View source for Zonisamide

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| verifiedrevid = 477869643
| image = Zonisamide structure.svg
| alt = 
| image2 = Zonisamide molecule ball.png
| alt2 = Ball-and-stick model of the zonisamide molecule

<!--Clinical data-->
| tradename = Zonegran, Zonisade
| Drugs.com = {{drugs.com|monograph|zonisamide}}
| MedlinePlus = a603008
| DailyMedID = Zonisamide
| pregnancy_AU = D
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = N03
| ATC_suffix = AX15

| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_UK = POM
| legal_US = Rx-only
| legal_US_comment = <ref name="Zonegran FDA label">{{cite web | title=Zonegran- zonisamide capsule | website=DailyMed | date=20 August 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d12de43e-3ac3-4335-bc85-70d7366a91eb | access-date=19 July 2022 | archive-date=27 January 2021 | archive-url=https://web.archive.org/web/20210127031507/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d12de43e-3ac3-4335-bc85-70d7366a91eb | url-status=live }}</ref><ref>{{cite web | title=Zonisade- zonisamide suspension | website=DailyMed | date=15 July 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac16fa15-32e9-4f92-8bc6-d8d41ae002c6 | access-date=21 January 2023}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Zonegran EPAR | website=European Medicines Agency | date=10 March 2005 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zonegran | access-date=24 May 2024}}</ref>

<!--Pharmacokinetic data-->
| bioavailability = ~100%<ref name = TGA/>
| protein_bound = 40%<ref name = TGA/>
| metabolism = [[Liver]] through [[CYP3A4]]<ref name = TGA/>
| elimination_half-life = 63 hours in [[Blood plasma|plasma]]<ref name = TGA/>
| excretion = [[Kidney]] (62%); Faeces (3%)<ref name = TGA/>

<!--Identifiers-->
| IUPHAR_ligand = 7047
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 68291-97-4
| PubChem = 5734
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00909
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5532
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 459384H98V
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00538
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10127
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 750
| PDB_ligand = ZON

<!--Chemical data-->
| IUPAC_name = benzo[d]isoxazol-3-ylmethanesulfonamide
| C=8 | H=8 | N=2 | O=3 | S=1
| smiles = O=S(=O)(N)Cc2noc1ccccc12
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UBQNRHZMVUUOMG-UHFFFAOYSA-N
| melting_point = 162
}}

'''Zonisamide''', sold under the brand name '''Zonegran''' among others, is a [[medication]] used to treat the symptoms of [[epilepsy]] and [[Parkinson's disease]].<ref name="PD2013">{{cite journal | vauthors = Grover ND, Limaye RP, Gokhale DV, Patil TR | title = Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson's disease | journal = Indian Journal of Pharmacology | volume = 45 | issue = 6 | pages = 547–55 | date = November–December 2013 | pmid = 24347760 | pmc = 3847242 | doi = 10.4103/0253-7613.121266 | doi-access = free }}</ref><ref name="MD">{{cite web|title=Zonisamide: Martindale: The Complete Drug Reference|url=https://www.medicinescomplete.com/mc/martindale/current/1668-x.htm|publisher=Pharmaceutical Press|website=MedicinesComplete|date=8 March 2016|access-date=19 August 2017| veditors = Brayfield A |location=London, UK|archive-date=27 August 2021|archive-url=https://web.archive.org/web/20210827200334/https://about.medicinescomplete.com/wp-content/uploads/2021/05/AMC-homepage-aboutMCsectionimage-May2021-896x364px.png|url-status=live}}</ref> Chemically it is a [[sulfonamide (medicine)|sulfonamide]]. It serves as an [[anticonvulsant]] used primarily as an [[Wiktionary:adjunct|adjunctive]] therapy in adults with Parkinson's disease, [[seizure|partial-onset seizure]]s; [[infantile spasm]], mixed seizure types of [[Lennox–Gastaut syndrome]], [[myoclonic]] and generalized [[tonic clonic seizure]].<ref>{{cite book|title=Comprehensive Pharmacy Review|date=2007|publisher=Williams & Wilkins|isbn=9780781765619|page=988|edition=6th| vauthors = Souney P, Mutnick A, Shargel L |oclc=869677890}}</ref> Despite this it is also sometimes used as a [[monotherapy]] for partial-onset seizures.<ref name="MD"/><ref name="AMH"/>

