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Psychotropic drugs and bruxism

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 Review

Psychotropic drugs and bruxism

Giovanni Falisi†, Claudio Rastelli, Fabrizio Panti, Horacio Maglione &
Raul Quezada Arcega
†
University of L’ Aquila, School of Dentistry, Department of Life, Health, and Environmental
1. Introduction Sciences, L’ Aquila, Italy

2. Methods Introduction: Sleep and awake bruxism is defined as ‘a parafunctional activity

3. Main findings including clenching, bracing, gnashing, and grinding of the teeth’. Some evi-
4. Conclusion dence suggests that bruxism may be caused by, or associated with, alterations
in the CNS neurotransmission. Several classes of psychotropic drugs interfer-
5. Expert opinion
ing with CNS activity may potentially contribute to bruxism. Thus, the purpose
of this study was to examine relevant peer-reviewed papers to identify and
describe the various classes of psychotropic substances that may cause, exacer-
Expert Opin. Drug Saf. Downloaded from informahealthcare.com by 95.240.67.55 on 09/09/14

bate or reduce bruxism as the result of their pharmacological action in

CNS neurons.
Areas covered: A literature search from 1980 to the present was performed
using PubMed database. The term ‘bruxism’ was used in association with
‘psychotropic’, ‘dopamine (DA)’, ‘serotonin’, ‘histamine’, ‘antipsychotics’,
‘antidepressants’, ‘antihistaminergics’ and ‘stimulants’.
Expert opinion: Studies on the effects of DA agonists (Levo-DOPA, psychosti-
mulants) and antagonists (antipsychotics) identified a central role of DA
in the pathogenesis of pharmacologically induced bruxism. Important
For personal use only.

information from studies on drugs acting on serotonin neurotransmission

(antidepressants) was recognized. Other mechanisms involving different
neurotransmitters are emerging. This is the case of antihistaminergic drugs
which may induce bruxism as a consequence of their disinhibitory effect on
the serotonergic system.

Keywords: antipsychotic, bruxism, dopamine, psychotropic drugs, selective serotonin reuptake

inhibitor, serotonin

Expert Opin. Drug Saf. [Early Online]

1. Introduction

Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of

the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct
circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or
during wakefulness (indicated as awake bruxism) [1]. Bruxism is a common problem
and may cause several symptoms which include jaw-muscle hypertrophy; tooth
wear; fracture or failure of teeth restorations or implants; sensitivity or pain of teeth,
muscles or joints; and temporomandibular joint (TMJ) disc displacements [2-4].

1.1 Causes of bruxism

The causes of bruxism are poorly understood. In the past, the predominant theory
has considered bruxism as caused by peripheral morphological alterations such as
malocclusion and defects in the anatomy of the bony structures of the orofacial
region [5]. However, most recent reports have evidenced that the role of occlusal
characteristics and other morphological factors in the etiology of bruxism is mini-
mal [4]. Thus, a second theory has emerged, suggesting that the causes of bruxism
are to be found in CNS dysfunctions [5-7]. In any case, it seems evident that bruxism
may have a multifactorial etiology [8,9]. Other factors such as psychosocial (e.g.,
stress) [10], physiological (e.g., neurochemicals and genetics) and exogenous factors

10.1517/14740338.2014.947262 © 2014 Informa UK, Ltd. ISSN 1474-0338, e-ISSN 1744-764X 1

