Past, present, and future of deep transcranial magnetic stimulation: A review in psychiatric and neurological disorders

Table 1 Development of deep transcranial magnetic stimulation in treatment-resistant depression

Ref.	Method	Result	Adverse events	Significance
Levkovitz et al[13], 2009	20 Hz DTMS stimulates FPC	Significant improvement in HDRS scores	Headaches	This is the first time that TRD has been treated with the new H-coil
McGirr et al[14], 2014	20 Hz stimulates DLFPC	Reduction in HAMD-21 scores	Unreported	Five-factor personality assessment may have prognostic value in DTMS for resistant MDD
Levkovitz et al[15], 2015	20 Hz DTMS stimulates PFC	HDRS-21 score was improved by 6.39 points	Unreported	It is efficacious and safe in patients not responding to antidepressant medications, and the effect remains stable
Feffer et al[16], 2017	18 HZ DTMS stimulation; right abductor pollicis brevis muscle	Depressive symptoms (HDRS-21 total score) decreased significantly	Headaches	The severity of the depressive episode is associated with a positive therapeutic effect of dTMS
Kaster et al[17], 2018	18 HZ DTMS stimulates DLPFC and VLPFC	Remission rate was significantly higher with active than sham rTMS (40.0% vs 14.8%)	Pain and discomfort from stimulus	High-dose DTMS appears to be safe, well tolerated, and efficacious in the treatment of LLD
Tendler et al[18], 2018	10 HZ DTMS combined with SSRIs	The remission rate was 35.3%	Headaches	DTMS can augment formerly ineffective SSRI treatment
Filipčić et al[19], 2019	18 HZ DTMS stimulates LDLPFC	The response was significantly better in H1-coil than in 8-coil group (OR = 2.33; 95%CI: 1.04-5.21; P = 0.040)	Unreported	DTMS had better response rate than rTMS
Matsuda et al[20], 2020	18 Hz DTMS stimulates LDLPFC	HDRS-21 was more significantly improved	Unreported	DTMS might be effective and safe for office workers with treatment-resistant depression
Bahun et al[21], 2022	18 Hz stimulates DLFPC	Cognitive function all showed mild to moderate improvement	Unreported	Can improve MDD symptoms

DLFPC: Dorsolateral prefrontal cortex; HDRS-21: Hamilton Depression Rating Scale-21; DTMS: Deep transcranial magnetic stimulation; HAMD-21: 21-item Hamilton Depression Rating Scale; VLPFC: Ventrolateral prefrontal cortex; MDD: Major depressive disorder.

Table 2 Development of deep transcranial magnetic stimulation in obsessive-compulsive disorder

Ref.	Method	Result	Adverse events	Significance
Modirrousta et al[30], 2015	1 Hz DTMS stimulates PFC	Improvement in Y-BOCS	Electric shocking sensation	Low frequency deep rTMS was effective in OCD symptom reduction
Carmi et al[27], 2018	20 Hz or 1 Hz DTMS stimulates mPFC and ACC	Improvement in Y-BOCS	Slight headache	DTMS has the ability to directly modify ACC activity
Carmi et al[31], 2019	20 Hz DTMS stimulates mPFC and ACC	Improvement in Y-BOCS	Slight headache	High-frequency DTMS in special region can significantly improve OCD symptoms
Ikawa et al[33], 2022	20 Hz DTMS stimulates mPFC and ACC	Improvement in Y-BOCS	Slight headache	DTMS treatment of OCD had a favorable therapeutic effect
Ikawa et al[33], 2022	20 Hz DTMS stimulates mPFC and ACC	Improvement in Y-BOCS	Electric shocking sensation	DTMS was found to be a safe and effective intervention for OCD symptoms in adolescents

Y-BOCS: Yale-Brown obsessive compulsive scale; mPFC: Medial prefrontal cortex; ACC: Anterior cingulate cortex; DTMS: Deep transcranial magnetic stimulation; PFC: Prefrontal cortex; OCD: Obsessive-compulsive disorder.

Table 3 Development of deep transcranial magnetic stimulation in Schizophrenia

Ref.	Method	Result	Adverse events	Significance
Birdi et al[36], 2023	1 Hz DTMS stimulates LTPC	Significant improvement in AHRS score	Transient headache	DTMS treatment was effective for chronic auditory hallucinations in schizophrenic patients
Rosenberg et al[38], 2011	20 Hz DTMS stimulates PFC	Cognition and negative symptoms are improved	Transient headache and fatigue	DTMS can improve negative symptoms and cognitive deficits for schizophrenia patients
Rosenberg et al[38], 2011	1 Hz DTMS stimulates LTPC	Significant improvement in AHRS score	Mild and self-limiting headaches	DTMS had no significant effect on auditory hallucinations
Rabany et al[43], 2014	20 Hz DTMS stimulates PFC	SANS was significantly reduced	Unreported	DTMS was effective for negative symptoms, but the effect was moderate
Linsambarth et al[44], 2019	18 Hz DTMS stimulates bilateral PFC	SANS was significantly reduced	Temporary headaches, scalp aches, and toothaches	DTMS contributed to negative symptoms in schizophrenia
Moeller et al[42], 2022	10 HZ DTMS stimulates the insular and prefrontal cortices	The DTMS group had a more pronounced decrease in insula blood flow than the sham operation group	Unreported	DTMS in smoking patients with schizophrenia was effective

AHRS: Auditory Hallucinations Rating Scale; DTMS: Deep transcranial magnetic stimulation; PFC: Prefrontal cortex; SANS: Scale for the Assessment of Negative Symptoms; TPC: Temporoparietal cortex.

