Nummer in search

Auteur, jaartal

Inclusie/Exclusie

Reden van exclusie

Cognitieve gedragstherapie (CGT)

2

Cima, 2014

Exclusie

Niet –gerandomiseerde studies, longitudinale/ follow-up studies en experimentele studies worden niet meegenomen. Van de studies die verschenen zijn na Martinez –Devesa, 2010 (Cochrane review) voldoet één studie aan de PICO (Cima, 2012). Deze is geïncludeerd.

10

Nyenhuis, 2013

Exclusie

Gaat over ‘self –help’ interventies

32

Hoare, 2011

Exclusie

Er is een review met hogere kwaliteit studies. High drop –out voornaamste reden voor exclusie of andere vergelijking (internet CBT versus CBT)

31

Hesser, 2011

Exclusie

Studies die voldoen aan PICO worden meegenomen in review Martinez –Devesa, 2010

57

Rief, 2005

Exclusie

Wordt meegenomen in review Martinez –Devesa, 2010

64

Andersson, 1999

Exclusie

Recentere review is verschenen (Martinez –Devesa, 2010)

Cochleaire implantatie

7

Vlastarakos, 2014

Exclusie

Geen exacte data beschikbaar en studies komen terug in Blasco, 2014

repetitieve Transcraniële Magnetische Stimulatie (rTMS)

12

Theodoroff, 2013

Exclusie

Studies komen terug in review Meng, 2011 (cross –over trials not included)

21

Muller, 2012

Exclusie

Er is een hogere kwaliteit review (Meng, 2011)

22

Peng, 2012

Exclusie

Studies komen terug in review Meng, 2011 (cross –over trials not included)

Overig

4

Hoare, 2014

Exclusie

Geen vergelijking met placebo, sham of gebruikelijke zorg (hearing aids versus sound generator)

8

Hilton, 2013

Exclusie

Andere interventie: ginkgo biloba

14

Baldo, 2012

Exclusie

Andere interventie: anti depressiva

16

Bennett, 2012

Exclusie

Andere interventie: hyperbare zuurstof

20

Kim, 2012

Exclusie

Andere interventie: acupunctuur

26

Savage, 2012

Exclusie

Bekijkt meerdere interventies, relevante reviews worden al bij betreffende uitgangsvraag geïncludeerd

33

Hoekstra, 2011

Exclusie

Andere interventie: Anticonvulsants

38

Hoare, 2011

Exclusie

Andere interventie: auditory perceptual training

43

Li, 2009

Exclusie

Andere interventie: acupunctuur

65

Dobie, 1999

Exclusie

Recentere reviews zijn verschenen

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/ notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Tinnitus Retraining Therapie (TRT)

Philips, 2010

Yes

Yes

Yes

Yes

n.a.

Yes, Cochrane Handbook à allocation, attrition and detection bias

n.a.

No

Yes

Cognitieve gedragstherapie (CGT)

Martinez –Devesa, 2010

Yes

Yes

Yes

Yes, method of reporting, drop outs and inclusion criteria

n.a.

Yes, Cochrane Handbook à allocation, attrition and detection bias.*

Yes**

No

No

Geluids verrijkende therapie

Hobson, 2012

Yes

Yes

Yes

Yes

n.a.

Yes, Cochrane Handbook à allocation, attrition and detection bias

No

No

No

Cochleaire implantatie

Blasco, 2014

Yes

Yes

No

Yes

Unclear

No

Yes

No

Yes

repetitieve Transcraniële Magnetische Stimulatie (rTMS)

Meng, 2011

Yes

 Yes

Yes

Yes

 n.a.

Yes

No

Yes

No

Transcranial Direct Current Stimulation (TDCS)

Song, 2012

Yes

No

No

No (important patient characteristics of the included studies (age, sex, etc.) are not reported in the article)

N.a.

