Editing Essential tremor (section)

==Treatment==
===Treatment approaches===
Currently, most treatments and therapies available for essential tremors are only treating symptoms since there is no cure available. Medical treatments for tremors are based on shared decisions between patients and their providers. The choices of treatments depended on tremor severity, affected body parts, and the impacts of tremor on the patient's physical, psychological, and quality of life.<ref name=":0">{{cite journal | vauthors = Rajput AH, Rajput A | title = Medical treatment of essential tremor | journal = Journal of Central Nervous System Disease | volume = 6 | pages = 29–39 | date = January 2014 | pmid = 24812533 | pmc = 3999812 | doi = 10.4137/JCNSD.S13570 }}</ref> People with mild tremors that do not interfere with daily activities and psychological well-being do not require pharmacological treatments. People with persistent tremors which impact daily functions and social interactions should be treated with the appropriate pharmacological therapies.<ref name=":0" />

==== Non-pharmacological Treatment ====
"Focused Ultrasound" is a treatment that was approved for coverage in the U.S. in 2022 for those with Medicare insurance.  Totally non-surgical, the treatment process is performed on a conscious patient and takes 2 to 3 hours.

The first approach in helping people to improve tremor symptoms is the discontinuation of triggering and exacerbating factors like medications including certain antidepressants, anti-epileptics, beta-agonists; or substances like caffeine.<ref name=":1">{{cite journal | vauthors = Hopfner F, Deuschl G | title = Managing Essential Tremor | journal = Neurotherapeutics | volume = 17 | issue = 4 | pages = 1603–1621 | date = October 2020 | pmid = 32915385 | pmc = 7851235 | doi = 10.1007/s13311-020-00899-2 }}</ref> In addition, getting adequate sleep and utilizing relaxation techniques can also help improve and reduce tremor symptoms in individuals who reported an increase in tremors following physical activities.<ref name=":1" />

Since tremors can affect different parts of the body (like limbs, head, chin/jaw, and vocal),<ref name=":2">{{cite journal | vauthors = Wagle Shukla A | title = Diagnosis and Treatment of Essential Tremor | journal = Continuum | volume = 28 | issue = 5 | pages = 1333–1349 | date = October 2022 | pmid = 36222768 | doi = 10.1212/CON.0000000000001181 }}</ref> different non-pharmacological therapeutic techniques are available that can support patients with the management of tremors including occupational therapy, speech therapy, and psychotherapy.<ref name=":1" /> Occupational therapy provides support to help people manage everyday tasks more easily through different approaches and interventions.<ref name=":2" /> Speech therapy is helpful in people with vocal tremor to help manage and maintain the vocal changes associated with tremor symptoms. Psychological impacts like embarrassment and anxiety are also important concerns of many people with ET which can lead to social isolation and depression. Psychotherapy can be very beneficial and play a key role in helping people to improve the mental health of ET people.<ref name=":2" />

==== Alcohol ====
Alcohol had been known to help provide short-term relief of tremor symptoms in some people, however, the therapeutic effects of alcohol on ET had not been studied in many clinical trials. It has been proposed that alcohol can help reduce tremors through the agonism mechanism of the gamma-aminobutyric acid GABAergic.<ref>{{cite journal | vauthors = Ondo WG | title = Current and Emerging Treatments of Essential Tremor | journal = Neurologic Clinics | volume = 38 | issue = 2 | pages = 309–323 | date = May 2020 | pmid = 32279712 | doi = 10.1016/j.ncl.2020.01.002 }}</ref> Since GABA can decrease neural activity, it is believed that alcohol can increase the activity of GABA which then can reduce involuntary muscle movements or tremors. However, the duration of action of alcohol on ET is around 3–4 hours, alcohol also had been associated with the rebound of tremor, not to mention the risk of development of long-term alcohol consumption and abuse.<ref name=":0" /> The use of alcohol as a possible treatment for ET is not recommended by healthcare providers.