All rights reserved: reproduction in whole or in part not permitted
 G. Falisi et al.
Article highlights.
. Bruxism may be seen as a centrally mediated condition
and may be modulated by drugs acting on the
neurotransmitters of the CNS.
. Bruxism may be exacerbated by dopamine (DA)
antagonists or suppressed by DA agonists through their
effects on the basal ganglia and the nigrostriatal
DA pathway.
. Psychostimulant drugs may cause bruxism by
deregulating the DA mesocortical pathway.
. Bruxism may be suppressed by serotonin (5-HT)
antagonists through their action on the raphe nucleus
which modulates the DA turnover in the
mesocortical pathway.
. Bruxism may be exacerbated by selective 5-HT reuptake
inhibitors through an increase in the inhibitory activity of
Expert Opin. Drug Saf. Downloaded from informahealthcare.com by 95.240.67.55 on 09/09/14
serotonergic neurons of the raphe nucleus on the
mesocortical dopaminergic pathway.
This box summarizes key points contained in the article.
(e.g., smoking) may contribute to disease’s etiology [9].
Thus, many forms (and causes) of bruxism may exist
simultaneously, as, for example, peripheral or central forms
[2,7-10].
For personal use only.
1.2 Bruxism as a centrally mediated condition
The theory of a central etiopathogenesis of bruxism is
based on the observation that bruxism appears to be modu-
lated by various neurotransmitters in the CNS [11]. More
specifically, disturbances in the central dopaminergic system
have been associated to the etiopathogenesis of bruxism
[12,13].
The adoption of this theory has as a corollary the likelihood
that bruxism may be modulated pharmacologically by
substances interfering with brain neurotransmission [14,15].
Unfortunately, a significant number of dental patients
affected by mental illness or mood disorders are under treat-
ment with psychotropic drugs that may potentially contribute
to etiopathogenesis of bruxism [16].
A psychotropic (or psychoactive) drug is a chemical sub-
stance that crosses the blood--brain barrier and acts primarily
on the CNS where it affects brain function, resulting in alter-
ations in perception, mood, consciousness, cognition and
behavior [17]. The term ‘psychotropic’ comprehends different
classes of substances, including antipsychotics, antidepressants
and generally all drugs blocking specific receptors in the
brain [17]. In addition, many dental patients may make use
of other psychoactive drugs, such as psychostimulants [18],
which affect the CNS neurotransmission.
Thus, the purpose of this study was to examine relevant
peer-reviewed papers to identify and describe the various clas-
ses of psychotropic drugs that may cause, exacerbate or reduce
bruxism as the result of their pharmacological action in the
CNS neurons.
2 Expert Opin. Drug Saf. (2014) 13(10)
2. Methods
2.1 Data sources
A systematic search from 1980 to the present in the National
Library of Medicine’s PubMed Database was performed to
identify all peer-reviewed papers dealing with the relationship
between bruxism and psychotropic drugs. All studies and
reviews discussing the contribution of these compounds to
the etiology of bruxism were analyzed.
2.2 Search strategy and literature selection
As a first step, a search was performed using the combination
of the keyword term ‘bruxism’ in association with ‘psychotropic
drugs’, ‘dopamine (DA)’, ‘serotonin’, ‘histamine’,
‘antipsychotics’, ‘antidepressants’, ‘antihistaminergics’ and
‘stimulants’. From the list of citations, papers were screened
based on their title, and those papers clearly not pertinent
to this review’s aim were excluded. The remaining citations
were selected for abstract reading, and those which were
of potential interest for this review based on their abstract
contents were retrieved in full text. Then, the retrieved
papers were read to decide on their inclusion/exclusion in the
review.
2.3 Inclusion criteria
Inclusion of the selected studies in the review was based on the
following criteria: clinical (longitudinal, randomized, case
report) studies showing a clear association between a single
psychotropic drug and bruxism; experimental studies showing
the effect of a specific psychotropic drug and bruxism; review
articles dealing with either psychotropic drugs in general or
specific to a single classes of psychotropic compounds (i.e.,
antipsychotic, antidepressants, anticonvulsants, etc.); medical
hypotheses on the possible mechanism of action of psychotro-
pic drug-induced bruxism.
2.4 Exclusion criteria
Given that the term ‘psychotropic’ comprehends different
classes of substances, the following exclusion criteria were
adopted: clinical studies where the effects of a psychotropic
compound could have been influenced or hidden by other
concomitant treatments or other medical conditions related
to bruxism; bias studies where more than one psychotropic
compounds was given simultaneously (i.e., studies dealing
with subjects affected by mental illnesses that requires admin-
istration of different classes of drugs, such bipolar patients);
and, last, duplicated studies.
2.5Literature searching, screening result and
characteristics of included studies (scientific value)
Information about the numbers of titles listed in PubMed
in various combinations of the terms ‘bruxism’ and
‘psychotropic drugs’ is reported in Table 1. After screening
for inclusion criteria, 38 relevant papers remained and were
 Psychotropic drugs and bruxism

Table 1. Numbers of titles listed in PubMed in various combinations of the terms ‘bruxism’ and ‘psychotropic
drugs’.

Search terms Citations Reviews RCT Case reports Selected papers

Bruxism and psychotropic drugs 81 15 8 32 35

Bruxism and dopamine(rgic) 45 9 5 10 33
Bruxism and serotonin(ergic) 35 4 2 18 10
Bruxism and histamine(rgic) 3 0 0 1 2
Bruxism and antipsychotic(s) 17 2 0 9 9
Bruxism and antidepressant(s) 38 4 4 22 10
Bruxism and antihistaminergic(s) 0 0 0 0 0
Bruxism and stimulant(s) 19 4 1 5 7

RCT: Randomized clinical trial.

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included in the review process. Of them, 15 were reviews or
medical hypotheses, 18 were case reports, 3 of them were case-
--control studies and two were experimental studies performed
in laboratory animals.
3. Main findings
A major role of drugs acting on the dopaminergic system
emerged, although there are evidences for the involvement
of psychotropic drugs affecting other neurotransmitters such
For personal use only.
sleep by about 20 to 30% with respect to the placebo. More
recent case report studies confirmed that DA agonists may
be successful in treating bruxism. Aripiprazole, a partial DA
agonist, has been shown to reduce antipsychotic-induced tar-
dive dystonia [20], whereas the DA D1/D2 receptor agonist
pergolide was used to reduce polysomnographically con-
firmed sleep bruxism [23].
All these data are in line with the proposed model of
Albin et al. [28] of basal ganglia disorders. According to the
model, depletion of DA innervation in this brain area appears

as serotonin (5-HT), norepinephrine and histamine. Accord-
ing to their specific mechanisms of action on these neuro-
transmitters, psychotropic drugs may either induce or
suppress bruxism. Thus, the interaction between bruxism
and the various classes of psychotropic drugs is discussed
below in separate sections.
3.1 Bruxism and dopaminergic drugs
As mentioned before, the role of DA in oromandibular move-
ment disorders is extensively documented [19,20]. DA plays a
major role in reward-motivated behavior [21] and in move-
ment controls [22]. Dopaminergic neurons involved in move-
ment control are located in the basal ganglia, which plays a
central role in motor control [21,23]. Neuropharmacological
studies in rodents have demonstrated that the striatum is the
brain structure involved in the appearance of gnawing/biting
behavior [12,13,24]. According to the experimental studies,
oral motor activity may be influenced by administration of
DA receptor agonists or antagonists [7,25].
3.1.1 DA agonists
Evidence for a positive effect on bruxism by drugs stimulating
the dopaminergic neurotransmission has been produced. In
the study by Lobbezoo et al. [26], a controlled clinical trial,
administration of the DA precursor levodopa (L-DOPA)
resulted in a significant decrease in the average number of
bruxism episodes per hour of sleep in patients free of medica-
tions or psychopathological disorders. The same effects were
obtained in a single-patient clinical trial [27] where administra-
tion of the DA -2 (D2) receptor agonist bromocriptine caused
a decrease in the number of bruxism episodes per hour of
to play a significant role in the pathogenesis of bruxism [5].
Therefore, drugs enhancing DA transmission, such as L-
DOPA and other DA D2 receptor agonists, such as bromo-
criptine, have positive effects on bruxism. However, in the
paper by Lavigne [11] where the neurobiological mechanisms
involved in sleep bruxism are reviewed, the role of striatal
DA is questioned by data obtained in drug-free patients
with a brain imaging technique with a DA-type 2 receptor
marker, iodine-123-iodobenzamide [29]. In that study,
although a side-to-side asymmetry in striatal DA binding
was reported, this was not necessarily associated with sleep
bruxism, suggesting the existence of an alternative pathway
for DA action in oral motor function. In this regard, in
2005, Mascaro et al. [13], in an elegant study performed in
rats, provided consisting data showing that oral motor control
is deputed not only to the striatal dopaminergic neurons but
also to the premotor neurons originating from other brain
regions including the ventral tegmental area and brainstem
nuclei. Studies on another class of DA agonists, the psychosti-
mulants, which act on the dopaminergic mesocortical path-
way, have indeed confirmed this idea as their use is often
associated with forms of iatrogenic bruxism.
3.1.2Psychostimulants
Psychostimulants are a class of psychoactive drugs which tem-
porarily enhance norepinephrine (noradrenaline) and/or DA
brain activity [30]. Psychostimulant of common use include
amphetamine (or methamphetamine), 3,4-methylenedioxy-
methamphetamine (MDMA, ‘Ecstasy’) and cocaine [30].
The paper of Friedlander and Gorelick [31] drew the atten-
tion on the dental problems associated with cocaine addiction

Expert Opin. Drug Saf. (2014) 13(10) 3

 G. Falisi et al.
in USA. Among cocaine users, awake bruxism symptoms
associated with pain in the TMJ and masticatory muscles
were reported [31].
Other studies have repetitively shown that amphetamine
use is associated with bruxism [18,32,33]. See and Tan [33]
reported the case of a 37-year-old man who inhaled and con-
sumed various types of amphetamines, including MDMA on
a daily basis. One month after the cessation of amphetamine
use, the subject experienced a severe form of awake and sleep
bruxism which was successfully cured with botulinum toxin.
Donaldson and Goodchild [32], in 2006, reviewed the den-
tal problems associated with methamphetamine abuse
describing, among other dental associated disorders, awake
and sleep bruxism as a result of the dopaminergic hyperactiv-
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ity. In 2010 [18], a large cohort study investigated the associa-
tion between methamphetamine use and dental diseases, and
the prevalence of bruxism and TMJ problems was consistent
with the descriptions provided by Donaldson and Goodchild
(22.3%). In the same year, Dinis-Oliveira et al. [34] reported a
case study of three patients suffering from awake bruxism after
chronic MDMA consumption.
In addition to these so-called recreational drugs, methyl-
phenidate, another psychostimulant used to treat psychiatric
disorders but acting in a similar manner on the dopaminergic
For personal use only.
neurotransmission, was found to induce sleep bruxism in a
child affected by attention-deficit hyperactivity disorder [35].
Although the prevalence of bruxism among psychostimu-
lant drug users has been attributed to drug-induced hyperac-
tivity to the dopaminergic mesocortical pathway [32], it is
worthy to mention that these drugs may act on other neuro-
transmitters, such as 5-HT and norepinephrine. For example,
the selective norepinephrine reuptake inhibitor atomoxetine
has been shown to exacerbate bruxism in a patient affected
by attention-deficit hyperactivity disorder [36]. Thus, this
form of bruxism may have multiple origins.
Altogether, these findings suggest that the relation between
dopaminergic drugs and bruxism may be complex because of
multiple DA -related circuits which, if altered in one or the
other direction, may provoke or suppress bruxism.
3.1.3 DA antagonists
DA antagonists are drugs which reduce the activity of the
dopaminergic pathways by blocking the DA receptors. Clin-
ically, the most relevant DA antagonists are the antipsy-
chotic drugs, used in the treatment of a large group of
psychiatric disorders, including schizophrenia, depression,
anxiety and dementia [37]. They are divided in two types
according to their antagonist activity. The so-called typical
antipsychotics exert their effects by antagonizing the
D2 DA receptors of the brain’s DA pathways [38]. ‘Atypical
or second generation’ antipsychotics do not only block the
D2 receptor but also block the 5-HT2A and 5-HT1A recep-
tors [39]. As for the DA agonists, these drugs may induce or
suppress bruxism as a consequence of their side effects to
the DA and/or 5-HT pathways.
4 Expert Opin. Drug Saf. (2014) 13(10)
Few data are available regarding typical antipsychotics and
their effects on bruxism. In 1993, Micheli et al. [40] described
eight cases of awake bruxism following long-term treatment
with haloperidol, one of the most common typical antipsy-
chotic. Interestingly, these patients did not present sleep brux-
ism, suggesting that the action of this drug is different from
that of the DA agonists described before. A similar effect of
haloperidol was observed in a patient suffering from Lewy
body dementia who developed bruxism following cessation
of antipsychotic medication [41].
In 2009, a case report of a patient who developed chronic
bruxism after exposure to multiple antipsychotics was
described [42]. Two other typical antipsychotics, chlorproma-
zine and trifluoperazine, were administered for 8 years to treat
a severe form of schizophrenia. At the end of the treatment,
the patient developed bruxism of mixed typed (grinding and
clenching) which persisted after drug withdrawal, suggesting
that long treatment with typical antipsychotics may induce
permanent modifications in the brain dopaminergic path-
ways. As for haloperidol, only awake bruxism was present.
These effects may be caused by extrapyramidal side effects of
these drugs on motor control which include tremor, abnormal
muscle contractions and an involuntary movement disorder
known as tardive dyskinesia [43]. According to this idea, these
authors describe this form of awake bruxism as a focal tardive
dystonia syndrome.
On the contrary, it appears that atypical drugs, which
antagonize both DA and 5-HT receptors, are successful in
treating bruxism. The above-described same patients who
developed awake bruxism after typical antipsychotic drug
exposure were successfully treated with the atypical drug clo-
zapine [42]. The therapeutic mechanism of these drugs is not
known but may be in part explained by the fact that these
‘second-generation’ drugs have been developed with the
attempt to reduce extrapyramidal side effects and possess a
lower affinity to the DA receptors. According to this idea, a
recent paper from Pekkan et al. [44] reports a case of a patient
suffering from tardive dyskinesia with temporomandibular
disorder which was resolved after clozapine administration
although in combination with botulinum toxin type A.
The fact that these drugs also antagonize the 5-HT recep-
tors may also contribute to explain their therapeutic effects.
As stated before, masticatory motor activity is controlled by
dopaminergic neurons of the mesocortical tract. DA inhibits
spontaneous movement, whereas 5-HT inhibits dopaminergic
transmission in this tract and, thus, releases the characteristic
repetitive muscle contractions of bruxism. Interestingly, selec-
tive 5-HT reuptake inhibitors (SSRIs) discussed below may
induce severe form of bruxism. In 2012, an indirect demon-
stration of a therapeutic 5-HT-mediated effect was provided
in the paper by Oulis et al. [45], where an obsessive-compulsive
patient undergoing long-term treatment with different SSRIs
was successfully treated for awake bruxism with aripiprazole,
an antipsychotic which differs from the previous ones because
it acts as a partial agonist, rather than antagonist, of the