In 2020, it was the 276th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022}}</ref><ref>{{cite web | title = Zonisamide - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Zonisamide | access-date = 7 October 2022}}</ref>

==Medical uses==

===Epilepsy===
Zonisamide is approved in the United States,<ref name="Zonegran FDA label" /><ref name="US_approval">{{cite web | title=Drug Approval Package: Zonegran (Zonisomide) NDA #20-789 | website=U.S. [[Food and Drug Administration]] (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/020789_Zonegran.cfm | access-date=20 July 2022 | archive-date=29 March 2021 | archive-url=https://web.archive.org/web/20210329072036/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/020789_Zonegran.cfm | url-status=dead }}</ref> and United Kingdom<ref name="UK_approval">{{cite web| author=Eisai Ltd.| year=2005| title=Zonegran Summary of Product Characteristics| work=electronic Medicines Compendium| publisher=Medicines.org.uk| access-date=13 November 2005| url=http://emc.medicines.org.uk/| archive-url=https://web.archive.org/web/20051108005342/http://emc.medicines.org.uk/| archive-date=8 November 2005| url-status=dead}}</ref> for adjunctive treatment of partial seizures in adults and Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.<ref name="DAINIP03">{{cite web | author = Dainippon Pharmaceutical Co., Ltd. | year = 2004 | url = http://www.e-search.ne.jp/~jpr/PDF/DAINIP03.PDF | title = EXCEGRAN Tablets 100&nbsp;mg & EXCEGRAN Powder 20% | access-date = 13 March 2006 | archive-url = https://web.archive.org/web/20070928063802/http://www.e-search.ne.jp/~jpr/PDF/DAINIP03.PDF | archive-date = 2007-09-28 | url-status = dead }}</ref> In Australia it is marketed as both an adjunctive therapy and monotherapy for partial seizures only.<ref name="AMH"/>

===Parkinson's disease===
It has been approved for the treatment of the motor symptoms of Parkinson's disease (PD), as an adjunct to [[levodopa]], in a few countries such as Japan.<ref name="PD2013"/><ref name="MD"/> In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009.<ref name="Murata_2007">{{cite journal | vauthors = Murata M, Hasegawa K, Kanazawa I | title = Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study | journal = Neurology | volume = 68 | issue = 1 | pages = 45–50 | date = January 2007 | pmid = 17200492 | doi = 10.1212/01.wnl.0000250236.75053.16 | s2cid = 894677 }}</ref>  In addition, there is clinical evidence that zonisamide in combination with levodopa control of motor symptoms of PD but evidence for the treatment of the non motor symptoms of PD lacking.<ref name="Grover_2013">{{cite journal | vauthors = Grover ND, Limaye RP, Gokhale DV, Patil TR | title = Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson's disease | journal = Indian Journal of Pharmacology | volume = 45 | issue = 6 | pages = 547–55 | date = 2013 | pmid = 24347760 | pmc = 3847242 | doi = 10.4103/0253-7613.121266 | doi-access = free }}</ref><ref name="pmid28157097">{{cite journal | vauthors = Matsunaga S, Kishi T, Iwata N | title = Combination Therapy with Zonisamide and Antiparkinson Drugs for Parkinson's Disease: A Meta-Analysis | journal = Journal of Alzheimer's Disease | volume = 56 | issue = 4 | pages = 1229–1239 | date = 2017 | pmid = 28157097 | doi = 10.3233/JAD-161068 }}</ref>

