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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 2  |  Page : 99-105

Repetitive transcranial magnetic stimulation in geriatric psychiatry: A clinical overview


1 Department of Psychiatry, Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India
2 Department of Psychiatry, Asha Hospital, Hyderabad, Telangana, India
3 Department of Geriatric Mental Health, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication29-Dec-2017

Correspondence Address:
Avinash Desousa
Carmel 18, St. Francis Road, Off S.V. Road, Santacruz West, Mumbai - 400 054, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jgmh.jgmh_48_16

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  Abstract 

Repetitive transcranial magnetic stimulation (rTMS) has been used widely in adult patients with depression and resistant auditory hallucinations. There is a paucity of data for rTMS use in geriatric patients for these indications. Recent research has revealed newer avenues for the use of rTMS in clinical geriatric psychiatry practice which includes mild cognitive impairment and dementia. rTMS is also being looked at as an effective treatment when combined with cognitive training in the management of Alzheimer's disease. The present review discusses the various uses of rTMS in geriatric psychiatry. This paper analyzes the various studies done with rTMS in older patients in various indications and the safety and efficacy of the procedure are also evaluated. The need for further studies in this area using larger samples is also mentioned.

Keywords: Alzheimer's disease, auditory hallucinations, dementia, geriatric depression, mild cognitive impairment, repetitive transcranial magnetic stimulation


How to cite this article:
Thakurdesai A, Thanki M, Desousa A, Rao G P, Tiwari S C. Repetitive transcranial magnetic stimulation in geriatric psychiatry: A clinical overview. J Geriatr Ment Health 2017;4:99-105

How to cite this URL:
Thakurdesai A, Thanki M, Desousa A, Rao G P, Tiwari S C. Repetitive transcranial magnetic stimulation in geriatric psychiatry: A clinical overview. J Geriatr Ment Health [serial online] 2017 [cited 2019 Jun 16];4:99-105. Available from: http://www.jgmh.org/text.asp?2017/4/2/99/221905




  Introduction Top


Repetitive transcranial magnetic stimulation (rTMS) has been used over the last decade in both the short- and long-term management of various psychiatric and neurological disorders.[1] The most common psychiatric indications for use in psychiatry includes major depression [2] and resistant auditory hallucinations in schizophrenia.[3] There is a large volume of literature and randomized controlled studies of rTMS use in adults, but data in children, adolescents, and geriatric patients are sparse. The indications for the use of rTMS in geriatric psychiatry are similar to that of adult psychiatry, namely, depression and resistant hallucinations, but there is emergence of recent reports of its uses in other indications as well. The current review is an overview of the role of rTMS in geriatric psychiatry, the research done so far, and the road ahead.


  Method of Conducting This Review Top


In conduct the present review, the first step was identification and assortment of the available literature. For identifying articles that focused on rTMS use in geriatric psychiatry, the terms “geriatric psychiatry,” “older patients,” “elderly patients,” “geriatric depression,” or “late-onset schizophrenia” and “resistant auditory hallucinations” were used. For identifying articles that focused on rTMS specific terms such as “rTMS” and “repetitive transcranial magnetic stimulation” were used. These two search strategy results were combined with an “and” statement in the following databases with the time frame being specified from 2000 to 2016. The databases used were Medline, PubMed, Google Scholar, and the Cochrane Database on Systematic Reviews. In total, 46 articles were identified which included reviews, case reports, and original research papers on the use of rTMS in geriatric psychiatry. We included 26 papers as the duplicate and irrelevant papers were excluded from the study. The articles chosen were articles that included case series, interesting case reports, and clinical studies both open-label and randomized controlled studies on the use of rTMS in geriatric psychiatry. Due to the scarcity of data available, no stringent inclusion or exclusion criteria were used. Of these, one was a meta-analysis, four were reviews, 16 were clinical studies, and four were case series.

