Systematic review and meta-analyses of randomized controlled trials examining tinnitus management.

2011·0.37 MB·English

by  Hoare, Derek J

TheLaryngoscope
VC 2011TheAmericanLaryngological,
RhinologicalandOtologicalSociety,Inc.
Systematic Review and Meta-Analyses of Randomized Controlled
Trials Examining Tinnitus Management
Derek J. Hoare, PhD; Victoria L. Kowalkowski, BA; Sujin Kang, MA; Deborah A. Hall, PhD
Objectives/Hypothesis: To evaluate the existing level of evidence for tinnitus management strategies identified in the
UK DepartmentofHealth’sGood PracticeGuideline.
StudyDesign: Systematicreviewof peer-reviewedliteratureandmeta-analyses.
Methods: Searches were conducted in PubMed, Cambridge Scientific Abstracts, Web of Science, and EMBASE (earliest to
August 2010), supplemented by hand searches in October 2010. Only randomized controlled trials that used validated
questionnaire measuresof symptoms(i.e., measuresof tinnitusdistress,anxiety,depression)were included.
Results: Twenty-eight randomized controlled trials met our inclusion criteria, most of which provide moderate levels of
evidencefortheeffectstheyreported.Levelsofevidenceweregenerallylimitedbythelackofblinding,lackofpowercalcula-
tions, and incomplete data reporting in these studies. Only studies examining cognitive behavioral therapy were numerous
and similar enough to perform meta-analysis, from which the efficacy of cognitive behavioral therapy (moderate effect size)
appearstobe reasonablyestablished. Antidepressants werethe onlydrugclassto showanyevidenceof potentialbenefit.
Conclusions: The efficacyof most interventions fortinnitus benefitremainsto be demonstratedconclusively. In particu-
lar, high-level assessment of the benefit derived from those interventions most commonly used in practice, namely hearing
aids,maskers, andtinnitusretrainingtherapyneedsto beperformed.
Key Words: Tinnitus, Good Practice Guidelines, UK Department of Health, cognitive behavioral therapy, tinnitus
retrainingtherapy,randomizedcontrolledtrial.
Level ofEvidence:1a.
Laryngoscope,121:1555–1564,2011
INTRODUCTION and management of tinnitus patients.5 It recommends
The ‘‘phantom’’ auditory experience of tinnitus that tinnitus severity is assessed using either the
affects 10% to 15% of people in the United Kingdom.1 It Tinnitus Handicap Inventory (THI)6 or the Tinnitus
is most clearly associated with noise exposure and age- Questionnaire.7 It also recommends that psychological
ing and can present with comorbid sleep disturbance, comorbidity is assessed using the Beck Depression
hearing difficulty, social withdrawal, and negative emo- Inventory (BDI) and Beck Anxiety Inventory8 or the
tional reactions such as anxiety and depression.2,3 Hospital Anxiety and Depression Scale (HADS).9 How-
Although a majority of tinnitus patients are male and ever,questionnaireuseinclinicalpracticeislimited.10
present with some form of hearing loss and higher-fre- In terms of management, therapeutic targets
quency steeply sloping hearing loss in particular, there include the sound itself (i.e., interrupt the neural signal
is no typical characteristic history or level of distress of generating the sound) or the associated symptoms of dis-
thehelp-seekingtinnituspatient.4 tress, anxiety, or depression that can accompany
In the United Kingdom, the Department of Health tinnitus. The GPG states that tinnitus patients will be
issued a Good Practice Guide (GPG) for the commission- given, as appropriate, information/education, hearing
ing of tinnitus services and for the clinical assessment aids, counseling and psychological support, relaxation
therapy, cognitive behavioral therapy (CBT) with the
From the National Institute for Health Research National requisite professional supervision, sleep management
Biomedical Research Unit in Hearing (D.J.H., V.L.K., S.K., D.A.H.), (including supervised CBT), sound enrichment therapy,
Nottingham; School of Clinical Sciences (D.J.H., V.L.K., S.K., D.A.H.), The
University of Nottingham, Nottingham; and Division of Psychology and tinnitus retraining therapy (TRT). The use of anti-
(D.A.H.), School of Social Sciences, Nottingham Trent University, depressants, anxiolytics, and night sedation is also
Nottingham,UnitedKingdom.
advocated. However, the GPG lacks an evidence base to
Editor’sNote:ThisManuscriptwasacceptedforpublicationMarch
support these recommendations and is in part based on
18,2011.
The National Biomedical Research Unit in Hearing is funded by anecdotalevidenceandexpertopinion.
theUKNationalInstituteforHealthResearch.Theauthorsarefunded This review asked the question, how much high-
bytheUKNationalInstituteforHealthResearch.
level evidence exists for the efficacy of the GPG-
Theauthorshavenootherfunding,financialrelationships,orcon-
flictsofinteresttodisclose. suggested tinnitus management strategies, and was re-
SendcorrespondencetoDr.DerekHoare,NIHRNationalBiomedi- stricted to randomized controlled trials (RCTs), the gold
cal Research Unit in Hearing, Ropewalk House, 113 The Ropewalk, standard for evaluating therapeutic interventions.11,12 A
Nottingham,UKNG15DU.E-mail:[email protected]
systematic search was used to identify RCTs that
DOI:10.1002/lary.21825
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1555
Fig. 1. Summary of the systematic
literaturesearch.
examined tinnitus management strategies and reported therapy AND/OR TRT OR antidepressant OR depression or
validated measures of tinnitus intrusiveness, anxiety, or anxiolytic OR anxiety OR night AND/OR nocturnal AND seda-
depression, therefore providing comparable measures of tion. Search results were screened to remove duplicate, non-
change in patient symptoms. Where possible, meta-anal- peer reviewed, and review articles. Two authors (D.J.H., V.L.K.)
screened abstracts according to the research question and
yses were conducted. The outcome of this review
PICOS criteria. All titles selected by either author were
provides high-level evidence that supports some, but not
retrievedtoscreentheirfulltextforfinalagreementandinclu-
all, GPG recommended strategies for tinnitus manage-
sion. The initial search was complimented with further hand
ment in the United Kingdom, and also highlights where
searches of key journals, Cochrane reviews, and the reference
furtherRCTswouldbeofimmediatebenefit. lists of all included studies. The stages and reasons for exclu-
sionsarepresentedinFigure1.