No

Yes

No (only studies were included in which percentage of change in tinnitus intensity was directly available)

1. 1.        Yes

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate  concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Cima et al., 2012

Computer-generated allocation sequence in a 1:1 ratio

unlikely

unlikely

unlikely

unlikely

unlikely

unlikely

unlikely

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Tinnitus Retraining Therapie (TRT)

Philips, 2010

individual study characteristics deduced from Philips, 2010

SR of RCTs

Literature search up to August 2009

A: Henry, 2006

Study design: Randomised controlled trial

Setting and Country:

Patients were recruited from a cohort of US military veterans.

Source of funding:

Not stated.

Inclusion criteria:

Military veterans (> 16 years) complaining of tinnitus.

Exclusion criteria:

Patients with pulsatile tinnitus or tinnitus in association with

otosclerosis, Ménière’s disease or tumours of the cerebellopontine

angle.

1 study included

Important patient characteristics at baseline:

N, age

123 patients, age not reported

Sex:

95% Male

Groups comparable at baseline?

Unclear.

Tinnitus retraining therapie (TRT):

a form of educational counselling and sound therapy given according to a specific protocol.

Tinnitus masking (TM)

End-point of follow-up:

18 months

For how many participants were no complete outcome data available?

12 patients

Tinnitus severity:

Defined as tinnitus severity

using three instruments (Tinnitus Handicap Inventory (THI), Tinnitus

Handicap Questionnaire (THQ), Tinnitus Severity Index (TSI)) for patients in three groups (’moderate

problem’, big problem’ or ’very big problem’).

At 18 months, improvements in three scores (TRT versus TM):

’moderate problem’:

THI: 18.2 versus 4.6

THQ: 489 versus 178

TSI: 7.5 versus 1.6

’big problem’:

THI: 29.2 versus 16.7

THQ: 799 versus 256

TSI: 12.1 versus 6.7

’very big problem’:

THI: 50.4 versus 10.3

THQ; 1118 versus 300

TSI: 19.7 versus 4.8

Quality of life:

Not reported.

Adverse effects:

Not reported.

High risk of bias. The

authors of the study used a non-specified form of random allocation

for the first patient, followed by alternation between treatment and control groups. The study was not blinded but issues

regarding incomplete data were addressed appropriately and all

data were presented in full.

Finally, the research sample may not be representative of the general tinnitus population. The age distribution of subjects, preponderance of male subjects and history

of acoustic trauma may be skewed in subjects from a veterans’ hospital; this might limit general applicability of the results.

Cognitieve gedragstherapie (CGT)

Martinez – Devesa, 2012

individual study characteristics deduced from Martinez –Devesa, 2012

SR and meta-analysis of  RCTs

Literature search up to 6 May 2010

A: Anderson 2005

B: Henry 1996

C: Kaldo 2007

D: Kroner Herwig 1995

E: Kroner Herwig 2003

F: Rief 2005

G: Weise 2008

H: Zachriat 2004

Study design:

A: Randomised controlled tria

B: Randomised controlled trial

C: Randomised controlled trial

D: Randomised controlled trial. Randomisation by drawing code numbers from a basket with the total sample

E: Randomised controlled trial. Randomisation by drawing code numbers from the total sample and the

sequential assignment to the treatment conditions until a pre-set number of subjects was reached

F:  Randomised controlled trial. Randomisation by a list of random sequence

G: Randomised controlled tria

H: Randomised controlled trial. Randomisation by throwing dice.

Setting and Country:

The participants invited to take part in these studies were recruited

from the general population through newspaper, internet

or other media adverts, attending the outpatient department or a combination of both methods .

Source of funding:

Not stated

Inclusion criteria SR: patients with unilateral or bilateral tinnitus as main symptom

Exclusion criteria SR: patients with pulsatile tinnitus and other somatic sounds, delusional auditory hallucinations and patients undergoing concurrent psychotherapeutic interventions.