Manual search using the internet for Indian literature was done using Google Scholar and the Indian Journal of Psychiatry, Indian Journal of Psychological Medicine, Journal of Geriatric Mental Health, and Journal of Mental Health and Human Behavior were searched for studies on rTMS use in geriatric psychiatry. All the authors reviewed literature and the most relevant papers were chosen for this review. All the authors were qualified psychiatrists working in a tertiary general hospital and medical college. The literature review in this paper is supplemented with the clinical experience of the authors that use rTMS routinely in their clinical work.


  Repetitive Transcranial Magnetic Stimulation in Geriatric Patients With Depression Top


The best evidence for rTMS in geriatric patients is that for major depression. The first study that discussed rTMS in the elderly with depression was conducted in 1998.[4] The study compared response to rTMS in older patients (>65 years) versus adult populations with depression. It was a negative study that demonstrated lower response rates to rTMS in older patients with depression but paved the way for further research into the use of rTMS in geriatric depression.

General comments on the studies reviewed

All the studies assessing rTMS in geriatric depression have included patients diagnosed with depression as per the Diagnostic Statistical Manual-IV/International Classification of Diseases-10 criteria.[5],[6] While most studies have included treatment-resistant or refractory depression [7] (the criteria for diagnosing the same vary between different studies, viz, failure to respond to adequate trial of one vis-à -vis two antidepressants), this has not been a strict inclusion criteria. A table with the major studies of rTMS in geriatric depression is available for perusal [Table 1].
Table 1: Overview of studies using repetitive transcranial magnetic stimulation in geriatric patients with major depression

Click here to view


Some studies included subjects only with vascular depression.[15] In most studies, concurrent psychotropic medication was continued with rTMS; however, few of the studies reviewed that antidepressant drugs were stopped a week before rTMS was started so that improvement, if any, could potentially be attributed to the brain stimulation alone. The types of studies reviewed here vary from uncontrolled/open-label to randomized controlled trials based on the available limited data. Blinding was reported to be a problem in many studies as the physician administering the rTMS sessions was often part of the assessing team and would know whether the stimulation was real or sham when used. A few studies reported that even sham stimulation may cause a small degree of cortical stimulation which may have a role in change in clinical parameters through a probable placebo effect.[16]

The mean age in all studies was >60 years. Hamilton Depression Rating Scale (HAM-D)[17] (most commonly 21-item) has been used as the primary outcome measure in all the studies with several studies have used secondary outcome measures such as Beck Depression Inventory,[18] Clinical Global Impression scale (CGI),[19] visual analog scale for depression,[20] Visual Analog Scale for anxiety,[21] visual analog scale for physical discomfort (VAS-PD),[22] and Hamilton Anxiety Rating Scale.[23] Response in most studies was considered to be a 50%–60% reduction in HAM-D score with a decrease by 30% indicating a partial response. A HAM-D score <8 with failure to meet criteria for depression was labeled as remission in most of the studies.

Improvement was evaluated differently in different studies. In some studies, the number of sessions was five for rTMS over 1 week [18] while recent studies have used 10–18 sessions over the period of 2–3 weeks.[20],[21],[22],[23] Intensity of stimulation varied from 80% of motor threshold to 141% of motor threshold in the studies. Frequency of stimulation varied from 5 to 25 Hz for high frequency to 1–2 Hz for low frequency in different studies.

The left-sided dorsolateral prefrontal cortex (DLPFC) was stimulated, the right-sided DLPFC in others while in some, a combination of the two was used. The site of stimulation was 5 cm anterior to the motor cortex (determined by observing optimal contraction of the contralateral abductor pollicis brevis muscle).[12]

Points of interest in the studies reviewed

The first study done in 1998[4] stated that the response rates of rTMS in the elderly population (>65 years) are much lower than seen in adults with depression. Only 23% of the geriatric patients responded to TMS compared to 56% of the adult patients. It has been hypothesized that the decreased efficacy of rTMS in elders with depression may be due to greater PFC-scalp distance in them due to cortical atrophy resulting in lower effective stimulation.[24] Research has suggested that higher stimulation intensity could have greater antidepressant effect in the elderly population as effective stimulation would increase.[25] However, this potentially increases the risk of a seizure. Studies conducted since 1998 have neither shown a very large change in response rates nor have they shown a higher risk of seizures.[26] The early study also demonstrated that 75% of elder patients with depression who had their first episode of depression before the age of 65 years responded better to rTMS than compared to just 11% with a first episode of depression having onset post 65 years of age. This was attributed to greater structural brain changes in the latter group.