MATERIALS AND METHODS
ThePRISMAStatementoutlinestheessentialcomponents
for transparent reporting of a systematic review13 and guided Data Extraction
ourreporting. Extracted data comprised participant numbers, baseline
tinnitus severity, age range, the intervention and control, vali-
dated questionnaire measures used, follow-up conducted, the
Systematic Search Strategy and Study Selection study design, and study findings. For all studies, data was
Studies were selected and screened according to the extracted independently by two authors (D.J.H., V.L.K.). Any dif-
ferences in reporting were reconciled by jointly revisiting the
research question and PICOS criteria. PICOS were: partici-
relevantpublication.
pants, adult humans with tinnitus; intervention, tinnitus
management strategies proposed by the Department of Health
(GPG); comparisons, a no-treatment group or suitable second
treatment group; outcomes, validated questionnaire measure of Quality Assessment
tinnitus intrusiveness, anxiety, depression; and study design, Study quality was based on a subset of extracted data.
randomized controlled trials only. Quasi- and pseudo-random- The quality assessment tool was based on one reported previ-
izationswereexcludedfromthisreview. ously.14Foreachcriterion,a scoreof2wasappliedif thestudy
Initial database searches were conducted in August 2010. metthecriteriontoahighstandard,1ifitpartlymetthecrite-
PubMed, Cambridge Scientific Abstracts (including Medline, rion, or a score of 0 if it was flawed or if the relevant
Toxbase, Biological Sciences), Web of Science, and EMBASE information was not stated. Two authors scored studies inde-
were searched using the search terms: 1) tinnitus AND 2) ran- pendentlybeforeagreeingonafinalscoreforeachcriterionand
dom AND/OR randomized AND/OR randomised AND 3) each study. The potential overall quality score varied from 0 to
information AND/OR education OR hearing AND aid(s) OR 16, giving grades of evidence from very low (0–4), low (5–8),
counselling OR counseling AND/OR psychological (support) OR moderate (9–12) to high (13–16). Qualitative descriptors for
relaxation (therapy) OR cognitive AND behavioural OR behav- these grades are given in Oxman et al.11 Essentially, the lower
ioral AND therapy AND/OR CBT OR sleep AND management the level of evidence, the more likely further studies are to
OR sound AND enrichment (therapy) OR retraining AND impactonourconfidenceintheestimateofeffectandarelikely
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to change that estimate. Only high-level evidence studies pro- Estimating Publication Bias Effects
vide conclusive evidence, after which additional research is Tosearchforevidenceofpublicationbiasandevaluatethe
unlikelytochangetheestimateofeffect. influence of individual studies on the outcome, funnel plots
were constructed. The estimate of effect (observed outcome)
fromeachstudywasplottedagainstits standarderror. Ifthere
Data Synthesis and Meta-Analyses is no publication bias, the data-points appear symmetrical
Where studies were sufficiently similar, a meta-analysis aroundthemeaneffect.Anasymmetricalplot,however,implies
wasperformed.Similarityisdefinedhereasthesameinterven- that studies giving significant results were more likely to be
tion and outcome measure, and low heterogeneity. The test for publishedthanstudiesgivingnonsignificantresults.
heterogeneity is detailed below. Where studies were not suffi- The ‘‘trim and fill’’ method16 was applied to calculate the
ciently similar to conduct a meta-analysis, data were number of studies that would be required to return the plot to
synthesized using a narrative approach. All analyses were per- ‘‘symmetry,’’andthereforeremovepublicationbias.Thismethod
formedinRusinglibrariesrmeta,epiR,andmeta. estimatessummaryeffectsizebasedontheassumptionthatall
suchstudieshadbeenpublished.
Effect Size Calculation for Individual Studies RESULTS
For each study, Cohen’s d effect size was calculated for
All studies included in this review were RCTs of
the primary treatment intervention and primary measure of
tinnitus management interventions mentioned in the
change compared to an independent control given by the for-
GPG. All participant groups were representative of a
mula below. An intention-to-treat analysis was used, and
clinically relevant population, and without exception all
follow-up assessments were not included in this analysis.
Limited by the available data, standard deviation (SD) of pre- studies reported one or more outcomes based on vali-
intervention and precontrol (baseline) scores were used as the dated questionnaire measures of tinnitus, anxiety, or
group-specific standard deviations of mean change scores depression. Unless otherwise stated, studies included
withingroups. adults of all ages, and baseline scores for outcome meas-
ures did not differ significantly between groups.
MeanChangeScores Throughout, statistical significance refers to a reliable
Interventioni
(cid:1)MeanChangeScores numerical difference between group means. Clinical sig-
Effectsize ¼ Controli ;
i PooledSD nificance refers to the specific questionnaire score
i
change that implies a functional improvement or wor-
seningofthecondition inanindividualpatient.
where
Adescriptivesummarytableofall28studiesispro-
vuffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi vided in the online supplemental information
uuu½ðNPreInterventioni(cid:1)1Þ(cid:2)SD2PreInterventioni accompanying this article. Table I shows the quality
t þðN (cid:1)1Þ(cid:2)SD2 (cid:3) assessmentscores foreachstudy.
PooledSD ¼ PreControli PreControli
i N þN (cid:1)2
PreInterventioni PreInterventioni
Information/Education (Directive Counseling)
and SDs and Ns are the group-specific standard deviations and Three RCTs were identified that assessed the effi-
samplesizesforstudyi. cacy of education/information giving. They provide
moderate levels of evidence and report small or moder-
ate effect sizes (Table I). Henry et al.17 found a
Test for Heterogeneity Across Studies
statistically significant reduction in Tinnitus Severity
Heterogeneity (v2) of aggregated effect sizes were calcu- Index18 score at 6-month follow-up in a group receiving
lated using Cochran’s Q statistic (significance level ¼ .05) and
a tinnitus education program delivered by audiologists,
I2index(percentagesofaround25%indicateslowheterogeneity
compared to a change in members of a self-help group.
and 0 indicates that sampling error only accounts for all the
Differences at all other time points were not significant.
variability in effectsize estimates within studies).Resultswere
checked for significance with K-1 degrees of freedom, where K In a study of CBT discussed later, Henry and Wilson19
¼numberofstudies. examined the efficacy of group education delivered by a
clinical psychologist versus a waiting-list control. In this
study they found no significant changes in the BDI, Tin-
Meta-Analysis: Summary Effect Size and nitus Handicap Questionnaire (THQ),20 or Tinnitus
Confidence Intervals ReactionQuestionnaire(TRQ).21
Fixed-effects meta-analyses of questionnaire measures Two further studies looked at the efficacy of a self-
were performed, using the standardized mean difference helpbookwithorwithouttelephonecontactwithathera-
method. In addition, weighted meta-analysis with fixed-effects pist, compared to a waiting list control.22,23 Kaldo et al.22
standard errors was performed to get a summary effect size
reported a significant reduction in TRQ score in their
(andits 95%confidence interval[CI]) for eachtype of interven-
intervention group compared to controls. Whether benefit
tion as appropriate. Weighting used the inverse variance
wasretainedisunclear,as15participantstriedadditional
procedure, where studies with a large standard error, typically
with small sample sizes, were given less weight.15 The statisti- interventions between the end of intervention and follow-
cal significance of the summary effect size was evaluated using up. In terms of clinically significant changes in TRQ (i.e.,
theZstatistic(Z ¼T/se(T)whereT istheeffectmeasurefrom a50%reduction),2132%oftheinterventiongroupand5%
i i i i
studyi).15 of the control group improved. In the second study,
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TABLEI.
