Epilepsy & Behavior 103 (2020) 106861

Contents lists available at ScienceDirect

Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

Review

Pyridoxine supplementation for levetiracetam-related neuropsychiatric

adverse events: A systematic review
Michele Romoli a,b,c,⁎, Emilio Perucca d,e,1, Arjune Sen b,1
a
Neurology Unit, Rimini “Infermi” Hospital – AUSL Romagna, Italy
b
Oxford Epilepsy Research Group, Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, Oxford, United Kingdom
c
Neurology Clinic, University of Perugia – S. Maria della Misericordia Hospital, Perugia, Italy
d
Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Italy
e
Clinical Trial Center, IRCCS Mondino Foundation, Pavia, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs)
Received 15 October 2019 that impact negatively on quality of life. It has been suggested that pyridoxine can ameliorate LEV-related NPAEs.
Revised 14 December 2019 We conducted a systematic review of studies on the use of pyridoxine supplementation to relieve NPAEs associ-
Accepted 14 December 2019 ated with LEV therapy.
Available online 6 January 2020
Methods: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) guidelines. Medline, EMBASE, Scholar, Cochrane-CENTRAL (2000–2019), and EThOS platform
Keywords:
Levetiracetam
were searched for studies on the use of pyridoxine in patients with LEV-related NPAEs. Proportions of patients
Adverse effects reported to benefit from pyridoxine supplementation were tabulated, and a random-effect model meta-analysis
Neuropsychiatric effects was conducted.
Pyridoxine Results: Eleven retrospective studies/case reports and one randomized prospective study, mostly including pedi-
Interaction atric populations, were identified. Retrospective studies, which were rated as low quality due to failure to control
for bias, reported an overall improvement of NPAEs after pyridoxine supplementation in 72.5% (108/149) of pa-
tients. The proportion of patients showing improvement in a pooled analysis of the four largest retrospective
studies (n = 134) was 72.1% (95% confidence interval (CI) 47.1–88.3), although there was high heterogeneity
across studies (I2 = 82%, pheterogeneity b 0.01). In the only prospective trial, patients randomized to pyridoxine
supplementation were more likely to show relief from NPAEs than patients not receiving supplementation (p
b 0.01), but outcomes might have been affected by assessment bias.
Conclusion: This systematic review suggests that pyridoxine might be of benefit in relieving LEV-related NPAEs.
However, the quality of the evidence is poor, and better-designed prospective studies that include quantitative
as well as qualitative data are needed to define the role of pyridoxine in the management of LEV-related NPAEs.
© 2019 Elsevier Inc. All rights reserved.

1. Introduction
Levetiracetam (LEV) is one of the most commonly prescribed antisei-
zure medications (ASMs), largely due to its effectiveness against multiple
seizure types, feasibility of fast titration, low risk of drug interactions, and
relatively favorable tolerability profile [1,2]. Neuropsychiatric adverse
events (NPAEs), however, occur in a considerable proportion of patients
Abbreviations: ASM, antiseizure medication; LEV, levetiracetam; NPAEs, neuropsychiatric
adverse events.
⁎ Corresponding author at: Neurology Unit, Rimini “Infermi” Hospital – AUSL Romagna,
viale Settembrini 2, Rimini, Italy.
E-mail address: michele.romoli@auslromagna.it (M. Romoli).
1
Senior authors.
treated with LEV [3] and can impact on quality of life [1,4,5], limiting pa-
tient adherence and seizure control. The need for strategies to monitor,
limit, or prevent ASM-related NPAEs, has been repeatedly emphasized
[2,6,7].
Despite attempts to develop tools to predict and quantify the occur-
rence of NPAEs [2], few studies have addressed the feasibility of
preventing or attenuating these effects. Low pyridoxine (vitamin B6)
levels have been associated with neuropsychiatric disorders [8,9], and
anecdotal reports have suggested that pyridoxine supplementation
can prevent or reverse NPAEs associated with LEV [10]. Hence, pyridox-
ine supplementation might provide a cost-effective strategy to improve
the tolerability of LEV in patients with epilepsy [10,11].
In this systematic review, we assessed reports on the impact of pyr-
idoxine supplementation on LEV-related NPAEs to determine the qual-
ity of the evidence supporting its use.

