Lo Stato dell'Arte in Psichiatria

1.

La necessità di mantenere un'attenzione critica in rapporto agli sviluppi della neopsichiatria urta, almeno per quanto mi riguarda, contro una difficoltà crescente: la noia infinita di leggere materiale spacciato come scientifico, che, di scientifico, ha solo i dati statistici e le tabelle, e che, per il resto, è una ripetizione canonica di formule standardizzate. La noia si traduce in irritazione allorché riesce evidente (praticamente sempre) che i lavori "scientifici" sono sponsorizzati dalle case farmaceutiche.

Medscape Psychiatry è il sito psichiatrico in assoluto più attivo, le cui newsletter sono veramente singolari. Ogni mese vengono segnalati progressi e successi nella cura dei disturbi mentali gravi (SMI) e sono proposti aggiornamenti sulle ricerche e sui trattamenti. Nonostante, purtroppo, sia costretto a frequentarlo assiduamente, non ho ricavato, negli ultimi anni, una sola notizia utile. La neopsichiatria - questa è la verità - ristagna nel suo brodo di organicismo radicale. L'unica autentica preoccupazione è quella di estendere a tutti i pazienti psichiatrici gravi il trattamento farmacologico protratto, che è l'obbiettivo delle case farmaceutiche.

Come prova di questo riporto in appendice uno degli ultimi articoli pubblicati: una messa a fuoco del trattamento a lungo termine della schizofrenia. L'articolo è in inglese, ma, per agevolarne la lettura, ho evidenziato in grassetto le frasi più significative.

Il commento deve partire da un dato statistico. Negli Stati Uniti, nel 2002, i pazienti dai diciotto anni in poi affetti da SMI, erano 17,5 milioni, vale a dire l'8,3% della popolazione! Si tratta di una cifra enorme, che sembra incomprensibile. In tutti i trattati di psichiatria, infatti, è scritto che la schizofrenia colpisce l'1% della popolazione e i disturbi dell'umore l'1,5%. La spiegazione è semplice. Le percentuali dei trattati di psichiatria fanno riferimento ad una sola generazione. Nonostante le terapie farmacologiche, i pazienti affetti da SMI partecipano del fenomeno sociologico dell'aumento dell'età media di sopravvivenza. Un paziente che ammala a 20 anni, se viene intrappolato nella rete dei servizi psichiatrici, continua ad ingurgitare medicine a 70 anni. In due generazioni, però, i casi nuovi si aggiungono a quelli vecchi.

Un'utenza di 17,5 milioni di pazienti rappresenta un'attrazione irresistibile per le case farmaceutiche, nonché per gli psichiatri. Nessun branca della medicina offre un bacino lontanamente paragonabile a quello psichiatrico. Sfortunatamente, secondo i neopsichiatri, si tratta però di un'utenza potenziale: solo il 10% dei pazienti, infatti, ricevono attualmente le cure di cui hanno bisogno. Assoggettare 17,5 milioni di pazienti ad una terapia farmacologica protratta vita natural durante, calcolando per ciascuno una spesa quotidiana di 5 dollari (tra neurolettici e stabilizzatori dell'umore, che ormai sono costantemente associati), significherebbe un budget annuo di oltre 31 miliardi di dollari, vale a dire all'incirca 60000 miliardi di vecchie lire! Se lo stesso modello venisse poi esteso a tutto il mondo, in nome della globalizzazione, i profitti raggiungerebbero livelli incalcolabili.

Per arrivare a conseguire questo risultato, i problemi però sono due: primo, la tendenza di gran parte dei pazienti a rifiutare i trattamenti farmacologici prolungati; secondo, la renitenza dello Stato e della comunità a investire una quota così rilevante di risorse a fini umanitari ma improduttivi. Come scalzare entrambe queste resistenze?

Qui entrano in gioco i neopsichiatri, con le loro "ricerche" prezzolate, di cui l'articolo in questione è un esempio.

