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Table 1 Clinical reports of CNZ/FNZ-associated MD

From: Cinnarizine- and flunarizine-associated movement disorder: a literature review

ReferenceCountry/yearN casesAgeSexSuspected drugDrug dose (mg)Time from drug-start to symptomsTime from withdrawal to recoveryFollow-upImportant clinical history and clinical management
Parkinsonism
 Mello-SouzaBrazil 19845NANAFNZNANANANA 
 Martí-Masso et al.Spain 19851165–83NACNZ1506–36 monthsNANA 
 Chouza et al.Uruguay 19861270FFNZ10–20 mg9 monthsNANoCH: PKN +orofacial DKN +severe AKT +moderate DPS. Even after 20 months of drug withdrawal, she was still with severe AKT. CM: Drug withdrawal
70FFNZ206 monthsNRCRCH: PKN +mild DPS. CM: Drug withdrawal
45FFNZ20–402 monthsNRCRCH: PKN +moderate DPS
56MFNZ201 monthNRCRCH: PKN +mild DPS. CM: Drug withdrawal
66FFNZ20–40Several monthsNRCRCH: PKN +severe DPS. CM: Drug withdrawal
63MFNZ2013 monthsNRCRCH: PKN +rabbit syndrome (DKN) +mild DPS. CM: Drug withdrawal
55FFNZ1015 monthsNRCRCH: PKN +moderate DPS. CM: Drug withdrawal
71FFNZ2012 monthsNRCRCH: PKN +orofacial DKN +mild DPS. CM: Drug withdrawal
72FFNZ401 monthNRCRCH: PKN +mild AKT +moderate DPS. CM: Drug withdrawal
65MFNZ10NRNRCRCH: PKN +moderate DPS. CM: Drug withdrawal
66FFNZ401 monthNRCRCH: PKN +rabbit syndrome (DKN) +moderate DPS. CM: Drug withdrawal
73FFNZ203 monthsNRCRCH: Only PKN. CM: Drug withdrawal
 D’Alessandro et al.Italy 1986667FFNZ10NR6 monthsCRCH: PKN +DPS. CM: Drug withdrawal
72MFNZ20NR3 monthsCRCH: PKN +DPS. CM: Drug withdrawal and amitriptyline started
72MFNZ10NRNANoCH: PKN +DPS. CM: Drug withdrawal and amineptine started
77FFNZ20NR3 monthsCRCH: PKN +DPS. CM: Drug withdrawal and amitriptyline started
77FFNZ10NR3 monthsCRCH: PKN +DPS. CM: Drug withdrawal and amitriptyline started
82MFNZ10NRNANoCH: PKN +DPS. CM: Drug withdrawal
 Laporte and CapellaSpain 19861478MCNZNR4.5 yearsNRNRCH: All had some tremor or bradykinesia; two individuals had to worsen PD. CM: Drug withdrawal
46FCNZ455 daysNRNo
48FCNZNR14 monthsNRNR
68MCNZ1502 daysNRCR
73MCNZ150NRNRCR
69FCNZ150NRNRNo
64FCNZ60–1801 yearNRNo
68MCNZ1502 daysNRCR
64FFNZ1028 daysNRCR
42MFNZ104 monthsNRCR
48FFNZ2011 daysNRNo
60FFNZ106 weeksNRCR
68MFNZ101 yearNRCR
69FFNZ108 monthsNRNo
 Meyboom et al.Netherlands 1986168MFNZ10NRSeveral monthsCRCH: PKN +AKT +mild DPS. CM: Drug withdrawal
 Martí-Masso et al.Spain 1987462.5 (mean)NACNZ15058 daysNRNACH: Randomized trial of CNZ in 10 patients with PD. After 1 month, 40% (4/10) had to withdraw from the study due to the worsening of bradykinesia and tremor
 Michele et al.Italy 19871061–77NAFNZNANANANADiscusses the range of symptoms of PKN +DPS associated with dosages of FNZ
 Micheli et al.Argentina 19871169MFNZ101 month3 monthsCRCM: Drug withdrawal
68FCNZ2254 years5 monthsCRCM: Drug withdrawal
82FFNZ11.51 year15 daysCRCH: PKN +DPS. CM: Drug withdrawal
73FCNZ15030 days17 daysCRCH: PKN +DPS. CM: Drug withdrawal
74FCNZ1504 years20 daysCRCH: PKN +DPS. CM: Drug withdrawal
61FFNZ11.53 months5 monthsCRCH: PKN +DPS +AKT +orofacial DKN. CM: Drug withdrawal
71FFNZ103 months1 monthCRCM: Drug withdrawal
73FCNZ2253 months3 monthsCRCM: Drug withdrawal
74MFNZ+CNZ10 + 1507 months–1 year1 monthCRCH: PKN +DPS. CM: Drug withdrawal
82FFNZ107 months24 daysCRCM: Drug withdrawal
67FFNZ1016 months6 monthsCRCH: PKN +DPS. CM: Drug withdrawal
 di Rosa et al.Italy 198742ElderlyNAFNZNRMonths12 weeksNACM: Drug withdrawal
 Bakchine et al.France 1988168FFNZ1010 weeks3 monthsCRCH: PKN +AKT +orofacial DKN +DPS. CM: Drug withdrawal
 Benvenuti et al.Italy 19882774 (mean)19F + 8MFNZ1014 months (mean)< 6 months (96%)CRCM: Drug withdrawal
 Capella et al.Spain 19883978 (mean)24F + 13MCNZ156 (mean)14.67 (mean)< 6 months (90%)CRCH: 3 patients were taking other drugs (sulpiride, thiethylperazine, dimenhydrinate, thioridazine); 8 were with a combination CNZ+FNZ 10 mg; 4 patients had DPS symptoms. CM: Drug withdrawal
 Lugaresi et al.Italy 19881072MFNZ1040 monthsNRNRCM: Drug withdrawal
56FFNZ105 monthsNRNRCM: Drug withdrawal
63FFNZ10Some monthsNRNRCM: Drug withdrawal
52FFNZ105 monthsNRNRCM: Drug withdrawal
72MFNZ10Some monthsNRNRCM: Drug withdrawal
63FFNZ105 monthsNRNRCM: Drug withdrawal
61FFNZ208 monthsNRNRCM: Drug withdrawal
70MFNZ56 monthsNRNRCM: Drug withdrawal
73FFNZ59 monthsNRNRCM: Drug withdrawal
93MFNZ104 monthsNRNRCM: Drug withdrawal
 de MarcoItaly 19881Yong adultMFNZNANANANA 
 Martinez-LageSpain 1988135.48 (mean)NRFNZ10NANANA 
 Moretti and LucantoniItaly 19882471.1 (mean)14F + 10MFNZ104.2 months (mean)< 4 months (50%)NACH: 10 individuals had PKN +DPS
 FontanariBrazil 1989862FFNZ106 months3 monthsCRCM: Drug withdrawal
65FFNZ105 months5 monthsCRCM: Drug withdrawal
68FFNZ103 months4 monthsCRCM: Drug withdrawal
62FFNZ1024 monthsNRNRCH: PKN +orofacial DKN. CM: drug withdrawal
63FFNZ1018 months3 monthsCRCM: Drug withdrawal
55FFNZ104 monthsNRCRCM: Drug withdrawal
60FFNZ103 months6 monthsCRCM: Drug withdrawal
63FFNZ106 months6 monthsCRCM: Drug withdrawal
 Kuzuhara et al.Japan 198931Adult20F + 7MFNZ106.1 months (mean)< 6 months (90%)CRCH: Attempts with levodopa, anticholinergic drugs, and bromocriptine had been ineffective until FNZ withdrawal. 16 individuals had PKN+DPS and 5 PKN+AKT
 Mangone et al.Argentina 19892168.5 (mean)16 F + 5 MFNZ/CNRNR15.7 months (mean)2.6 monthsCRCM: Drug withdrawal
268.5 (mean)2FFNZ/CNRNRNANANACH: Worsening of PD symptoms
 Micheli et al.Argentina 19898169.7 (mean)69F + 31M51FNZ/31CNZ/8CNZ+FNZ13.4/154.4 (mean)32.1/14.1 months (mean)80.5/105 days (mean)CRCH: 46 individuals had PKN +DPS. CM: Drug withdrawal
