Schizophrenia and sleep disorders: links, risks, and management challenges

Figures & data

Figure 1 PRISMA diagram detailing the literature search and review process.

Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Table

Sleep disorder (N articles)	Articles	Population	Findings
Insomnia (N=14)	Kajimura et al^Citation74	SZa (N=6)	M: Zopiclone treatment resulted in lower BPRS negative and lower total scores compared to treatment with benzodiazepines.
	Shamir et al^Citation75	SZa (N=19)	L: SZ patients had reduced endogenous melatonin; M: melatonin improved sleep efficiency in low-efficiency more than in high-efficiency sleepers.
	Chemerinski et al^Citation24	SZ/SAD/SDa (N=122)	L: Antipsychotic discontinuation lead to worsening sleep quality; R: total insomnia score prior to antipsychotic withdrawal predicted the severity of psychotic symptoms at the end of the medication-free period.
	Luthringer et al^Citation68	SZb (N=36) SZa (N=40)	M: Paliperidone extended-release benefitted schizophrenia patients with insomnia by improving their sleep continuity and sleep architecture. Moreover, it did not cause daytime drowsiness, it was well tolerated, and ameliorated symptoms of schizophrenia.
	Suresh et al^Citation76	SZa (N=24); SADa (N=4)	M: Melatonin treatment ameliorated the quality, depth, and duration of sleep. It also improved mood and daytime functioning.
	Freeman et al^Citation25	DDa (N=2)	L: Out of all psychiatric patients (PP), 54% experienced severe clinical insomnia and moderate clinical insomnia; R: severity of insomnia symptoms predicted intensity of persecutory ideation.
	Xiang et al^Citation57	SZa (N=255)	L: Prevalence of insomnia in SZ was 36%. Older age, fewer psychiatric hospitalizations, symptoms of depression, and use of hypnotics were all associated with worse insomnia symptoms; R: insomnia and other sleep disturbances predicted a poorer physical quality of life in SZ.
	Tek et al^Citation73	SZ/SADa (N=39)	M: In the SZ group treated with eszopiclone, there was an improvement in the Insomnia Severity Index and in a working memory test. Psychiatric symptoms remained stable.
	Hou et al^Citation58	SZc (N=623)	L: 28.9% of SZ patients had one type of insomnia; R: patients with insomnia had worse symptoms and poorer mental quality of life.
	Waters et al^Citation63	SZ/SADa (N=14)	M: For insomnia management, 71% of all PP identified behavioral therapies as acceptable, 57.2% for melatonin, and only 22.5% for medication-based treatment. However, pharmacotherapy was considered useful for short-term and acute sleep problems by the majority of patients.
	Chiu et al^Citation65	SZd (N=36); SADd (N=6)	L: Behavioral factors are common in both psychiatric and healthy groups suffering from insomnia (e.g., nighttime rumination);
	Freeman et al^Citation67	SZa (N= 38); SADa (N=10)	M: psychological therapy (i.e., sleep education, cognitive and behavioral strategies) can be effectively used to correct wrong sleep habits.
	Li et al^Citation62	SZc (N=308); SADc (N=26); DDc (N=16)	M: Cognitive behavioral therapy had the longest efficacy on insomniac PP. Beneficial effects were still present at 24-week follow-ups. L: SSD prevalence of insomnia =19%, SSD prevalence of nightmare =9%; R: severity of insomnia predicted number of suicide attempts.
	Chiu et al^Citation66	SSDc (N= 14)	L: Prevalence of insomnia =100%, circadian dysfunctions =78.6%, delayed sleep phase =21.4%, night terrors =21%, sleepwalking =14.3%, sleep disordered breathing =42.9%; R: sleep difficulties had a strong negative effect on daytime functions and caused disability in these patients.
Restless leg syndrome (RLS) and periodic limb movement (PLM) disorder (N=4)	Walters et al^Citation30	NIAc (N=9); RLS (N=11)	L: The RLS group had more sleep disturbances and longer sleep latency, whereas both groups had more awakenings and less sleep efficiency. RLS patients had also worse symptoms at night and resting.
	Ancoli-Israel et al^Citation28 Staedt et al^Citation27	SZc (N=44); SADc (N=8) SZa (N=10)	L: Only 14% of the patients had at least five limb movements per hour of sleep. L: PLMs were detected in every patient. This finding suggests a connection between long-term neuroleptic treatment and PLMD.
	Kang et al^Citation29	SZa (N=182)	L: 39% of SZ had RLS and 87% met one criteria; R: BPRS and Athens Insomnia Scale (AIS) were higher in the RLS group.
Obstructive sleep apnea (OSA) (N=6)	Ancoli-Israel et al^Citation28	SZc (N=44); SADc (N=8)	L: 48% of patients with SZ had at least 10 respiratory events per hour of sleep, which were associated with daytime sleepiness.
	Alam et al^Citation32	PPc (N=100; SZ=56; SAD=18)	L: 69% of the patient population was at high risk for OSA; among them, 62% had a SZ diagnosis; 85% of the patients were taking clozapine (N=42) and 69% of those on risperidone (N=42) had a positive STOP-BANG screening for OSA.
	Winkelman^Citation33	PPc (N=364; SZa =46)	L: OSA was more prevalent in SZ, regardless of age, gender, BMI, and chronic neuroleptic use. However, SZ had a higher BMI compared to other patients.
	Waters et al^Citation55	PPc (N=74; SZa=52)	L: 25% of patients with SZ were at high risk for OSA. High-risk SZ patients were on more than one antipsychotic medication and on higher doses compared to the other patients at low risk for OSA.