https://doi.org/10.1016/j.yebeh.2019.106861
1525-5050/© 2019 Elsevier Inc. All rights reserved.
2 M. Romoli et al. / Epilepsy & Behavior 103 (2020) 106861

2. Materials and methods 2.2. Eligibility, data extraction, and outcome measures

2.1. Search strategy
The systematic review and meta-analysis followed the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines [12]. The protocol, not registered, was agreed by all authors.
All studies addressing the use of pyridoxine among patients with LEV-
related NPAEs were included. Medline, EMBASE, Google Scholar, and
Cochrane-CENTRAL were searched from 1st January 2000 to 3rd June
2019 using the combination of keywords and MeSH terms for ‘levetirac-
etam’ AND (‘behavior’ OR ‘behaviour’) AND ‘pyridoxine’, including: (i)
‘levetiracetam’ OR ‘Keppra’ OR ‘Matever’ OR ‘Roweepra’ OR ‘Spritam’;
(ii) ‘Drug-Related Side Effects and Adverse Reactions’ OR ‘behavior/
drug effect’ OR ‘behavior/drug therapy’ OR ‘behav*’ OR ‘neurpsych*’
OR ‘psych*’; (iii) ‘pyridoxine’ OR ‘vitamin B 6’ OR ‘B 6’ OR ‘B6’ (Supple-
mentary material). We also hand-searched reference lists of all articles
identified in the electronic search, EThOS, and proceedings of epilepsy
international congresses for relevant abstracts. No limitations for lan-
guage, article type, and study design were defined. Data from case reports,
retrospective, and prospective studies were summarized separately.
Studies identified by the search were reviewed to verify their
reporting on outcomes of LEV-related NPAEs after pyridoxine supple-
mentation. Neuropsychiatric adverse events and outcomes were de-
fined according to the original report. Specifically, the term “NPAEs”,
as used in this review, refers to a wide range of neurological/psychiatric
adverse effects (see Table 1 for details). For eligible studies, data were
extracted on the characteristics of the study population; dosing infor-
mation; improvement/worsening of NPAEs after pyridoxine treatment;
and time to experiencing benefit after pyridoxine supplementation. Risk
of bias was assessed via Newcastle–Ottawa scale (NOS) and Cochrane
Risk of Bias tool [13,14].
2.3. Statistical analysis
Heterogeneity was assessed by means of Cochrane's Q test and I2
statistic [15]. The proportion of patients with improvement in NPAEs
after pyridoxine supplementation was meta-analyzed by using a ran-
dom-effects model (R-v3.3.1) due to consistent differences in design
and outcome assessment, as well as global heterogeneity (p b 0.10, I2

Table 1
Characteristics of patients and outcome data for each of the studies retrieved by the systematic search.

Author (ref) Study design Number and characteristics of Age, years NPAEs LEV dose Pyridoxine dose Outcome of NPAEs Time to benefit
patientsa mean (range, reported mean (range, mean (range, if after pyridoxine after pyridoxine
if reported) if reported) reported) supplementation supplementation