Per quanto riguarda la prima resistenza, si tratta di procedere verso una "compliance" universale, vale a dire verso un consenso pienamente partecipato al trattamento farmacologico. I pazienti hanno diverse ragioni per rifiutare i farmaci: alcuni non credono di essere malati, altri non pensano di potere vivere meglio con gli psicofarmaci, altri, infine, hanno sperimentato troppi effetti collaterali con gli antipsicotici tradizionali usati in passato. Si tratta di convincerli che la loro malattia è una malattia come le altre, nonostante la persistenza dei giudizi sociali che su essa incombono; che la possibilità di stare meglio, esclusa la guarigione, esiste; e, infine, che i nuovi antipsicotici sono infinitamente più efficaci di quelli tradizionali e non producono praticamente disturbi collaterali.

Quest'opera di persuasione e di culturalizzazione è affidata ai neopsichiatri. Il suo successo ovviamente è remunerativo su due fronti: i profitti legati alla pratica professionale privata e il denaro elargito (sotto banco) dalle case farmaceutiche. L'umanitarismo della crociata contro il male e il profitto si coniugano a questo livello come se fossero la stessa cosa.

La seconda resistenza è ancora più ostica. Il problema, da questo punto di vista, è il costo esorbitante dei nuovi farmaci, che costano in media tremila vecchie lire a compressa. Data la popolazione dei pazienti in questione, occorre rivolgersi allo Stato perché le Assicurazioni rifiutano di sobbarcarsi la spesa per le cure psichiatriche. Come convincere dunque la comunità ad un salasso improduttivo delle risorse pubbliche a favore delle multinazionali dei farmaci? E' semplice. Basta dimostrare che l'investimento è produttivo. Migliorando nettamente la qualità della vita dei malati, gli psicofarmaci - secondo le valutazioni dei neopsichiatri - riducono il costo globale della cura. In un numero consistente di casi, addirittura, essi consentono ai pazienti di reintegrarsi nel mondo del lavoro, e di partecipare, dunque, al sacrificio economico collettivo producendo un reddito e pagando le tasse.

Certo, non ci si può affidare solo agli psicofarmaci, che comunque rappresentano il fondamento del trattamento. L'umanitarismo dei neopsichiatrici giunge fino al punto di tradursi in un progetto di presa in carica totale della persona malata. Tale presa in carico avviene attraverso la riabilitazione: case-famiglia, comunità e laboratori protetti, risocializzazione, ecc. A tale fine, occorre un ulteriore dispendio di denaro pubblico. Ma, secondo i neopsichiatri, il gioco vale la candela. Se la qualità della vita dei pazienti migliora, essi sono in grado di vivere con la malattia, evitano le recidive e possono contribuire in qualche modo al buon andamento della società.

La cura farmacologica e la riabilitazione sono i due capisaldi del trattamento a lungo termine della schizofrenia. La conclusione dell'articolo è stereotipato. Le cose per ora stanno così, ma i futuri progressi della psichiatria permetteranno di sicuro di migliorarle.

2.

Che cosa c'è che non va in un progetto che sembra sostanzialmente pragmatico? Che cosa giustifica il fatto che, ogniqualvolta leggo cose del genere, mi si rivoltano le viscere? Non sarò ancora affetto dal morbo antipsichiatrico? Penso di no. Non ho dubbi, come risulta chiaro da tutti gli scritti, che la schizofrenia e la psicosi maniaco-depressiva siano forme d'esperienza psicopatologica che richiedono una cura.

Il problema è che la neopsichiatria è iatrogenetica. Formulando diagnosi precoci e senza scampo, riconducendosi al presupposto che i disturbi psichiatrici gravi sono espressione di una malattia biologica di origine genetica, ignorando la storia sociale, familiare, personale e interiore dei pazienti, e instaurando trattamenti psicofarmacologici ad alte dosi, essa crea la cronicità che poi intende curare.