8  studies included, 468 participants

Important patient characteristics at baseline:

The  participants were homogeneously

distributed between the different groups of the studies

and, with respect to age, sex and the various degrees of severity of both tinnitus and depression associated with tinnitus, could be

considered to be representative of the typical patient that attends

an outpatient clinic.

N, mean age

A: 23 patients, 70.1 yrs

B: 60 patients, 64 yrs

C: 72 patients, 45.9 yrs

D: 43 patients, 38 yrs

E: 95 patients, 46.8 yrs

F: 43 patients, 46.75 yrs

G: 111 patients, 51 yrs

H: 77 patients, 53.8 yrs

Sex:

A: 52 % Male

B: 86 % Male

C: 50% Male

D: 60.5% Male

E: 48.4% Male

F: 53.25% Male

G: 46% Male

H: 66.6% Male

Groups comparable at baseline?

Yes

Cognitive behavioural therapy treatment consisted of six to 11

group sessions (six to eight individuals) of 60 to 120 minutes duration, with a qualified psychologist or student psychologists

under supervision or the use of a self-help book and

weekly therapist contact.

A: CBT (12pt)

B: Combined cognitive educational programme (pt per group unknown)

C: CBT: This was administered by a self-help book and 7 weekly

phone calls from a therapist over a period of 6 weeks (34 pt)

D: (1) Tinnitus Coping Training 1 (TCT1 = 7 patients)

(2) Tinnitus Coping Training 2 (TCT2 = 8 patients

E: Tinnitus Coping Training

F: Psychophysiologically-oriented intervention (23 patients)

The psychophysiologically-oriented intervention comprised 9 sessions of 60 minutes duration conducted by 5 supervised graduate student psychologists

G: Biofeedback-based behavioural intervention (52 patients) The biofeedback-based behavioural intervention consisted of 12 individual therapy sessions of 60 minutes duration conducted by 4 trained therapists. Each session contained biofeedback as well as CBT elements

following a structured manual

H: Tinnitus Coping Training (TCT = 29 patients)

No treatment or other treatments

Most of the studies compared cognitive behavioural therapy to

a waiting list control and/or other intervention/s, namely educational,

yoga or other psychotherapeutic treatment, in two to

four study arms.

A: waiting list  (11 pt)

B: (A) Education alone (both treatments involved a 90-minute session per week for 6 weeks, given by the

same clinical psychologists, in groups of 5 to 7 participants)

(B) A waiting-list control

C: Waiting list (38 pt)

D: (3) Yoga training (9 patients)

(4) A waiting list control (WLC = 19 patients)

E: (2) ’Minimal contact - education’ (MC-E = 16 patients)

(3) Minimal Contact - Relaxation (MC-R = 16 patients)

(4) A waiting list control (WLC = 20 patients)

F: A waiting list control (WLC = 20 patients)

G: A waiting list control (59 patients)

H: Habituation-based treatment (HT = 31 patients), Educational intervention (EDU = 23 patients)

All studies aimed to report results at baseline (pre-treatment), posttreatment

and at follow-up periods that varied from three to 18

months. Reporting of patients lost during treatment and follow up was good with total drop-out varying from 4.65%

to 21.66%, which would be more than adequate for these types of trials.

End-point of follow-up:

A: 6 weeks (3 month-measurement unable to use)

B: 12 months

C: 12 months

D: 3 months

E: 6 months

F:  6 months

G: 6 months

H: 18 months

For how many participants were no complete outcome data available?

(intervention/control)

A:No drop-outs

B: Drop-out 21.66%

C: Drop-out 12%

D: Drop-out 20.9%

E: Drop out 22.1%, 13/43 TCT, 4/16 MC-E, 4/16 MC-R

F: Drop-out 4.65% (2 patients, 1/23 i-group, 1/20 c-group)

G: Drop-out 14.6%

H: Drop-out 10.4% (2/29 in the TCT group, 1/31 in

HT group and 3/23 in EDU group)

The assessment tools used in these studies varied

greatly, but could be divided in three main groups:

1. audiological;

2. psychometric questionnaires and well-being scales (such as

Tinnitus Questionnaire and Tinnitus Handicap Questionnaire);

and

3. subjective score in a tinnitus diary (loudness, tinnitus

awareness and tinnitus control etc.).