Alsaadi et al., Retrospective 51 adults with idiopathic generalized 34.2b “behavioral” 2208 mg/db 54.5 mg/d 66.6% (34/51) Within 2 weeks
2015 [10] observational or focal epilepsy (50–100 mg/d) improved
33.3% (17/51) no
benefit
Chez et al., 2005 Retrospective 16 patients with epilepsy (unspecified 8.16 (3–21) “behavioral” 313 mg/dc 118 mg/d 75% (12/16) improved NR
[11] observational type) (50–400 mg/d) 12.5% (2/16) no
benefit
Davis et al., Case report 1 child with ‘seizure-like activity’, 6 Agitation, 40 mg/kg/d 50 mg/d Amelioration of Immediate
2009 [19] intellectual disability, cerebral palsy, confusion, irritability
Chiari II stereotypic
movements
Kawakami et al., Case report 1 child with bilateral tonic–clonic 9 Psychosis 1000 mg/d NR No benefit, regression NR
2015 [18] seizures of NPAEs after LEV
withdrawal
Khan et al., Case report 1 infant with neonatal seizures NR Irritability NR 50 mg/d Benefit NR
2011 [20]
Kossoff et al., Case report 1 child with benign rolandic epilepsy 11.8 “moody” 40 mg/kg NR No benefit NR
2007 [21]
Major et al., Retrospective 22 patients with mixed or focal 9.9 “behavioral” 63 mg/kg/d 6 mg/kg/d 9 (41%) improved, NR
2008 [17] observational seizure semiology (3.4–19.3)d (11.3–139.5 (100–200 8 (36%) no change,
mg/kg/d)d mg/d)d 4 (18%) worsened,
1 uncertain
Marino et al., Randomized 50 children with generalized or focal 9.76 (7–16) Anxiety, 39.2 mg/kg/d 7 mg/kg/d (up LEV discontinued Mean 9 days
2018 [16] prospective epilepsy. After 30 days on LEV, 25 depression (pyridoxine to 350 mg/d) because of NPAEs in 8%
case–control were given pyridoxine and 25 (Children's group) of pyridoxine children
study continued LEV without pyridoxine Depression 38.6 mg/kg/d vs 76% of controls
Inventory) (control
group)
Miller, 2002 Retrospective 6 children with focal/focal to bilateral NR (2–10) Insomnia, 21 mg/kg/d 7 mg/kg/d 83.3% (5/6) resolved Within 1 week
[23] observational tonic–clonic seizures (n = 5) and agitation, 16.7% (1/6) improved
case series migraine (n = 1) anxiety, lability
Obeid and Pong, Retrospective 2 children with refractory epilepsy NR Irritability, 73.5–150 NR 50% (1/2) improved NR
2010 [22] observational hyperactivity mg/kg/de 50% (1/2) no benefit
Sajja et al., 2017 Retrospective 45 patients with epilepsy (not NR Insomnia, 1000 mg/d 100 mg/d 93.3% (43/45) NR
[24] observational otherwise specified) anxiety, (median) improved
agitation 6.7% (2/45) no benefit
Sharp et al., Retrospective 3 children with new-onset epilepsy NR Sleepiness, NR NR 66.6% (2/3) resolved NR
2006 [25] observational (not otherwise specified) “behavioral”