L'ho detto tante volte che mi dispiace ripeterlo. La schizofrenia, intesa come condizione psicopatologica irreversibile, non esiste come malattia d'esordio, bensì come esito a lungo termine di una crisi le cui manifestazioni psicotiche, quali che siano (comprese le allucinazioni e i deliri), possono essere sempre comprese in termini psicodinamici, tenendo conto della storia familiare, personale e interiore del soggetto. Se questa comprensibilità viene messa tra parentesi o negata, e il paziente viene sottoposto solo a cure farmacologiche, egli non ha alcuna possibilità di prendere coscienza dei conflitti che alberga. Essendo questi dinamici, continuano a funzionare a livello inconscio, anche se i farmaci (e non avviene neppure sempre) assicurano il controllo dei sintomi o ne causano la regressione. Lo scollamento tra la coscienza e l'inconscio produce infine, dopo anni, le recidive e la disgregazione della persoanlità.

Ma cosa può importare questo ai neopsichiatri. Una diagnosi di schizofrenia formulata per un ragazzo di 18 anni significa, tra ricoveri, visite e cure un budget di almeno 500 milioni di vecchie lire nel corso di una vita. Certo, non è detto che il paziente e la famiglia si rivolgano sempre allo stesso psichiatra. Se questi però perde un paziente che ha avviato verso la cronicizzazione, ne acquisisce un altro che è stato "marchiato" da un collega.

C'è qualcosa di disgustoso in tutto ciò. Da questo circolo vizioso speculativo, si potrà uscire però solo quando i pazienti e le famiglie prenderanno coscienza del "giuoco" (piuttosto sporco) a cui sono sottoposti. Per cambiare la neopsichiatria, alla quale aderiscono ormai il 90% degli psichiatri (alcuni purtroppo in buona fede, cioè per ignoranza), si può sperare solo in uno schock esogeno.

 Outcome measurements and evidence-based practice for persons with serious and persistent mental illness have undergone a paradigm shift in recent years. As the psychiatric world studies and embraces the psychiatric rehabilitation world and vice-versa, we begin to understand as a society that a diagnosis of schizophrenia or serious bipolar disorder does not have to be a commendation to an unfulfilling and unproductive life. New clinical technologies such as the newer generation of antipsychotic medications have made recovery or reintegration possible for this group of persons. Reintegration therefore begins with state-of-the-art psychiatric treatment.

For years, the treatment of schizophrenia and related disorders focused only on positive symptom relief (eg, delusions, hallucinations, thought disorder, and aberrant behaviors). Negative symptoms, such as affective flattening, alogia, apathy, avolition, and social withdrawal, as well as cognitive impairments, were identified, but the older generation of antipsychotic medications not only did not help, but often exacerbated these symptoms. Numerous studies have shown marked improvement from the newer-generation agents, particularly in the areas of cognition and negative symptoms.[1] These improvements are made possible by a gentler side effect profile, due to a significant drop in extrapyramidal symptoms (EPS). Fewer side effects result in better compliance, which in turn allows the patient to stay in treatment for longer periods of time and focus on recovery.

In 2002, there were an estimated 17.5 million adults aged 18 years or older with serious mental illness (SMI). This represents 8.3% of all adults. According to the National Survey on Drug Use and Health, the rates of SMI were highest for individuals aged 18 to 25 years (13.2%) and lowest for those aged 50 years or older (4.9%). The percentage of females vs males was 10.5% vs 6.0%, and, in general, rates were higher for women than men in all age groups.[2]

The rate of SMI was highest among individuals reporting 2 or more races (13.6%) and American Indian/Alaska Natives (12.5%) and lowest among Native Hawaiian or other Pacific Islanders (5.4%) (Figure 2). Those who did not complete high school had the highest rates of SMI (9.6%), while individuals who completed college had the lowest rate (5.8%).

Rates of SMI in 2002 were highest among unemployed persons (14.2%) and lowest among persons employed full time (7.3%). The rate among persons employed part time was 9.7%. However, among persons aged 26 to 49 years, the highest rate of SMI was among persons not in the labor force (15.5%).