AssessmentofEightQualityCriteria,OverallQualityRating,andEffectSizeforEachofthe28Studies.
Similarity Cohen’sd
Study Outcome Between Potential External EffectSize
Reference Design* Blinding† Measures‡ Compliance§ Controls|| Groups¶ Bias# Validity** StudyQuality (Variable)
Information/education
Henryetal.(2007)17 2 0 2 1 2 2 2 1 Moderate —
Kaldoetal.(2007)22 2 0 2 2 1 2 2 1 Moderate 0.52(TRQ)
Malouffetal.(2010)23 1 0 2 1 1 1 2 1 Moderate 0.25(TRQ)
Relaxationtherapy
Biesingeretal.(2010)25 1 0 2 2 1 1 1 1 Moderate 0.43(TBF-12)
Irelandetal.(1985)27 2 0 1 0 1 1 1 1 Low 0.05(BDI)
Weiseetal.(2008)29 2 0 2 1 1 2 2 2 Moderate 1.63(TQ)
Cognitivebehavioraltherapy
Abbottetal.(2009)31 1 0 2 2 2 1 1 0 Moderate 0.21(TRQ)
Anderssonetal.(2002)30 2 0 2 2 1 1 2 2 Moderate 0.45(TRQ)
Anderssonetal.(2005)34 2 0 2 1 1 2 2 1 Moderate 0.65(TRQ)
HenryandWilson(1996)19†† 2 0 2 1 2 1 1 1 Moderate 0.37(TRQ)
HenryandWilson(1998)36 1 0 2 1 2 0 1 1 Low 0.6(TRQ)
Kaldoetal.(2008)32 2 0 2 1 1 2 1 1 Moderate (cid:1)0.18(TRQ)
Kro¨ner-Herwigetal.(1995)37 2 0 2 1 1 2 1 1 Moderate —
Kro¨ner-Herwigetal.(2003)39‡‡ 2 0 2 1 2 1 2 1 Moderate 0.67(TQ)
Riefetal.(2005)42 2 0 2 1 1 2 1 2 Moderate 0.58(TQ)
Robinsonetal.(2008)38 2 1 2 2 1 1 2 2 High —
ZachriatandKro¨ner-Herwig 1 0 2 1 2 2 1 1 Moderate 0.66(TQ)
(2004)41§§
Soundenrichment
Davisetal.(2008)43 0 0 2 1 2 1 0 1 Low —
Herraizetal.(2010)45 2 0 2 2 1 2 2 1 Moderate 0.44(THI)
StephensandCorcoran(1985)24 1 0 1 0 2 1 2 1 Low —
Tinnitusretrainingtherapy
Caffieretal.(2006)47 2 0 2 0 1 1 1 1 Low —
Seydeletal.(2010)48 2 0 2 0 1 1 1 1 Low —
Antidepressants
Robinsonetal.(2005)49 2 2 2 2 2 2 1 2 High 0.09(THQ)
Sullivanetal.(1993)50 1 2 2 1 2 1 2 1 Moderate 0.88(HAM-D)
Zo¨geretal.(2006)52 1 2 2 2 2 2 1 2 High 0.35(HAM-D)
Anxiolytics
Jalalietal.(2009)56 2 2 2 1 1 1 2 2 High 0.07(THI)
Nightsedation
Nerietal.(2009)57 2 0 2 2 1 1 1 1 Moderate —
Rosenbergetal.(1998)58 2 2 2 2 2 2 1 1 High —
*Studydesign:fullyrandomized(score2)orstratified(score1).
†Blindingofparticipants(score1)andinvestigators(score1).
‡Validatedquestionnairemeasures(score2ifappropriate,1ifweak).
§Compliancemeasures(score1)andreporting(score1).
||Qualityofcontrolcondition(score2ifwell-controlledintervention,score1forwaiting-listcontrol).
¶Similarityofgroups:baselinetinnitusseverity(score2ifnosignificantdifferences,1ifminordifferencesorunder-reported,0ifgroupsnotmatched).
#Biasrelatedtofunding(score2ifstatedandnoevidenceofbias,1ifacademicwithnostatementoffundingsource).
**Externalvalidityrepresentativeaclinicalpopulation(score1);powercalculationwasconducted(score1).
††Alsoexaminededucation.
‡‡Alsoexaminededucationandrelaxation.
§§AlsoexaminedTRT.
TRQ ¼ Tinnitus Reaction Questionnaire, TBF-12 ¼ Tinnitus Handicap Inventory-12, BDI ¼ Beck Depression Inventory, TQ ¼ Tinnitus Questionnaire
(Goebel-Hiller);THI¼TinnitusHandicapInventory,THQ¼TinnitusHandicapQuestionnaire,HAM-D¼HamiltonDepressionScale.
Malouff et al.23 used the same self-help book but without improvement in mean TRQ score. Twenty-five percent of
therapist contact by phone. Despite a high attrition rate the intervention group had a clinically significant reduc-
(35%), they also reported a statistically significant tion in TRQ score versus 14% of controls. Because Kaldo
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etal.22useda self-help bookwithweekly therapistphone In summary, there is evidence for the efficacy of
calls and Malouff et al.23 used only the self-help book, relaxation therapy for tinnitus intrusiveness, mixed evi-
meta-analysiscouldnotbeperformed. dence of its efficacy for depressive symptoms, and no
In summary, information/education delivered in evidenceforaneffectonanxiety.
the form of a book or therapist-led educational sessions
had significant effects over no intervention or undir-
ected self-help. Furthermore, providing a self-help book Cognitive Behavioral Therapy
and therapist contact appears to have greater benefit Eleven RCTs examined CBT for tinnitus, the major-
than providing a self-help book alone. Education alone ity of which provided moderate levels of evidence (Table
is sufficient for some patients because it also makes I). Three studies examined the efficacy of CBT delivered
them aware of other potential management interven- via the internet.30–32 Andersson et al.30 examined the ef-
tions (i.e., some individuals may use that information to ficacy of internet-based CBT but compared to a waiting-
explore other strategies, as was observed by Kaldo list control. Attrition was 51% in this study (leaving
et al.22). fewer participants than their calculated sample size).
