support- for use by patients and their families in making informed ing studies in these areas were of relatively short duration, treatment choices in collaboration with their mental the extent to which more intensive treatment with these health providers. This latest update of the PORT recom- interventions leads to greater improvements is not mendations has identified 24 treatment areas that have known, but merits continued investigation to inform fu- strong empirical evidence for improving outcomes and ture iterations of treatment guidelines such as the PORT.
which should comprise the basic menu of treatments It is hoped that designation of these treatments, along and services available to all people with schizophrenia.
with psychosocial interventions for co-occurring sub- Consistent with the paradigm shift in schizophrenia stance use disorders, as evidence-based practices recom- treatment from a focus on long-term disability to one mended by the PORT will increase awareness of several focused on optimism and recovery, the ultimate goal high prevalence and life-threatening conditions that con- of the Schizophrenia PORT has been to increase the tribute significantly to poor outcomes and disability in use of evidence-based treatments in order to optimize outcomes by reducing illness symptoms and the disability Other new developments in this PORT update include and burden associated with the illness.
the deletion of 3 previous recommendations for the 2009 Schizophrenia PORT Treatment Recommendations psychopharmacologic management of schizophrenia.
a major addition to this PORT effort, the ERGs prepared For 2 of these areas, the evidence base consisted primarily parallel summary statements and evidence syntheses for of case reports and other nonexperimental study designs those treatments for which the evidence is currently insuf- that did not meet criteria for inclusion in the PORT re- ficient to support a recommendation. This information is view. Therefore, the recommendation to use clozapine in individuals who had previously experienced NMS, tar- in the 2 companion articles in this issue (Buchanan et al dive dystonia, or tardive dyskinesia and the recommen- and Dixon et al). The summary statements and accompa- dation around obtaining antipsychotic plasma levels nying evidence syntheses are analogous in format to that were eliminated. Further, although antidepressant med- of the treatment recommendations and were similarly cri- ications are widely prescribed for individuals with schizo- tiqued by the PORT Expert Panel. By calling comparable phrenia, the evidence base supporting the effectiveness of attention to areas of unmet treatment need for schizo- these medications is limited primarily to studies of older phrenia, we hope that researchers and funding agencies antidepressants in combination with first-generation an- will use this information to inform future efforts to ex- tipsychotic medications. Because the few randomized pand the evidence base in areas where few, if any, treat- controlled trials examining the effects of newer, more widely prescribed antidepressants (eg, selective serotonin Although this PORT review confirms that a number of reuptake inhibitors) in individuals receiving second-gen- evidence-based treatments for schizophrenia do have eration antipsychotic medications have been largely neg- sound empirical support, it is worth noting that the clin- ative, this recommendation was also removed. Although ical results of such treatments are often incomplete for the research evidence is currently insufficient to support individual patients. These treatments do not ‘‘cure’’ http://schizophreniabulletin.oxfordjournals.org/ a PORT recommendation in this area, the absence of schizophrenia or fully ameliorate symptoms and prob- a recommendation is not a proscription against the use lems for the majority of affected individuals; such objec- of antidepressants or any other approach to ameliorating tives remain for future generations of research. These depressive or other symptoms in affected individuals.
limitations of PORT recommended treatments stem Rather, patients and clinicians should exercise due cau- from several causes. A critical issue is that many of the tion when employing treatments where the benefits are recommended treatments have modest effect sizes. Fur- less certain and should promptly discontinue such treat- ther, there is the inherent tension between the internal ments if no benefits are observed. Of note, this PORT re- and external validity of randomized controlled trials view revealed a surprising lack of robust empirical upon which the PORT and other evidence-based guide- investigation of other widely prescribed adjunctive psy- lines are based. Although strides in effectiveness research chopharmacologic treatments (eg, mood stabilizers, ben- for schizophrenia treatments have certainly been made zodiazepines), underscoring the need for continued over the past 5 years, eg, with the completion of the CAT- research on the safety and efficacy of polypharmacy in IE and CUtLASS studies, it remains logistically and fis- cally difficult to conduct research in the ‘‘real world’’ As mentioned, with very few exceptions, the vast where people with schizophrenia typically present with majority of the studies we reviewed for this update a complex array of clinical problems and symptoms. Psy- were randomized controlled trials, reflecting the PORT’s chosocial treatment studies may include more ‘‘typical’’ continuing mission of identifying treatments supported patients, but the training needs and expertise required to by the most robust empirical