SMI was not strongly correlated with alcohol use. The rate of past year alcohol use among adults with SMI was almost the same as the rate among adults without SMI (71.1% vs 69.7%, respectively, in 2002). However, SMI was correlated with binge alcohol use, defined as drinking 5 or more drinks on the same occasion on at least 1 day in the past 30 days. Among adults with SMI, 28.8% were binge drinkers, while 23.9% of adults without SMI were binge drinkers. There was also a high correlation of SMI with substance dependence or abuse. Among adults with SMI in 2002, a total of 23.2% were dependent on or abused alcohol or illicit drugs, while the rate for adults without SMI was only 8.2%. Of note, an estimated 4.0 million adults met the criteria for both SMI and substance dependence or abuse in the past year. Of these, approximately 0.8 million with SMI were dependent on or abused both alcohol and illicit drugs, 0.9 million with SMI were dependent on or abused an illicit drug only, and 2.4 million with SMI were dependent on or abused alcohol only.

Antipsychotics

A number of recent studies have evaluated the impact of pharmacologic and nonpharmacologic treatments, quality of life, and costs in working with patients with SMI. A study by Mauskopf and colleagues[3] reviewed published studies to understand the effect of switching from typical to atypical antipsychotic medications over a 3-year period in individuals diagnosed with schizophrenia. The researchers evaluated the domains of individual, family, and societal outcomes. They measured what they termed as "symptom days" or days with symptoms of schizophrenia, "EPS days" or days with EPS, as well as suicide rates, employment rates, and cost analysis. They found that after switching to atypical drugs, symptom days decreased by up to 33%, EPS days decreased by up to 50%, suicide rates fell, and employment rates increased. They concluded that switching to atypical drugs would likely reduce total medical care costs and decrease other disease burdens for people with schizophrenia, their families, and society.

A study underway to evaluate the effectiveness of treatments in 1500 individuals with schizophrenia, known as the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, will provide extensive information about antipsychotic drug effectiveness over at least 18 months and determine community-based treatments.[4]

There are a number of randomized trials that show that a specific form of vocational rehabilitation, known as supported employment, is effective. In a review, Bond and colleagues[5] described that a number of obstacles must be overcome in order to implement evidence-based practices. These include state and federal bureaucracy, funding, access to services, standardization of services, and staff training. Nevertheless, the field of mental health services is slowly committing itself to providing research-based services as the foundation of care. In general, supported employment programs are most successful in agencies that make a commitment to competitive employment as the outcome.

Treatment for schizophrenia and related disorders cannot be based on pharmacologic interventions alone; there is a vast array of "wrap-around services" needed to reach a successful outcome. By wrap-around services, we mean that an important element in caring for individuals with SMI is taking care of the entire person. Part of the "magic" in making such a goal work is to gain an individual's respect and confidence in the care that we are providing. Getting people to cooperate and participate in their care is the true meaning of the concept of compliance. This means much more than merely taking medications -- it means being an active participant in the treatment process. The elements of treatment for SMI patients need to include medications, supervised or independent housing, rehabilitation and work environment, socialization, and medical care. Psychiatric rehabilitation, whatever the modality, is as important a tool as the medication. We then add the opportunity for independent housing, something meaningful to do, and a network of friends and family, and we now have the key ingredients for success.

Unfortunately, less than 10% of persons with serious and persistent mental illness receive any form of psychiatric rehabilitation. In fact, less than half of adults with SMI received treatment or counseling for their illness in 2001.[2] There are numerous reasons for this unfortunate statistic, but stigma and prejudice against persons with schizophrenia and related disorders are at the top of the list. This is compounded by the low level of expectation that society has set for persons with serious and persistent mental illness. One of the most frightening aspects of mental illness for the individual, the family, and the general public is the sense that behaviors and symptoms cannot be adequately controlled. New treatments with fewer side effects and greater effectiveness are increasing our ability to ameliorate disturbing symptoms. As knowledge concerning the effectiveness of these treatments becomes more widely disseminated, there will be a greater acceptance and willingness to view psychiatric symptoms as both explainable and treatable.

For too long, the notion of recovery or reintegration for persons with schizophrenia and serious and persistent mental illness was an unobtainable goal. During the end of the last century and in particular in this new one, work, independent living, and relationships for persons with schizophrenia and its related disorders have become more prominent. In fact, in a few studies, competitive employment for individuals with these disorders became the principle outcome of treatment.