They did, however, report significant statistical improve-
ments in TRQ score in the CBT group compared to
Hearing Aids controls. Thirty-one percent had a clinically significant
No RCTs investigated hearing-aid use as a primary improvement. Andersson et al.30 also reported statisti-
intervention for tinnitus and obtained a validated out- cally significant improvements in both anxiety and
come measure. Stephens and Corcoran24 did include a depression. In a second study from the same research
subgroup of individuals who received hearing aids (dis- group, Abbott et al.31 compared internet-based CBT to
cussed later under sound enrichment). Sometimes internet-based education without CBT elements. They
hearing-aid provision forms part of TRT, and therefore reported 75% (24 of 32) attrition for the CBT interven-
thesestudies arediscussedlater. tion and 21% in controls. Participants reported that the
intervention was not engaging enough. The authors also
suggested that this intervention may be too much of a
Counseling and Psychological Support commitment and therefore inappropriate for those with
No specific RCTs involved counseling or psychologi- low baseline tinnitus distress levels. Unsurprisingly, no
cal support. When counseling was given, it was more significant effects on TRQ or Depression, Anxiety and
appropriate to consider it as information/education, Stress Scale33 scores were identified. In a third study,
relaxationtherapy,CBT,orTRT. Kaldo et al.32 compared internet-delivered CBT with
therapist-delivered group CBT. This study found no sig-
nificant differences in THI, TRQ, or HADS score
Relaxation Therapy changes between groups (i.e., one mode of delivery was
Three RCTs assessed the efficacy of relaxation not superior to the other). In this study, 38% of partici-
therapies, providing low to moderate levels of evi- pants failed to complete the internet CBT compared to
dence, of small to large effect sizes (Table I). Biesinger 24% who received the group CBT intervention. Internet
et al.25 examined the efficacy of Qigong, a mindful CBTwasdeemedlesscrediblebyparticipants.
exercise and active relaxation technique. They Four studies examined the efficacy of CBT deliv-
reported high compliance and a significant mean ered as group sessions by either clinical psychologists
improvement in Tinnitus Beeintra¨chtigungs Fragebo- or a psychiatrist, compared to waiting-list controls.
gen Questionnaire26 score in the intervention group Andersson et al.34 made this comparison in elderly tin-
versus waiting-list control. However, in this study the nitus patients. They found a statistically significant
control group reported a significantly higher baseline improvement in TRQ score for their CBT group com-
tinnitus severity, limiting the interpretative weight of pared to controls. There were no significant
their finding. In a second study, Ireland et al.27 com- improvements in HADS or Anxiety Severity Index
pared group (progressive muscle) relaxation training (ASI)35 scores. In fact, the ASI score increased signifi-
to a waiting-list control. They found no significant dif- cantly in their control group. In terms of clinical
ferences in change on BDI or State-Trait Anxiety significance, 42% of CBT participants showed clinical
Inventory scores28 between groups. They did, however, improvement in TRQ, but this reduced to 25% at 3-
note greater improvement in three participants who month follow-up. Henry and Wilson36 also reported
said their tinnitus was stress related. This study was statistically significant improvement in TRQ score in
rated as low-level evidence and did not report a vali- their CBT group compared to controls. They found no
dated measure of tinnitus distress. The third study of changes in either BDI or THQ scores. Kro¨ner-Herwig
relaxation therapy from Weise et al.29 used electromy- et al.37 reported a significant improvement in TQ score.
ography biofeedback with a waiting-list control. They In Robinson et al.,38 attrition was 32% in the CBT
found significant improvements in both Tinnitus Ques- group (participants reported that they were not dis-
tionnaire (Goebel-Hiller) (TQ) and BDI scores in their tressed enough or that participation was too demanding
intervention group. The methodologies used in the on time). Noncompleters had experienced tinnitus sig-
three studies of relaxation training were not suffi- nificantly longer than those who completed the
ciently similar to perform meta-analysis. intervention, suggesting that CBT is less indicated in
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1559
very chronic cases. A power calculation was conducted A final meta-analysis was performed for therapist-
for this study, but again, because of high attrition, the deliveredCBTwhenmeasuredusingtheTQ(Fig.2C).The
sample size estimate was not met. Furthermore, as is overalleffectsizewas0.64(mediumeffect)witha95%CI
unforeseeable with full randomization, the intervention of 0.31 to 0.98 (z ¼ 3.74 and P < 0.001). Again therefore,
group had a significantly higher baseline TRQ than patientsundergoing therapist-deliveredCBTreported sig-
controls, making the groups less comparable. A signifi- nificant improvement compared to controls. The funnel
cant effect was also reported for changes in BDI score plot for the therapist-delivered CBT with TQ (Fig. 2E)
in the CBT group compared to controls. shows considerablesymmetry (i.e.,thereisno evidence of
Three studies compared the efficacy of psychologist- bias,andthereforewecanbeconfidentofthiseffect).
delivered group CBT to education or relaxation training. In summary, 10 RCTs compared CBT to a non-CBT
Henry and Wilson36 examined group CBT versus educa- control, of which nine reported significant improvements
tion alone, aswell aswaiting-list controls, and reported a in tinnitus intrusiveness. Of the seven studies that mea-
significant reduction in TRQ score in the CBT. However, sured depression, only two found improvements, and of
the difference between groups was not significant at 12- thethreestudiesthatmeasuredanxiety,justonereported
month follow-up. THQ score also reduced significantly in improvement.CBTisthereforespecificallyassociatedwith
theirCBTgroupversuscontrols.Therewasnosignificant reductionsinself-reportedtinnitusseveritywithlittleevi-
effect on BDI scores. Kro¨ner-Herwig et al.39 compared dence to suggest it has any benefit for tinnitus-related
group CBT to a minimal contact education or relaxation anxiety ordepression. Thiseffect appears tobeindepend-
intervention and a waiting-list control. The group who ent of whether CBT is compared to an educational or
received CBT were significantly more improved on TQ waiting-list control, suggesting that either measure
score than all other groups. Changes in the General adequatelycontrolsforplaceboeffectsinthesestudies.
Depression Scale (ADS)40 were not significant, which the The effect size for therapist-delivered CBT is larger
authorattributesto‘‘flooreffects.’’Inthisstudy,thegroups than that for internet CBT, although the one study that
who received either the education or relaxation interven- assessed the relative efficacy of these two methods
tion did not show significant improvement in TQ scores (Kaldo et al.)32 did not find any significant differences in
comparedtocontrols.Inthethirdstudy,ZachriatandKro¨- their outcome measures (HADS, THI, or TRQ). Of note
ner-Herwig41 compared CBT, TRT, and an education-only in this study, however, is that email contact, part of the
intervention.TQscoresweresignificantlyimprovedinthe internet-delivered CBT, was tailored to perceived need,
CBT group compared to controls. The difference between whereby considerably more email contact was main-
groups remained significant 6 months following interven- tained with some participants than might have occurred
tionbutwasnotsignificantatasubsequentfollow-up. in other studies. Although internet-delivered CBT might
The final study of CBT reviewed here, from Rief be accessible and cost effective, it had the highest attri-
et al.,42 examined the efficacy of one-to-one CBT com- tionofallinterventionsin thisreview.
pared to waiting-list controls. They found a significant Subanalyses conducted in studies of CBT do not
improvement in TQ score for the CBT group compared suggest that the intervention is less indicated for
tocontrols.Thebenefitwasmaintainedafter6months. patients with milder tinnitus or longer-term tinnitus,
Effect sizes were calculated for each study of CBT and does not appear to be effective alone for depressive
(Table I). Meta-analysis was performed to determine over- oranxietysymptoms.