Tinnitus severity:

Defined as subjective tinnitus loudness, measured on a numeric scale.

Effect measure: Std. Mean Difference [95% CI]:

B: -0.01 [ -0.63, 0.61 ]

C: 0.14 [ -0.33, 0.60 ]

D: 0.09 [ -0.70, 0.88 ]

E: 0.13 [ -0.40, 0.67 ]

F: 0.03 [ -0.58, 0.64 ]

G: 0.72 [ 0.33, 1.10 ]

Pooled effect (random effects model):

0.24 [95% CI -0.02, 0.51 ]

favoring treatment (CBT vs waiting list)

Heterogeneity (I²): 32%

Sensitivity analysis: Excluding Weise 2008: effect size 0.09 (95% CI -0.17 to 0.34; I²

= 0%).

Quality of life:

Defined as evaluation of quality of life for patients (tinnitus handicap questionnaire or other validated assessment method.

Effect measure: Std, mean difference [95% CI]:

A: 0.34 [ -0.49, 1.16 ]

B: 0.75 [ 0.10, 1.39 ]

C: 0.78 [ 0.30, 1.26 ]

E: 0.84 [ 0.29, 1.39 ]

G: 1.56 [ 1.13, 1.98 ]

Pooled effect (random effects mode):

0.91 [95% CI  0.50, 1.32 ]

favoring treatment (CBT vs waiting list)

Heterogeneity (I²): 63%

Sensitivity analysis: Excluding Weise 2008: effect size SMD 0.73 (CI 0.44 to 1.03; I2 = 0%).

Adverse effects:

worsening of symptoms, suicidal tendencies, negative thoughts.

à there were no adverse/side effects reported in any trial.

It was impossible to analyse long-term follow up as in all trials that use waiting list control groups, the participants in these groups end up receiving the same treatment after the initial waiting period.

Geluidsverrijkende therapie

Hobson et al., 2012

individual study characteristics deduced from Hobson, 2012

SR of RCTs

Literature search up to February 2012.

A: Dineen, 1999

B: Goebel, 1999

Study design: Randomised controlled trials

Source of funding:

None, not specified.

Inclusion criteria:

Adults in whom there is a complaint of persistent, distressing, subjective tinnitus of any aetiology

Exclusion criteria:

A: not reported

B: patients with Meniere’s disease, acoustic neuroma, otosclerosis, severe general health problems or psychoses.

2 studies included

Important patient characteristics at baseline:

N, mean age

A: 96 patients, 54.37 years

B: 52 patients, 44 years

Sex:

A: 62.5% Male

B: not reported

Groups comparable at baseline?

Yes

Sound therapy

A: Two groups:

1) information plus long-term, low-level white noise

2) information plus relaxation plus

long-term, low-level white noise.

Sound therapy

was provided with custom-made Starkey devices providing

stable wide-band noise with as wide a frequency range as possible.

B: Noise generators (Viennatone

Silent Star)

Placebo, sham or usual care

A: Two groups:

1) information only

2) information plus relaxation

Information consisted of general

pathophysiological information on tinnitus as well as information

on coping strategies and stress reduction techniques.

Relaxation involved a relaxed breathing technique and the use of

positive mental imagery.

B: No treatment

End-point of follow-up:

A: not reported

B: 4 months

For how many participants were no complete outcome data available?

(intervention/control)

A: 13

B: not reported

Tinnitus severity:

A: Defined as subjective measures of tinnitus perception (visual analogue scales and (TRQ). There were relative decreases of

41.5% for visual acuity scale of tinnitus loudness,

64.6% for visual acuity scale of tinnitus annoyance,

24.6% for visual acuity scale of tinnitus coping,

73.9% for TRQ and

30.8% for change awareness. Only relative percentage change with no other data were given and no confidence intervals quoted.

