2014 afonso treatment

8/10/2019 2014 Afonso Treatment

1/7

Treatment adherence and quality of sleep inschizophrenia outpatients

Pedro Aonso1, Soa Brissos1,2, Fernando Caas3, Julio Bobes4& Ivan Bernardo-Fernandez5

1Lisbons Psychiatric Hospitalar Center, Lisbon, Portugal, 2Janssen Pharmaceutical, Queluz de Baixo,Portugal, 3Departamento de Psiquiatra, Universidad de Oviedo, Centro de Investigacin Biomdica enRed de Salud Mental, CIBERSAM, Oviedo-Asturias, Espaa, 4Hospital Dr. R. Lafora. Madrid. Spain, and5Janssen Pharmaceutical, Madrid, Spain

AbstractObjective.Patients with schizophrenia (SZ) ofen present sleep complaints, and patients with sleep dis-turbances are at a greater risk or symptom worsening afer antipsychotic discontinuation. Long-termadherence to antipsychotic treatment remains a challenge or clinicians, and the relationship betweenquality o sleep and treatment adherence in SZ outpatients has been poorly studied. Methods. In thiscross-sectional, non-interventional study, 811 adult outpatients with a diagnosis o SZ were divided into twogroups according to the presence (or absence) o sleep disturbances, and assessed using measures osymptom severity, quality and patterns o sleep, adherence/compliance to treatment, and amily supportdegree. Results.Patients with sleep disturbances were signicantly more symptomatic (p0.0001), andscored signicantly higher on the Pittsburgh Sleep Quality Index (PSQI) as compared with patients withoutsleep disturbances (p0.0001). More compliant patients showed less sleep disturbances (p0.0001);moreover, patients with worse compliance to pharmacological treatment showed signicantly higherscores on the PSQI (p0.0001). Regarding amily support degree, patients with sleep disorders presenteda lower amily support (p0.0236), and patients with worse treatment adherence had worse amily sup-port (p0.0001). Conclusions.Our ndings show that SZ outpatients reporting sleep disturbances showgreater symptom severity, and worse adherence/compliance to treatment, as well as a lower amily support.

Key words: Compliance, positive and negative symptoms, schizophrenia, sleep quality, treatmentadherence

Abbreviations: BPRS, Brie Psychiatric Rating Scale; DSM-IV, Diagnostic and Statistic Manual 4thedition; PSQI, Pittsburgh Sleep Quality Index; REM, Rapid eye movement; RLS, Restless leg syndrome;SWS, Slow wave sleep; S, otal sleep time

(Received 3 October 2012; accepted 9 September 2013)

Despite the advances over the last decades, treatmentadherence remains a challenge or health care proession-als who treat SZ patients, some clinicians regarding partialadherence as inevitable (Masand et al. 2009). Patients whoail to take their medication as prescribed are at a greatlyincreased risk o not attaining remission (San et al. 2007)and o having a relapse (Masand et al. 2009; Weiden et al.2004; Robinson et al. 1999; Masand and Narasimhan 2006),even in the early stages (Emsley et al. 2012), with devastatingconsequences on the course o the disorder.

Nonadherence to medication is widely agreed to be one othe most important actors limiting the success o treatment.Additionally, it may constitute a determinant actor affectingthe magnitude o health care costs and the cost effectivenesso antipsychotic medications, since high adherence levels cangreatly reduce the risk o relapse and subsequent hospitaliza-tion costs (National Collaborating Centre or Mental Healthcommissioned by the National Institute or Health ( ClinicalExcellence 2010).

SZ patients with sleep disturbances are at a greater riskor symptom worsening afer antipsychotic discontinuation(Chemerinski et al. 2002). Furthermore, ollowing antipsy-chotic discontinuation, insomnia is one o the prodromal

Int J Psychiatry Clin Pract2013; Early Online: 17. 2013 Inorma HealthcareISSN 1365-1501 print/ISSN 1471-1788 online. DOI: 10.3109/13651501.2013.845219

SHOR REPOR

informahealthcare.com/ijpcp

Introduction

Patients with schizophrenia (SZ) ofen sleep worse thanhealthy individuals (Wulff et al. 2012).