==Adverse effects==
'''<big>Adverse effects by incidence:</big>'''<ref name = TGA>{{cite web|title=Zonegran Product Information|work=TGA eBusiness Services|publisher=SciGen (Australia) Pty Ltd|date=4 April 2013|access-date=18 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02002-3|format=PDF|archive-date=15 October 2018|archive-url=https://web.archive.org/web/20181015231609/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02002-3|url-status=live}}</ref><ref>{{cite web|title=Zonegran 25, 50, 100 mg Hard Capsules|work=electronic Medicines Compendium|date=8 October 2013|access-date=18 November 2013|url=http://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran+25%2c+50%2c+100+mg+Hard+Capsules/|publisher=Eisai Ltd|archive-date=12 January 2015|archive-url=https://web.archive.org/web/20150112051257/http://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran+25,+50,+100+mg+Hard+Capsules/|url-status=live}}</ref><ref name = MSR>{{cite web|title=zonisamide (Rx) - Zonegran|work=Medscape Reference|publisher=WebMD|access-date=18 November 2013|url=http://reference.medscape.com/drug/zonegran-zonisamide-343025|archive-date=4 December 2013|archive-url=https://web.archive.org/web/20131204211228/http://reference.medscape.com/drug/zonegran-zonisamide-343025|url-status=live}}</ref>

'''Very common (>10% incidence) adverse effects include:'''
{{colbegin|colwidth=18em}}
* [[Anorexia (symptom)|Anorexia]]
* [[Somnolence]]
* Dizziness
* Agitation
* Irritability
* Confusional state
* Depression
* [[Diplopia]]
* Memory impairment
* Decreased bicarbonate
{{colend}}

'''Common (1–10% incidence) adverse effects include:'''

{{colbegin|colwidth=22em}}

* [[Ecchymosis]]
* Hypersensitivity
* Affect lability
* Anxiety
* [[Insomnia]]
* Psychotic disorder
* [[Bradyphrenia]]
* Disturbance in attention
* [[Nystagmus]]
* [[Paraesthesia]]
* Speech disorder
* [[Tremor]]
* Abdominal pain
* [[Constipation]]
* [[Diarrhoea]]
* [[Dyspepsia]]
* Nausea
* Rash
* [[Pruritus]]
* [[Alopecia]]
* [[Nephrolithiasis]]
* [[Fatigue (medical)|Fatigue]]
* Influenza-like illness
* [[Pyrexia]]
* [[Oedema peripheral]]
* Weight loss
{{colend}}

Incidence unknown

* Reproductive toxic effects<ref>{{cite journal | vauthors = Karaduman AB, Kilic V, Atli-Eklioglu O, Baysal M, Aydogan-Kılıc G, Ucarcan S, Ilgin S | title = Reproductive toxic effects and possible mechanisms of zonisamide in male rats | journal = Human & Experimental Toxicology | volume = 38 | issue = 12 | pages = 1384–1396 | date = December 2019 | pmid = 31476894 | doi = 10.1177/0960327119871094 | s2cid = 201804214 | bibcode = 2019HETox..38.1384K }}</ref>

=== Interactions ===
Zonisamide and other [[carbonic anhydrase]] inhibitors such as [[topiramate]], [[furosemide]], and [[hydrochlorothiazide]] have been known to interfere with [[amobarbital]], which has led to inadequate anesthetization during the [[Wada test]].<ref name=zonisamide-amobarbital>{{cite journal | vauthors = Bookheimer S, Schrader LM, Rausch R, Sankar R, Engel J | title = Reduced anesthetization during the intracarotid amobarbital (Wada) test in patients taking carbonic anhydrase-inhibiting medications | journal = Epilepsia | volume = 46 | issue = 2 | pages = 236–43 | date = February 2005 | pmid = 15679504 | doi = 10.1111/j.0013-9580.2005.23904.x | s2cid = 20730895 | doi-access = free }}</ref> Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.<ref name = TGA/>