B: No significant difference in VAS –score of tinnitus annoyance.

I: TQ dropped from 56 ±9 to

55 ±13. Not significant.

C: TQ remained unchanged (54 ±8)

Quality of life:

Not reported

Adverse effects:

Not reported

Cochleaire implantatie

Blasco, 2014

SR en meta-analysis

Literature search up to June 2013

A: Van de Heyning, 2008

B: Arndt, 2010

C: Ramos, 2012

Study design:

Case series

Setting and Country:

A: University Hospital Antwerp, Belgium

B: University Medical Center Freiburg, Freiburg, Germany

C: Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Hospital Ramón y Cajal, Madrid, Spain

Source of funding:

Not reported

Inclusion criteria:

Patients with sudden profound unilateral hearing loss with normal thresholds remaining in the contralateral ear. Cause of hearing loss was acute and rapidly progressive. Aetiologies of sudden hearing loss included sudden sensorineural hearing loss, acute traumatic or postoperative hearing loss, and acute hearing loss secondary to acute infection.

Exclusion criteria:

Patients that were included in more than one study

3 studies included

Important patient characteristics at baseline:

N, (N selected for analysis by Blasco, 2014)

A: 21(9)

B: 11(9)

C: 10(4)

Mean age at hearing loss (yr)

A: 40,78 (20,0-60,0)

B: 36,94 (22,7-65,4)

C: not reported

Mean age at CI (yr)

A: 46,67 (22-62)

B: 42,44 (23-68)

C: 42,7 (34-62)

Describe intervention:

Cochlear implantation (CI)

A: Implantation of a multichannel CI

B: All subjects received the Nucleus Freedom Implant and use the Nucleus Freedom speech processor

C: All patients had been implanted and, depending on the degree of their hearing loss, were carriers

of a cochlear implant model Freedom, 

Nucleus

CI

512

(1)

or

Nucleus

Hybrid

L24

(5)

(Table

2).

Describe  control:

In all three studies, patients served as their own control; severity of tinnitus was scored before and after CI

End-point of follow-up:

Length of follow-up (mo):

A: 6-24

B: 6

C: 3-18

For how many participants were no complete outcome data available?

Not reported

Tinnitus severity:

Mean difference in reduction in severity of tinnitus on the tinnitus VAS-scale between no CI and CI, [95%-CI] (fixed model):

A: 5.94 [4.62, 7.26]

B: 3.66 [1.25, 6.07]

C: 5.00 [3.20, 6.80]

Mean tinnitus severity reduction is 5,29 [95% CI 4,32, 6,27].

P<0,00001, I²= 28%

Quality of life:

not reported

Side-effects:

not reported

Facultative:

Caveats for this meta-analysis and systematic review are that the actual numbers of patients in each branch of the study remain low

repetitieve Transcraniële Magnetische Stimulatie (rTMS)

Meng, 2011

SR and meta-analysis of RCTs

Literature search up to May 2011.

A: Anders, 2010

B: Ghossaini, 2004

C: Khedr, 2008

D: Marcondes, 2010

E: Roland, 1993

Study design: Randomised controlled trials

Setting and Country:

A: Teaching hospital, Charles university, Czech republic

B: Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, USA.

C: University hospital, Egypt

D: Tinnitus Research Group of University of Sao Paulo school of Medicine, Brazil

E: Liverpool Tinnitus Association, UK

Source of funding:

None, not specified.

Inclusion criteria:

Patients experiencing unilateral or bilateral tinnitus for more than 6 months.

Exclusion criteria:

Patients with pulsatile tinnitus and other somatic sounds, auditory hallucinations and patients with a history of epilepsy, severe psychiatric or internal disease, cardiac pacemakers,

or any other kind of metal implant.