===Pharmacological Treatments===
Currently, the available pharmacological therapy options for ET are [[Beta blocker|Beta-adrenergic blockers]], [[Anticonvulsant]]s, Benzodiazepines/GABAergic agents, [[Calcium channel blocker]]s, and Atypical neuroleptic agents. The two most effective medications which had been approved by the FDA as first line agents for the treatment of ET are propranolol and primidone.
{| class="wikitable"
|+Summary of main drugs used in pharmacological treatment of essential tremor<ref>{{cite journal | vauthors = Hedera P, Cibulčík F, Davis TL | title = Pharmacotherapy of essential tremor | journal = Journal of Central Nervous System Disease | volume = 5 | pages = 43–55 | date = December 2013 | pmid = 24385718 | pmc = 3873223 | doi = 10.4137/JCNSD.S6561 }}</ref><ref>{{cite journal | vauthors = Ondo WG | title = Current and Emerging Treatments of Essential Tremor | journal = Neurologic Clinics | volume = 38 | issue = 2 | pages = 309–323 | date = May 2020 | pmid = 32279712 | doi = 10.1016/j.ncl.2020.01.002 | series = Treatment of Movement Disorders }}</ref><ref>{{cite journal | vauthors = Alonso-Navarro H, García-Martín E, Agúndez JA, Jiménez-Jiménez FJ | title = Current and Future Neuropharmacological Options for the Treatment of Essential Tremor | journal = Current Neuropharmacology | volume = 18 | issue = 6 | pages = 518–537 | date = 2020-06-22 | pmid = 31976837 | pmc = 7457404 | doi = 10.2174/1570159X18666200124145743 }}</ref><ref name="The Pathophysiology and Treatment o"/>
!Drugs
!Mechanism of action
!Efficacy
!Side-effects
|-
! colspan="4" |'''First-line therapies'''
'''FDA-approved or supported by double-blinded, placebo-controlled studes (class I evidence)'''
|-
|[[propranolol]]
|non-selective [[Beta blocker|β-adrenergic receptor antagonist]] (probable mechanism: antagonism at peripheral [[Beta-2 adrenergic receptor|β<sub>2</sub> receptors]])
|50-70% (>50% response)
|frequent (>60%): hypotension, bradycardia, fatigue, dizziness, exertional dyspnea
|-
|[[primidone]]
|antiepileptic brabituric acid-derivative (probable mechanism: interaction with [[voltage-gated sodium channels]] or opening and potentiating [[GABA receptors]])
|50-70% (30-50% response)
|sedation, fatigue, drowsiness, dizziness, ataxia, confusion, gastrointestinal upset, loss of coordination, anorexia
|-
! colspan="4" |Second-line therapies
Supported by double-blinded, placebo-controlled trials (class II evidence or lower)
|-
|[[topiramate]]
|[[voltage-gated sodium channel]] and [[Voltage-gated calcium channel|high voltage-activated calcium channels]] (antitremor mechanism unknown)
|20-37% (30-40% response)
|paresthesias, trouble concentrating, gastrointestinal upset, somnolence, fatigue, confusion (discontinuation rate: 30%)
|-
|[[gabapentin]], [[pregabalin]]
|[[Voltage-gated calcium channel|α<sub>2</sub>δ subunit voltage-gated calcium N-type channel]] blockers (antitremor mechanism unknown)
|30-40% (30-50% response)
|sleepiness, dizziness, ataxia, nausea, weight gain, psychiatric disturbances (including suicidal ideation)
|-
|[[alprazolam]], [[clonazepam]]
|benzodiazepines
|30-50% (>50% response)
|sedation, cognitive impairment, tolerance, dependency and abuse, withdrawal effects (discontinuation rate: 50%)
|-
|[[atenolol]]
| rowspan="2" |competitive β1-adrenergic antagonist
|37%
| rowspan="2" |similar to propranolol
|-
|[[metoprolol]]
|single dose efficacy equal to propranolol (no effect after chronic use)
|-
|[[nadolol]], [[sotalol]], [[indenolol]], [[artinolol]], [[timolol]]
|non-selective β-adrenergic receptor antagonists
|effective only in patients responsive to propranolol
|similar to propranolol with addidional reduction of alertness
|-
! colspan="4" |Third-line therapies
Supported by open-label studies or case series
|-
|[[nimodipine]], [[flunarizine]], [[nicardipine]]
|voltage-gated L-type channel blockers
|50% (>50% response)
|hypotension, oedema, headache, diziness, nausea, constipation, fatigue, palpitations
|-
|[[clozapine]]
|[[Atypical antipsychotic|atypical antypsychotic]] (complex mechanism)
|50% (75% response)
|sedation, orthostatic hypotension, tachycardia, syncope, weight gain, metabolic syndrome, rare side effects include agranulocytosis
|-
|[[olanzapine]], [[quetiapine]]
|atypical antypsychotics (complex mechanism)
|<50%
|insomnia, anxiety, headache, sedation, somnolence, diziness, weight gain, orthostatic hypotension, extrapyramidal symptoms
|}