Several polysomnographic abnormalities have beenidentied: sleep continuity disturbance, poor sleep effi ciency,slow-wave sleep decits, and short rapid eye movement(REM) sleep latencies (Wulff et al. 2012; Keshavan et al.1998; andon et al. 1992; Wirz-Justice et al. 2001; Benson2008). Studies with actigraphy have also revealed that thereare disturbed sleepwake cycles in a substantial number opatients (Wulff et al. 2012; Bromundt et al. 2011).

Most atypical antipsychotics are associated with improve-ments in sleep quality parameters, related to an increase inS and/or sleep effi ciency (DeMartinis and Winokur 2007;Cohrs 2008). Nevertheless, even clinically stable, medicatedpatients maintain sleep disturbances; these can be suffi cientlysevere to warrant independent clinical attention, and cannegatively affect patients quality o lie (Aonso et al. 2011;Hostetter et al. 2005; Ritsner et al. 2004).

Correspondence: Pedro Aonso, Lisbons Psychiatric Hospitalar Center,Av. do Brasil n. 53, 1749-002 Lisbon, Portugal. el: 351 217917000.Fax:351 217 952 989. E-mail: [email protected]


2/7

2 P. Afonso et al. Int J Psychiatry Clin Pract 2013;Early Online:17

symptoms associated with psychotic relapse or exacerbation(Chemerinski et al. 2002; Dencker et al. 1986). Neverthe-less, the relationship between quality o sleep and treatmentadherence in SZ outpatients has been under-studied.

We aimed to assess the differences between treatmentadherence/compliance, symptom severity, amily support,

and sleep quality perceived by SZ outpatients with and with-out sel-reported sleep disturbances. We hypothesized thatworse treatment adherence/compliance would be associatedwith greater symptom severity, worse quality o sleep, andworse amily support.

Material and methods

Study designIn this multicenter, Iberic, cross-sectional, non-interventionalstudy, outpatients with a diagnosis o SZ aged 18 years orolder were screened or the presence o sleep disturbances.1

ParticipantsFrom a total o 1492 screened patients, 811 patients wererecruited rom psychiatric departments rom Novem-ber 2010 to July 2011 (709 in Spain and 102 in Portugal).Patients were asked to subjectively report whether they hadsleep disturbances or not; 401 patients considered them-selves to have sleep disorders, while 410 did not. Inclusioncriteria were as ollows: outpatients with a diagnosis o SZaccording to DSM-IV criteria (American Psychiatric Asso-ciation 2000), ascertained rom interview with their psychi-atrist and medical chart review, aged 18 years or older, andhaving been on a stable dose o antipsychotic or at least 6

months prior to interview. Patients with any type o severesleep disturbances related to disorders other than SZ (e.g.nightmares, nocturnal ears, and restless leg syndrome)were excluded. Schizoaffective disorder, organic impair-ment, or cognitive decits that could inuence patients

sel-report were also considered exclusion criteria. Patientswere excluded mainly due to unstable antipsychotic treat-ment, non-consent, lack o cognitive ability, or other sleepdisorders.

Patients were mainly prescribed atypical antipsychotics:risperidone (37%), olanzapine (21%), paliperidone (20%),

quetiapine (13%), aripiprazol (12%), clozapine (11%), halo-peridol (9%), amisulpride (6%), levomepromazine (5%),zuclopentixol (5%), uenazine (4%), ziprasidone (4%),and others (4%). Tere were no statistically signicant di-erences between patients with sleep disorders as comparedto patients without sleep disorders regarding type o antip-sychotic treatment (able I); however, patients with sleepdisorders were prescribed signicantly more anxiolytics andhypnotics (able I).

Te investigators were aware o the patients diagnosisand overall clinical status.

Te local Ethics committees approved the study, and allparticipants provided written inormed consent.

Assessment instrumentsSymptom severity was evaluated with the Brie PsychiatricRating Scale (BPRS) (Overall and Gorham 1988).

Te quality and patterns o sleep were measured with thePittsburgh Sleep Quality Index (PSQI) (Buisse et al. 1989).Tis sel-report questionnaire rates sleep quality and pat-terns during the previous month, and evaluates seven com-ponents o sleep: subjective quality, latency, duration, usualeffi ciency, sleep disturbances, medication use, and daytimedysunction. Te total PSQI score ranges rom 021, calcu-lated as the sum o its seven component scores (each ranging

rom 03), with total scores

5 indicating good sleep qualityand higher scores meaning worse sleep quality.Adherence/compliance to treatment was rated as ollows:

1) complete adherence, 2) good adherence, 3) regular adher-ence, and 4) bad adherence.