In a randomized sham-controlled study, it was found that there was no significant difference between the HAM-D score reduction between the real and sham stimulation group.[8] Thirty percent of the patients in both the active treatment and sham group responded to rTMS. In both groups, 20% of patients showed remission. Responders were found to have significantly greater frontal lobe volume than nonresponders and greater side effects though tolerable was reported in active treatment group. The authors proposed that subthreshold stimulation parameters used in the study could explain similar response rates in both the groups.

Other researchers have also found that there was no significant difference in the reduction of HAM-D scores between the groups undergoing real stimulation compared to the sham group. The mean HAM-D score reduction was found to be 20% and 17% in the active and sham groups, respectively, in a study.[9] In an open-label noncontrolled study, the authors found that there was 35% reduction in HAM-D scores over 3 weeks of rTMS. 27.77% of the patients responded to TMS, 22.22% achieved remission, and additional 16.66% had partial response to TMS. In the study, stimulation intensity ranging from 103% to 141% of motor threshold was used adjusting to the relative prefrontal atrophy so that the effective stimulation of PFC was not compromised.[10] The study also showed that the distance between skull and PFC increases with age and it is critical to ensure that sufficient intensity of stimulation reaches the PFC. This study had also evaluated for white matter hyperintensities using brain imaging but did not establish any relationship between the white matter hyperintensities and nonresponse of subjects.[10]

Studies have reported findings similar to those of the study above without any intensity adjustment. In another open-label study, 31.6% reduction in HAM-D score was noted. 31.6% of the patients responded while 10.5% of the patients remitted without any intensity adjustment.[11] Authors have compared response to high-frequency left DLPFC stimulation with response to low-frequency right DLPFC stimulation and found response rates to be similar in both forms of TMS.[12] This was an unexpected finding as the different hemispheres are said to have opposing roles in modulation of mood. The authors have suggested that right-sided, low-frequency stimulation should be considered in the future research and clinical practice as it may be safer and more economical.[27] A reduction of 24.7% was observed in HAM-D scores for the entire patient population after ten treatments in this study, with the reduction approaching 30% in 4 weeks after the treatment completion. All these research have led to the hypothesis that greater age and treatment refractoriness are markers of a poor treatment response to rTMS in depression.[28]

In a randomized control study, researchers recruited only those patients who fulfilled the criteria for vascular depression (major depressive disorder at ≥50 years of age with a history of subcortical stroke and/or at least three cardiovascular risk factors among arterial hypertension, diabetes mellitus, obesity, hyperlipidemia, smoking). Two experimental approaches were carried out. The two experiments differed in the number of sessions the subjects underwent with subjects in experiment two undergoing more number of sessions and more cumulative total dose of impulses. In experiment 1, there was a significant difference between reduction in HAM-D scores in the real and sham group with a 33.1% and a 13.6% mean reduction in HAM-D scores being observed. 33.3% patients in active group and 6.7% patients in sham group showed >50% reduction while 13.3% patients in active group and 6.7% patients in sham group were in remission at the end of the study. However, this difference was not found to be statistically significant.[13] In experiment 2, mean HDRS score reductions were 42.2% and 17.5%, response rates were 39.4% and 6.9%, and remission rates were 27.3% and 3.5% in active and sham groups, respectively. This difference in outcome was statistically significant.[13] This study also showed that response rates correlated negatively with age and positively with higher frontal gray matter volume.

