Tinnitus – psychiatric comorbidity and treatment using transcranial magnetic stimulation (TMS)

Tinnitus is the perception of sound in the absence of any external noise. It severely impairs the quality of life in 1-2% of people. Tinnitus is frequently associated with depression, anxiety, and insomnia. The exact pathophysiology of tinnitus is still unclear. No curative therapy exists for chronic tinnitus, and treatment focuses on symptomatic relief. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used for treating depression and neuropathic pain. The evidence of its efficacy for chronic tinnitus is still inconclusive, and the optimal treatment protocols are thus still obscure. This thesis aimed to further evaluate the use of rTMS for chronic tinnitus and investigate the psychiatric comorbidity of tinnitus patients. The first (open pilot) study utilized electric field (E-field) navigated rTMS for very severe chronic tinnitus with promising results. In the second (randomized placebo-controlled) study, the effects of 1-Hz E-field rTMS targeted according to the tinnitus pitch to the left auditory cortex were analyzed. Despite the significant improvements in tinnitus, active rTMS was not superior to the placebo, possibly due to large placebo-effect and wide inter-individual variation in treatment efficacy. The third study on parallel groups compared the effects of neuronavigated rTMS to nonnavigated rTMS (based on the 10-20 EEG localization system). Both groups benefitted from the treatment, but the method of coil localization was not a critical factor for treatment outcome. In the fourth study, current and lifetime DSM-IV diagnoses of Axis I (psychiatric disorders) and Axis II (personality disorders) were assessed in tinnitus patients using structured clinical interviews (SCID-I and -II). Tinnitus patients were prone to episodes of major depression, and they often had obsessive-compulsive personality features. Psychiatric disorders in this study seemed to be comorbid or predisposing conditions rather than the consequences of tinnitus.Tinnitus – psykiatrinen sairastavuus ja hoito transkraniaalisella magneettistimulaatiolla (TMS) Tinnituksen ääniaistimus syntyy ilman ulkoista äänilähdettä. Se heikentää vakavasti elämänlaatua 1-2%:lla ihmisistä. Tinnitus yhdistetään usein masennukseen, ahdistukseen ja unettomuuteen. Tinnituksen tarkka syntymekanismi on vielä epäselvä. Pitkäaikaiselle tinnitukselle ei ole parantavaa hoitoa, vaan hoidossa keskitytään oireiden lievittämiseen. Transkraniaalinen magneettistimulaatio sarjapulssein (rTMS) on kajoamaton aivojen toimintaa muokkaava menetelmä, jota käytetään masennuksen ja hermoperäisen kivun hoidossa. Sen teho pitkäaikaiseen tinnitukseen on vielä epävarmaa ja optimaaliset hoitoprotokollat ovat selvittämättä. Tämän väitöskirjan tavoitteena oli arvioida rTMS:n käyttöä pitkäaikaisen tinnituksen hoidossa ja lisäksi tutkia tinnituspotilaiden psykiatrista sairastavuutta. Ensimmäisessä osatyössä (avoin pilotti) käytettiin sähkökenttäohjattua (E-field) navigoivaa rTMS:a pitkäaikaiseen, erittäin vaikeaan tinnitukseen lupaavin tuloksin. Toisessa osatyössä (satunnaistettu lumekontrolloitu) arvioitiin tinnitusäänen korkeuden mukaan vasemmalle kuuloaivokuorelle suunnatun 1- Hz:n sähkökentän mukaan navigoidun rTMS:n vaikutuksia. Vaikka tinnitus helpottui merkittävästi, ei aktiivi-rTMS ollut lumehoitoa parempi, mahdollisesti johtuen suuresta lumevaikutuksesta ja laajasta yksilöiden välisestä vaihtelusta hoidon tehossa. Kolmannessa osatyössä verrattiin rinnakkaisryhmien välillä neuronavigoidun rTMS:n ja sokko rTMS:n (10-20 EEG-systeemiin perustuva paikannus) vaikutuksia. Molemmat ryhmät hyötyivät hoidosta, eikä kelan paikannusmenetelmä ollut ratkaiseva tekijä hoidon lopputuloksen kannalta. Neljännessä osatyössä nykyiset ja elämänaikaiset akselin I (psykiatriset häiriöt) ja akselin II (persoonallisuushäiriöt) DSM-IV diagnoosit määritettiin tinnituspotilailta käyttäen strukturoituja psykiatrisia haastatteluja (SCID-I ja -II). Tinnituspotilaat olivat alttiita vakaville masennusjaksoille ja heillä oli usein vaativan persoonallisuuden piirteitä. Psykiatriset häiriöt vaikuttivat olevan ennemmin samanaikaisia tai altistavia tiloja kuin tinnituksen seurauksena ilmaantuneita häiriöitä