====Beta-adrenergic Blockers====
[[File:Propranolol.svg|thumb|Chemical structure of Propranolol, one of the most effective medication for treating ET]]
When symptoms are sufficiently troublesome to warrant treatment, the first choice medication is [[propranolol]], a non-selective beta-blocker, which has been shown effective in reducing tremor by 70% in 50% of patients in clinical studies.<ref name=":7">{{cite journal | vauthors = Sharma S, Pandey S | title = Treatment of essential tremor: current status | journal = Postgraduate Medical Journal | volume = 96 | issue = 1132 | pages = 84–93 | date = February 2020 | pmid = 31575730 | doi = 10.1136/postgradmedj-2019-136647 }}</ref> Based on the guidelines from the American Academy of Neurology and the Italian Movement Disorders Association, propranolol is most effective in limb tremors, also there is little to no effect on head tremors. The recommended doses of propranolol range from 60 to 360&nbsp;mg daily, and it is based on the patient's specific factors.<ref name=":7" /> The commonly reported side effects of propranolol are bradycardia, bronchospasm, fatigue, and hypotension.<ref name=":8">{{cite journal | vauthors = Patel MD, Patel M, Jani R, Patel KG, Patel P, Gandhi SK | title = Essential Tremors: A Literature Review of Current Therapeutics | journal = Cureus | volume = 16 | issue = 5 | pages = e59451 | date = May 2024 | pmid = 38826876 | pmc = 11141324 | doi = 10.7759/cureus.59451 | doi-access = free }}</ref> In patients that have contraindicated comorbidities to propranolol, other beta-blockers such as [[Atenolol]], [[pindolol]], [[Sotalol]], and [[nadolol]] have shown some potential efficacy, but they are not very well studied and have limited evidence in their efficacy on the treatment of ET.<ref name=":0" />

==== Anticonvulsants ====
[[File:Primidone metaboliti.PNG|thumb|chemical structures of primidone and two metabolites, phenobarbital and phenylethylmalonamide]]
[[Primidone]] is another first line agent recommended in the treatment of ET. Primidone is an anticonvulsant which metabolized into phenobarbital and phenylethymalnonamide.<ref name=":0" /> This medication has shown the same beneficial effects in reducing tremors as propranolol and is recommended for use based on guidelines from the American Academy of Neurology and the MDS Task Force on Tremor. The initial dose of primidone is recommended at 25&nbsp;mg per day and should be increased up to the maximum dose of 250&nbsp;mg per day. This strategy was recommended to help avoid the possible side effects of nausea, vomiting, and excessive sedation of primidone.<ref name=":1" /> Primidone is the preferred medication for the treatment of ET in the geriatric population compared to propranolol. In addition, Combination therapy of both Propranolol and Primidone is recommended for people who do not show benefits from either propranolol or primidone as monotherapy.<ref name=":8" />