Additionally, the metabolism of zonisamide is inhibited by [[ketoconazole]], [[ciclosporin]], [[miconazole]], [[fluconazole]] and [[carbamazepine]] (in descending order of inhibition) due to their effects on the [[CYP3A4]] enzyme.<ref name=inhibit>{{cite journal | vauthors = Nakasa H, Nakamura H, Ono S, Tsutsui M, Kiuchi M, Ohmori S, Kitada M | title = Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data | journal = European Journal of Clinical Pharmacology | volume = 54 | issue = 2 | pages = 177–83 | date = April 1998 | pmid = 9626925 | doi = 10.1007/s002280050442 | s2cid = 6508614 | doi-access = free }}</ref>

Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.<ref name="eMC">{{cite web | publisher=Electronic Medicines Compendium (eMC) | title=Zonegran 25, 50, 100 mg Hard Capsules | url=https://www.medicines.org.uk/emc/medicine/16240 | access-date=12 April 2017 | archive-date=14 February 2019 | archive-url=https://web.archive.org/web/20190214194132/https://www.medicines.org.uk/emc/medicine/16240 | url-status=live }}</ref>

==Mechanism of action==
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks [[sodium ion channel|sodium]] and [[T-type calcium channel]]s, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity).<ref name = AMH/> It is also known to be a weak [[carbonic anhydrase]] inhibitor (similarly to the anticonvulsant [[topiramate]]). It is also known to modulate [[Gamma-aminobutyric acid|GABAergic]] and [[glutamate]]rgic neurotransmission.<ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref><ref name=leppik-mech>{{cite journal | vauthors = Leppik IE | title = Zonisamide: chemistry, mechanism of action, and pharmacokinetics | journal = Seizure | volume = 13 | issue = Suppl 1 | pages = S5–9; discussion S10 | date = December 2004 | pmid = 15511691 | doi = 10.1016/j.seizure.2004.04.016 | s2cid = 13458791 | doi-access = free }}</ref><ref name=Mimakietal1990-1>{{cite journal | vauthors = Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H | title = Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain | journal = Medical Journal of Osaka University | volume = 39 | issue = 1–4 | pages = 13–7 | date = March 1990 | pmid = 1369646 }}</ref><ref name=Mimakietal1990-2>{{cite journal | vauthors = Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H | title = [3H]zonisamide binding in rat brain | journal = Medical Journal of Osaka University | volume = 39 | issue = 1–4 | pages = 19–22 | date = March 1990 | pmid = 1369647 }}</ref><ref name=Ueda_etal_2003>{{cite journal | vauthors = Ueda Y, Doi T, Tokumaru J, Willmore LJ | title = Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures | journal = Brain Research. Molecular Brain Research | volume = 116 | issue = 1–2 | pages = 1–6 | date = August 2003 | pmid = 12941455 | doi = 10.1016/S0169-328X(03)00183-9 }}</ref>

==Pharmacokinetics==

===Absorption===
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8–3.9 hours. [[Bioavailability]] is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption.<ref>{{cite web|url=https://www.drugbank.ca/drugs/DB00909|title=Zonisamide|website=www.drugbank.ca|access-date=2019-01-31|archive-date=2019-01-31|archive-url=https://web.archive.org/web/20190131093517/https://www.drugbank.ca/drugs/DB00909|url-status=live}}</ref><ref name="eMC" />

===Metabolism===
Zonisamide is metabolized mostly by the [[CYP3A4]] [[isoenzyme]], but also [[CYP3A7]] and [[CYP3A5]],<ref name=enzymes>{{cite journal | vauthors = Ohmori S, Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, Kitada M | title = Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1380 | issue = 3 | pages = 297–304 | date = May 1998 | pmid = 9555064 | doi = 10.1016/s0304-4165(97)00156-6 }}</ref> to 2-(sulphamoylacetyl)-phenol via reductive [[bond cleavage|cleavage]] of the 1,2-[[benzisoxazole]] ring.<ref name=reduct>{{cite journal | vauthors = Stiff DD, Robicheau JT, Zemaitis MA | title = Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative | journal = Xenobiotica | volume = 22 | issue = 1 | pages = 1–11 | date = January 1992 | pmid = 1615700 | doi = 10.3109/00498259209053097 }}</ref>

==History==
Zonisamide was discovered by Uno and colleagues in 1972<ref name=Levy_2002>{{cite book |vauthors=Shah J, Kent S, Daniel MC |veditors=René H, Levy RH, Brian SM, Perrucca E |title=Antiepileptic Drugs |orig-year=1972 |access-date=2007-11-07 |edition=Fifth |date=2002-06-15 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=0-7817-2321-3 |chapter=Zonisamide |chapter-url=https://books.google.com/books?id=HAOY0qG-vAYC&q=zonisamide+synthesized&pg=PA873 |page=873 |archive-date=2021-08-27 |archive-url=https://web.archive.org/web/20210827200322/https://books.google.com/books?id=HAOY0qG-vAYC&q=zonisamide+synthesized&pg=PA873 |url-status=live }}</ref> and launched by [[Dainippon Sumitomo Pharma]] (formerly Dainippon Pharmaceutical) in 1989 as '''Excegran''' in Japan.<ref name=excegran_1989>{{cite web |author=Dainippon Sumitomo Pharma Co. Ltd.  |year=2005  |title=Company History  |work=Company Information  |publisher=Dainippon Sumitomo Co., Ltd.  |url=http://www.ds-pharma.co.jp/english/profile/history.html  |access-date=12 November 2005  |archive-url=https://web.archive.org/web/20060213055236/http://www.ds-pharma.co.jp/english/profile/history.html  |archive-date=13 February 2006  |url-status=dead  }}</ref> It was marketed by [[Élan]] in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to [[Eisai (company)|Eisai Co., Ltd.]] in 2004.<ref name=elan_to_eisai>{{cite web |author=Dainippon Pharmaceutical Co. Ltd.  |year=2004  |url=http://www.ds-pharma.co.jp/english/news/dainippon_2004.html  |title=Transfer of Rights Agreement for North America and Europe Reached on Zonegran  |work=News Releases for Dainippon Pharmaceutical in 2004  |publisher=Dainippon Sumitomo Pharma Co., Ltd  |access-date=12 November 2005  |archive-url=https://web.archive.org/web/20060213055615/http://www.ds-pharma.co.jp/english/news/dainippon_2004.html  |archive-date=13 February 2006  |url-status=dead  }}</ref> Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)<ref name=Asia>{{cite web |author=Dainippon Pharmaceutical Co. Ltd.  |year=2005  |title=Dainippon Pharmaceutical and Eisai Conclude Agreement for the Development, Manufacture and Marketing of the Anti-Epileptic Agent Zonisamide in Asia  |work=Dainippon Pharmaceutical News Releases for 2005  |publisher=Dainippon Sumitomo Pharma Co., Ltd.  |url=http://www.ds-pharma.co.jp/english/news/dainippon_2005/no_002.html  |access-date=12 November 2005  |archive-url=https://web.archive.org/web/20060222095009/http://www.ds-pharma.co.jp/english/news/dainippon_2005/no_002.html  |archive-date=22 February 2006  |url-status=dead  }}</ref> and Europe (starting in Germany and the United Kingdom).<ref name=Germany_UK>{{cite web | author=Eisai Co. Ltd. | year=2005 | title=Eisai Announces Launch of Zonegran (zonisamide), Treatment For Epilepsy In the UK and Germany | work=Eisai 2005 News Releases | publisher=Eisai Co., Ltd. | url=http://www.eisai.co.jp/enews/index.html | access-date=12 November 2005 | archive-url=https://web.archive.org/web/20051028020742/http://www.eisai.co.jp/enews/index.html | archive-date=2005-10-28 | url-status=dead }}</ref> <!--[[Kyowa Yakuhin]] makes the '''Excemide''' brand, sold in-->

== Research ==
===Tardive dyskinesia===
In an open-label trial zonisamide attenuated the symptoms of [[tardive dyskinesia]].<ref>{{cite journal | vauthors = Iwata Y, Irie S, Uchida H, Suzuki T, Watanabe K, Iwashita S, Mimura M | title = Effects of zonisamide on tardive dyskinesia: a preliminary open-label trial | journal = Journal of the Neurological Sciences | volume = 315 | issue = 1–2 | pages = 137–40 | date = April 2012 | pmid = 22285275 | doi = 10.1016/j.jns.2011.12.010 | s2cid = 460261 }}</ref>

===Obesity===
It has also been studied for [[obesity]]<ref name=anti_obesity>{{cite journal | vauthors = Gadde KM, Franciscy DM, Wagner HR, Krishnan KR | title = Zonisamide for weight loss in obese adults: a randomized controlled trial | journal = JAMA | volume = 289 | issue = 14 | pages = 1820–5 | date = April 2003 | pmid = 12684361 | doi = 10.1001/jama.289.14.1820 | doi-access =  }}</ref> with significant positive effects on body weight loss and there are three ongoing clinical trials for this indication.<ref name=BED_obesity>{{cite web | author = University of Cincinnati | year = 2005 | title = Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity | work = ClinicalTrials.gov | url = http://clinicaltrials.gov/show/NCT00221442 | access-date = 2006-05-04 | archive-date = 2006-10-13 | archive-url = https://web.archive.org/web/20061013165457/http://clinicaltrials.gov/show/NCT00221442 | url-status = live }}</ref><ref name=drug-induced-obesity>{{cite web | author1 = Tuscaloosa Research | author2 = Education Advancement Corporation | year = 2005 | title = Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial | work = ClinicalTrials.gov | url = http://clinicaltrials.gov/show/NCT00203450 | access-date = 2006-05-04 | archive-date = 2007-05-04 | archive-url = https://web.archive.org/web/20070504062857/http://clinicaltrials.gov/show/NCT00203450 | url-status = live }}</ref><ref name=just_obesity>{{cite web | author = National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | year = 2006 | title = Zonisamide for Weight Reduction in Obese Adults | work = ClinicalTrials.gov | url = http://clinicaltrials.gov/show/NCT00275834 | access-date = 2006-05-04 | archive-date = 2006-10-11 | archive-url = https://web.archive.org/web/20061011172240/http://clinicaltrials.gov/show/NCT00275834 | url-status = live }}</ref> It was to be sold, when combined with [[bupropion]], under the brand name [[Empatic]], until its development was discontinued.<ref>{{cite web|title=Bupropion/zonisamide|website=AdisInsight|publisher=Springer|date=20 May 2017|access-date=19 August 2017|url=http://adisinsight.springer.com/drugs/800024638|archive-date=19 August 2017|archive-url=https://web.archive.org/web/20170819105130/http://adisinsight.springer.com/drugs/800024638|url-status=live}}</ref>

===Migraine===
Zonisamide has been studied for and used as a [[migraine]] preventative medication, when [[topiramate]] is either ineffective or cannot be continued due to side effects.<ref name="MD"/>

===Bipolar depression===
It has also been used [[off-label]] by psychiatrists as a mood stabilizer to treat bipolar depression.<ref name="Bellaire Neurology">{{Cite web|url=http://www.bellaireneurology.com/seizure/epil_trt_zonegran.html|title=Zonegran|access-date=2006-11-29|year=2004| vauthors = Loftus BD |archive-date=2008-10-23|archive-url=https://web.archive.org/web/20081023172014/http://www.bellaireneurology.com/seizure/epil_trt_zonegran.html|url-status=live}}</ref><ref>{{cite journal | vauthors = Hasegawa H | title = Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital | journal = Current Medical Research and Opinion | volume = 20 | issue = 5 | pages = 577–80 | date = May 2004 | pmid = 15140322 | doi = 10.1185/030079904125003313 | s2cid = 43580909 }}</ref>

== References ==
{{Reflist}}

{{Anticonvulsants}}
{{Channelergics}}
{{Portal bar | Medicine}}

[[Category:Anticonvulsants]]
[[Category:Benzisoxazoles]]
[[Category:Calcium channel blockers]]
[[Category:Carbonic anhydrase inhibitors]]
[[Category:Sodium channel blockers]]
[[Category:Sulfonamides]]