Legend. LEV: levetiracetam; NPAEs: neuropsychiatric adverse effects; NR: not reported.
a
Patients treated with pyridoxine after developing LEV-related NPAEs.
b
Information on mean age and mean LEV dosage refers to a cohort of 88 patients that included 51 patients receiving pyridoxine after developing LEV-related NPAEs.
c
Information on mean LEV dosage refers to a cohort of 21 patients that included 16 patients treated with pyridoxine after developing LEV-related NPAEs.
d
Information on age and doses refer to a cohort of 42 patients that included the 22 patients treated with pyridoxine after developing LEV-related NPAEs.
e
Dose range in 4 children who developed LEV-related NPAEs. Of those, only two were treated with pyridoxine.
 M. Romoli et al. / Epilepsy & Behavior 103 (2020) 106861
N 40%). To minimize risk of bias related to heterogeneity among reports,
only studies with NOS scores N 1 were included in the meta-analysis. For
the purposes of analysis, outcomes after pyridoxine supplementation
were dichotomized as (i) improvement or resolution of NPAEs and (ii)
persistence or worsening of NPAEs. Studies reporting on the use of pyr-
idoxine as prophylaxis against the occurrence of LEV-related NPAEs
[16,17] were excluded from statistical analyses.
3. Results
3.1. Results of the literature search and characteristics of eligible studies
Among 29 articles retrieved, 12 were eligible for data extraction (Fig.
1; Supporting information). Two were case reports [18,19], and four
were retrospective case series with less than ten patients receiving pyr-
idoxine [20–23]. Five were larger retrospective studies [10,11,17,23,24],
and one was a prospective randomized trial [16] (Table 1). All retro-
spective studies were likely to have been influenced by selection,
reporting, and assessment bias. In all studies, NPAEs were assessed qual-
itatively without the use of standardized instruments, except for the
randomized study [16], which used the Children's Depression Inventory
questionnaire. The latter study was presented as a single-blind trial, but
there was no indication of either the investigators or the patients being
unaware of the treatment allocation, or of any measure being in place to
minimize assessment bias [16] (Supplementary material).
Fig. 1. Study flow chart.
3
Most studies included children and young adults [16–23,25]. One
study did not report the age of participants [24], and one enrolled pa-
tients 18 years and older [10,11]. Pyridoxine was used to treat LEV-re-
lated NPAEs in all reports identified by the search. In two studies,
pyridoxine was also prescribed in some participants prior to the devel-
opment to NPAEs [16,17]. Levetiracetam was used as monotherapy in
11.9 to 100% of participants, when this information was reported. Pyri-
doxine dose, when specified, ranged from 50 to 400 mg/day (Table 1).
3.2. Neuropsychiatric outcomes
The 11 retrospective studies reported data on 149 patients who re-
ceived pyridoxine supplementation for LEV-related NPAEs. Of these,
72.5% (n = 108) reported improvement or resolution of NPAEs after pyr-
idoxine supplementation. In studies with small sample size (n b 10), out-
comes varied, with one case report [19] and three retrospective studies
reporting improvement of NPAEs after pyridoxine [20,23,25], while
three studies reported no benefit [18,21,22]. The larger retrospective
studies with NOS score N1 [10,11,17,24] reported improvement of LEV-
related NPAEs after pyridoxine supplementation in 41 to 93% of patients
(Table 1). Meta-analysis of data from these larger studies showed that 97
of 134 participants (72.1%) reported improvement after pyridoxine sup-
plementation (95%CI 47.1–88.3%), though significant heterogeneity was
detected across studies (I2 82%; pheterogeneity b 0.01) (Fig. 2). Three
4 M. Romoli et al. / Epilepsy & Behavior 103 (2020) 106861
Fig. 2. Forest plot showing proportions of patients in whom neuropsychiatric adverse effects related to levetiracetam therapy improved after pyridoxine supplementation.
studies (n = 83) reported on time to apparent benefit, which ranged