Neuronavigated Versus Non-navigated Repetitive Transcranial Magnetic Stimulation for Chronic Tinnitus: A Randomized Study

Repetitive transcranial magnetic stimulation (rTMS) has shown variable effect on tinnitus. A prospective, randomized 6-month follow-up study on parallel groups was conducted to compare the effects of neuronavigated rTMS to non-navigated rTMS in chronic tinnitus. Forty patients (20 men, 20 women), mean age of 52.9 years (standard deviation [SD] = 11.7), with a mean tinnitus duration of 5.8 years (SD = 3.2) and a mean tinnitus intensity of 62.2/100 (SD = 12.8) on Visual Analog Scale (VAS 0–100) participated. Patients received 10 sessions of 1-Hz rTMS to the left temporal area overlying auditory cortex with or without neuronavigation. The main outcome measures were VAS scores for tinnitus intensity, annoyance, and distress, and Tinnitus Handicap Inventory (THI) immediately and at 1, 3, and 6 months after treatment. The mean tinnitus intensity (hierarchical linear mixed model: F3 = 7.34, p = .0006), annoyance (F3 = 4.45, p = .0093), distress (F3 = 5.04, p = .0051), and THI scores (F4 = 17.30, p F3 = 2.96, p = .0451) favoring the non-navigated rTMS. Reduction in THI scores persisted for up to 6 months in both groups. Cohen’s d for tinnitus intensity ranged between 0.33 and 0.47 in navigated rTMS and between 0.55 and 1.07 in non-navigated rTMS. The responder rates for VAS or THI ranged between 35% and 85% with no differences between groups (p = .054–1.0). In conclusion, rTMS was effective for chronic tinnitus, but the method of coil localization was not a critical factor for the treatment outcome.</p

Neuronavigated Versus Non-navigated Repetitive Transcranial Magnetic Stimulation for Chronic Tinnitus: A Randomized Study

Repetitive transcranial magnetic stimulation (rTMS) has shown variable effect on tinnitus. A prospective, randomized 6-month follow-up study on parallel groups was conducted to compare the effects of neuronavigated rTMS to non-navigated rTMS in chronic tinnitus. Forty patients (20 men, 20 women), mean age of 52.9 years (standard deviation [ SD ] = 11.7), with a mean tinnitus duration of 5.8 years ( SD  = 3.2) and a mean tinnitus intensity of 62.2/100 ( SD  = 12.8) on Visual Analog Scale (VAS 0–100) participated. Patients received 10 sessions of 1-Hz rTMS to the left temporal area overlying auditory cortex with or without neuronavigation. The main outcome measures were VAS scores for tinnitus intensity, annoyance, and distress, and Tinnitus Handicap Inventory (THI) immediately and at 1, 3, and 6 months after treatment. The mean tinnitus intensity (hierarchical linear mixed model: F 3  = 7.34, p  = .0006), annoyance ( F 3  = 4.45, p  = .0093), distress ( F 3  = 5.04, p  = .0051), and THI scores ( F 4  = 17.30, p  < .0001) decreased in both groups with non-significant differences between the groups, except for tinnitus intensity ( F 3  = 2.96, p  = .0451) favoring the non-navigated rTMS. Reduction in THI scores persisted for up to 6 months in both groups. Cohen’s d for tinnitus intensity ranged between 0.33 and 0.47 in navigated rTMS and between 0.55 and 1.07 in non-navigated rTMS. The responder rates for VAS or THI ranged between 35% and 85% with no differences between groups ( p  = .054–1.0). In conclusion, rTMS was effective for chronic tinnitus, but the method of coil localization was not a critical factor for the treatment outcome

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study

<p><i>Objective</i>: Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. <i>Design</i>: Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0–100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). <i>Study sample:</i> Thirty-nine patients (mean age 50.3 years). <i>Results</i>: The mean tinnitus intensity (<i>F</i>₃ = 15.7, <i>p</i> < 0.0001), annoyance (<i>F</i>₃ = 8.8, <i>p</i> = 0.0002), distress (<i>F</i>₃ = 9.1, <i>p</i> = 0.0002) and THI scores (<i>F</i>₄ = 13.8, <i>p</i> < 0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (<i>p</i> = 0.082 and <i>p</i> = 0.065). <i>Conclusions</i>: Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.</p

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018)

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150–206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance