Abstract
Bruxism associated with antidepressant use is an under-recognized phenomenon. The use of citalopram has gained wide acceptance in the treatment of depression and anxiety disorders; however, the consumption of this medication during lactation and pregnancy has not been carefully characterized. There are limited studies about its side effects in the breastfeeding period. Here, we report a rare case of citalopram-induced sleep bruxism in a 9-month-old female breastfed infant whose mother used SSRI agent citaloporm for her anxiety disorder. Within 2 weeks of initiating her citalopram treatment, with a starting dose of 10 mg/day, the patient reported sleep bruxism in her infant. Thorough examinations of the infant were performed and no abnormal finding was reported. After ruling out other possible causes, the new-onset bruxism symptoms were attributed to the motherās recent use of citalopram, which was discontinued thereafter. The infantās symptoms of bruxism disappeared following the discontinuation of the medication by her mother. These findings and similar reports could draw more attention to bruxism or other possible symptoms in breastfed infants of mothers consuming psychotropic medications.
Introduction
Selective serotonin reuptake inhibitors (SSRIs) are the most prevalent drugs utilized for the treatment of major depressive disorder. SSRIs work by targeting the serotonin transporter (SERT),1 which leads to higher extracellular levels of serotonin; this is considered the basis of their mechanism of action, although other mechanisms have been proposed (1). SSRIs are generally safe and well tolerated. However, certain side effects have been reported to be associated with the use of SSRIs, including: sexual dysfunction, dry mouth, bleeding, weight gain, and gastrointestinal symptoms (2). They also have some side effects on the central nervous system, including akathisia, tremor, dystonia, and bruxism (3, 4).Antidepressant-associated bruxism may occur in pediatric and adult patients, most commonly among female patients (5). Both short-term and long-term use of antidepressants have been associated with bruxism. The most commonly reported offending agents are fluoxetine, sertraline, and venlafaxine. Symptoms may begin within 3ā4 weeks of medication initiation and may resolve within 3ā4 weeks of drug discontinuation, with the addition of buspirone, or by substitution with another pharmacologic agent. The incidence of this phenomenon is unknown (5).
āBruxismā is an umbrella term under which fall various motor activities of the jaw muscles, such as grinding and clenching of the teeth as well as thrusting of the mandible (6). According to Lobbezoo et al., sleep bruxism and awake bruxism have been defined as āa masticatory muscle activity during sleep, characterised as rhythmic or non-rhythmic in otherwise healthy individualsā and āa masticatory muscle activity during wakefulness characterised by repetitive or sustained tooth contact and/or bracing or thrusting of the mandible in otherwise healthy individualsā respectively. It should also be noted that in both definitions, bruxism is not considered a movement disorder or sleep disorder (7).
Bruxism, characterized by teeth clenching or grinding, is considered an involuntary nonfunctional activity of the masticatory system. It might happen during sleep or while awake, consciously or unconsciously, and is not classified as a disorder, but as a behavior. This habit is common during childhood. Its prevalence in children ranges from 13 to 49% (8) and may have negative consequences on the stomatognathic system (9). SSRIās, including citalopram, have been shown to potentially induce sleep and/or awake bruxism (10).
Intergenerational effects, whether through medication or other means, have increasingly become of interest, especially in the field of psychiatry (11). We here, would like to report a case of citalopram-associated sleep bruxism in a female breastfed infant, which resolved by discontinuation of her motherās medication.
Case presentation
A 33-year-old Persian female patient referred to Ibn-Sina outpatient psychiatry clinic in Mashhad, Iran, in June 2019, with a mixed anxiety depressive disorder during her breastfeeding period. She had a history of anxiety prior to her pregnancy, and was under treatment with sertraline. She had previously shown symptoms of agitation and become irritable with her sertraline treatment, and had no tendency to continue using this medication. The patient was unemployed; described her familyās economic status as āstableā and mentioned she had āstrong emotional supportā from her spouse. Her past surgical history included only a recent Cesarean section. She was breastfeeding her then, 9-month-old infant. Pregnancy seemed to have been a significant psychosocial stressor for her. The patient presented to our general adult psychiatry outpatient clinic with a 3-month history of mood symptoms; including low mood, anhedonia, insomnia, anxiety, loss of energy, and decreased appetite. Symptoms had significantly worsened over the 1-month period before she referred to us.
She had no suicidal or homicidal thoughts, intent, or plans as well as no history of suicide attempts or self-harm. The patient also had no history of psychotic symptoms or manic episodes. She had never smoked, nor used alcohol, cannabis, or any illicit substances. There were no significant findings in her physical examination. Her electrocardiography (EKG), including her corrected QT interval (QTc) was normal. Considering the patientās past history of sertraline-associated agitation, a 10-mg daily starting dose of citalopram was prescribed for her. Her symptoms began to decline 10 days after her consumption of citalopram was initiated. However, 2 weeks after the initiation of her treatment, she reported symptoms of bruxism in her infant. The infant was a term 9-month-old female, delivered through Cesarean section after an uneventful pregnancy, with no history of physical disorders, illnesses, or hospital admissions and no use of medications except supplements. The infantās diet consisted of her motherās breast milk five to six times per day, as well as standard supplementary nutrients given for 9-month-old infants consisting of such as fruits, vegetables, meat, and biscuits. She was not being fed with milk powder or any other formula and was not consuming any medications. The patient reported that her infant had sporadic, pulsatile, and momentary movements in her jaws, which usually began with movements of the head, especially during sleep. Furthermore, the mother mentioned her child had a habit of biting and clenching her teeth while awake.
Clinical findings
A thorough physical examination, including extra-oral and intra-oral assessment of the child by a pediatrician showed no abnormalities. Another intraoral examination was performed by a pediatric dentist who reported appropriate teeth growth and development in the child. The dentist reported no pathologic findings. The infant had no salivary drooling and was able to swallow efficiently with no evident cranial nerve dysfunction. However, bruxism was observed by the dentist during the examination.
Diagnostic assessment
After somatic and organic problems were ruled out, the infantās symptoms of bruxism were attributed to the excretion of citalopram in the motherās milk.
Therapeutic intervention
Citalopram, which was hypothesized as the main cause of the childās symptoms of bruxism, was discontinued, with bruxism symptoms resolving 72 h thereafter.
Follow-up and outcomes
The mother and her child were followed for 2 years. The infantās symptoms of bruxism stopped after her motherās use of citalopram was discontinued. She no longer had teeth clenching or grinding while awake or during sleep. The mother resumed to breastfeeding right away after the infantās symptoms disappeared with no further consequences and was referred to a psychotherapist for cognitive behavioral therapy (CBT) with improvements in both her depressive and anxiety symptoms.
Discussion
In this paper, we report sleep bruxism in a breastfed 9-month-old infant whose mother was under treatment with citalopram. The point of this case was to bring attention to the excretion of medications like SSRIs into breastmilk. Considering the onset of bruxism in the infant shortly after the initiation of her motherās citalopram treatment and the cessation of this symptom following the discontinuation of the medicine, the infantās symptoms of bruxism were attributed to her motherās use of citalopram after ruling out other physical or organical causes. This is unique, as there are no similar studies in the current literature.
There is transfer of SSRIās including citalopram and escitalopram to human breast milk. A study by Pogliani et al. reported that all lactating women treated with fluoxetine or citalopram had relative infant doses (RIDās) exceeding 10% (12). Previous studies have reported weight loss and drowsiness in breastfed infants of mothers who used citalopram (13). It should also be noted that the individual genetical characteristics of the mother and/or infant may also play a role in how their body metabolizes and responds to a medication. It has been reported that the polymorphism of CYP2C19 plays a crucial role in the N-demethylation of citalopram. As a result, poor metabolizers and extensive metabolizers of CYP2C19 show a significant difference in the disposition of citalopram in vivo (14). In this patient, the symptoms regressed merely by cessation of the medication. This was possibly due to the low level of the drug in the infantās serum.
A review paper by Wallem et al. had also concluded that there is an āapparentā relationship between treatment with SSRIās and the development of bruxism (15). Another systematic review by Melo et al. had found an association between the development of sleep bruxism in children and the use of psychotropic medications such as duloxetine, paroxetine, venlafaxine, and methylphenidate. However, they found no significant correlation between symptoms of bruxism and the utilization of medications such as citalopram, escitalopram, fluoxetine, and mirtazapine (16).
It is also noteworthy to take into consideration the possible effects of intra-uterine exposure to SSRIās on fetus brain development (17), although our patient was not using any antidepressant medication during her pregnancy. It is also of importance to note the fact that many factors in the early home environment can impact brain development in infants and children (18). According to Orsolini et al., paroxetine and sertraline have better neonatal safety profiles during breastfeeding compared to other SSRI medications (19).
Several therapeutic modalities have been suggested, but there is no consensus about which is the most efficient. Some studies have reported hydroxyzine to be an efficient treatment for sleep bruxism in children (20). Occlusal splints, orthodontic, physical, and psychological interventions have also shown to be effective in reducing bruxism (21).
Generally, symptoms tend to appear within 3ā4 weeks of the initiation of antidepressant treatment or of undergoing dose titration. Symptom resolution may be achieved the addition of serotonin 1A (5HT1A) partial agonists (buspirone, tandospirone), by dose reduction, by medicine cessation, or by the addition of other pharmacologic agents including tricyclic antidepressants (amitriptyline), antipsychotics (aripiprazole, chlorpromazine), opipramol, norepinephrine-dopamine reuptake inhibitors (bupropion), or serotonin 2A/2C antagonist and reuptake inhibitors (trazodone) (22). Studies have also shown that clonidine can effectively reduce symptoms of sleep bruxism (23). Symptoms may also resolve over time without pharmacological intervention. The use of low-dose quetiapine has also been reported to be effective in the treatment of mandibular dystonia and SSRI-induced bruxism (24). The addition of buspirone has been reported to be successful in alleviating symptoms of bruxism in several cases. Buspirone, a weak 5-HT2C receptor antagonist, can potentially compete with serotonin to bind with 5-HT2C receptor, which can lead to improvement of bruxism (25).
This observation along with considering medications used for bruxism treatment can be instructive in both understanding the underlying pathophysiological mechanisms of antidepressant-associated bruxism, as well as in providing a foundation for treatment recommendations.
Limitations and suggestions for future studies
One of the limitations of this study is that since it is a case report, direct causal relationships cannot be determined. We should also take into account that as previously cited, given how common bruxism is in children, the infantās symptoms of bruxism may have been caused by other factors. In this patient, 2 weeks after the consumption of the drug (and thus, its excretion into the motherās breastmilk), the infant began to show symptoms. Another limiting factor is that this study reports the phenomenon observed in only one patient; larger sample sizers are needed to investigate this possible association.
In future studies, instrumental measures such a assessing sleep bruxism using polysomnography as well as genetical testings can be helpful as well. In addition, measuring citalopram concentration levels in the infantās serum or her motherās breastmilk would help make this attribution more concise. It is suggested that further studies be conducted on possible side effects and symptoms in breastfed children of mothers being treated with psychotropic medications. More studies containing larger populations are required to investigate the possible association of SSRI medications, including citalopram, with sleep bruxism. Similar results, if proven, could lead to pediatricians and other clinicians considering the possibility of medication-induced bruxism in children so that this phenomenon would not be overlooked, missed, or undiagnosed.
Conclusion
The use of SSRI medications has been associated with symptoms of bruxism in some individuals. The case presented in this study, was a breastfed infant whose mother was using citalopram. The infant began manifesting symptoms of sleep bruxism shortly after, which resolved following the discontinuation of the medication. Similar results, if proven, could suggest that breastfed infants of mothers being treated with SSRIās including citalopram, may present symptoms of bruxism. This could lead to a better understanding of the pathophysiological mechanisms underlying bruxism and the functions of SSRIās as well as provide pediatricians, psychiatrists, as well as other clinicians with more holistic and effective diagnostic and treatment plans.
Statements
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving human participants were reviewed and approved by the Mashhad University of Medical Sciences Research Ethics Committee. Written informed consent to participate in this study was provided by the participantsā legal guardian/next of kin. Written informed consent was obtained from the minor(s)ā legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisherās note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Footnotes
1.^Serotonin transporter (SERT or 5-HTT).
References
1.
SanchezCReinesEMontgomerySA. A comparative review of escitalopram, paroxetine, and sertraline: are they all alike?Int Clin Psychopharmacol. (2014) 29:185ā96. 10.1097/YIC.0000000000000023
2.
WangSHanCBahkWLeeSPatkarAMasandPet alAddressing the side effects of contemporary antidepressant drugs: a comprehensive review.Chonnam Med J. (2018) 54:101ā12. 10.4068/cmj.2018.54.2.101
3.
UvaisNSreerajVSathish KumarS. Sertraline induced mandibular dystonia and bruxism.J Family Med Prim Care. (2016) 5:882ā4. 10.4103/2249-4863.201168
4.
RaveendranathanDRaoS. Sertraline induced acute mandibular dystonia.J Neurosci Rural Pract. (2015) 6:586ā7. 10.4103/0976-3147.169804
5.
GarrettAHawleyJS. SSRI-associated bruxism: a systematic review of published case reports.Neurol Clin Pract. (2018) 8:135ā41. 10.1212/CPJ.0000000000000433
6.
PaesaniDLobbezooFGelosCGuarda-NardiniLAhlbergJManfrediniD. Correlation between self-reported and clinically based diagnoses of bruxism in temporomandibular disorders patients.J Oral Rehabil. (2013) 40:803ā9. 10.1111/joor.12101
7.
LobbezooFAhlbergJRaphaelKWetselaarPGlarosAKatoTet alInternational consensus on the assessment of bruxism: report of a work in progress.J Oral Rehabil. (2018) 45:837ā44. 10.1111/joor.12663
8.
BulandaSIlczuk-RypuÅaDNitecka-BuchtaANowakZBaronSPostek-StefaÅskaL. Sleep bruxism in children: etiology, diagnosis, and treatment-a literature review.Int J Environ Res Public Health. (2021) 18:9544. 10.3390/ijerph18189544
9.
AlharbyAAlzayerHAlmahlawiAAlrashidiYAzharSSheikhoMet alParafunctional behaviors and its effect on dental bridges.J Clin Med Res. (2018) 10:73ā6. 10.14740/jocmr3304w
10.
de BaatCVerhoeffMAhlbergJManfrediniDWinocurEZweersPet alMedications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism.J Oral Rehabil. (2021) 48:343ā54. 10.1111/joor.13061
11.
DuarteCMonkCWeissmanMPosnerJ. Intergenerational psychiatry: a new look at a powerful perspective.World Psychiatry. (2020) 19:175ā6. 10.1002/wps.20733
12.
PoglianiLBaldelliSCattaneoDPileriPClementiECetinIet alSelective serotonin reuptake inhibitorsā passage into human milk of lactating women.J Matern Fetal Neonatal Med. (2019) 32:3020ā5. 10.1080/14767058.2018.1455180
13.
National Library of Medicine.Drugs and lactation database (LactMed) [Internet].Bethesda, MD: National Library of Medicine (2006).
14.
YuBChenGHeNOuyangDChenXLiuZet alPharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19.Drug Metab Dispos. (2003) 31:1255ā9. 10.1124/dmd.31.10.1255
15.
WallemAFelipe-SpadaNTomĆ s-AliberasJ. Influence of selective serotonin reuptake inhibitors (SSRIs) in the development of bruxism.Cranio. (2022). [Epub ahead of print]. 10.1080/08869634.2022.2120277
16.
MeloGDutraKRodrigues FilhoROrtegaAPorporattiADickBet alAssociation between psychotropic medications and presence of sleep bruxism: a systematic review.J Oral Rehabil. (2018) 45:545ā54. 10.1111/joor.12633
17.
Lugo-CandelasCChaJHongSBastidasVWeissmanMFiferWet alAssociations between brain structure and connectivity in infants and exposure to selective serotonin reuptake inhibitors during pregnancy.JAMA Pediatr. (2018) 172:525ā33. 10.1001/jamapediatrics.2017.5227
18.
BushNWakschlagLLeWinnKHertz-PicciottoINozadiSPieperSet alFamily environment, neurodevelopmental risk, and the environmental influences on child health outcomes (ECHO) initiative: looking back and moving forward.Front Psychiatry. (2020) 11:547. 10.3389/fpsyt.2020.00547
19.
OrsoliniLBellantuonoC. Serotonin reuptake inhibitors and breastfeeding: a systematic review.Hum Psychopharmacol. (2015) 30:4ā20.
20.
IerardoGMazurMLuzziVCalcagnileFOttolenghiLPolimeniA. Treatments of sleep bruxism in children: a systematic review and meta-analysis.Cranio. (2021) 39:58ā64. 10.1080/08869634.2019.1581470
21.
ChisiniLSan MartinACademartoriMBoscatoNCorreaMGoettemsM. Interventions to reduce bruxism in children and adolescents: a systematic scoping review and critical reflection.Eur J Pediatr. (2020) 179:177ā89. 10.1007/s00431-019-03549-8
22.
SakaiTKatoTYoshizawaSSuganumaTTakabaMOnoYet alEffect of clonazepam and clonidine on primary sleep bruxism: a double-blind, crossover, placebo-controlled trial.J Sleep Res. (2017) 26:73ā83. 10.1111/jsr.12442
23.
WieckiewiczMMartynowiczHWieczorekTWojakowskaASluzalec-WieckiewiczKGacPet alConsecutive controlled case series on effectiveness of opipramol in severe sleep bruxism management-preliminary study on new therapeutic path.Brain Sci. (2021) 11:146. 10.3390/brainsci11020146
24.
ZandifarAMohammadiMBadrfamR. Low-dose quetiapine in the treatment of SSRI-induced bruxism and mandibular dystonia: case series.Iran J Psychiatry. (2018) 13:227ā9.
25.
AkbasBBilgiƧA. Fluoxetine-induced sleep bruxism rapidly treated with once-nightly dosing of buspirone in a 6-year-old girl.Clin Neuropharmacol. (2018) 41:197ā8. 10.1097/WNF.0000000000000293
Summary
Keywords
bruxism, citalopram, selective serotonin reuptake inhibitors (SSRIs), breastfeeding, side effect, antidepressant, case report
Citation
Akbarzadeh F, Behravan G, Modaresi F and Eslamzadeh M (2023) Citalopram-induced sleep bruxism in a breastfed infant: A case report. Front. Psychiatry 14:1051346. doi: 10.3389/fpsyt.2023.1051346
Received
22 September 2022
Accepted
12 January 2023
Published
02 February 2023
Volume
14 - 2023
Edited by
Mohammadreza Shalbafan, Iran University of Medical Sciences, Iran
Reviewed by
Pedro Kowacs, Instituto de Neurologia de Curitiba, Brazil; Mieszko Wieckiewicz, WrocÅaw Medical University, Poland
Updates
Copyright
Ā© 2023 Akbarzadeh, Behravan, Modaresi and Eslamzadeh.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Mahboubeh Eslamzadeh, eslamzadehmh@mums.ac.ir
This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.