from 1 day to within 2 weeks of starting supplementation [10,19,23]
(Table 1).
The single randomized prospective study enrolled 50 children with
focal or generalized epilepsy aged 6 to 16 years, who had been treated
with LEV monotherapy for 30 days and had no seizures for 15 days
after reaching the target LEV dose [16]. Patients were randomized to
two groups and allocated to receive either pyridoxine supplementation
(7 mg/kg/day, up to a maximum of 350 mg/day, n = 25) or no supple-
mentation (n = 25). Prior to randomization, NPAEs had developed in
80% of cases in the group that went on to receive LEV alone and in
75% of cases in the cohort that were additionally given pyridoxine. Dur-
ing the 12-month follow-up, 76% of patients in the LEV alone group
discontinued LEV because of NPAEs. In the LEV plus pyridoxine group,
NPAEs resolved in most cases after 9 days (number of improved patients
not reported), and only 8% of patients discontinued LEV treatment be-
cause of NPAEs (p b 0.001 versus LEV alone group). A significant im-
provement in Children Depression Inventory scores was reported for
the group allocated to pyridoxine supplementation at one year (p b
0.01 compared with pretreatment) [16]. However, no raw data were
available to extract prevalence of NPAEs and their regression after pyr-
idoxine supplementation. Similarly, no data were available regarding
the impact of pyridoxine treatment on different NPAEs, or in relation
to previous history of psychiatric disturbances.
3.3. Adverse effects of pyridoxine treatment
Adverse effects of pyridoxine treatment were reported in one retro-
spective observational study [17]. In that study, 4 of 42 patients were re-
ported to have developed behavioral problems (n = 2) or increased
frequency of seizures (n = 2) [17]. No other report described any ad-
verse effect from pyridoxine supplementation.
4. Discussion
Improvement of neurobehavioral symptoms with pyridoxine sup-
plementation has been reported in premenstrual syndrome [26], and
there is suggestive evidence that pyridoxine can ameliorate some cogni-
tive functions in patients with psychosis [27]. Despite anecdotal reports
on the use of pyridoxine for LEV-related NPAEs, to date, only a few stud-
ies have investigated its value for this potential indication [16].
The present systematic review identified 12 relevant original re-
ports. In the 11 retrospective studies, pyridoxine supplementation was
reported to associate with improvement of LEV-related NPAEs in
about 70% of patients overall, with a putative onset of benefit usually
within 2 weeks. In the only randomized study conducted to date, the ap-
parent benefit from pyridoxine was even greater, with 8% of patients
discontinuing LEV treatment because of NPAEs in the pyridoxine
group compared with 72% in the control group. While these data are en-
couraging, the quality of evidence was generally poor, owing to the
likely influence of selection, reporting, and assessment biases. Even
the results of the randomized trial [16] raise interpretative concerns
because of the lack of blinding, small sample size, unusually high rate
of LEV discontinuation due to NPAEs in the group treated with LEV
alone, and lack of information about when LEV discontinuations
occurred.
Multiple limitations were highlighted by our systematic review in-
cluding the lack of well-designed randomized controlled trials; large
heterogeneity of the retrieved studies; variable definition and categori-
zation of NPAEs across studies; failure to use standardized tools to as-
sess NPAEs; and frequent lack of information about risk factors for
NPAEs, such as a previous history of psychiatric disturbances. The un-
controlled nature of the reports and the prominent heterogeneity across
studies limit the value of our meta-analysis, the results of which should
be interpreted cautiously.
Based on these considerations, there seems inadequate evidence
to fully assess the value of pyridoxine in the management of LEV-re-
lated NPAEs. However, considering the skew towards positive results
in the current literature, the low cost of pyridoxine, and good tolera-
bility at doses reported to be effective (well below those that associ-
ate with neuropathy [28]), further studies seem justified. Ideally,
such studies would include a randomized double-blind design, ade-
quate statistical power, well-defined eligibility criteria, and the use
of standardized quantitative assessment tools [1,2,6,7]. In addition
to testing pyridoxine effectiveness against established NPAEs, future
studies may also consider assessing its potential value as prophylaxis
against the occurrence of NPAEs in patients requiring initiation of
LEV therapy.
5. Conclusion
The current evidence supporting utilization of pyridoxine to miti-
gate LEV-related NPAEs is limited, and large-scale controlled studies
are needed to determine the value of pyridoxine supplementation for
this specific indication.
Funding
This research did not receive any specific grant from funding agen-
cies in the public, commercial, or not-for-profit sectors.
Ethical publication statement
We confirm that we have read the Journal's position on issues in-
volved in ethical publication and affirm that this report is consistent
with those guidelines.
Declaration of competing interest
This work was supported by the Oxford NIHR Biomedical Research
Centre. EP has received speaker and/or consultancy fees from Amicus
Therapeutics, Biogen, Eisai, GW Pharma, Intas Pharmaceuticals, Lundbeck,
Sanofi, Sun Pharma, Takeda, UCB Pharma and Xenon Pharma. AS has re-
ceived research monies/honoraria/speaker's fees from Bial, Eisai Europe
 M. Romoli et al. / Epilepsy & Behavior 103 (2020) 106861
Limited, GW Pharma, Livanova, and UCB Pharma. MR has received no
funding or honoraria.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.yebeh.2019.106861.
References
[1] Bedetti C, Romoli M, Maschio M, Di Bonaventura C, Nardi Cesarini E, Eusebi P, et al.
Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epi-
lepsy: an Italian multicentre prospective observational study. Eur J Neurol 2017;24:
1283–9. https://doi.org/10.1111/ene.13375.
[2] Josephson CB, Engbers JDT, Jette N, Patten SB, Singh S, Sajobi TT, et al. Prediction
tools for psychiatric adverse effects after levetiracetam prescription. JAMA Neurol
2019;76:440–6. https://doi.org/10.1001/jamaneurol.2018.4561.
[3] Hansen CC, Ljung H, Brodtkorb E, Reimers A. Mechanisms underlying aggressive be-
havior induced by antiepileptic drugs: focus on topiramate, levetiracetam, and
perampanel. Behav Neurol 2018;2018:1–18. https://doi.org/10.1155/2018/2064027.
[4] Halma E, De Louw AJA, Klinkenberg S, Aldenkamp AP, Ijff DM, Majoie M. Behavioral
side-effects of levetiracetam in children with epilepsy: a systematic review. Seizure
2014;23:685–91. https://doi.org/10.1016/j.seizure.2014.06.004.
[5] White JR, Walczak TS, Leppik IE, Rarick J, Tran T, Beniak TE, et al. Discontinuation of
levetiracetam because of behavioral side effects: a case–control study. Neurology
2003;61:1218–21. https://doi.org/10.1212/01.WNL.0000091865.46063.67.
[6] Romoli M, Eusebi P, Siliquini S, Bedetti C, Calabresi P, Costa C. Liverpool Adverse
Events Profile: Italian validation and predictive value for dropout from antiepileptic
treatment in people with epilepsy. Epilepsy Behav 2018;81:111–4. https://doi.org/
10.1016/j.yebeh.2018.01.028.
[7] Romoli M, Costa C, Siliquini S, Corbelli I, Eusebi P, Bedetti C, et al. Antiepileptic drugs
in migraine and epilepsy: who is at increased risk of adverse events? Cephalalgia
2018;38:274–82. https://doi.org/10.1177/0333102416683925.
[8] Moore K, Hughes CF, Hoey L, Ward M, Cunningham C, Molloy AM, et al. B-vitamins
in relation to depression in older adults over 60 years of age: the Trinity Ulster De-
partment of Agriculture (TUDA) Cohort Study. J Am Med Dir Assoc 2019. https://doi.
org/10.1016/j.jamda.2018.11.031.
[9] Mitchell ES, Conus N, Kaput J. B vitamin polymorphisms and behavior: evidence of
associations with neurodevelopment, depression, schizophrenia, bipolar disorder