	Annamalai et al^Citation35	SZ/SADc (N=175)	L: 14.6% of all patients had a OSA diagnosis, 57.7% were at high risk. SZ with a OSA had higher BMI; M: treatment compliance with CPAP was 53.8%.
	Stubbs et al^Citation31	SSDc (N=138,700)	L: In SZ patients the prevalence of OSA was 15.4%, and was associated with older age and higher BMI.
Circadian rhythm disorders (N=5)	Martin et al^Citation39	SZc (N=28)	L: Medicated patients with SZ slept more hours both night and during the day (i.e., more naps). R/L: SZ patients who performed better in neurophysiological tests slept more during the night and were more alert during the daytime.
	Poulin et al^Citation37	SZ/SADc (N=150)	L: SZ patients had longer sleep latency, time in bed, total sleep time, and more naps during the day than healthy controls.
	Afonso et al^Citation50	SZc (N=23)	L: More than 50% of SZ patients presented irregular sleep–wake patterns. SZ had more disrupted sleep and a lower quality of life compared to healthy controls.
	Wulff et al^Citation36	SZc (N=20)	L: 17 SZ patients had abnormal wake–sleep patterns, including longer sleep periods (5), irregular/broken sleep/wake cycles (5), delayed sleep cycles (6), and delayed and non-24-hour sleep–wake cycles (4). The last two groups had a delayed melatonin peak and non-24-hour melatonin cycle, respectively.
	Afonso et al^Citation38	SZc (N=34)	L: SZ patients slept more at night, but had lower sleep efficiency, longer sleep latency, more awakenings during the night, and poorer quality of sleep. Advanced sleep-phase syndrome (N=3) and irregular sleep-wake patterns (N=3) were also found in a small subset of patients.
Night eating syndrome (NES) (N=2)	Palmese et al^Citation42	SZ/SADc (N=175)	L: 44% of SZ patients had clinical insomnia. SZs with severe insomnia had higher depression scores, lower quality of life score, and higher BMI. SZs with severe insomnia had higher scores in the Night Eating Questionnaire (NEQ).
	Palmese et al^Citation41	SZ/SAD^Citation2 (N=100)	L: The prevalence of NES among SZs was 12%, with additional 10% who had a subthreshold condition. R: SZ patients with both full and subthreshold NES were more depressed and had worse insomnia.
Narcolepsy (NT) (N=2)	Huang et al^Citation46	SZa (N=13); NC (N=37) NCSZa (10)	L: NCSZ patients had higher BMI than NC patients at narcolepsy onset. NCSZ patients had more severe psychotic symptoms and more frequent depressive symptoms than SZ. Long-term response to treatment was poorer. NCSZ group had higher recurrence of DQB1(*)-03:01/06:02 genes (70%).
	Plazzi et al^Citation44	NT (N=28); SZa (N= 21)	L: NT type 1 hallucinations are more frequently multimodal and hypnagogic/hypnopompic. Positive and negative symptoms were higher in SZ patients.
Sleep disturbances that do not meet criteria for sleep disorders (N=10)	Göder et al^Citation53	SZa (N=17)	R: Reduced SWS and sleep efficiency in SZ patients predicted an impaired performance in visuospatial memory tasks.
	Müller et al^Citation69	SZa (N= 10)	M: After a 4-weeks treatment with olanzapine, PANSS scores, sleep efficiency, SWS sleep, and REM sleep were all improved.
	Yamashita et al^Citation71	SZa (N=86)	M: Olanzapine, quetiapine, and risperidone showed more efficacy in treating sleep disturbances than other atypical antipsychotics. Higher improvement was observed in elderly patients with schizophrenia, as well as in patients with longer sleep latency and worse daytime dysfunction.
	Hofstetter et al^Citation59	SZ a(N=23); SAD a (N= 6)	R: Association between lower sleep quality and lower quality of life. SZ patients with sleep disturbances had less positive reappraisal in stressful situations.
	Waters et al^Citation60	SSDd (N=67)	L: 60% reported fatigue, 67% sleep disturbances, and 28.4% both; R: poorer functional health for SZ patients with higher levels of fatigue.
	Brissos et al^Citation61	SZd (N=811)	L: SZ patients with sleep problems had more symptoms; R: association between SZ quality of sleep and patients’ and caregivers’ satisfaction with their life.
	Kluge et al^Citation70	SZc (N=26); SADc (N=3); SDc (N=1)	M: Treatment with both olanzapine and clozapine improved sleep continuity, whereas olanzapine alone resulted in longer REM sleep and SWS duration. Neither of these medications caused RLS-related symptoms.
	Afonso et al^Citation51	SZc (N= 811)	R: SZ patients with sleep disturbances had more symptoms. SZ patients less compliant with pharmacological treatment had higher rates of sleep disturbances.
	Mulligan et al^Citation52	SZd (N= 22)	R: Association between sleep fragmentation and reduction in subjective and objective sleep efficiency with auditory hallucinations the following day. Association between objective sleep fragmentation and a reduction in subjective sleep quality with paranoia and delusions.
	Faulkner and Bee^Citation64	SZd(N=8); SADd (N=6); DDd(N=1)	R: Association between sleep disturbances and a reduction in the participation in valued activities; M: concerns related to side effects of pharmacotherapy. Antipsychotics were preferred to hypnotics. Importance of discussing pharmacological and other treatments with the patients.