all effect sizes comparing the pre-change versus post- Effective CBT interventions were either delivered
change, and 95% CIs for CBT when delivered via the as a software package, or face-to-face by a clinical psy-
internet (Fig. 2A) or by a therapist (Fig. 2B, 2C). Because chologist or psychiatrist. Crucially, no RCT was
Kaldo et al.32 used standard group-based CBTas a control identified where CBTwas delivered by an audiologist or
group and Robinson et al.38 did not provide postinterven- hearing therapist. Given the limited availability of clini-
tiondata,theywereexcludedfrommeta-analyses. cal psychology support in the United Kingdom,10 it is
There was no significant heterogeneity or degree of important that the efficacy of audiologist-delivered CBT,
inconsistencybetweenanyofthestudiesgroupedformeta- as advocated by the GPG, is assessed with an RCT. Fur-
analysis(P¼notsignificant,I2index¼0%inallcases). thermore, individual studies report delivering CBT for
The overall effect size for internet-delivered CBT between 7 and 22 hours in total, over a period of 6 to 15
(Fig. 2A) was 0.38 (small effect) with a 95% CI of 0.07– weeks.The issuesofpatient and clinician burden, and of
0.68 (z ¼ 2.41 and P ¼ .016) (i.e., patients undergoing costbenefit, arethereforealsoimportantconsiderations.
internet-delivered CBTreportedsignificantimprovement
comparedtocontrols).
Sleep Management
The overall effect size for therapist-delivered CBT
No RCTs specifically examined sleep management
when measured using THQ scores (Fig. 2B) was 0.54
practices for tinnitus patients, beyond those for CBT or
(medium effect) with a 95% CI of 0.12-0.96 (z ¼ 2.51 and
nightsedation.
P ¼.012) (i.e., the patients undergoing CBT improved).
The funnel plot (Fig. 2D) for these studies suggests that
two additional studies would need to be added to bring Sound Enrichment Therapy
the funnel plot back to symmetry. If these two studies Three RCTs assessed the efficacy of different forms
were added then the estimated treatment effect (fixed- of sound enrichment. These studies provide low to mod-
effectmodel)woulddrop from0.54to0.44. erate levels of evidence, and where calculable, indicate a
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1560
Fig.2.Meta-analysesofcognitivebehavioraltherapy(CBT)interventions.Pooledeffectsizesand95%confidenceintervals(CI)aregivenin
boldandasdiamondshapesintheforestplot(right).(A)Comparisonofinternet-CBTversuscontrolusingTinnitusReactionQuestionnaire
(TRQ)totalscorespreinterventionandpostintervention.(B)Comparisonoftherapist-deliveredCBTversuscontrolTRQtotalscorespreinter-
ventionandpostintervention.(C)Comparisonoftherapist-deliveredCBTversuscontrolTinnitusQuestionnaire(TQ)totalscorespreinterven-
tion and postintervention. (D) Funnel plot shows estimated effect against standard error (SE) for the therapist delivered CBTstudy using
TRQ (filledcircles). There isconsiderable asymmetry aroundmeaneffect size(evidenceof publication bias).Opencirclesshowcalculated
position of results from studies that would be required to bring the plot back to symmetry. (E) Funnel plot shows estimated effect against
SEforthetherapistdeliveredCBTstudiesusingTQ.Thereisgoodsymmetryandthereforenoevidenceofpublicationbias.*Samplesizes
wereassumed.[Colorfigurecanbeviewedintheonlineissue,whichisavailableatwileyonlinelibrary.com.]
small effect size (Table I). Davis et al.43 examined the ef- Neuromonics participants; 47% of participants received
ficacy of Neuromonics (customized spectrally modified noise generator and counseling, and just 23% received
music) compared to counseling with or without a noise counseling alone. Although this is encouraging, study
generator.Theoriginalstudydesignincludedtwogroups quality was rated low because of inadequate randomiza-
with different modules of Neuromonics intervention, but tion, a lack of blinding, and under-reporting of study
participants self-adjusted the prescribed treatment for detail, therefore there is significant uncertainty of the
what they felt worked best, such that that the interven- estimated effect. In an earlier study, Stephens and Cor-
tion was no longer different between groups and their coran24 examined the efficacy of maskers, hearing aids
data was pooled. Davis et al.43 reported clinically signifi- or combination devices, tailored to individual hearing
cant changes in TRQ at 6 months for 86% of loss, compared to limited counseling without a sound
Laryngoscope 121:July2011 Hoareetal.: Evidence-Basefor Tinnitus Management
1561
device. There were no improvements in this study. In Antidepressants
fact, one group using maskers reported a significant Three RCTs examining the efficacy of antidepres-
increase in anxiety (Crown Crisp Experiential Index)44 sants were identified, providing moderate-to-high level
compared to controls. This study also provided only low- evidence of negligible to large-effect sizes (Table I). Rob-
level evidence of the reported effect, but given the lack inson et al.49 compared paroxetine (up to 50 mg daily, as
of evidence to suggest otherwise, contraindicates mask- tolerated) to placebo. They found no significant changes
ingdevices fortinnituspatientspresentingwithanxiety. in tinnitus intrusiveness, anxiety, or depression. Fur-
An active form of sound enrichment was used by thermore, they noted several significant adverse events:
Herraiz et al.45 Participants undertook frequency dis- sexual dysfunction, excessive drowsiness, and dry
crimination training, after which there was a reduction mouth. Sullivan et al.50 compared nortriptyline (up to
in THI score in their intervention groups compared to 100 mg at night, as tolerated) to placebo (lactose). They
waiting-list controls. Although this was statistically sig- reported a significant reduction in Hamilton Depression
nificant, it was not clinically significant. This finding Rating Scale,51 score for the intervention group com-
may be in part limited by their eligibility criteria, which pared to controls. Sub-analysis suggested that those
excludedthosewithmoreseveretinnitus. reporting greatest benefit were women and individuals
Sound enrichment interventions and outcome meas- reporting insomnia. Zo¨ger et al.52 compared sertraline to
ures were not sufficiently similar for us to perform placebo. They reported significant improvements on the
meta-analysis. It is surprising that so little evidence Tinnitus Severity Questionnaire53 and the Hamilton
exists for the efficacy of sound enrichment given that, in Anxiety Scale (HAM-A)54 for the group receiving sertra-
the United Kingdom at least, prescription of hearing line compared to placebo. This study is slightly
aids and maskers for tinnitus is commonplace.10 In par- complicated, as nine participants were given oxazepam
ticular, it is crucial to establish the efficacy of hearing in the first 2 weeks to alleviate expected worsening of
aids for patients with mild hearing loss, who may or distress. But oxazepam itself is a benzodiazepine, which
may not be offered a hearing aid depending on the clini- may have an effect on tinnitus.55 Zo¨ger et al.52 reported
cians’ own personal belief about efficacy. This is quite a 24% attrition in this study, but none of the dropouts had
widespread practicein theUnitedKingdom.10 received oxazepam, suggesting that it may have affected
theirresult.