Caregiver support degree was rated by the investigator as1) very high, 2) high, 3) medium, 4) low, and 5) null.

Statistical analysisWe compared sociodemographic and clinical variables opatients reporting sleep disturbances versus a control groupo patients without sleep disturbances using Chi2 test orqualitative variables. As the quantitative variables comply

1In the Spanish version o the study, there was a time-rame o 1 weekwhen six patients were included in the case and control study (threepatients reporting sleep disturbances and three patients denying sleepdisturbances). In Portugal, investigators included 10 patients in thestudy: ve with sleep disorders and ve without. In case no patientswere recruited or the period o 1 week, the investigator was allowedto continue recuitment or the ollowing weeks.

able I. Medication prescribed to patients with and without sleep disorders.

reatment until visitday

Patients withoutsleep disturbances

(N410)

Patients with sleepdisturbances

(N401)All patients(N811)

N (%) N (%) N (%) Chi2 pvalue

Atypical antipsychotics 384 (93.7) 372 (92.8) 756 (93.2) 0.2543 0.6141ypical antipsychotics 88 (21.5) 88 (22.0) 176 (21.7) 0.0277 0.8678Antidepressants 101 (24.6) 122 (30.4) 223 (27.5) 3.4087 0.0649Anxiolytics 133 (32.4) 162 (40.4) 295 (36.4) 5.5501 0.0185Mood stabilizers 34 (8.3) 46 (11.5) 80 (9.9) 2.3037 0.1291Anticholinergics 55 (13.4) 65 (16.2) 120 (14.8) 1.2560 0.2624Hypnotics/sedatives 51 (12.4) 107 (26.7) 158 (19.5) 26.2216 0.0001Others 15 (3.7) 26 (6.5) 41 (5.1) 3.3712 0.0663


3/7

DOI: 10.3109/13651501.2013.845219 Treatment adherence and quality of sleep 3

with the assumption o normality and homoscedasticity, thecomparison between groups was done by the parametricnon-paired Student-t test or F-Snedecor test. Te associa-tions between unctionality, sleep, and treatment adherencewere calculated using Pearsons correlation coeffi cient. Weused SAS 9.3 Copyright 20022010 by SAS Institute Inc.,Cary, NC, USA.

Results

Patients were predominantly male (67%), and the majoritywas not working (76%); their social, demographic, and clini-cal characteristics are presented in able II.

Although there were no statistically signicant differ-ences between the groups regarding antipsychotic treat-ment type (able I), patients with sleep disturbances hadhad signicantly more changes in treatment (Chi262.239,

p0.0001).he PSQI revealed that habitual bedtime was similar

or both patients groups (median o 22 h, Q121 h,Q323 h, or patients reporting sleep disturbances, andmedian o 22 h, Q12 h, Q3 23 h or patients with-

out sleep disturbances); however, patients without sleepdisturbances usually woke up later (median 8 h, Q18h, Q39 h 30 min) than patients reporting sleep distur-bances (median 8h30, Q17 h, Q310 h). Patients withsleep disturbances were signiicantly more symptomatic(able II), and scored signiicantly higher on all compo-nents o the PSQI (p0.0001), revealing worse qualityo sleep, as compared with patients without sleep distur-bances (able III).

Patients with worse adherence/compliance to phar-macological treatment presented more sleep disturbances(Chi24.0800, p0.0001), and signicantly higher scoreson the PSQI (p0.0001) (Figure 1).

Regarding caregiver support degree, patients withsleep disorders presented a lower support (Chi22.2636,

p0.0236).For all patients, treatment adherence/compliance was

signicantly correlated with sleep quality (r0.20191,p0.0001), indicating that patients with worse treatmentadherence/compliance have worse quality o sleep. More-over, caregiver support was also signicantly associated withtreatment adherence (r0.15616, p0.0001), indicatingthat patients with worse caregiver support may have worsetreatment adherence.

Discussion

As hypothesized, we ound that patients reporting sleep dis-turbances show greater symptom severity, worse quality o

able II. Sociodemographic and clinical characteristics.