Table 4 Development of deep transcranial magnetic stimulation in substance use disorders

Ref.	Method	Result	Adverse events	Significance
Girardi et al[49], 2015	20 Hz DTMS stimulates DLFPC	Craving scores dropped significantly	Unreported	DTMS was well tolerated and found to be effective in AUD
Harel et al[50], 2022	10 Hz DTMS stimulates mPFC and ACC	A lower percentage of heavy drinking days	Moderate to severe headaches	DTMS was a safe and well-tolerated intervention, with promising initial evidence for efficacy in alcohol addiction

DLFPC: Dorsolateral prefrontal cortex; DTMS: Deep transcranial magnetic stimulation; SUD: Substance use disorders; mPFC: Medial prefrontal; ACC: Anterior cingulate cortices; AUD: Alcohol use disorder.

Table 5 Development of deep transcranial magnetic stimulation in Alzheimer’s disease

Ref.	Method	Result	Adverse events	Study design	Significance
Avirame et al[65], 2016	10 Hz DTMS for PF stimulation	60%-70% of AD patients’ cognitive function was improved	Light headache and occasional tiredness	Case series study	DTMS led to preservation and even improvement of cognitive functions
Leocani et al[66], 2020	10 Hz DTMS	ADAS-cog at 4 and 8 wk compared with baseline was improved	Temporary headaches	Double-blind, placebo-controlled pilot study	DTMS was feasible and safe in patients with probable AD

ADAS-cog: Alzheimer’s disease assessment scale-cognitive; AD: Alzheimer’s disease; DTMS: Deep transcranial magnetic stimulation; PF: Bilateral prefrontal regions.

Table 6 Development of deep transcranial magnetic stimulation in aphasia

Ref.	Method	Result	Adverse events	Significance
Spagnolo et al[72], 2013	10 Hz DTMS stimulates Broca’s area and DLPFC	Improvement of language function	Unreported	This observation opens new possibilities for treatment of drug-unresponsive neurodegenerative disorders
Trebbastoni et al[73], 2013	hf-rTMS stimulates DLPFC	Improved language in LPPA	Unreported	DTMS improved the linguistic skills
Chieffo et al[71], 2014	10 Hz DTMS stimulates Broca’s area	Significant improvement in the naming power	Unreported	Deep brain rTMS improved naming in right-handed chronic poststroke aphasic patients

LPPA: Primary progressive aphasia logopenic variant; DLPFC: Dorsolateral prefrontal cortex; DTMS: Deep transcranial magnetic stimulation; hf-rTMS: High frequency-repetitive transcranial magnetic stimulation; rTMS: Repetitive transcranial magnetic stimulation.

Table 7 Development of deep transcranial magnetic stimulation in post-stroke motor dysfunction

Ref.	Method	Result	Adverse events	Significance
Chieffo et al[76], 2014	20 Hz DTMS	Significant improvement in lower limb motor function	Unreported	DTMS could induce improvements in lower limb functions in the chronic post-stroke period
Chieffo et al[77], 2018	20 Hz DTMS	Upper limb motor function improved significantly	Transitory dizziness, toothache, and muscle twitches	DTMS combined with exercise training is more effective (upper limb motor function)

DTMS: Deep transcranial magnetic stimulation.

Table 8 Development of deep transcranial magnetic stimulation in Parkinson’s disease

Ref.	Method	Result	Adverse events	Significance
Spagnolo et al[84], 2014	10 Hz DTMS for PF stimulation	UPDRS was improved	Slight and transitory hypotension and headache	DTMS might be a safe treatment for PD motor symptoms
Cohen et al[87], 2018	M1 + PFC or M1	M1 + PFC OR M1 group was improved in T-UPDRS and M-UPDRS	Mild and transient head discomfort, transient fatigue, and rare mild visual transient hallucinations during stimulation	DTMS improved PD motor symptoms but the effect was moderate
Torres et al[80], 2015	M1 + PFC	UPDRS was improved	Sleepiness, headaches, and nausea	DTMS improved motor, postural, and motivational symptoms of PD patients
Cohen et al[88], 2016	1 Hz DTMS M1 and 10 Hz DTMS PFC	UPDRS was improved	Headache, dizziness, pain in the head or neck during treatment; nausea, general weakness, and transient aggravation of gait disturbance	DTMS improved motor, but no advantage compared to sham treatment
Spagnolo et al[85], 2020	M1 + PFC or M1	UPDRS was improved	Mild, not-distressing, and transient dyskinesias	DTMS was a safe and potentially effective procedure
Cohen et al[87], 2018	1 Hz M1 or 10 Hz PFC	UPDRS was improved	Headache, nausea, and discomfort of the eye region or tearing of the eyes during stimulation	DTMS can decrease the subjective motor symptom severity and depression

PF: Bilateral prefrontal regions; M1 + PFC: Sequential stimulation of low frequency over the primary motor cortex and then high frequency over the prefrontal cortex; M1: Low-frequency stimulation over the primary motor cortex alone; UPDRS: Unified Parkinson’s Disease Rating Scale; M-UPDRS: Motor UPDRS; T-UPDRS: Total UPDRS; DTMS: Deep transcranial magnetic stimulation; PFC: Prefrontal cortex; PD: Parkinson’s disease.