 Mukai et al.Japan1AdultNAFNZNANANANACH: Showed slightly decreased signal intensity of the putamen on brain MRI
 Sa and HeinischBrazil 19891975MFNZ2010 months30 daysCRCM: Previous of FNZ withdrawal was attempted anticholinergic and levodopa without success
62FFNZ202 months4 monthsCRCM: Previous of FNZ withdrawal was attempted anticholinergic and levodopa without success
71MFNZ209 months30 daysCR 
76FFNZ102 months60 daysCRCM: Previous of FNZ withdrawal was attempted anticholinergic without success
72FFNZ101 year6 monthsCRCM: Previous of FNZ withdrawal was attempted levodopa without success
65FFNZ108 months4 monthsCR 
37FFNZ208 months4 monthsCRCH: PKN +DPS
67FFNZ107 months3 monthsCRCM: Previous of FNZ withdrawal was attempted anticholinergic without success
64FFNZ105 months60 daysCRCH: PKN +DPS. CM: Previous of FNZ withdrawal was attempted anticholinergic and imipramine without success
54FFNZ106 months3 monthsCRCM: Previous of FNZ withdrawal was attempted anticholinergic and imipramine without success
69FFNZ101 year50 daysCRCH: PKN +DPS
47FFNZ1015 days7 daysCRCH: PKN +DPS
72FFNZ1011 months30 daysCRCH: PKN +DPS
72FFNZ10NR60 daysCRCM: Previous of FNZ withdrawal was attempted anticholinergic and levodopa without success
68FFNZ10NR60 daysCRCM: Previous of FNZ withdrawal was attempted anticholinergic without success
76FFNZ1011 months10 monthsCRCM: Previous of FNZ withdrawal was attempted anticholinergic without success
74FFNZ405 months60 daysCRCH: PKN +DPS. CM: Previous of FNZ withdrawal was attempted levodopa without success
NRFFNZ207 days20 daysCRCH: PKN +DPS
66FFNZ403 months60 daysCRCH: PKN +DPS. CM: Previous of FNZ withdrawal was attempted imipramine without success
 Trevisol-BittencourtBrazil 1990172MFNZ108 months30 daysCRCM: Drug withdrawal and biperiden started
 FontanariBrazil 19901AdultFFNZNRNRNRNoCH: She had PKN due to FNZ; the drug was removed, and she started to developing choreoathetotic DKN. Anticholinergics and levodopa did not ameliorate the DKN symptoms
 Gimenez-Roldan and MateoSpain 19912470.6 (mean)15F + 9MCNZ181.3 (mean)4.2 years (mean)NRNR 
 Garcia-Ruiz et al.Spain 19923272.6 (mean)26F + 6M4FNZ/27CNZ/1FNZ+CNZ8.75/122.5 (mean)15 months (mean)NRNRCH: Only 3 patients had a full recovery. 44% had PKN +DPS. Patients younger than 73 years recovered better than older individuals
 Morgante et al.Italy 19924AdultNRFNZNRNRNRNRCH 1 individual FNZ +alpha methyldopa; 3 only FNZ
 Negrotti et al.Italy 199225AdultNRFNZ/CNZNRNRNRNRCH: In the CNZ/FNZ-induced PKN there was a positive family history for PD or essential tremor with a greater percentage than the general population
 Amancio et al.Brazil 19931AdultNRFNZNRNRNRNR 
 Cunha et al.Brazil 19931167 (mean)8F + 3MFNZ/CNZ20/150 (mean)24 months (mean)2 months (mean)CRCH: 63% had PKN +DPS.
 Galhardo et al.Brazil 1993148FFNZ103 months90 daysCRCM: FNZ withdrawal; methixene and levodopa started
 Llau et al.France 19941665 (mean)10F + 6MFNZ/CNZNR15.76 months (mean)NANA 
 Anjaneyulu and MohandasIndia 19952NANAFNZNANANANA 
 Baquero et al.Spain 19951866 (mean)NAFNZ/CNZNA1 year (mean)NANA 
 ClapsChile 1995> 1NANAFNZNANANANA 
 Handforth et al.USA 1995137FFNZ60NANANACH: Assessment of FNZ for the treatment of epilepsy in the USA
 Biary et al.Arabia 1995152MFNZ1018 monthsNRNR 
 Jimenez-Jimenez et al.Spain 19963070 (mean)24F + 6MFNZ/CNZNR60.9 months (mean)4.5 months (mean)CR 
 Lee and LeeKorea 1996364.33 (mean)2F + 1MFNZ103 months (mean)4 monthsCRCH: 2 PKN +DPS; 1 only PKN. Only one had a full recovery; others needed to take levodopa after the event
 MartinezChile 1996> 1NANAFNZ/CNZNANANANA 
 Morgante et al.Italy 1996474MFNZ10NRNRCRCM: Drug withdrawal
72MFNZ20NRNRCRCM: Drug withdrawal
93FFNZ10NRNRNoCM: Drug withdrawal
62MFNZ10NRNRNRCM: Drug withdrawal
 Negrotti and CalzetiItaly 19971169.5 (mean)F8FNZ/3CNZ10/1507 monthsNANoCH: 6 orofacial DKN; 3 limb DKN. No recovery. CM: Drug withdrawal
 Cardoso et al.Brazil 199820NRNR8FNZ/12CNZNRNRNRNR 
 Errea-Abad et al.Spain 199819Elderly14F + 5M4FNZ/15CNZNRNRNRNR 
 Garcia-Ruiz et al.Spain 19983671.7 (mean)30F + 6M6FNZ/29CNZ/1FNZ+CNZNRNRNRNRCH: Only 4 individuals had a full recovery.CM: Drug withdrawal
 Marti-Masso and PozaSpain 19988775 (mean)NR13FNZ/69CNZ/5FNZ+CNZ 33 months (mean)5 months (mean)CR (90%) 
 Orti-Pareja et al.Spain 1999775.6 (mean)5F + 2M7 CNZNR45.8 monthsNRNACH: PKN +orofacial DKN
175.6 (mean)F1CNZNRNANRNACH: PKN +DTN
375.6 (mean)3F3CNZNRNANRNACH: PKN +AKT
375.6 (mean)3F3CNZNRNANRNACH: Only PKN. CM: Drug withdrawal
 Stucchi-Portocarrero et al.Peru 1999125FCNZNA11 daysNANACH: PKN +AKT +DPS. CM: Drug withdrawal; benzodiazepines, propranolol, and orphenadrine were started
 Zamora and ArgoteColombia 1999965FFNZ104 yearsNANACH: Possible interaction with verapamil
77FFNZ101 yearNANACH: Possible interaction with verapamil
65MFNZ106 monthsNANA 
76MFNZ106 monthsNANA 
51FFNZ103 monthsNANACH: PKN +DPS
51FFNZ10NRNANA 
57FCNZ753 yearsNANA 
68FFNZ103 yearsNANA 
62FFNZ10NRNANACH: Possible interaction with verapamil
 Benito-Leon et al.Spain 20039NANA8CNZ/1FNZNANANANA 
 Fabiani et al.Brazil 2004461.75 (mean)2F + 2M2FNZ/2CNZ11.2/72.1 (mean)16.5 months (mean)NRNRCH: Only PKN. CM: Drug withdrawal
187FFNZ+CNZ10 + 7516.5 months (mean)NRNRCH: PKN +orofacial DKN +DPS
176FFNZ+CNZ10 + 7516.5 months (mean)NRNRCH: PKN +orofacial DKN
566 (mean)5F3CNZ/1FNZ/1CNZ+FNZ11.2/72.1 (mean)16.5 months (mean)NRNRCH: PKN +DPS
 Trevisol-Bittencourt et al.Brazil 2005373.2 (mean)FCNZ/FNZNRNRNRNR 
 Barbosa et al.Brazil 20061373.5 (mean)NR7FNZ/6CNZNRNRNRNR 
 Louter and TrompNetherlands 20091AdultNRCNZNRNRNRCRCM: Drug withdrawal
 Ma et al.Korea 2009671.5 (mean)NRFNZNR6.3 months (mean)NRNR 
 Mattos et al.Brazil 2009174FFNZ101 year10 monthsCRCH: Progressive supranuclear palsy like syndrome. CM: Drug withdrawal; levodopa, tolcapone, and memantine were started
 Munhoz et al.Brazil 20104760.8 (mean)NA34FNZ/13CNZNANANANA 
 Masmoudi et al.France 2011180FFNZ10MonthsNRNoCH: PKN +orofacial DKN; possible interaction with trimetazidine; she did not recover the DKN
 AriasColombia 2012235FFNZ20NR10 weeksCRCH: PKN +DPS. CM: Drug withdrawal
28MFNZ206 weeks10 weeksCRCH: PKN +DPS. CM: Drug withdrawal
 Pioner et al.Brazil 2012156FCNZ25NRNRCRCM: Drug withdrawal
 Kim et al.Korea 2013665FFNZ1012 monthsNRNRCH: PKN. CM: Drug withdrawal
62MFNZ101 monthNRNRCH: PKN. CM: Drug withdrawal
84FFNZ103 monthsNRNRCH: PKN. CM: Drug withdrawal
70FFNZ1048 monthsNRNRCH: PKN. CM: Drug withdrawal
58FFNZ101 monthNRNRCH: PKN +oromandibular DTN
66FFNZ103 monthsNRNRCH: PKN. CM: Drug withdrawal
 Gotardelo et al.Brazil 2014172FFNZ10Years2 monthsCRCM: Drug withdrawal; biperiden started
 Miguel et al.Portugal 20143073.3 (mean)22F + 8MFNZ/CNZNRNRNRCR (43%)CH: 43% recovered only with withdrawal; the others needed a dopaminergic treatment for improving the symptoms
 Chary and KrishnanIndia 2016137FFNZ151 month1 weekCRCH: PKN +DPS. CM: Drug withdrawal; trihexyphenidyl started
 Munhoz et al.Brazil 20165874.1 (mean)NR38FNZ/20CNZ9.1/45 (mean)6 monthsNRNR 
 Nistico et al.Italy 2016264.19 (mean)2FFNZNRNRNRNR 
 Sung et al.Korea 2016170.85 (mean)1FCNZNRNRNRNR 
Dyskinesia
 Micheli et al.Argentina 1987264FFNZ103 months2 monthsCRCH: Orofacial DKN (probably rabbit syndrome). CM: Drug withdrawal
62FFNZ102 yearsNANoCH: Orofacial DKN +DPS. CM: Drug withdrawal, but without symptoms resolution
 Gabellini et al.Italy 1989162FFNZ101 year3 weeksCRCH: Transient tongue tremor. CM: Drug withdrawal
 Mangone et al.Argentina 1989668.5 (mean)5F + 1 MFNZ/CNRNRNR2 monthsNRCH: Orofacial DKN. CM: Drug withdrawal
168.5 (mean)1FFNZ/CNRNRNR2 monthsCRCH: Rabbit syndrome + AKT. CM: Drug withdrawal
 Micheli et al.Argentina 1989974FFNZ1036 monthsNANoCH: Orofacial DKN +AKT. CM: Drug withdrawal
59MCNZ22536 months2 weeksCRCH: Orofacial DKN +PKN +DPS. CM: Drug withdrawal
62FCNZ15024 months1 monthCRCH: Orofacial DKN. CM: Drug withdrawal
64FFNZ104 months1 monthCRCH: Orofacial DKN +PKN. CM: Drug withdrawal
61FFNZ11.53 months5 monthsCRCH: Orofacial DKN +AKT +PKN +DPS. CM: Drug withdrawal
70FFNZ+CNZ25/10 mg24 monthsNANoCH: Orofacial DKN +AKT. CM: Drug withdrawal
68FFNZ1048 months5 monthsCRCH: Orofacial DKN +PKN +DPS. CM: Drug withdrawal
64FFNZ1024 monthsNANoCH: Orofacial DKN +AKT +DPS. CM: Drug withdrawal
84MCNZ1504 monthsNANoCH: Orofacial DKN +PKN. CM: Drug withdrawal
 Jimenez-Jimenez et al.Spain 1996270 (mean)2FFNZ/CNRNR60.9 months (mean)4.5 months (mean)CR 
 Orti-Pareja et al.Spain 1999175.6 (mean)FFNZNA45.8 monthsNANA 
 Fabiani et al.Brazil 2004172MFNZ1016.5 months (mean)NRNR 
Akathisia
 Micheli et al.Argentina 1987154MCNZ754 h1 dayCRCM: Drug withdrawal
 Micheli et al.Argentina 1989470FFNZ3048 months2 monthsCRCH: AKT +bruxism + PKN. CM: Drug withdrawal
49FFNZ208 months2 monthsCRCH: AKT +PKN +DPS. CM: Drug withdrawal
66FFNZ1018 months2 monthsCRCH: AKT +PKN +DPS. CM: Drug withdrawal
74MFNZ2018 months8 monthsCRCH: AKT +PKN +DPS. CM: Drug withdrawal
 Garcia and UriarteSpain 19911AdultNAFNZNANANANA 
 Anand and ThiagarajanIndia 19931AdultNAFNZNANANANACH: AKT +DPS
 Jimenez-Jimenez et al.Spain 1996270 (mean)2FFNZ/CNRNR60.9 months (mean)4.5 months (mean)CR 
Dystonia
 Micheli et al.Argentina 1987137MFNZ+CNZ10 + 1503 daysNANACH: Cervical DTN. CM: FNZ+CNZ was maintained
 Mangone et al.Argentina 1989668.5 (mean)1F + 5MFNZ/CNRNRNRNRCRCH: Acute DTN that resolved after drug withdrawal
 Micheli et al.Argentina 1989167FFNZ+CNZ20 + 15018 monthsNANoCH: Blepharospasm + oromandibular DTN. CM: Drug withdrawal
 Biary et al.Arabia 1995131FFNZ103 monthsNRNRCH: Cervical DTN
 Jimenez-Jimenez et al.Spain 1996270 (mean)2FFNZ/CNRNR60.9 months (mean)4.5 months (mean)CR 
 Koukoulis et al.Spain 1997130FFNZ102 months1 monthCRCH: Blepharospasm. CM: Drug withdrawal
 Fabiani et al.Brazil 2004161FFNZ+CNZ11.2/72.1 (mean)16.5 months (mean)NANA 
 Alonso-Navarro and Jimenez-JimenezSpain 2006153FCNZ406 years1 yearCRCH: Blepharospasm; she also had a history of DTN with thiethylperazine and sulpiride. CM: Drug withdrawal
 Mathews et al.India 2017117FCNZ25Single-dose1.5 daysCRCH: Oromandibular and cervical DTN; possible interaction between CNZ and prochlorperazine. CM: Drug withdrawal; diphenhydramine started
 Gallop et al.UK 2019110.5 (mean)FFNZ5 mgNANANACH: Worsening of DTN; Sturge-Weber syndrome
Myoclonus
 Turner et al.Israel 200612.5FCNZOverdoseNANANACH: Possible MCL (twitching in both hands)
 Lopez-Castellanos et al.El Salvador 2017458MFNZ+CNZNR1 week3 daysCRCH: Multifocal MCL. CM: Drug withdrawal
66FFNZNR20 years1 monthCRCH: Multifocal MCL. CM: Drug withdrawal
70FCNZNR8 yearsNANoCH: Multifocal MCL. CM: Drug withdrawal
69MCNZNR3 years5 yearsCRCH: Multifocal MCL. CM: Drug withdrawal
Cases not clearly defined
 Martí-MassoSpain 1986> 1PKNCase series showing that the worsening of PD is reversible with CNZ, but the MD may last several days or even weeks
 Giannaula et al.Argentina 198627EPSReport of 27 individuals that developed PKN +DPS after CNZ/FNZ use
 AmeryBelgium 1987> 1EPSReports about EPS following the use of FNZ
 Baldrati et al.Italy 19871TremorA young female presented with unilateral postural tremor after 10 mg FNZ for 2 months. Later, 4 months, she developed DPS. No signs of PKN were observed
 Herskovits and MangoneArgentina 1987> 1EPSEPS following the use of CNZ/FNZ
 Assmann et al.Netherlands 1988> 1EPSEPS following the use of FNZ
 di RosaItaly 1988> 1EPSEPS following the use of FNZ
 RostinFrance 1988> 1EPSAssessment of the efficacy of FNZ to the prophylactic treatment of migraine
 Hefner and FischerGermany 1989> 1PKNWorsening of PD symptoms with FNZ
 Jongerius and van GoolNetherlands 1989> 1EPSEPS following the use of FNZ
 Mangone et al.Argentina 19898TremorThe symptoms started within 15 months of the beginning of the FNZ/CNZ and recovery in two months after drug withdrawal
 PetriNetherlands 1989> 1EPSEPS following the use of FNZ
 Centozone et al.Italy 19901TremorAssessment of the efficacy of FNZ to the prophylactic treatment of migraine
 Micheli et al.Argentina 19902BradykinesiaAssessment of the efficacy of FNZ to the management of Tourette’s syndrome
 Senard et al.France 19906EPSReport of 5F + 1M with 71.5 years (mean) who were n use of FNZ 11.66 mg when the EPS occurred. The EPS appeared after 7.0 (mean) months and disappeared after 2.2 (mean) months respectively
 Wilder-Smith et al.Switzerland 19911TremorAssessment of the efficacy of CNZ as an antiemetic for platin chemotherapy, possible interaction with metoclopramide and lorazepam
1AKT
 Curran and LangCanada 19933TremorAssessment of the efficacy of FNZ in 10 patients with essential tremor. 3 individuals developed worsening of the symptoms
 Beghi et al.Italy1994> 1PKNPharmaco-epidemiological study about the prevalence of PKN in Italy. Exposure to FNZ, neuroleptics was observed in 8 patients
 Brucke et al.Austria 1995NAEPSSPECT assessment in 26 individuals under FNZ/CNZ. It was observed that older age and long-term treatment are predisposing factors for EPS
 Martí-MassoSpain 1996> 1PKNDetermine the prevalence of DIP in general neurology practice. During 1981–1988, the drug most often implicated was CNZ, though its relative impact decreased after
 Vecchio et al.Italy 19963TremorAssessment of the efficacy of FNZ in 12 patients with essential tremor. 3 individuals had worsening of tremor, in the others nothing change
 Verspeelt et al.Germany 199643EPSAssessment of the efficacy of FNZ in vestibular vertigo and migraine
 Orti-Pareja et al.Spain 19992TremorReports of tremor following the use of CNZ (1) or FNZ (1)
 Vazquez-Alen et al.Spain 2000> 1PKNTo determine demographic changes in an outpatient clinic in Spain about MD. It was observed a 40% decrease of the PKN during 1991–1998; the authors hypothesized that this occurred because of a reduction in prescriptions of CNZ/FNZ and flupentixol
 Schillevoort et al.Netherlands 2002> 1PKNData obtained from the PHARMO-database 1986–1998. CNZ/FNZ users were more likely to receive antiparkinsonian medication than non-users. Also, the use of antiparkinsonian medication was already elevated with CNZ/FNZ low doses and increased with increasing dose and duration of use
 Martí-MassoSpain 20052PKNRetrospective study about the adverse effects of trimetazidine on motor functions. 4 patients were taking CNZ two developed PKN, and the other 2 did not have any adverse event
 OteroSpain 20061EPSReport of an infant male who developed EPS +DPS after the use of FNZ 10 mg
 Bisol et al.Brazil 2008> 1AKTAssessment of the efficacy of FNZ in the management of schizophrenia and schizoaffective disorder
 Benito-Leon et al.Spain 2009> 1PKNA population-based study of the PD incidence. It was observed 6 reports of possible PKN with cinnarizine, flunarizine, clebopride
 Diaz-Corrales et al.Spain 20092PKNAssessment of SPECT in the differentiation of DIP and PD. 1 individual had DIP secondary to CNZ and other to FNZ
 Bondon-Guitton et al.France 201110PKNReports of DIP to a pharmacovigilance center in France from 1993 to 2009. 7 individuals had PKN with FNZ, and the other 3 with CNZ
 Kizilay et al.Turkey 20111MyokymiaReport of a young adult female who used FNZ and developed fasciculation–myokymia
 Foubert-Samier et al.France 2012NAPKNAssessment of the long-term risk of developing PD after past exposure to neuroleptics and neuroleptic-like drugs. Concerning phenothiazines, the association with the risk of PD was mainly due to FNZ/CNZ (RR, 3.39; 95% CI, 1.20–9.58). Without FNZ/CNZ, the association was not statistically significant for phenothiazines (RR, 1.81; 95% CI, 0.71–4.64)
 Lin et al.Taiwan 2016280PKNA population-based study assessing the risk for PKN in patients receiving FNZ/CNZ. The adjusted hazard ratio for PKN was 5.11 (CI = 3.758–6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the studied drugs were not
 Jhang et al.Taiwan 2017497EPSA population-based study assessing the risk for PKN in patients receiving FNZ/CNZ. The hazard ratios of EPS for FNZ CNZ were 8.03 (CI 6.55–9.84) and 3.41 (CI 2.50–4.63)
 Yang et al.China 2017NAPKNA population-based study assessing the risk of PKN in patients with DM. When FNZ is present, the hazard risk ratio is (1.21, 1.08–1.35)
 Karsan et al.UK 201811EPSAssessment of FNZ for the management of migraine. 11 individuals had possible EPS; 9 tremors and 2 with micrographia
 Liang et al.Taiwan 2018NAPKNAssessment of the risk of developing PKN after FNZ in patients with type 2 diabetes. The adjusted odds ratio was 2.75 (2.26–3.36)
 Byun et al.Korea 2019NAPKNAssessment of the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide Korean data. From 2009 to 2015, it was observed a compound annual growth rate of 7.42% to FNZ
 Jhang et al.Taiwan 2019NAPKNAssessment of the risk of developing MD after FNZ. FNZ was associated with 240 PKN +48 hyperkineses. Higher exposure dose and duration, older age, history of essential tremor, and cardiovascular disease were associated with FNZ-associated MD
 Kim et al.Korea 2019NAPKNAssessment of the association between drug exposure and the risk of PKN using Korean population-based data. The odds ratio of FNZ when compared to those that never used it was 4.95 (2.71–9.03)
 Lin et al.Taiwan 2019NAPKNAssessment of the risk of developing PKN after FNZ in the database of Taiwan’s National Health Insurance Research Database. It is associated with older age, history of comorbidities, exposure to FNZ high-dose, and longer duration of exposure to FNZ
  1. Abbreviations: AKT akathisia, BD bipolar disorder, CH clinical history, CM clinical management, CNZ cinnarizine, CR complete recovery, DIP drug-induced parkinsonism, DKN dyskinesia, DPS depression, DTN dystonia, EPI epilepsy, EPS extrapyramidal symptoms, F female, FNZ flunarizine, M male, MCL myoclonus, MD movement disorder, NA not applicable/not available, NR not reported, PKN parkinsonism, PD Parkinson’s disease, FNZ/CNZ flunarizine or cinnarizine, FNZ+CNZ flunarizine combined with cinnarizine