Characteristics

Patients withoutsleep disturbances

(N410)

Patients with sleepdisturbances

(N401) Chi2 pvalue

Gender (men:women) 270:140 270:131 1.990 0.925Educational level

No educationPrimary educationSecondary educationUniversity education

30166147

67

24174148

55

1.939 0.585

Employment statusEmployedUnemployedRetiredSick leaveHousewieStudentOther

568384

134241712

548688

14115

98

5.600 0.469

Mean (SD) Mean (SD) t-Student pvalue

Age 42.7 (11.64) 42.4 (11.72) 0.36 0.716Age o diagnosis (years) 25.8 (8.67) 25.2 (7.90) 0.90 0.368Illness duration (years) 16.9 (10.64) 17.2 (11.13) 0.29 0.768BPRS total score 12.8 (8.27) 16.6 (9.43) 6.05 0.001

PSP scale total score 60.6 (16.89) 56.2 (17.60) 3.58 0.001

BPRS, Brie Psychiatric Rating Scale; PSP, Personal and Social Perormance; SD, standard deviation.

able III. Sleep quality reported by SZ patients with and without sleepdisorders.

Patientswithout sleepdisturbances

(N410)

Patients withsleep

disturbances(N401)

Characteristics Mean (SD) Mean (SD) t-Student pvalueSubjective sleep

quality0.8 (0.63) 1.8 (0.63) 23.68 0.001

Sleep latency 0.9 (0.84) 2.2 (0.99) 20.75 0.001Sleep duration 0.3 (0.62) 1.1 (1.00) 13.87 0.001Habitual sleep

effi ciency0.4 (0.84) 1.6 (1.25) 15.71 0.001

Sleep disturbances 0.9 (0.46) 1.2 (0.51) 8.62 0.001Use o sleep

medication0.7 (1.23) 2.2 (1.22) 16.95 0.001

Daytimedysunction

0.8 (0.79) 1.6 (0.87) 12.37 0.001

PSQI otal 4.8 (3.30) 11.6 (3.96) 26.72 0.001

PSQI, Pittsburgh Sleep Quality Index;SD, standard deviation.


4/7


et al. 1999; Mller et al. 2004). Furthermore, a signicantenhancement o SWS has been noted in SZ patients treatedwith risperidone (Yamashita et al. 2002). Paliperidone hasbeen shown to improve both subjective quality o sleepand daytime somnolence, and also sleep effi ciency, totalsleep time, and Stage 2 and stage REM minutes as wellas decreased sleep latency, waking, and Stage 1 minutes(Luthringer et al. 2007). Concerning quetiapine, ziprasi-

done, and aripiprazole, we are not aware o studies withthese antipsychotics on the quality o sleep o SZ patients.Despite that, quetiapine and ziprasidone improve sleepinduction and consolidation in healthy individuals (Cohrset al. 2005; Cohrs et al. 2004).

On the other hand, antipsychotic treatment can produceakathisia and restless legs syndrome (RLS) (Cohrs 2008). Teprevalence o RLS in antipsychotic-treated schizophrenicpatients has been reported to be more than twice that ohealthy controls (Kang et al. 2007). Clinicians should beaware or these side effects, since they can cause signicantsleep disruption.

However, to disentangle the effects o SZ itsel rom the

inuence o medication on sleep is diffi cult (Cohrs 2008),but although we did not stratiy the patients by type and/ordose o medication, it seems unlikely that treatment alonecould explain the differences ound between the groups.Nevertheless, treatment adherence, either by reducing

N 302 407 88 14

MEAN 7.14 8.42 10.15 11.29

SD 4.83 4.82 5.54 4.97

MIN. 0.00 0.00 0.00 3.00

MAX. 19.00 20.00 20.00 20.00

Q1 3.0 4.0 5.0 6.0

MEDIAN 6.00 8.00 10.00 12.00

Q3 11.0 13.0 15.0 15.0

Pharmacological treatment compliance level

PSQISCORE

Figure 1. Pittsburgh Sleep Quality Index global score versus compliance with pharmacological treatment. PSQI, Pittsburgh Sleep Quality Index;SD, standard deviation.

sleep, and worse treatment adherence/compliance, and mayhave worse caregiver/amily support.

We ound that patients with worse treatment adherence/compliance showed more sleep disturbances. One expla-nation could be the lower support degree. Family supportimproves long-term antipsychotic adherence (Glick et al.2011), which was strongly associated with a better sleepquality measured by PSQI.

Daytime somnolence is a common side effect o antipsy-chotic treatment, ranging rom 24% to 31% o SZ patients(Lieberman et al. 2005), and may contribute to noncompli-ance and a potentially poorer outcome. Somnolence can leadto daytime naps, and patients can develop sleep reversals andpolyphasic sleep patterns with a negative impact on night-time sleep.