5 studies included

Important patient characteristics at baseline:

N, age

A: 52 patients, 18 -70 yrs

B: 37 patients, 23 -83 years

C: 66 patients (16 in 1 Hz group, 17 in 10 Hz group, 17 in 25 Hz group), mean 41 yrs (SD 15)

D: 20 patients, over 18 years

E: 58 patients, 36 -82 yrs

Sex:

A: 55.8% Male (completed)

B: not reported

C: 40.9% Male

D: not reported

E: not reported

Groups comparable at baseline?

Yes.

Repetitieve transcranial

magnetic stimulation (rTMS) delivered through a focal coil

A: 2 × 5 sessions, 1 Hz rTMS, stimulation intensity 110% of the

individual resting motor threshold, 1500 stimuli per session, coil position over the left

primary auditory cortex

B: Used the Diapulse device (model D103) 3 times per week for 1 month. High-frequency

(27.12 MHz) pulsed electromagnetic energy in 65-μs bursts with a repetition rate of

600 pulses per second at 975 W peak and a 6-inch penetration depth

C: Each patient received 5 daily sessions of rTMS for 2 consecutive weeks. Giving 1500 pulses at 1, 10 or 25 Hz daily for 2 weeks

over the region of the left auditory cortex

D: Five sessions of rTMS were performed on 5 consecutive business days. At each session of 17 minutes, 1020 stimuli were administered with an intensity of 110% motor threshold at a frequency of 1 Hz over the left temporoparietal cortex

E: 15 minutes per day for 1 week

The device was placed over the top of the neck and mastoid process of each ear

Sham rTMS delivered through a focal coil

A: Sham stimulation by distortion of the magnetic coil 45° away from the skull with one wing touching the skull

B: Placebo machines were identical in appearance, sounds and presence of light when

activated

C: 1 Hz over the occipital cortex

D: A sham coil system which mimics the sound of active stimulation, without producing a

magnetic field

E: Disabled devices displayed a red light when turned on

End-point of follow-up:

A: 26 weeks

B: 1 month

C: 4 months

D: 6 months

E: unclear, each patient was treated for one week

For how many participants were no complete outcome data available?

(intervention/control)

A: I: 4, C: 6 (19.2%)

B: 2 (5.0%)

C: none

D: 1 (5.0%)

E: 4 (6.9%)

Tinnitus severity:

Defined as tinnitus severity

using validated tinnitus specific questionnaires (THI or TQ)

A and D: compared THI score difference pre /post treatment

B: categorized the severity and disability pre- and post-treatment based on THI score: no handicap to mild handicap (0 to 36) and moderate to severe handicap (38 to 100)

C: categorised the patients’ improvement based on THI score: good (reduction of THI > 80%), partial (21% to 80% reduction) and none (0%to 20%reduction) pre-, post-treatment and at 4 months

Low frequency (1 Hz):

Effect measure: RR [95% CI]:

A: after 26 weeks:

5.57 (95% CI -8.03 -19.17) P=0.42 favours control

C: after 4 months:

Good improvement: 0.33 (95% CI 0.04 – 2.87) P=0.32)

Partial improvement 12.00 (95% CI 1.76 – 81.74) P =0.011)

No improvement: 0.25 (95% CI 0.09 – 0.72) P=0.010

D: after 6 months:

-6.8 (95% CI -25.85 -21.55) P=0.48 favours experimental

High frequency (10, 25 Hz):

Effect measure: RR [95% CI]:

B: no statistical change (data not reported)

C: after 4 months:

Good improvement: 1.73 (95% CI 0.56 – 5.34) P=0.34)

Partial improvement: 6.59 (95% CI 0.95 – 45.84) P =0.057)

No improvement: 0.35 (95% CI 0.19 – 0.66) P=0.001

Improvement of tinnitus loudness:

Using selfrating scales.