research evidence. By def- carry out psychosocial interventions with high fidelity inition, treatment areas where research utilizing experi- limit the effectiveness of these models. As such, more re- mental study designs is not feasible are not addressed search is needed to better understand which individuals by the PORT, as mentioned in the ‘‘Methods’’ section respond most favorably to treatments with demonstrated of this article. The PORT is also silent on treatment areas efficacy. More research is also needed to understand how where research findings are suggestive of benefits but evidence-based psychopharmacological and psychosocial in the opinion of experts cannot be elevated to recom- treatments should best be combined or sequenced to op- mendation status because of limitations of the available timize outcomes for individual patients, another aspect of evidence (eg, cognitive remediation, switching antipsy- treatment planning upon which the PORT is unable to chotics for weight loss, [newer] antidepressants for de- pressive or negative symptoms). There are also some As a major contribution of the Schizophrenia PORT areas of treatment for schizophrenia where adequate re- project to both science and service over the past 15 years, search is available but for which the results suggest exist- the straightforward format of the treatment recommen- ing treatment options are ineffective (eg, antipsychotic dations has enabled researchers and policy makers to use medications for improving cognition). By remaining si- them as a foundation to devise quality of care indica- lent on these treatments, the PORT has risked being tors.5–9 Unfortunately, several studies have drawn atten- viewed as overly conservative and even indifferent to ma- tion to continuing deficiencies in the quality of jor areas of unmet treatment need for schizophrenia. As medication prescribing and lack of access to most evidence-based psychosocial interventions in clinical a challenge both for continued treatment and implemen- practice, lending support to concerns that, despite the availability of evidence-based guidelines, the quality ofschizophrenia treatment may not be improving.17 Al-though the efforts of the PORT and others to synthesize the research literature to identify effective treatments for schizophrenia are a necessary prerequisite to implemen- tation of evidence-based practices, they are certainly notsufficient. Research in implementation science indicatesthat passive dissemination of clinical guidelines alone, such as publication in a peer-reviewed journal as has National Institute of Mental Health (R13 MH080593 to been the tradition with the PORT, is generally insuffi- J.K.); the Department of Veterans Affairs (Mental Health cient for effecting successful implementation and improv- ing patient outcomes.18 While widespread disseminationof the treatment recommendations and implementation of evidence-based practices remains beyond the scope of the Schizophrenia PORT project, some progress hasbeen made, including implementation and evaluation The authors and other members of the Schizophrenia of the TMAP algorithm for psychopharmacologic treat- PORT would like to acknowledge the following ments and the National Implementing Evidence-Based members of the Expert Panel who attended the http://schizophreniabulletin.oxfordjournals.org/ Practices project for several psychosocial interventions.17 We hope these implementation efforts will continue and November 2008 and provided feedback on multiple expand with this latest update of the Schizophrenia drafts of the updated treatment recommendations: Concepcion Barrio, PhD, MSW; Gary Bond, PhD; As the clinical treatment literature continues to evolve John Boronow, MD; Peter Buckley, MD; William T.
and expand, so have approaches to developing and Carpenter, Jr, MD; Judith Cook, PhD; John Davis, updating clinical guidelines and treatment recommenda- MD; Robert Drake, MD, PhD; Ken Duckworth, MD; tions.19–21 However, it should be noted that the PORT Susan Essock, PhD; Eden Evins, MD, MPH; Fred ERGs did not provide the panel with assessments of Frese, PhD; James Gold, PhD; Howard Goldman, the quality of the research design of each study compris- MD, PhD; Donald Goff, MD; Shirley Glynn, PhD; ing the evidence base, a procedure commonly employed Eric Granholm, PhD; Robert Gresen, PhD; Lisa when clinical practice guidelines are developed and Halpern, MPP; Ralph Hoffman, MD; John Kane, updated using studies characterized by a combination MD; Ira Katz, PhD; Richard Keefe, PhD; Jeffrey of experimental and nonexperimental designs. Given Lieberman, MD; Stephen R. Marder, MD; Thomas the PORT’s reliance on randomized controlled trials, McGlashan, MD; Alexander Miller, MD; Kim Mueser, we did not adopt this approach because the likelihood PhD; John Newcomer, MD; Diana Perkins, MD, of our detecting any substantive differences in quality MPH; Georgios Petrides, MD; Delbert Robinson, MD; across the trials using one of the widely available, but relatively generic, quality rating scales was quite low.22 Linmarie Sikich, MD; Steve Silverstein, PhD; Scott It was beyond the scope of the PORT project to de- velop and validate individual quality rating scales tai- Alexander Young, MD, MSHS. We also acknowledge lored to each of the 41 different treatment areas we Susan Borowy, Charrise James, and Natalie Johnson for coordinating the Schizophrenia PORT Treatment Overall appraisal of the PORT’s third set of treatment Recommendations Update Conference and arranging recommendations underlines both the movement for- for travel and lodging for all conference participants.