Several studies in the last few years evaluated the impact of rehabilitation programs on success in obtaining competitive employment. A study from Fountain House in New York City concluded that patients who received vocational services were significantly more likely to become employed and hold a job. The researchers suggested that their findings demonstrate the importance of having vocational programs continuously available to all people with SMI, and the need for integrating these services into routine mental healthcare.[6] Another study by Jones and colleagues[7] dismissed the notion that clinical characteristics were related to use of rehabilitation services and success in obtaining competitive work. They suggested an individualized participant-driven model of services and that barriers to community employment should be removed.

The dopamine hypothesis of schizophrenia led to a major emphasis on dopamine antagonists. The older generation of antipsychotic medications, in fact, worked predominately as dopamine antagonists. Unfortunately, dopamine blockade, although it improves positive symptoms, also affects other pathways, causing Parkinson-like symptoms that would manifest with EPS and, less frequently, a blunting of the senses. This blunting of the senses as reported by patients often leads to discontinuing treatment. This correlation has not received the attention it deserves. There has been an acceptance of this side effect because we did not have any alternatives. With the advent of newer antipsychotic agents, such as clozapine, olanzapine, and quetiapine, D2 blockade is either absent or minimal. Therefore, both EPS and the blunted feelings are not present, and patient compliance is greatly improved. With risperidone, however, at higher doses (4-7 mg), D2 blockade will contribute to EPS, resulting in greater noncompliance.[8]

Quality-of-life issues as outcome measures for persons with serious and persistent mental illness have not been elucidated as well as they should be. In part, expectations have been kept low, and key measures of quality of life are often overlooked for this group. Results from a preliminary study by Gee and colleagues[9] suggest 10 preliminary domains identified by participants as being important issues to deal with to accomplish a more positive quality of life in schizophrenia. These include: (1) barriers placed on relationships; (2) reduced control of behaviors and actions; (3) loss of opportunity to fulfill occupational roles; (4) financial constraints on activities and plans; (5) subjective experience of psychotic symptoms; (6) side effects and attitudes to medication; (7) psychological responses to living with schizophrenia; (8) labeling and attitudes from others; (9) concerns for the future; and (10) positive outcomes from experiences.

Relapse and rehospitalization rates remain the most looked at measurements for persons with serious and persistent mental illness. Noncompliance is the most important factor for relapse. Cognitive impairments have been also cited as an important factor for this noncompliance. It is often difficult to assess whether the cognitive impairments are due to the nature of the illness or secondary to the older pharmacologic interventions along with the antiparkinsonian agents that often contribute to this diminished compliance. As far as we can tell, this is predominately due to a combination of older-generation medications and the anticholinergic actions of the antiparkinsonian agents

With cognitive improvements comes the capacity for a person with schizophrenia or related disorders to take those first steps toward reintegration. The ability to learn new things is fundamental for any form of recovery. Deficits of attention, memory, motor function, and executive functions are common and more strongly correlated with outcome than any other aspect of schizophrenia.[10] Based on anecdotal reports from staff in the vocational rehabilitation programs, there are many people with flagrant hallucinations able to put in a full day's work. Once again, with the newer agents such as clozapine, olanzapine, quetiapine, risperidone, and aripiprazole, we see enhancement of neurocognitive functioning.[11]

In a study by Bark and associates,[12] the researchers concluded that there can be a positive impact on the symptoms of schizophrenia using cognitive remediation. They also found, using the Positive and Negative Syndrome Scale, that psychiatric symptom profile is not predictive and, in fact, is somewhat independent from the degree to which cognitive symptoms respond to cognitive remediation. In studies by Harvey and colleagues[13] and Gur and colleagues,[14] patients treated with olanzapine or risperidone clearly showed improvement in abstraction, spatial memory, and other cognitive domains as well as showing improvement in negative symptoms. New areas of investigation are suggesting that augumentation of atypical antipsychotics with an acetylcholinesterase inhibitor might improve functionality of networks necessary in working memory and internal concept generation.[15]

We use the word "rehabilitation" often, but forget that for many persons with serious and persistent mental illness who become ill in the prime of their learning phase, acquisition of the skills and education needed to be an active participant in our society may have never occurred. We suggest that there is a more appropriate concept -- habilitation -- a more apt description that better applies to many of our patients. In cases such as these, where the illness has been so severe, it is even more important to provide cognitive enhancement for improving overall functioning.