B and E:

Abolished: Not estimable (N=0)

B and E:

Improved: RR 4.17 (95% CI 1.30 – 13.40) P =0.016

B:

Unchanged: RR 1.03 (95% CI 0.64 – 1.66) P =0.90

B:

Worse:  

RR 0.76 (95% CI 0.24 – 2.35) P= 0.63

Quality of life:

Improvement of depression and mood disturbances by VAS 2 on a scale of 0 (no disruption at all) to 10 (disrupts them quite seriously) after 26 weeks

A: RR 12.72 (95% CI -3.85 – 29.29) P= 0.13

Adverse effects:

Severe: epileptic seizures;

Not severe: worsening of symptoms, changes in auditory threshold, sensation of pain during stimulation, headache and other side effects associated with rTMS that do not threaten life.

àNo serious adverse effects were reported in any of the trials.

àA, B,C: Non-severe adverse effects (worsening of tinnitus)

I: 11/94 patients

C: 5/59 patients

P=0.46 (odds ratio 1.54, 95%CI 0.50 to 4.74)

Each study described the use of a different rTMS device that delivered different waveforms at different frequencies.

Studies suggest that rTMS is a safe treatment for tinnitus in the short-term, however there were insufficient data to provide any support for the safety of this treatment in the long-term.

Transcranial Direct Current Stimulation (TDCS)

Song, 2012

SR and meta-analysis of open-label studies and RCTs

Literature search from January, 1998 up to August, 2002

A: Fregni, 2006

B: Garin, 2011

Study design

2 RCTs

Setting and Country:

A: Harvard Medical School, Boston, MA, USA.

B: CHU Mont-Godinne, Université Catholique de Louvain, Belgium.

Source of funding:

Not reported

Inclusion criteria SR:

Inclusion criteria for the meta-analysis:

1. articles published in a peer-reviewed journal

2. reporting on tDCS in the management of tinnitus

3. dealing with original data of open-label or RCT with tinnitus loudness as the outcome measure

4. performed by randomized parallel or crossover design, with sham control

5. both participants and raters were unaware of treatment condition

A: Chronic tinnitus

B: (1) tinnitus that could not be cured by other means, (2) stable tinnitus for at least 2 months, (3) age 18–80 years, and (4) stable hypoacousia.

Exclusion criteria SR: articles other than review, human species and English language

A: Not reported

B: (1) Meniere’s disease or fluctuating audition, (2) pure transduction hearing loss, (3) hyperacousia, (4) major cognitive impairment or psychiatric disorders, (5) severe comorbidity (e.g., heart failure, unstable diabetes), (6) contraindications to tDCS, including epilepsy, (7) chronic intake of alcohol or drugs that chronically affect brain functions (e.g., antidepressants, antiepileptics) stopped less than 1 month ago, and (8) pregnancy

2 RCTs are included in the meta-analysis

Important patient characteristics at baseline:

N

A: 7

B: 20

Mean age (yr):

A: 51,7 (± 8,4)

B: 50.9 (± 12.9)

Describe intervention:

Active Transcranial Direct Current Stimulation (tDCS)

A: Direct current was transferred by a saline-soaked pair of surface sponge electrodes (35 cm2) and delivered by a specially developed, battery-driven, constant current stimulator with a maximum output of 10 mA. Each patient received anodal and cathodal stimulation of LTA and sham stimulation

B: Transcranial direct current stimulation was delivered by an Eldith DC-Stimulator through electrodes embedded in sponges soaked with NaCl 0.9%. The target cortical area was the left temporoparietal area (LTA), defined as being halfway between C3 and T5 measured with the 10-20 international EEG system. A 35 cm2 electrode was positioned over the LTA and a 50 cm2 electrode was positioned on the right scalp between T4 and F8

Duration

A: 3 minutes

B: 20 minutes

Describe  control:

Sham tDCS

A: For sham stimulation, the electrodes were placed in the same position; however, the stimulator was turned off after 5 seconds

B: For sham tDCS, the polarity of the LTA electrode was anodal in 50% of the patients; after a short up-ramp, brief current pulses (110 lA over 15 ms, peak current 3 ms) were delivered every 550 ms, eliciting a tingling sensation similar to that felt during real stimulation

Duration

A: 5 seconds

B: 20 minutes

End-point of follow-up:

A: Follow-up period not reported

B: 2 weeks’ wash-out period between active and sham sessions

For how many participants were no complete outcome data available?