ward of research on schizophrenia treatments as well as the frustratingly slow pace of knowledge acquisition Cephalon and Pfizer; Consultant: Abbott, Glaxo- in this field. While we reviewed over 600 studies for this update and identified 24 evidence-based practices, in- cluding 7 newly recommended treatments, we do not see Merck, Pfizer, Roche, Solvay Pharmaceuticals, Inc., dramatic break through psychosocial treatments or med- ications. Further, not all people with schizophrenia have Kreyenbuhl, Dickerson, and Dixon have no competing full access to these treatments, and when available, their interests or financial support to disclose. The content application is sometimes incomplete and many produce is solely the responsibility of the authors and does not only modest effects. Thus, our recommendations issue necessarily represent the official views of the National 2009 Schizophrenia PORT Treatment Recommendations Institute of Mental Health, the National Institutes of first-generation antipsychotic drugs in schizophrenia: cost Health, or the Department of Veterans Affairs.
Utility of the Latest Antipsychotic Drugs in SchizophreniaStudy (CUtLASS 1). Arch Gen Psychiatry. 2006;63:1079–1087.
12. Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment rec- 1. Lehman AF, Steinwachs DM. Translating research into prac- ommendations and summary statements. Schizophr Bull.
tice: the Schizophrenia Patient Outcomes Research Team 13. Dixon LB, Dickerson FB, Bellack AS, et al. The 2009 schizo- phrenia PORT psychosocial treatment recommendations and 2. Lehman AF, Kreyenbuhl J, Buchanan RW, et al. The Schizophre- summary statements. Schizophr Bull. 2009; doi:10.1093/ nia Patient Outcomes Research Team (PORT): updated treat- ment recommendations 2003. Schizophr Bull. 2004;30:193–217.
14. Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, 3. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guide- Richardson WS. Evidence based medicine: what it is and line for the treatment of patients with schizophrenia. 2nd ed.
what it isn’t. BMJ. 1996;312:71–72.
15. Shekelle PG, Ortiz E, Rhodes S, Morton SC, et al. Validity of 4. Moore TA, Buchanan RW, Buckley PF, et al. The Texas Med- the Agency for Healthcare Research and Quality clinical ication Algorithm Project antipsychotic algorithm for schizo- practice guidelines: how quickly do guidelines become out- phrenia: 2006 update. J Clin Psychiatry. 2007;68:1751–1762.
dated? J Am Med Assoc. 2001;286:1461–1467.
5. Lehman AF, Steinwachs DM. Patterns of usual care for 16. Colton CW, Manderscheid RW. Congruencies in increased schizophrenia: initial results from the Schizophrenia Patient mortality rates, potential years of life lost, and causes of death Outcomes Research Team (PORT) client survey. Schizophr among public mental health clients in eight states. Prev Bull. 1998;24:11–20 discussion 20–32.
http://schizophreniabulletin.oxfordjournals.org/ 6. Young AS, Sullivan G, Burnam MA, Brook RH. Measuring 17. Drake RE, Bond GR, Essock SM. Implementing evidence- the quality of outpatient treatment for schizophrenia. Arch based practices for people with schizophrenia. Schizophr 7. Dickey B, Normand SL, Hermann RC, et al. Guideline rec- 18. Shojania KG, Grimshaw JM. Evidence-based quality im- ommendations for treatment of schizophrenia: the impact provement: the state of the science. Health Aff (Millwood).
of managed care. Arch Gen Psychiatry. 2003;60:340–348.
8. Leslie DL, Rosenheck RA. Adherence of schizophrenia phar- 19. Eccles M, Rousseau N, Freemantle N. Updating evidence-based macotherapy to published treatment recommendations: pa- clinical guidelines. J Health Serv Res Policy. 2002;7:98–103.
tient, facility, and provider predictors. Schizophr Bull.
20. Moher D, Tsertsvadze A, Tricco AC, et al. When and how to update systematic reviews. Cochrane Database Syst Rev.
9. Busch AB, Lehman AF, Goldman H, Frank RG. Changes over time and disparities in schizophrenia treatment quality.
21. Voisin CE, de la Varre C, Whitener L, Gartlehner G. Strate- gies in assessing the need for updating evidence-based guide- 10. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of lines for six clinical topics: an exploration of two search antipsychotic drugs in patients with chronic schizophrenia. N methodologies. Health Info Libr J. 2008;25:198–207.
22. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality 11. Jones PB, Barnes TR, Davies L, et al. Randomized con- of reports of randomized clinical trials: is blinding necessary? trolled trial of the effect on Quality of Life of second- vs.
Control Clin Trials. 1996;17(1):1–12.

Source: http://www.bedrepsykiatri.dk/media/7093/schizophr-bull-2010-kreyenbuhl-94-103.pdf