Editing Essential tremor (section)

===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>