Notes:

a Treated,

b untreated,

c combination,

d partial or data absent.

Abbreviations: BMI, body mass index; BPRS, Brief Psychiatric Rating Scale; CPAP, continuous positive airway pressure; DD, delusional disorder; NC, narcoleptic-cataplectic; NCSZ, narcoleptic-cataplectic schizophrenia; NIA, neuroleptic-induced akathisia; PANSS, Positive and Negative Syndrome Scale; PLMD, periodic limb movement disorder; REM, rapid eye movement; SAD, schizoaffective disorder; SD, schizophreniform disorder; SSD, schizophrenia spectrum disorder; SWS, slow-wave sleep; SZ, schizophrenia; L, links; R, risks; M, management.

KajimuraNKatoMOkumaTSekimotoMWatanabeTTakahashiKA comparative study of benzodiazepine hypnotics and zopiclone in schizophrenia: effects on polysomnograms and BPRS scoresPsychiatry Clin Neurosci1994484815822

 Google Scholar

ShamirELaudonMBarakYMelatonin improves sleep quality of patients with chronic schizophreniaJ Clin Psychiatry200061537337710847313

 PubMed Web of Science ®Google Scholar

ChemerinskiEHoBCFlaumMArndtSFlemingFAndreasenNCInsomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophreniaCompr Psychiatry200243539339612216015

 PubMed Web of Science ®Google Scholar

LuthringerRStanerLNoelNA double-blind, placebo- controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophreniaInt Clin Psychopharmacol200722529930817690599