Compliance or adherence to treatment is the foundation for success. Years of side effects, including EPS, sexual dysfunction, cognitive impairments, and an overall blunting of the senses, often make it difficult for persons with mental illness to believe in the medication and continue to take that pill every day. Shifting the focus of treatment from symptom relief to obtaining life goals is, in theory, a good beginning, but it is not always enough. Early on in the treatment, guaranteeing the individual takes the medication has to be a primary goal. In the past, different formulations have been available to help with these problems. Liquid (concentrated), rapid intramuscular, and long-acting depot injections were particularly helpful for the delivery of medication with the older generation of antipsychotic medications. Although there were some improvements with compliance, at the heart of the problem remained the side effect profile inherent to this older generation of medications.

Studies have demonstrated increased compliance with the atypical agents, even when compared with intramuscular long-acting decanoate preparations of typical agents. Approximately 50% of patients are noncompliant with traditional medications within 1 year after discharge.[16] Thirty percent to 60% of patients treated with typical neuroleptics do not make their initial outpatient visit after hospital discharge.[17]

In a review of injectable medications by Altamura and colleagues,[18] intramuscular formulations of novel antipsychotics (olanzapine and ziprasidone) appeared to possess a better tolerability profile than the older-generation antipsychotics while evidencing an equivalent efficacy to the parenteral typical agents. They pointed out, however, that parenteral or depot formulations of the atypical antipsychotics are not yet widely available.

With the advent of the new generation of antipsychotic medications, new formulations have taken shape. Risperidone has a concentrated formulation that helps ensure that patients receive the needed dosage, but another newer formulation that we have seen with immediate positive effects is an orally disintegrating pill, olanzapine Zydis*.[19] In our clinical practice, where supportive housing is the first step for reintegration, medication supervision or support is a key component and an issue that often comes to the forefront of treatment. In one supportive residence for 57 persons with a long and difficult history of mental illness, 30 patients with documented history of noncompliance have responded well to the use of this oral disintegrating formulation. Staff concerns diminish, because they are able to observe in an easier fashion that the medication is actually taken. What we have also seen is that the patient expresses a greater willingness to take medication as per the novelty of this new formulation. This, in turn, leads to a better relationship between the residence workers and the patient. We have also found that the orally disintegrating formulation has similar efficacy and side-effect profile to pill formulation of olanzapine, with equal ease of use. Risperdal M-Tab is a also a rapidly disintegrating tablet that is bioequivalent to the traditional formulation and offers similar convenience to staff and patients.

For another group of persons with serious and persistent mental illness -- young adults living with their families -- medication taking becomes a kind of ritual where the person taking the medication will take this new formulation after dinner in a show of mutual help through self help. What we have found, therefore, is a greater willingness to take medications, in part due to the new formulation, but more importantly because of the greater efficacy provided by these medications.

Another important piece of the reintegration puzzle is the concept of total wellness. Over the last 10 years, we have been looking at the problem of medical comorbidity in our population. For years, psychiatry has struggled with EPS and tardive dyskinesia. Often, we did not have the opportunity to examine the greater medical comorbidities that can be present in persons with serious and persistent mental illness. With greater compliance comes greater stability and longer periods of time in treatment. That allows for a coordination of care that can encourage patients to get annual physicals, blood work, and electrocardiograms to document and monitor any concomitant medical problems. Partnering with primary care physicians can have a positive impact on compliance and general health.[20,21]

The process of reintegration for individuals with schizophrenia and other SMI is a complex equation. Using all of the tools that psychiatry and medicine have to offer, we need to construct a model for this population to become as much a part of the mainstream of society as possible. This must be a multifaceted approach with appropriate medications that can minimize symptoms and increase compliance and "habilitation," which allows the person with SMI to make choices and function and work as independently as possible while having the structure of state-of-the-art treatment and support. Finally, we need to continue evidence-based research to document progress and offer a higher standard of care.