and cognitive decline. Neurosci Biobehav Rev 2014;47:307–20. https://doi.org/10.
1016/j.neubiorev.2014.08.006.
[10] Alsaadi T, El Hammasi K, Shahrour TM. Does pyridoxine control behavioral symp-
toms in adult patients treated with levetiracetam? Case series from UAE. Epilepsy
Behav Case Reports 2015;4:94–5. https://doi.org/10.1016/j.ebcr.2015.08.003.
[11] Chez M, Murescan M, Kerschner S. Retrospective review of the effect of vitamin B6
(pyridoxine) as add-on therapy for behavioral problems associated with levetirace-
tam (Keppra) therapy. Epilepsia 2005;46:146.
5
[12] Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items
for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 2009;
89:873–80.
[13] Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The
Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ
2011;343:d5928. https://doi.org/10.1136/bmj.d5928.
[14] Luchini C, Stubbs B, Solmi M, Veronese N. Assessing the quality of studies in meta-
analyses: advantages and limitations of the Newcastle Ottawa Scale. World J Meta-
Analysis 2017;5:80. https://doi.org/10.13105/wjma.v5.i4.80.
[15] Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med
2002;21:1539–58. https://doi.org/10.1002/sim.1186.
[16] Marino S, Vitaliti G, Marino SD, Pavone P, Provvidenti S, Romano C, et al. Pyridoxine
add-on treatment for the control of behavioral adverse effects induced by levetirac-
etam in children: a case–control prospective study. Ann Pharmacother 2018;52:
645–9. https://doi.org/10.1177/1060028018759637.
[17] Major P, Greenberg E, Khan A, Thiele EA. Pyridoxine supplementation for the treat-
ment of levetiracetam-induced behavior side effects in children: preliminary results.
Epilepsy Behav 2008;13:557–9. https://doi.org/10.1016/j.yebeh.2008.07.004.
[18] Kawakami Y, Okazaki T, Takase M, Fujino O, Itoh Y. A girl with idiopathic epilepsy
showing forced normalization after levetiracetam administration. J Nippon Med
Sch 2015;82:250–3. https://doi.org/10.1272/jnms.82.250.
[19] Davis GP, McCarthy JT, Magill DB, Coffey B. Behavioral effects of levetiracetam miti-
gated by pyridoxine. J Child Adolesc Psychopharmacol 2009;19:209–11. https://doi.
org/10.1089/cap.2009.19202.
[20] Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous leveti-
racetam for management of acute seizures in neonates. Pediatr Neurol 2011;44:
265–9. https://doi.org/10.1016/j.pediatrneurol.2010.11.005.
[21] Kossoff EH, Los JG, Boatman DF. A pilot study transitioning children onto levetirace-
tam monotherapy to improve language dysfunction associated with benign rolandic
epilepsy. Epilepsy Behav 2007;11:514–7. https://doi.org/10.1016/j.yebeh.2007.07.
011.
[22] Obeid M, Pong AW. Efficacy and tolerability of high oral doses of levetiracetam in
children with epilepsy. Epilepsy Res 2010;91:101–5. https://doi.org/10.1016/j.
eplepsyres.2010.06.009.
[23] Miller G. Pyridoxine ameliorates adverse behavioral effects of levetiracetam in chil-
dren. Epilepsia 2002;43:62.
[24] Sajja K, Sankaraneni R, Singh SP. Role of pyridoxine (vitamin B6) in the treatment of
levetiracetam induced behavioral effects in epilepsy patients. Am Epilepsy Soc Annu
Meet 2017;2017. https://doi.org/10.13140/RG.2.2.26891.59682 Abstract 1308.
[25] Sharp G, Van Lierop A, Shbarou R, ME A, El-Nabbout B, Lange B, et al. Levetiracetam
monotherapy in new onset pediatric epilepsy. Epilepsia 2006;47:149.
[26] Wyatt KM, Dimmock PW, Jones PW, O'brien PMS. Efficacy of vitamin B-6 in the
treatment of premenstrual syndrome: systematic review. Bmj 1999;318:1375–81.
https://doi.org/10.1136/bmj.318.7195.1375.
[27] Allott K, McGorry PD, Yuen HP, Firth J, Proffitt TM, Berger G, et al. The vitamins in
psychosis study: a randomized, double-blind, placebo-controlled trial of the effects
of vitamins B 12, B 6, and folic acid on symptoms and neurocognition in first-episode
psychosis. Biol Psychiatry 2019:1–10. https://doi.org/10.1016/j.biopsych.2018.12.
018.
[28] Kulkantrakorn K. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy:
revisited. Neurol Sci 2014;35:1827–30. https://doi.org/10.1007/s10072-014-1902-6.