In a more recent open-label study involving 65 patients, stimulation of 25 Hz was given for 6 days/week for 3 weeks, which is highest among all the studies till date (total 18 sessions). It showed 51.41% reduction in HAM-D scores after 3 weeks of stimulation. Fifty-eight percent of the patients responded while 41.54% of the patients showed partial response.[14] Thus, studies suggest that a greater number of rTMS sessions and higher total cumulative stimulus dose would show greater results in geriatric depression.


  Other Indications for Repetitive Transcranial Magnetic Stimulation in Geriatric Psychiatry Top


Auditory hallucinations associated with dementia

In a published case report, improvement in auditory hallucinations with threatening content associated with vascular-degenerative dementia in a 76-year-old woman has been reported.[29] High frequency (20 Hz) rTMS was applied over temporoparietal area (T3 and P3 as per electroencephalogram electrodes) in 15 sessions with each session consisting of 13 trains of 200 TMS pulses 50 s apart. At the end of 15 sessions, improvement was noted in frequency and content (no more threatening) of hallucinations.

Repetitive transcranial magnetic stimulation in mild cognitive impairment

In a study,[30] authors studied effect of rTMS in 34 elderly patients having mild cognitive impairment fulfilling Petersen's criteria.[31] In a randomized double-blinded study, 15 and 19 patients received active and sham stimulation, respectively. Assessment done at baseline, after last session of the study, and 1 month after last session showed significantly greater improvement in everyday episodic memory. Rivermead Behavioural Memory Test [32] scores were significantly higher in active group at the end as well as at 1 month after the study indicating that the improvement with rTMS was sustained for at least 1 month after last session. Side effects were mild, transient, and well tolerated.

Repetitive transcranial magnetic stimulation in Alzheimer's disease

In a two-staged study on ten patients with the first stage having randomized double-blind crossover design and the second stage having open-label design, the effect of rTMS in Alzheimer's disease was assessed. In the first stage, real and sham groups received 13 sessions of rTMS at 20 Hz with intensity of 90%–100% of MT on bilateral DLPFC over 4 weeks. They received total 2000 pulses per se ssion of rTMS. The groups crossed over after a 2 weeks washout period. Patients were kept cognitively active by object/action naming during the sessions. In the second stage, 6 out of 10 were given 10 sessions of rTMS over 2 weeks every 3 months. The study showed that changes in scores on cognitive assessment were significantly better in active group during at the end of the first stage. In the second stage, it was found that the patients generally had less cognitive decline than expected. Overall, it showed that rTMS is effective tool for improving cognition of patients in early and moderate stages of Alzheimer's disease.[33]

A recent meta-analysis of rTMS on cognitive functions has found robust data that rTMS may result in improvement in several areas of cognitive functions, including executive functions, learning, and memory.[34] Another study aimed to investigate whether the application of high-frequency rTMS to the left DLPFC may lead to significant facilitation of language production and/or comprehension in patients with moderate Alzheimer's dementia. Ten patients were randomly assigned to one of two groups. The first group underwent a 4-week real rTMS stimulation protocol, while the second underwent a 2-week placebo treatment, followed by 2-week of real rTMS stimulation. No significant effects were observed on naming performance. However, a significant effect was observed on auditory sentence comprehension after 2 weeks of real rTMS sessions as compared to sham.[35]

A study tried to compare the long-term efficacy of high- versus low-frequency rTMS, applied bilaterally over the DLPFC, on cortical excitability and cognitive function in patients with Alzheimer's dementia. The high-frequency rTMS group improved significantly more than the low frequency and was assessed using the mini-mental status examination (MMSE), instrumental daily living activity scale, and the Geriatric Depression Scale. The improvement was maintained for 3 months postsessions. It was thus concluded that high-frequency rTMS may be a useful addition to therapy for the treatment of patients with mild to moderate degree of Alzheimer's disease.[36]