References

1. Weickert TW, Goldberg TE, Marenco S, Bigelow LB, Egan MF, Weinberger DR. Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds. Neuropsychopharmacology. 2003;28:1491-1500. Abstract

2. NSDUH Survey 2002. United States Department of Health and Human Services, Office of Substance Abuse and Mental Health Services Administration. 2002. Available at: http://www.samhsa.gov/oas/NHSDA/2k2NSDUH/Results/2k2results.htm#chap9. Accessed September 19, 2003.

3. Mauskopf J, Muroff M, Gibson PJ, Grainger DL. Estimating the costs and benefits of new drug therapies: atypical antipsychotic drugs for schizophrenia. Schizophr Bull. 2002;28:619-635. Abstract

4. Swartz MS, Perkins DO, Stroup TS, McEvoy JP, Nieri JM, Haak DC. Assessing clinical and functional outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Schizophr Bull. 2003;29:33-43. Abstract

5. Bond GR, Becker DR, Drake RE, et al. Implementing supported employment as an evidence-based practice. Psychiatr Serv. 2001;52:313-322. Abstract

6. Macias C, DeCarlo LT, Wang Q, Frey J, Barreira P. Work interest as a predictor of competitive employment: policy implications for psychiatric rehabilitation. Adm Policy Ment Health. 2001;28:279-297. Abstract

7. Jones CJ, Perkins DV, Born DL. Predicting work outcomes and service use in supported employment services for persons with psychiatric disabilities. Psychiatr Rehabil J. 2001;25:53-59. Abstract

8. Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S. The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci. 1995;57:PL103-107. Abstract

9. Gee L, Pearce E, Jackson M. Quality of life in schizophrenia: a grounded theory approach. Health Qual Life Outcomes. 2003;1:31.

10. Penades R, Boget T, Catalan R, Bernardo M, Gasto C, Salamero M. Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia. Schizophr Res. 2003;63:219-227. Abstract

11. Sharma T, Antonova L. Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am. 2003;26:25-40. Abstract

12. Bark N, Revheim N, Huq F, Khalderov V, Ganz ZW, Medalia A. The impact of cognitive remediation on psychiatric symptoms of schizophrenia. Schizophr Res. 2003;63:229-235. Abstract

13. Harvey PD, Napolitano JA, Mao L, Gharabawi G. Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder. Int J Geriatr Psychiatry. 2003;18:820-829. Abstract

14. Gur RE, Kohler C, Ragland JD, et al. Neurocognitive performance and clinical changes in olanzapine-treated patients with schizophrenia. Neuropsychopharmacology. 2003 Aug 6; Epub ahead of print.

15. Nahas Z, George MS, Horner MD, et al. Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study. Neurocase. 2003;9:274-282. Abstract

16. Weiden PJ, Olfson M. Cost of relapse in schizophrenia. Schizophr Bull. 1995;21:419-429. Abstract

17. Aquila R, Weiden PJ, Emanuel M. Compliance and the rehabilitation alliance. J Clin Psychiatry. 1999;60(suppl 19):23-27; discussion 28-29.

18. Altamura AC, Sassella F, Santini A, Montresor C, Fumagalli S, Mundo E. Intramuscular preparations of antipsychotics: uses and relevance in clinical practice. Drugs. 2003;63:493-512. Review.

19. Kinon BJ, Hill AL, Liu H, Kollack-Walker S. Olanzapine orally disintegrating tablets in the treatment of acutely ill non-compliant patients with schizophrenia. Int J Neuropsychopharmacol. 2003;6:97-102. Abstract

20. Meadows GN. Overcoming barriers to reintegration of patients with schizophrenia: developing a best-practice model for discharge from specialist care. Med J Aust. 2003;178(suppl):S53-56. Abstract

21. Carr VJ, Johnston PJ, Lewin TJ, Rajkumar S, Carter GL, Issakidis C. Patterns of service use among persons with schizophrenia and other psychotic disorders [Erratum in: Psychiatr Serv. 2003;54:339.]. Psychiatr Serv. 2003;54:226-235. Abstract