Atypical antipsychotics tend to improve sleep inductionand/or sleep maintenance in SZ (Monti and Monti 2004),and most atypical antipsychotics cause an increase in totalsleep time (S) and/or sleep effi ciency (Cohrs 2008).Clozapine has been shown to increase the S, sleep effi -ciency, and Stage 2 sleep and decrease sleep latency and

wake time afer sleep onset (Cohrs 2008; Hinze-Selch et al.1997; Lee et al. 2001). Olanzapine demonstrates compa-rable inuence on sleep variables with an overall improve-ment in parameters o sleep effi ciency and an increaseo REM sleep and slow wave sleep (SWS) (Salin-Pascual


5/7


symptomatology, or by other unknown effects, mayimprove quality o sleep in SZ patients. Since the major-ity o patients are known to abandon treatment at somestage o the illness, and/or adhere only partially to theprescribed medication (Masand et al. 2009; Kane 2006),strategies to improve treatment adherence may also havea positive impact on patients sleep. Tis could, in turn,reect into better cognition, social unctioning, satisac-

tion with lie, and quality o lie (Aonso et al. 2011). Giventhe success in improving sleep through sleep hygiene edu-cation in various populations (Morin et al. 2006) it mightbenet patients with SZ as well.

Regarding symptomatology, insomnia has been asso-ciated with increased positive symptoms (Poulin et al.2003), and these, namely suspiciousness, hallucinations,and hyperactivity, are associated with more disruptedsleep/wake patterns and circadian activity rhythms in SZpatients (Aonso et al. 2011). On the other hand, patientswith negative syndrome present low motor activity lev-els (Walther et al. 2009), possibly acilitating sleep, whileimproved sleep itsel may reduce negative symptoms (Kato

et al. 1999).Our study has several limitations: the lack o objec-

tive evaluation o sleep (i.e. polisomnography or actigra-phy) allowed only or the study o patients perceptions.Te same applies to the evaluation o treatment adher-ence; it is well known that clinicians ofen overestimatetheir patients level o adherence (Masand et al. 2009),but unortunately there is still no recognized method toadequately determine patients compliance/adherence totreatment. Furthermore, the antipsychotic drugs can inu-ence, by the ubiquitous receptor blockade (e.g. serotonin,noradrenaline, dopamine, acetylcholine, and histamine),

the orchestration o wakeulness and sleep. For that rea-son, it appears diffi cult to relate the pharmacological prop-erties o antipsychotics to the effects they have on sleepin schizophrenic patients. Te inclusion o patients whowere taking benzodiazepines and other psychotropics mayhave biased the results. Stimulant (e.g. coffee, tea, etc.) andalcohol use were also not controlled or. Although sleepapnea was an exclusion criterion, we cannot guarantee thatsome o our sample may have undiagnosed sleep apnea,which may contribute to sleep diffi culties. Severe insomniahas been associated with signicantly higher bodymassindexes (Palmese et al. 2011), which we did not controlor. Moreover, we did not use a sleep diary to record bed

and wake-up times, neither a sel-assessment question-naire to evaluate circadian sleep rhythm (e.g.Morningness-Eveningness questionnaire). Tis would have allowed us toevaluate diary variations on wake-up and bedtimes, sincethe Pittsburgh scale reports the mean times or patientsin the previous month. For that reason our methodologydoes not support any reliable inormation to discuss circa-dian sleep rhythms in SZ.

Our patients presented elevated symptom levels, andthereore our results may not be applicable to patients inremission. Finally, our results rom an Iberic population maynot apply to other countries/cultures, and thereore need ur-ther replication. Strengths o the study include the sample

size, its naturalistic nature, representing real-lie patients,and its innovative results.

Conclusions

Our ndings show that patients reporting sleep distur-bances present greater symptom severity, worse quality osleep, worse adherence/compliance to treatment, and mayhave lower caregiver support. Tese disturbances may rein-

orce altered sleep patterns, cognitive decits, and socialengagement associated with SZ, with a negative impact onrehabilitation strategies. Besides pharmacological interven-tions, caregiver/amily support, sleep hygiene, and otherbehavioral treatments may also have benecial effects onthese patients.