(intervention/control)

Not reported

Tinnitus severity:

Reduction of tinnitus intensity: Measured with the Visual Analogue Scale tinnitus reduction (score 0-4)

A: 0,936 [95% CI -0,104 to 1,976] in favor of active tDCS

B: 0,709 [95% CI 0,082 to 1,336] in favor of active tDCS

Pooled effect (random model effect sizes): Hedges’s g effect size: 0,77 [95% CI 0,233 to 1,307] favoring active tDCS.

Quality of life:

not reported

Adverse effects:

A: No side effects were reported by patients included in this study

B: not reported

Facultative:

“The efficacy of tDCS in tinnitus could not be fully confirmed by the current study because of

the limited number of studies, but all studies included in the current systemic review and meta-analysis demonstrated significant

tinnitus intensity improvement”

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Cima et al., 2012

Type of study:

RCT

Setting:

Outpatient clinic for audiological

rehabilitation. Patients from Adelante Department of Audiology and

Communication (Hoensbroek) between September 2007 and January 2011.

Country:

Netherlands

Source of funding:

Netherlands Organisation for Health Research and Development (ZonMW).

Inclusion criteria:

Adult patients with a primary

complaint of subjective tinnitus

Exclusion criteria:

Patients who were unable to read and write in Dutch, had health issues that impaired

attendance or prevented participation (eg, terminal illness or physical disability), or had undergone treatment

at the centre within 5 years before trial enrolment

N total at baseline:

Intervention: 245

Control: 247

Important prognostic factors²:

Mean age (SD), years:

I: 53.7 (11.1)

C: 54.6 (12.0)

Sex:

I: 65% M

C: 61% M

Groups comparable at baseline?

Yes.

Stepped-wise cognitive behaviour therapy (CBT)-based specialized care (SC)

Step 1: Audiological diagnostics and counseling, 2 hr educational group session, psychological intake and counseling

Step 2: CBT group

therapy

Group sessions (intensity varies across group treatments A, B, and C)

CBT; Psychoeducation,

Cognitive restructuring,

exposure techniques, mindfulnessbased

elements, stress relief and

attention redirecting techniques by means of movement therapy, applied relaxation, and themed group

counseling sessions (including

partners)

Usual care (UC)

Step 1: Audiological

diagnostics, prescription

of sound generators/hearing

aids, information

Step 2: Counseling by

social worker (maximally

10 contacts)

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention:

N =74 (30%)

Reasons (describe):

-part of a couple allocated to different treatments

-not able to attend

-not able to proceed (other medical issues)

-did not complete questionnaires

-unable to complete questionnaires due to stress

-not able to complete

Control:

N =86 (35%)

Reasons (describe):

-part of a couple allocated to different treatments

-withdrew

-did not complete questionnaires

-no longer affected by tinnitus

-chose other health-care provider

-not able to proceed (other medical issues)

-died

Tinnitus severity:

Tinnitus severity (TQ) mean (SD) at 12 months

I: 33.43 (16.89)

C: 42.12 (19.81)

P= <0.0001

Tinnitus impairment (THI) mean (SD) at 12 months

I: 26.45 (18.81)

C: 33.51 (23.25)

P= <0.0001

Quality of life:

Health-related quality of life (HUI) mean (SD) at 12 months

I: 0.681 (0.250)

C: 0.631 (0.279)

P= 0.0009

Adverse effects:

No adverse effects.

No waiting list control (WLC) group

The treatment was done in an outpatient clinic for audiological rehabilitation. Thus, whether the results can be generalised to other health-care settings or if generalisability is dependent on their similarity to the present setting is unclear.