 PubMed Web of Science ®Google Scholar

SureshKPAndradeCBhaktaSGSinghNMMelatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled studyJ Clin Psychiatry200768223724117335321

 PubMed Web of Science ®Google Scholar

FreemanDPughKVorontsovaNSouthgateLInsomnia and paranoiaSchizophr Res2009108128028419097752

 PubMed Web of Science ®Google Scholar

XiangYTWengYZLeungCMTangWKLaiKYUngvariGSPrevalence and correlates of insomnia and its impact on quality of life in Chinese schizophrenia patientsSleep200932110510919189785

 PubMed Web of Science ®Google Scholar

TekCPalmeseLBKrystalADThe impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: a double-blind, randomized, placebo-controlled trialSchizophr Res2014160118018525454802

 PubMed Web of Science ®Google Scholar

HouCLLiYCaiMYPrevalence of insomnia and clinical and quality of life correlates in Chinese patients with schizophrenia treated in primary carePerspect Psychiatr Care2015532808626388498

 PubMed Web of Science ®Google Scholar

WatersFChiuVWJancaAAtkinsonAReeMPreferences for different insomnia treatment options in people with schizophrenia and related psychoses: a qualitative studyFront Psychol2015699026236265

 PubMed Web of Science ®Google Scholar

ChiuVWHarveyRHSloanNBCognitive and behavioral factors associated with insomnia in inpatients with schizophrenia and related psychosesJ Nerv Ment Dis20152031079880326356092

 PubMed Web of Science ®Google Scholar

FreemanDWaiteFStartupHEfficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trialLancet Psychiatry201521197598326363701

 PubMed Web of Science ®Google Scholar

LiSXLamSPZhangJSleep disturbances and suicide risk in an 8-year longitudinal study of schizophrenia-spectrum disordersSleep20163961275128227091530

 PubMed Web of Science ®Google Scholar

ChiuVWReeMJancaAWatersFSleep in Schizophrenia: exploring subjective experiences of sleep problems, and implications for treatmentPsychiatr Q201687463364826687510

 PubMed Web of Science ®Google Scholar

WaltersASHeningWRubinsteinMChokrovertySA clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndromeSleep19911443393451682986

 PubMed Web of Science ®Google Scholar

Ancoli-IsraelSMartinJJonesDWSleep-disordered breathing and periodic limb movements in sleep in older patients with schizophreniaBiol Psychiatry199945111426143210356624

 PubMed Web of Science ®Google Scholar

StaedtJDewesDDanosPStoppeGCan chronic neuroleptic treatment promote sleep disturbances in elderly schizophrenic patients?Int J Geriatr Psychiatry200015217017610679848

 PubMed Web of Science ®Google Scholar

KangSGLeeHJJungSWCharacteristics and clinical correlates of restless legs syndrome in schizophreniaProg Neuropsychopharmacol Biol Psychiatry20073151078108317459547

 PubMed Web of Science ®Google Scholar

AlamAChengappaKRGhinassiFScreening for obstructive sleep apnea among individuals with severe mental illness at a primary care clinicGen Hosp Psychiatry201234666066422832135

 PubMed Web of Science ®Google Scholar

WinkelmanJWSchizophrenia, obesity, and obstructive sleep apneaJ Clin Psychiatry2001621811

 PubMed Web of Science ®Google Scholar

WatersFHankenKRockDSleep-disordered breathing in schizophrenia: an auditSchizophr Res2013143239339423276481

 PubMed Web of Science ®Google Scholar

AnnamalaiAPalmeseLBChwastiakLASrihariVHTekCHigh rates of obstructive sleep apnea symptoms among patients with schizophreniaPsychosomatics2015561596625023923

 PubMed Web of Science ®Google Scholar

StubbsBVancampfortDVeroneseNThe prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: a systematic review and meta-analysisJ Affect Disord201619725926726999550

 PubMed Web of Science ®Google Scholar

MartinJJesteDVCaliguiriMPPattersonTHeatonRAncoli-IsraelSActigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patientsSchizophr Res2001471778611163547