Despite the established association between sleep qualityin SZ patients and psychopathology, quality o lie, cogni-tive unction, and personal and social unctionality, and nowtreatment adherence/compliance, this eld o research hasreceived little attention rom both investigators and clini-cians. We await with interest the development o these prom-ising lines o research, so that uture treatments also have apositive impact on these variables.

Key points

Patients with SZ ofen present sleep complaints, andpatients with sleep disturbances are at a greater riskor symptom worsening afer antipsychotic discon-tinuation.Patients reporting sleep disturbances present greatersymptom severity, worse adherence/compliance totreatment, as well as a lower amily support.Tese sleep disturbances may reinorce altered sleeppatterns, cognitive decits, and social engagementassociated with SZ, with a negative impact on reha-bilitation strategies.

Acknowledgements

Te authors thank the ollowing study investigators: Portugal:Antnio Bajouco, Gisela Borges, Pedro Carvalho, Elsa Lara,Luciano Marmelada, and Fernanda Rosa; and Spain: AlbertoFuentes, Alexandre Pons i Villanueva, Alonso Rodrguez,Alredo Cortell, Alredo Galindo, Ana Isabel Gonzlez,Andrs Gonzlez, Andrs Martn, Andrs Porcel, ngelRoyuela, Antonio Agera, Antonio Carrillo, Antonio Galbis,Antonio Martnez, Blanca Fernndez-Abascal, Carlos Jos

Pino, Carlos Riaza, Carmen Moreno, Carmen Perna, CsarAntn, Clara Pedrejn, Consuelo de Dios, Cristina Garca,Desiderio Mejas, Luis Goenechea, Ignacio Zarranz, PatriciaLlorens, Elena de las Heras, Elisabet Gorgues i Queralt,Elosa Gloria Romn, Enrique Daniel Vega, Esther Garca,Eva Fontela, Evaristo Nieto, Francisco Arnau Feir, Franciscode Vicente, Francisco del Ro, Francisco Gzquez, FranciscoJavier Fernndez, Guillermo Lahera, Guillermo Masana,Horacio Watman, Jaqueline Mayoral, Javier Alberca, JessEnrique Mesones, Jess Salomn, Joan Cadevall, JorgeDomingo Ribas, Jos Antonio Juan, Jos Carlos Rodrguez,Jos Carmona, Jos Luis Glvez, Jos Manuel Crespo, JosManuel Perea, Jos Mara Martnez, Jos Salazar, Juan Carlos


6/7


Garca, Juan Carlos Gimnez, Juan Carlos Gmez, JuanCarlos Lpez, Juan Carlos Ortigosa, Juan Jos Fernndez,Juan Jos Gea, Juan Pablo Vedia, Julia Fraga, Julia Garca-Albea, Ladislao Garca, Leonardo Moyano, Luis IgnacioRodrguez, Luis Mnguez, Luis Santa-Mara, Lydia Gayubo,Maria Carmen Garca Maha, Maria Eulalia Jan, MariaLourdes Fernndez, Maria Rosario Cejas, Manuel Soria,Mara Arnzazu Snchez, Mara Elena Caruezo, Mara Jos

Mrquez, Mara Peitas Ros, Merc Aubareda, MercedesGuzmn, Micaela Gonzlez-Quirs, Miguel Alonso Garca,Miguel Hernndez, Miguel Lliteras, Miguel Soler, OlgaSobrino, Pablo lvarez, Pedro A. Sopelana, Pedro Ecnarro,Pedro Vicente Canut, Raael Fernndez G-Andrade, RamnPlanet, Raquel Largo, Ral Vzquez-Noguerol, Rosa Cataln,Rosa Gonzlez, Rosa Villanueva, Salustiano Campos,Salvador Martnez, Salvador Ros, Santiago Navarro, SantiagoSnchez, Sara Gonzlez, Sara Sole, Saulo Prez Gil, Susanalvarez, Valero Prez, Vicente Berenguer, Vicente ordera,Victoria Carams, and Virgilio raid, Xavier Fluvi.

Statement of interestTis study was supported by Janssen. Te sponsor o thestudy had no role in the collection, analysis, interpretation oresults, or preparation o the manuscript.

Soa Brissos and Ivan Bernardo Fernandez are ull-timeemployees o Janssen Pharmaceutical in Portugal and Spainrespectively, as Medical Affairs Managers.

Pedro Aonso, Fernando Canas and Julio Bobes report noconicts o interest.

ReferencesAonso P, Brissos S, Figueira ML, Paiva . Schizophrenia patients with

predominantly positive symptoms have more disturbed sleep-wake

cycles measured by actigraphy. Psychiatry Res 2011;189:6266.American Psychiatric Association. Diagnostic and statistical manual

o mental disorders. Washington, DC, 4th ed. (DSM IV-R); 2000.Benson KL. Sleep in schizophrenia. Sleep Med Clin 2008;3:251260.Bromundt V, Kster M, Georgiev-Kill A, Opwis K, Wirz-Justice A,

Stoppe G, Cajochen C. Sleep-wake cycles and cognitive unctioningin schizophrenia. Br JPsychiatry 2011;198:269276.

Buisse DJ, Reynolds CF, Monk H, Berman SR, Kuper DJ. Tepittsburgh sleep quality index: a new instrument or psychiatricpractice and research. Psychiatry Res 1989;28:193213.

Chemerinski E, Ho B, Flaum M, Arndt S, Fleming F, Andreasen NC.Insomnia as a predictor or symptom worsening ollowingantipsychotic withdrawal in schizophrenia. Compr Psychiatry2002;43:393396.

Cohrs S, Meier A, Neumann AC, Jordan W, Rther E, Rodenbeck A.

Improved sleep continuity and increased slow wave sleep and REMlatency during ziprasidone treatment: a randomized, controlled,crossover trial o 12 healthy male subjects. J Clin Psychiatry2005;66:989996.

Cohrs S, Rodenbeck A, Guan Z, Pohlmann K, Jordan W, Meier A,Rther E. Sleep-promoting properties o quetiapine in healthysubjects. Psychopharmacology 2004;174:421429.

Cohrs S. Sleep disturbances in patients with schizophrenia: Impactand effect o antipsychotics. CNS Drugs 2008;22:939962.

DeMartinis NA, Winokur A. Effects o psychiatric medications on sleepand sleep disorders. CNS Neurol Disord Drug argets 2007;6:1729.

Dencker SJ, Malm U, Lepp M. Schizophrenic relapse afer drugwithdrawal is predictable. Acta Psychiatr Scand 1986;73:181185.

Emsley R, Oosthuizen PP, Koen L, Niehaus DJ, Martinez G. Symptomrecurrence ollowing intermittent treatment in first-episode

schizophrenia successully treated or 2 years: a 3-year open-labelclinical study. J Clin Psychiatry 2012;73:e541e547.

Glick ID, Stekoll AH, Hays S. Te role o the amily and improvementin treatment maintenance, adherence, and outcome orschizophrenia. J Clin Psychopharmacol 2011;31:8285.

Hinze-Selch D, Mullington J, Orth A, Lauer CJ, Pollmcher . Effectso clozapine on sleep: a longitudinal study. Biol Psychiatry 1997;42:260266.

Hostetter JR, Lysaker PH, Mayeda AR. Quality o sleep in patientswith schizophrenia is associated with quality o lie and coping.BMC Psychiatry 2005;5:13.

Kane JM. Utilization o long-acting antipsychotic medication inpatient care. CNS Spectr 2006;11:17.

Kang SG, Lee HJ, Jung SW, Cho SN, Han C, Kim YK, et al. Charac-teristics and clinical correlates o restless legs syndrome inschizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:10781083.

Kato M, Kajimura N, Okuma , Sekimoto M, Watanabe , YamaderaH, akahashi K. Association between delta waves during sleep andnegative symptoms in schizophrenia. Pharmaco-eeg studies byusing structurally different hypnotics. Neuropsychobiology 1999;39:165172.

Keshavan MS, Reynolds CF III, Miewald MJ, Montrose DM, SweeneyJA, Vasko RC Jr, Kuper DJ. Delta sleep deficits in schizophrenia:evidence rom automated analyses o sleep data. Arch Gen

Psychiatry 1998;55:443448.Lee JH, Woo JI, Meltzer HY. Effects o clozapine on sleep

measures and sleep-associated changes in growth hormone andcortisol in patients with schizophrenia. Psychiatry Res 2001;103:157166.

Lieberman JA, Stroup S, McEvoy JP, Swartz MS, Rosenheck RA,Perkins DO, et al.; Clinical Antipsychotic rials o InterventionEffectiveness (CAIE) Investigators. Effectiveness o antipsychoticdrugs in patients with chronic schizophrenia. N Engl J Med 2005;353:12091223.