Cognitive training (CT) interlaced with rTMS has also been explored in patients with Alzheimer's dementia. Eight patients with mild to moderate probable Alzheimer's disease AD were subjected to daily rTMS-CT sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for additional 6 months. The following six regions, located individually by MRI, were stimulated: Broca and Wernicke (language functions), right and left dorsolateral PFC (judgment, executive functions, and long-term memory), and right and left parietal somatosensory association cortex (spatial and topographical orientation and praxias). CT tasks were developed to fit these regions. Primary outcome measures were average improvement of Alzheimer disease assessment scale-cognitive (ADAS) and CGI of change; secondary objectives were average improvement of MMSE, the ADAS activities of daily living, HAM-D, and neuropsychiatric inventory.[37] Positive findings of this study provide direct evidence that rTMS is helpful in restoring brain functions and could reflect rTMS potential to recruit compensatory networks that underlie memory and other cognitive functions.[38],[39],[40]


  Safety and Precautions for Repetitive Transcranial Magnetic Stimulation in Geriatric Patients Top


Due to their age and its associated vulnerabilities (preexisting cognitive deterioration, cardiovascular problems, impaired metabolism) and the known adverse effects of other brain stimulation modalities, especially in the elderly population, a clinically relevant yet unaddressed issue is the safety of rTMS in the geriatric patients.[41]

The most commonly reported adverse effect in all studies was headache. These were generally mild and did not even require analgesic treatment. In one study, there were two dropouts due to pain in the left frontal scalp area during treatment. The pain stopped after treatment was stopped and did not require further medical management. One of the studies used VAS-PD at the baseline and then after the procedure. There was no significant change in score indicating that there was no physical discomfort in the patients' postprocedure. This in keeping with findings reported in studies with adult patients.[42] Mild degree of discomfort, not requiring any medical intervention, resolving spontaneously was reported by patients in many studies.

All the studies reviewed have evaluated the safety profile of rTMS using the MMSE. No cognitive decline was found in any study reviewed even those which included patients with dementia.

No cardiovascular complications were found in any study. Blood pressure was monitored routinely in most studies and a general vigilance for cardiovascular complications was maintained. There is a remote risk of seizures associated with rTMS.[43] No subjects in the studies reviewed here reported occurrence of a seizure. Spread of motor excitation indicated by muscular contractions during treatment (associated with higher frequency of stimulation) has been reported but not of great clinical significance.[44] While rTMS-induced mania has been reported in adult patients with depression, no such report exists in geriatric patients.[45]

Overall rTMS appears to be safe in geriatric populations. It is best that the patients are informed about common side effects before the procedure and that all necessary monitoring, for example, pulse rate, blood pressure monitoring, cognitive testing be done during the course of treatment. Most studies have excluded medically unstable patients, so the safety of TMS in these patients is still to be determined.


  Conclusions Top


rTMS is a promising modality of treatment for geriatric psychiatric disorders such as major depression and probable dementia, but further research in this area is needed. While studies show varying response rates based on different stimulation protocols used, there is a need to have well-designed rTMS protocols for geriatric depression just like we have for adult depression. rTMS needs to be studied further with regard to efficacy in the improvement of mild cognitive impairment and positive symptoms in late-onset psychosis. rTMS is under studied and a novel treatment approach when compared to electroconvulsive therapy (ECT) in geriatric patients. ECT has been used widely in geriatric patients while studies of rTMS are still in a nascent state. There is a need for further head on comparisons with ECT to ascertain which treatment modality works better in geriatric depression.

The safety profile which is a general cause of concern in the geriatric patients is quite favorable for rTMS. There is also a need to study the effects of rTMS in vascular dementia and other forms of dementia as well as bipolar depression in the elderly. Further well-designed longitudinal randomized studies shall help use ascertain the true efficacy of rTMS in geriatric patients and help clinicians determine the place of rTMS in treatment algorithms for the management of psychiatric problems in the geriatric patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Abstract
Introduction
Method of Conduc...
Repetitive Trans...
Other Indication...
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