 PubMed Web of Science ®Google Scholar

PoulinJChouinardSPampoulovaTLecomteYStipEGodboutRSleep habits in middle-aged, non-hospitalized men and women with schizophrenia: a comparison with healthy controlsPsychiatry Res2010179327427820493544

 PubMed Web of Science ®Google Scholar

AfonsoPBrissosSFigueiraMLPaivaTSchizophrenia patients with predominantly positive symptoms have more disturbed sleep–wake cycles measured by actigraphyPsychiatry Res20111891626621257208

 PubMed Web of Science ®Google Scholar

WulffKDijkDJMiddletonBFosterRGJoyceEMSleep and circadian rhythm disruption in schizophreniaBr J Psychiatry2012200430831622194182

 PubMed Web of Science ®Google Scholar

AfonsoPFigueiraMLPaivaTSleep–wake patterns in schizophrenia patients compared to healthy controlsWorld J Biol Psychiatry201415751752423316764

 PubMed Web of Science ®Google Scholar

PalmeseLBDeGeorgePCRatliffJCInsomnia is frequent in schizophrenia and associated with night eating and obesitySchizophr Res2011133123824321856129

 PubMed Web of Science ®Google Scholar

PalmeseLBRatliffJCReutenauerELTonizzoKMGriloCMTekCPrevalence of night eating in obese individuals with schizophrenia and schizoaffective disorderCompr Psychiatry201354327628122959340

 PubMed Web of Science ®Google Scholar

American Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders (DSM-5®)American Psychiatric Pub2013

 Google Scholar

HuangYSGuilleminaultCChenCHLaiPCHwangFMNarcolepsy–cataplexy and schizophrenia in adolescentsSleep Med2014151152224268496

 PubMed Web of Science ®Google Scholar

PlazziGFabbriCPizzaFSerrettiASchizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristicsNeuropsychobiology201571421822426279454

 PubMed Web of Science ®Google Scholar

GöderRBoigsMBraunSImpairment of visuospatial memory is associated with decreased slow wave sleep in schizophreniaJ Psychiatr Res200438659159915458855

 PubMed Web of Science ®Google Scholar

MüllerMJRossbachWMannKSubchronic effects of olanzapine on sleep EEG in schizophrenic patients with predominantly negative symptomsPharmacopsychiatry2004370415716215467971

 PubMed Web of Science ®Google Scholar

YamashitaHMoriKNagaoMOkamotoYMorinobuSYamawakiSInfluence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia: comparison of middle-aged and older adultsAm J Geriatr Psychiatry200513537738415879586

 PubMed Web of Science ®Google Scholar

HofstetterJRLysakerPHMayedaARQuality of sleep in patients with schizophrenia is associated with quality of life and copingBMC Psychiatry2005511315743538

 PubMed Web of Science ®Google Scholar

WatersFNaikNRockDSleep, fatigue, and functional health in psychotic patientsSchizophr Res Treatment2013201342582623738067

 PubMedGoogle Scholar

BrissosSAfonsoPCañasFBobesJBernardo FernandezIGuzmanCSatisfaction with life of schizophrenia outpatients and their caregivers: differences between patients with and without self-reported sleep complaintsSchizophr Res Treatment2013201350217224288609

 PubMedGoogle Scholar

KlugeMSchachtAHimmerichHOlanzapine and clozapine differently affect sleep in patients with schizophrenia: results from a double-blind, polysomnographic study and review of the literatureSchizophr Res2014152125526024315135

 PubMed Web of Science ®Google Scholar

AfonsoPBrissosSCañasFBobesJBernardo-FernandezITreatment adherence and quality of sleep in schizophrenia outpatientsInt J Psychiatry Clin Pract2014181707624047426

 PubMed Web of Science ®Google Scholar

MulliganLDHaddockGEmsleyRNeilSTKyleSDHigh resolution examination of the role of sleep disturbance in predicting functioning and psychotic symptoms in schizophrenia: a novel experience sampling studyJ Abnorm Psychol2016125678827362488

 PubMed Web of Science ®Google Scholar

FaulknerSBeePExperiences, perspectives and priorities of people with schizophrenia spectrum disorders regarding sleep disturbance and its treatment: a qualitative studyBMC Psychiatry201717115828464848

 PubMed Web of Science ®Google Scholar