Luthringer R, Staner L, Noel N, Muzet M, Gassmann-Mayer C,alluri K, et al. A double-blind, placebo-controlled, randomizedstudy evaluating the effect o paliperidone extended-release tabletson sleep architecture in patients with schizophrenia. Int ClinPsychopharmacol 2007;22:299308.

Masand PS, Narasimhan M. Improving adherence to antipsychoticpharmacotherapy. Curr Clin Pharmacol 2006;1:4756.

Masand PS, Roca M, urner MS, Kane JM. Partial adherence toantipsychotic medication impacts the course o illness in patientswith schizophrenia: a review. Prim Care Companion J ClinPsychiatry 2009;11:147154.

Monti JM, Monti D. Sleep in schizophrenia patients and the effects oantipsychotic drugs. Sleep Med Rev 2004;8:133148.

Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA,Lichstein KL. Psychological and behavioral treatment oinsomnia:update o the recent evidence (19982004). Sleep 2006;29:13981414.

Mller MJ, Rossbach W, Mann K, Rschke J, Mller-Siecheneder F,Blmler M, et al. Sub chronic effects o olanzapine on sleep EEGin schizophrenic patients with predominantly negative symptoms.Pharmacopsychiatry 2004;37:157162.

National Collaborating Centre or Mental Health commissioned bythe National Institute or Health & Clinical Excellence.Schizophrenia: Core Interventions in the reatment andManagement o Schizophrenia in Adults in Primary and SecondaryCare. National Clinical Guideline Number 82. Te BritishPsychological Society & Te Royal College o Psychiatrists,2010.

Overall JE, Gorham DR. Te Brie Psychiatric Rating Scale (BPRS):recent developments in ascertainment and scaling. Psycho-pharmacol Bull 1988;24:9799.

Palmese LB, DeGeorge PC, Ratliff JC, Srihari VH, Wexler BE,Krystal AD, ek C. Insomnia is requent in schizophrenia andassociated with night eating and obesity. Schizophr Res 2011;133:238243.


7/7


Poulin J, Daoust AM, Forest G, Stip E, Godbout R. Sleep architectureand its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia. Schizophr Res 2003;62:147153.

Ritsner M, Kurs R, Ponizovsky A, Hadjez J. Perceived quality o lie inschizophrenia: relationships to sleep quality. Qual Lie Res 2004;13:783791.

Robinson D, Woerner MG, Alvir JM, Geisler S, Koreen A, SheitmanB, et al. Predictors o relapse ollowing response rom a first episodeo schizophrenia or schizoaffective disorder. Arch Gen Psychiatry1999;56:241247.

Salin-Pascual RJ, Herrera-Estrella M, Galicia-Polo L, LaurrabaquioMR. Olanzapine acute administration in schizophrenic patientsincreases delta sleep and sleep effi ciency. Biol Psychiatry 1999;46:141143.

San L, Ciudad A, Alvarez E, Gilaberte I. Symptomatic remission andsocial/vocational unctioning in outpatients with schizophrenia:prevalence and associations in a cross-sectional study. EurPsychiatry 2007;22:490498.

andon R, Shipley JE, aylor S, Greden JF, Eiser A, DeQuardo J, GoodsonJ. Electroencephalographic sleep abnormalities in schizophrenia:relationship to positive/negative symptoms and prior neuroleptictreatment. Arch Gen Psychiatry 1992;49:185194.

Walther S, Koschorke P, Horn H, Strik W. Objectively measured motoractivity in schizophrenia challenges the validity o expert ratings.Psychiatry Res 2009;169:187190.

Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risko rehospitalization among Caliornia Medicaid patients withschizophrenia. Psychiatr Serv 2004;55:886891.

Wirz-Justice A, Haug HJ, Cajochen C. Disturbed circadian rest-activity cycles in schizophrenic patients: an effect o drugs?Schizophrenia Bul 2001;27:497502.

Wulff K, Dijk DJ, Middleton B, Foster RG, Joyce EM. Sleep andcircadian rhythm disruption in schizophrenia. Br J Psychiatry2012;200:308316.

Yamashita H, Morinobu S, Yamawaki S, Horiguchi J, Nagao M. Effecto risperidone on sleep in schizophrenia: a comparison withhaloperidol. Psychiatry Res 2002;109:137142.

2014 afonso treatment

Documents