In summary, three RCTS examining antidepres-
Tinnitus Retraining Therapy sants report three different findings. Meta-analysis was
The aim of TRT is to promote habituation to tinni- notperformed.
tus through a combination of sound enrichment and
directive counseling.46 In addition to the study reported
earlier (Zachriat and Kro¨ner-Herwig),41 two further Anxiolytics
RCTs of TRTwere identified, both of which provide low- One RCT examined the efficacy of an anxiolytic.
level evidence. Caffier et al.47 compared TRT to a wait- Jalali et al.56 compared alprazolam (a benzodiazepine)
ing-list control, finding a significant reduction in TQ with chlorpheniramine (antihistamine), excluding partic-
score in their TRT group versus controls at 12 months. ipants scoring more than 14 points on the HAM-A
Interpreting efficacy is difficult. TRT was not delivered anxiety questionnaire. They found no significant change
according to a single protocol but was highly individual in THI score between groups. Changes in anxiety and
between participants, as was the use of prescribed devi- depressionwerenot reported.
ces, and additional treatment for anxiety or depression.
Authors indicate that there was more improvement in
Night Sedation
participants undertaking (as opposed to rejecting) addi-
Two RCTs were identified that examined the effi-
tional treatment for anxiety or depression if it was
cacy of the neurohormone sedative melatonin. Neri
indicated. Seydel et al.48 compared TRT (modified to
etal.57 comparedmelatonin (3mgat nightfor80nights)
include psychosomatic treatment, cognitive-behavioral
to a no-treatment control group. There were no signifi-
elements, and relaxation treatment) with a waiting-list
cant changes in THI score between groups. Rosenberg
control. After 3 months of treatment, mean TQ score
etal.58 comparedmelatonin (3mgat nightfor30nights)
was significantly reduced in the TRT group compared to
to placebo (lactose) and also found no significant effect
controls. ADS scores, indicating anxiety and depression,
on THI score between groups. Anxiety and depression
also reduced significantly in the TRT group compared to
were not measured in these studies. Meta-analysis was
controls. The authors noted greater improvement in
notperformed.
individuals with a higher baseline depression score. Fol-
low-up was not well controlled, but the TQ score of the
TRT group remained low after 1 year, whereas ADS DISCUSSION
score returned to baseline after 6 months. As in Caffier The aim of this review was to evaluate the evidence
etal.47treatmentwastailoredtoindividualneed. base for those tinnitus management interventions rec-
The efficacy of TRT may depend on its adaptability ommended by the Department of Health’s Good Practice
asaninterventionratherthanasafixed,protocol-driven Guide.5 Where possible, we aimed to identify the condi-
intervention. The two studies of TRT were not suffi- tions under which these interventions are efficacious,
ciently similartoperformmeta-analysis. andconsiderwhethertheseinterventionsaresufficiently
Laryngoscope 121:July2011 Hoareetal.: Evidence-Basefor Tinnitus Management
1562
researched or in need of further study. We also asked three-armed controlled design seems most appropriate
which patients benefit most, but report little on this (i.e., a formal intervention such as CBT or TRT
question due to limited information in those studies compared to a simpler intervention such as a self-help
reviewed. book) and a no-intervention or waiting-list control. This
In a previous review of RCTs of tinnitus interven- design was used in some studies reviewed here and
tions, Dobie did not find any that demonstrated a partly controls for placebo/nonspecific effects (e.g., learn-
significant benefit of intervention over typically large ing more about tinnitus, clinical contact time) and
placeboeffects.12He concludedthatnowhere in theliter- toward identifying which components of the treatments
ature were there studies similar enough to attempt arelikely responsibleforchange.
meta-analysis. Two recommendations from that review Adequate numbers of participants are also impor-
were that future RCTs needed consensus outcome meas- tant. Only seven of 28 RCTs conducted a power
ures and adequate sample sizes. There is a now calculation of their required sample size, and only five
reasonable consensus in the tinnitus research commu- met that sample size. Power calculations represent a
nity on which validated measures to use.59 In this simple way to improve future study quality in tinnitus
review, the most widely used tinnitus questionnaire was research.
the TRQ. It appeared in 10 of the 28 studies and was By design, all RCTs reviewed here reported vali-
used here in two separate meta-analyses. However, only dated measures of tinnitus intrusiveness, anxiety, or
seven of 28 studies used a power calculation to estimate depression. Although many authors reported clinically
their required sample size. Therefore, more than 10 as well as statistically significant changes, some limited
years on, although we have greater RCT-level evidence their reports to the statistical changes only, which may
and some opportunities for meta-analysis, there is still havenorealmeaningin the clinic.In similarterms,it is
little evidence for the efficacy of most recommended also important to note the significance of nonspecific
treatmentstrategies. effects. For example, Rief et al.42 reported a 5-point
It is striking that many authors ascribed null reduction in TQ score as a significant improvement com-
results for changes in depression and anxiety to the fact pared to waiting-list controls. However, elsewhere in the
that participants have low baseline scores, often quoting literaturea5-pointreductioninTQscore(fromacompa-
floor effects. It may well be that, as authors suggest, rable baseline) was observed between two repeated
more distressed individuals are less likely to put them- measures,62 suggesting that this reduction is within
selves forward for clinical trials. However, it may the expected variability or test-retest value of the mea-
equally be that major depression or other comorbidities sure. More thorough reporting of clinical and statistical
are less common than anecdotally suggested. Studies of significance, or the provision of individual scores, is rec-
theprevalenceofcomorbiddepressionoranxietysuggest ommended for transparency and to facilitate future
it is no more an issues for tinnitus patients than it is for meta-analyses.
non-tinnitus ENT patients.60,61 Given that the screening
and management of anxiety and depression is high-
lighted in the GPG, more routine clinical assessment of CONCLUSION
anxiety and depression at baseline and outcome is Tinnitus care and research has long been and con-
neededtoexplorethisobservation. tinues to be a challenge. The efficacy of most tinnitus
management interventions recommended for clinical
practice remains to be demonstrated conclusively as
Improving the Quality of Tinnitus Research there are currently too few studies to make informed
Of the 28 studies identified, six were rated as low- conclusions. Most studies reviewed here provide only
level evidence, 17 as moderate, and five as high-level moderate levels of evidence largely due to a lack of
evidence (Table I). Unsurprisingly, four of the high-level power and incomplete data reporting. Interventions
trials involved drug therapies. Only one high-level trial most in need of high-level evidence studies are hearing
of CBT was identified. For therapies involving sound aids/sound enrichment and TRT, whereas the efficacy of
enrichment or TRT, studies were rated as providing lit- therapist-delivered CBT appears to be reasonably estab-
tle ornoevidence abovelow-level. lished. If audiologists are to deliver CBT, however, this
The main factor limiting study quality was blinding will require new investigation. Although the overall
of participants to the intervention or expected outcome, quality of CBT studies is moderate, there is sufficient
and blinding of investigators to the expected outcome. consistency within these results to be confident of its
There are ethical limitations to blinding that may be benefit for tinnitus intrusiveness. In terms of pharmaco-
insurmountable; it would be unethical to deliver a psy- therapy, only antidepressant use shows any evidence of
chological intervention such as CBT in a way that is potentialbenefit.
wrong. Blinding of investigators, however, could be used
more routinely as outcomes can easily be measured by a
researcher who is blind to the intervention received. BIBLIOGRAPHY
Only six of 28 studies reported the use of blinding, five
1. Davis A, El Rafaie A. Epidemiology of tinnitus. In: Tinnitus Handbook.
ofwhichweredrugtrials. SanDiego:SingularPublishingGroup;2000:1–23.
Use of appropriate controls is an issue. Given the 2. SteinmetzLG,ZeigelboimBS,LacerdaAB,MorataTC,MarquesJM.The
characteristicsoftinnitusinworkersexposedtonoise.BrazJOtorhino-
nature of some tinnitus management interventions, a laryngol2009;75:7–14.
Laryngoscope 121:July2011 Hoareetal.: Evidence-Basefor Tinnitus Management
1563
3. FerreiraLMBD,RamosJ,MendesEP.Characterizationoftinnitusinthe 34. AnderssonG,PorsaeusD,WiklundM,KaldoV,LarsenHC.Treatmentof
elderlyanditspossiblerelateddisorders.BrazJOtorhinolaryngol2009; tinnitusintheelderly:acontrolledtrialofcognitivebehaviortherapy.
75:249–255. IntJAudiol2005;44:671–675.
4. Kro¨ner-HerwigB,ZachriatC,WeigandD.Dopatientcharacteristicspre- 35. ReissS,PetersonRA,GurksyDM,McNallyRJ.Anxietyseverity,anxiety
dictoutcomeintheoutpatienttreatmentofchronictinnitus?Psychosoc frequencyandthepredictionoffearfulness.BehavResTher1986;24:1–8.
Med2006;3:Doc7. 36. HenryJL,WilsonPH.Anevaluationoftwotypesofcognitiveintervention
5. Department of Health. Provision of Services for Adults With Tinnitus. A in the management of chronic tinnitus. Cogn Behav Ther 1998;27:
Good Practice Guide. Central Office of Information. London, United 156–166.
Kingdom;2009. 37. Kro¨ner-HerwigB,HebingG,vanRijn-KalkmannU,FrenzelA,Schilkow-
6. Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus skyG,EsserG.Themanagementofchronictinnitus—comparisonofa
Handicap Inventory. Arch Otolaryngol Head Neck Surg 1996;122: cognitive-behaviouralgrouptrainingwithyoga.JPsychosomRes1995;
143–148. 39:153–165.
7. GoebelG,HillerW.Thetinnitusquestionnaire.Astandardinstrumentfor 38. RobinsonSK,ViirreES,BaileyKA,etal.Arandomizedcontrolledtrial
gradingthedegreeoftinnitus.Resultsofamulticenterstudywiththe of cognitive-behavior therapy for tinnitus. Int Tinnitus J 2008;14:
tinnitusquestionnaire.HNO1994;42:166–172. 119–126.
8. BeckAT,SteerRA,BallR,CiervoCA,KabatM.UseoftheBeckAnxiety 39. Kro¨ner-Herwig B, Frenzel A, Fritsche G, Schilkowsky G, Esser G. The
andDepressionInventoriesforprimarycarewithmedicaloutpatients. managementofchronictinnitus:comparisonofanoutpatientcognitive-
Assessment1997;4:211–219. behavioral group training to minimal-contact interventions. J Psycho-
9. ZigmondAS,SnaithRP.TheHospitalAnxietyandDepressionScale.Acta somRes2003;54:381–389.
PsychiatricaScandinavica1983;67:361–370. 40. Hautzinger M, Bailer M. Allgemeine Depressionsskala. Go¨ttingen, Ger-
10. HoareDJ,GanderP,CollinsL,SmithS,HallDA.Managementoftinnitus many:Hogrefe;1993.
inEnglishNHSAudiologyDepartments:anevaluationofcurrentprac- 41. Zachriat C, Kro¨ner-Herwig B. Treating chronic tinnitus: comparison of
tice.JEvalClinPract2011;DOI:10.1111/j.1365-2753.2010.01566.x. cognitive-behavioural and habituation-based treatments. Cogn Behav
11. Oxman AD; GRADE working group. Grading quality of evidence and Ther2004;33:187–198.
strengthofrecommendations.BMJ2004;328:1490–1494. 42. RiefW,WeiseC,KleyN,MartinA.Psychophysiologictreatmentofchronic
12. DobieRA.Areviewofrandomizedclinicaltrialsintinnitus.Laryngoscope tinnitus:arandomizedclinicaltrial.PsychosomMed2005;67:833–838.
1999;109:1202–1211. 43. DavisPB,WildeRA,SteedLG,HanleyPJ.Treatmentoftinnituswitha
13. LiberatiA,AltmanDG,TetzlaffJ,etal.ThePRISMAstatementforreport- customized acoustic neural stimulus: a controlled clinical study. Ear
ingsystematicreviewsandmeta-analysesofstudiesthatevaluatehealth NoseThroatJ2008;87:330–309.
careinterventions:explanationandelaboration.BMJ2009;339:b2700. 44. CrownS,CrispAH.ManualoftheCrown-CrispExperientialIndex.Kent,
14. HoareDJ,StaceyPC,HallDA.Theefficacyofauditoryperceptualtrain- UnitedKingdom:Hodder&Stoughton;1979.
ingfortinnitus:asystematicreview.AnnBehavMed2010;40:313–324. 45. HerraizC,DigesI,CoboP,AparicioJM,ToledanoA.Auditorydiscrimina-
15. DohooI,MartinW,StryhnH.VeterinaryEpidemiologicResearch. 2nded. tion training for tinnitus treatment: the effect of different paradigms.
Charlottetown,Canada:VERInc.;2010. EurArchOtorhinolaryngol2010;267:1067–1074.
16. DuvalS,TweedieR.Trimandfill:asimplefunnel-plot–basedmethodof 46. JastreboffPJ,HazellJW.Aneurophysiologicalapproachtotinnitus:clini-
testing and adjusting for publication bias in meta-analysis.Biometrics calimplications.BrJAudiol1993;27:7–17.
2000;56:455–463. 47. CaffierPP,HauptH,SchererH,MazurekB.Outcomesoflong-termoutpa-
17. Henry JA, Loovis C, Montero M, et al. Randomized clinical trial: group tienttinnitus-copingtherapy:psychometricchangesandvalueoftinni-
counseling based on tinnitus retraining therapy. J Rehabil Res Dev tus-controlinstruments.EarHear2006;27:619–627.
2007;44:21–32. 48. Seydel C, Haupt H, Szczepek AJ, Klapp BF, Mazurek B. Long-term
18. Folmer RL, Griest SE, Meikle MB, Martin WH. Tinnitus severity, loud- improvement in tinnitus after modified tinnitus retraining therapy
ness,anddepression.OtolaryngolHeadNeckSurg1999;21:48–51. enhanced by a variety of psychological approaches. Audiol Neurootol
19. HenryJL,WilsonPH.Thepsychologicalmanagementoftinnitus:compari- 2010;15:69–80.
sonofacombinedcognitiveeducationalprogram,educationaloneanda 49. Robinson SK, Viirre ES, Bailey KA, Gerke MA, Harris JP, Stein MB.
waiting-listcontrol.IntTinnitusJ1996;2:9–20. Randomizedplacebo-controlledtrialofaselectiveserotoninreuptakein-
20. KukFK,TylerRS,RussellD,JordanH.Thepsychometricpropertiesofa hibitor in the treatment of nondepressed tinnitus subjects. Psychosom
tinnitushandicapquestionnaire.EarHear1990;11:434–445. Med2005;67:981–988.
21. WilsonPH,HenryJ,BowenM,HaralambousG.Tinnitusreactionques- 50. SullivanM, Katon W, Russo J, DobieR, Sakai C. A randomized trial of
tionnaire: psychometric properties of a measure of distress associated nortriptylineforseverechronictinnitus.Effectsondepression,disabil-
withtinnitus.JSpeechHearRes1991;34:197–201. ity,andtinnitussymptoms.ArchInternMed1993;11:2251–2259.
22. KaldoV,CarsS,RahnertM,LarsenHC,AnderssonG.Useofaself-help 51. HamiltonM.Aratingscalefordepression.JNeurolNeurosurgPsychiatry
book with weekly therapist contact to reduce tinnitus distress: a 1960;23:56–62.
randomizedcontrolledtrial.JPsychosomRes2007;63:195–202. 52. Zo¨gerS,SvedlundJ,HolgersKM.Theeffectsofsertralineonseveretinni-
23. MalouffJM,NobleW,SchutteNS,BhullarN.Theeffectivenessofbiblio- tus suffering—a randomized, double-blind, placebo-controlled study. J
therapyinalleviatingtinnitus-relateddistress.JPsychosomRes2010; ClinPsychopharmacol2006;26:32–39.
68:245–251. 53. ColesRRA,LutmanME,AxelssonA,HazellJWP.Tinnitusseveritygrad-
24. StephensSD,CorcoranAL.Acontrolledstudyoftinnitusmasking.BrJ ings:cross-sectionalstudies.In:AranJ-M,DaumanR,eds.Tinnitus91,
Audiol1985;19:159–167. Proceedings of the Fourth International Tinnitus Seminar, Bordeaux,
25. BiesingerE,KipmanU,Scha¨tzS,LangguthB.Qigongforthetreatment France, August 27-30. Amsterdam, The Netherlands: Kugler Publica-
oftinnitus:aprospectiverandomizedcontrolledstudy.JPsychosomRes tions;1991:453–455.
2010;69:299–304. 54. HamiltonM.Theassessmentofanxietystatesbyrating.BrJMedPsy-
26. Greimel KV, Leibetseder M, Unterrainer J, Albegger K. Can tinnitus be chol1959;32:50–55.
measured? Methods for assessment of tinnitus-specific disability and 55. LectenbergR,ShulmanA.Benzodiazepinesinthetreatmentoftinnitus.J
presentation of the Tinnitus Disability Questionnaire. HNO 1999;47: LaryngolOtol1984;98(suppl9):271–276.
196–201. 56. JalaliMM,KoushaA,NaghaviSE,SoleimaniR,BananR.Theeffectsof
27. Ireland CE, Wilson PH, Tonkin JP, Platt-Hepworth S. An evaluation of alprazolamontinnitus:across-overrandomizedclinicaltrial.MedSci
relaxationtraininginthetreatmentoftinnitus.BehavResTher1985; Mon2009;15:I55–I60.
23:423–430. 57. NeriG,BaffaC,DeStefanoA,etal.Managementoftinnitus:oraltreat-
28. SpeilbergerCD,GorsuchRL,LusheneRE.STAIManual.PaloAlto,Cali- mentwithmelatoninandsulodexide.JBiolRegulandHomeostAgents
fornia:ConsultingPsychologistsPress;1970. 2009;23:103–110.
29. WeiseC,HeineckeK,RiefW.Biofeedback-basedbehavioraltreatmentfor 58. RosenbergSI,SilversteinH,RowanPT,OldsMJ.Effectofmelatoninon
chronictinnitus:resultsofarandomizedcontrolledtrial.JConsutlClin tinnitus.Laryngoscope1998;108:305–310.
Psychol2008;76:1046–1057. 59. LangguthB, GoodeyR, AzevedoA,et al.Consensusfortinnitus patient
30. Andersson G, StromgrenT, Strom L, Lyttkens L. Randomizedcontrolled assessment and treatment outcome measurement: Tinnitus Research
trialofinternet-basedcognitivebehaviortherapyfordistressassociated Initiative meeting, Regensburg, July 2006. Prog Brain Res 2007;166:
withtinnitus.PsychosomMed2002;64:810–816. 525–536.
31. AbbottJA,KaldoV,KleinB,etal.Aclusterrandomisedtrialofaninter- 60. AdogaAA,AdogaAS,ObindoJT.Tinnitusandtheprevalenceofco-morbid
net-based intervention program for tinnitus distress in an industrial psychologicalstress.NigerJMed2008;17:95–97.
setting.CognBehavTher2009;38:162–173. 61. Grunfeld EA, Gresty MA, Bronstein AM, Jahanshahi M. Screening for
32. KaldoV,LevinS,WidarssonJ,BuhrmanM,LarsenHC,AnderssonG.Inter- depressionamongneuro-otologypatientswithandwithoutidentifiable
netversusgroupcognitive-behavioraltreatmentofdistressassociatedwith vestibularlesions.IntJAudiol2003;42:161–165.
tinnitus:arandomizedcontrolledtrial.BehavTher2008;39:348–359. 62. DohrmannK,ElbertT,SchleeW,WeiszN.Tuningthetinnitusperceptby
33. Lovibond SH, Lovibond PF. Manual for Depression, Anxiety and Stress modificationofsynchronousbrainactivity.RestorNeurolNeurosci2007;
Scales.Sydney,Australia:PsychologicalFoundationofAustralia;1995. 25:371–378.
Laryngoscope 121:July2011 Hoareetal.: Evidence-Basefor Tinnitus Management
1564