[[Topiramate]] is an antiepileptic medication which had been studied to assess the efficacy and safety in the treatment of ET.<ref name=":8" /> Overall, it is considered a second-line therapy alone or in combination with other medications when first-line treatments fail to show improvement or medication intolerance. Topiramate has been shown effective in reducing limb tremors at the maximum dose of 200&nbsp;mg, however, there was a higher risk for the development of adverse effects including weight loss, anorexia, cognitive impairment, and kidney stones.<ref name=":1" />

====Other second-line medications====
Additional medications that have been reported to show efficacy in treating ET are [[gabapentin]], [[benzodiazepines]] such as [[alprazolam]], [[clonazepam]], and [[zonisamide]], and [[pregabalin]].<ref name=":0" /> However, most of the medications have limited evidence-based to support their clinical usage as treatments for ET. Some systematic reviews of medications for the treatment of ET have been conducted.  A 2017 review of [[topiramate]] found limited data and low-quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects,<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Quattrocchi G, Allegra R, Filippini G, Colosimo C, Zappia M | title = Topiramate for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 4 | pages = CD009683 | date = April 2017 | pmid = 28409827 | pmc = 6478240 | doi = 10.1002/14651858.CD009683.pub2 }}</ref> a 2017 review of [[zonisamide]] found insufficient information to assess efficacy and safety,<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Filippini G, Quattrocchi G, Colosimo C, Zappia M | title = Zonisamide for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 8 | pages = CD009684 | date = August 2017 | pmid = 28836659 | pmc = 6483684 | doi = 10.1002/14651858.CD009684.pub2 }}</ref> and a 2016 review of [[pregabalin]] determined the effects to be uncertain due to the low quality of evidence.<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Quattrocchi G, Filippini G, Colosimo C, Zappia M | title = Pregabalin for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD009682 | date = October 2016 | pmid = 27763691 | pmc = 6461190 | doi = 10.1002/14651858.CD009682.pub2 }}</ref>

==== Botulinum Toxin (BoNT) ====
[[Botulinum toxin]] is a neurotoxin produced by a gram-positive, rod-shaped bacteria called [[Clostridium botulinum]]. BoNT works by inhibiting acetylcholine release at the presynaptic terminal by inactivating the SNARE proteins (SNAP-25), which interfere with muscle contraction.<ref>{{cite journal | vauthors = Anandan C, Jankovic J | title = Botulinum Toxin in Movement Disorders: An Update | journal = Toxins | volume = 13 | issue = 1 | pages = 42 | date = January 2021 | pmid = 33430071 | pmc = 7827923 | doi = 10.3390/toxins13010042 | doi-access = free }}</ref> BoNT type A injections have shown benefits in several clinical trials for the treatments of limb, voice, and head. However, the associated side effects included muscle weakness, stiffness reported within studies of limb tremors, and neck muscle pain, weakness, and dysphagia in clinical trials of head tremors.<ref name=":8" /> Botulinum toxin type A has been found to be helpful in treating voice tremors.<ref>{{cite journal | vauthors = Adler CH, Bansberg SF, Hentz JG, Ramig LO, Buder EH, Witt K, Edwards BW, Krein-Jones K, Caviness JN | title = Botulinum toxin type A for treating voice tremor | journal = Archives of Neurology | volume = 61 | issue = 9 | pages = 1416–1420 | date = September 2004 | pmid = 15364688 | doi = 10.1001/archneur.61.9.1416 }}</ref>

=== Additional procedures ===

====Ultrasound====
[[File:MRI-guided HIFU, essential tremor, 10-14 135, pointed.png|thumb|Frontal MRI four days after MRgFUS (MRI-guided high-intensity focused ultrasound): Left ventral intermediate nucleus (Vim) thalamotomy. 79-year-old man with essential tremor.]]
Additionally, [[MRI]]-guided [[high-intensity focused ultrasound]] is a nonsurgical treatment option for people with essential tremor who are medication refractory.<ref name=pmid28503363>{{cite journal | vauthors = Rohani M, Fasano A | title = Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of Current Hurdles | journal = Tremor and Other Hyperkinetic Movements | volume = 7 | pages = 462 | year = 2017 | pmid = 28503363 | pmc = 5425801 | doi = 10.7916/D8Z89JN1 | doi-broken-date = 25 February 2025 }}</ref><ref name=FDA2016>{{cite press release |title=FDA approves first MRI-guided focused ultrasound device to treat essential tremor |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-mri-guided-focused-ultrasound-device-treat-essential-tremor |archive-url=https://web.archive.org/web/20201108091524/https://www.fda.gov/news-events/press-announcements/fda-approves-first-mri-guided-focused-ultrasound-device-treat-essential-tremor |url-status=dead |archive-date=November 8, 2020 |publisher=FDA |date=24 March 2020 }}</ref> MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life by reducing the tremor manifestation.<ref name=FDA2016 /><ref>{{cite journal|date=2023|volume=9|issue=1|pages=17–20|doi=10.1515/cdbme-2023-1005|vauthors=Aharonson V, Postema M, Gebbie R, Van Der Merwe J, Schlesinger I|title=Sobel edge detection for quantifying the effectiveness of focused ultrasound thalamotomy for tremor relief|journal=Current Directions in Biomedical Engineering|doi-access=free}}</ref> While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment.<ref name=pmid29265546>{{cite journal | vauthors = Chang JW, Park CK, Lipsman N, Schwartz ML, Ghanouni P, Henderson JM, Gwinn R, Witt J, Tierney TS, Cosgrove GR, Shah BB, Abe K, Taira T, Lozano AM, Eisenberg HM, Fishman PS, Elias WJ | title = A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up | journal = Annals of Neurology | volume = 83 | issue = 1 | pages = 107–114 | date = January 2018 | pmid = 29265546 | doi = 10.1002/ana.25126 | s2cid = 4437809 }}</ref> To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, [[paresthesia]]s, [[headache]], skin burns with ulcerations, skin retraction, scars, and blood clots.<ref name=pmid28503363/><ref name="FDA2016" /><ref name="Hedera2017">{{cite journal | vauthors = Hedera P | title = Emerging strategies in the management of essential tremor | journal = Therapeutic Advances in Neurological Disorders | volume = 10 | issue = 2 | pages = 137–148 | date = February 2017 | pmid = 28382111 | pmc = 5367648 | doi = 10.1177/1756285616679123 | type = Review }}</ref> This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others.<ref name="FDA2016" /> The US Food and Drug Administration ([[Food and Drug Administration|FDA]]) approved Insightec's Exablate Neuro system to treat essential tremor in 2016.<ref name="FDA2016" />

==== Deep Brain Stimulation (DBS) ====
[[File:Adaptive Deep Brain Stimulation.png|thumb|Illustration of the placement of electrodes and stimulator of Deep Brain Stimulation surgical treatment.]]
Another invasive surgical treatment of essential tremor is deep brain stimulation (DBS). DBS is a surgical procedure that involves the placement of a permanent electrode with 4-8 contacts within the brain with connecting wires connected to a pulse stimulator implanted near the patient's collarbone.<ref name=":1" /> In the treatment of tremor, the electrodes are placed in the ventral intermediate nucleus (Vim) of the thalamus.

The pulse stimulator delivers constant electrical pulses to the target area, which interfere with activity of the target area, which has been shown to improve tremor symptoms.<ref>{{cite journal | vauthors = Singh M, Agrawal M | title = Deep Brain Stimulation for Tremor and Dystonia | journal = Neurology India | volume = 68 | issue = Supplement | pages = S187–S195 | date = 2020 | pmid = 33318349 | doi = 10.4103/0028-3886.302472 | doi-access = free }}</ref> At one year following the surgical intervention with DBS, patients showed 66% improvement and 48% improvement at 10 years.<ref name=":8" /> DBS is considered an effective surgical treatment of ET, but there are associated side effects and complications that have been reported with DBS in clinical trials, including imbalance or gait instability, dystonia, paresthesia, hemorrhage.<ref name=":7" />