D2 and 5-HT receptors. The authors hypothesize that the
beneficial effect on bruxism is mainly attributable to its
partial-antagonist action on 5-HT1A receptors, as this antipsy-
chotic is efficacious only in SSRI-induced bruxism.
3.2 SSRIs and buspirone (5-HT receptor agonist)
SSRIs are drugs which prevent the reuptake of 5-HT by the
presynaptic neuron. These drugs are commonly prescribed
to treat mood and affective disorders, such as depression, anx-
iety disorders and obsessive-compulsive disorder [46].
In the past 15 years, numerous studies have reported cases
of iatrogenic nocturnal bruxism after administration of
numerous SSRIs. In 2001, Wise reported a case of sleep brux-
ism induced by citalopram that was hidden by concomitant
Expert Opin. Drug Saf. Downloaded from informahealthcare.com by 95.240.67.55 on 09/09/14
treatment with buspirone [47]. More recently, similar effects
were reported with other common SSRIs. Without going
into further details, in all these case reports the patient under-
going treatment with SSRIs of common use (paroxetine [48],
duloxetine [49], venlafaxine [50,51], fluvoxamine [52]) displayed
sleep bruxism, which was resolved by adding buspirone and/
or reducing the antidepressant dose.
The pathophysiology of SSRI-associated nocturnal bruxism
is unclear. It has been proposed that the close relation between
5-HT and DA in regulating motor pathways is the origin of
For personal use only.
SSRI-induced bruxism [14,53]. The mechanism hypothesized
is that an excess of 5-HT in the synapses leads to an inhibitory
effect on the release of DA from the mesocortical tract that
evolves itself in specific forms of oromandibular akathisia,
thereby leading to bruxism [53,54].
Buspirone is an agonist of the 5-HT1A receptor that
increases dopaminergic neuron firing in the ventral tegmen-
tal area and increases the synaptic release of DA in the pre-
frontal cortex. These effects ameliorate drug-induced
bruxism. Buspirone can also ameliorate extrapyramidal side
effects, such as akathisia and tardive dyskinesia, and this
property may be an additional explanation for the
bruxism-related effects of the drug [48-51,54]. Nonetheless,
in 2012, one interesting paper by Iskandar et al. [55]
reported a case where fluoxetine-induced sleep bruxism dis-
appeared spontaneously without the use of buspirone. Thus,
the authors suggest that, in cases of SSRI-induced sleep
bruxism, before changing the medication regimen or adding
buspirone medication, a consultation of a trained dental
professional should be considered to not compromise
patient progress response to antidepressant therapy.
4. Conclusion
In conclusion, despite the studies analyzed have evidenced a
crucial role of the dopaminergic system, the mechanism of
psychotropic drug-induced bruxism is still poorly understood.
Psychotropic drugs modulate other neurotransmitters as well
and this may cause different and sometimes opposite effects
on either awake or sleep bruxism. This means that the interac-
tion of DA with the other neurotransmitters requires
Expert Opin. Drug Saf. (2014) 13(10)
Psychotropic drugs and bruxism
additional research before drawing definite conclusions on
the effects of psychotropic drugs on this parafunctional activ-
ity with multiple potential mechanisms.
5. Expert opinion
The possibility that bruxism may be a disease that is centrally
modulated has emerged in the recent years [7]. The aim of this
review was to analyze and possibly interpret the clinical and
experimental evidences that bruxism may be caused or modu-
lated by administration of ‘psychotropic’ drugs.
In Table 2, the effects of the different classes of psychotropic
drugs on sleep or awake bruxism are summarized. Each of
these classes may add further details useful in providing a cen-
tral model of bruxism pathogenetic mechanism.
Studies on the effects of antipsychotic drugs point out a
central role of DA in the pathogenesis of bruxism. This is
intuitive because DA is the major neurotransmitter involved
in the regulation of motor control. However, there is an
apparent difference when different dopaminergic pathways
are inhibited or stimulated by the action of these drugs.
On one hand, when antipsychotic drugs block the nigros-
triatal pathway which transmits DA from the substantia
nigra to the striatum, this is reflected in the appearance of
iatrogenic bruxism as a consequence of the loss of motor
control. It is well established that the prolonged use of these
drugs induce extrapyramidal symptoms and phenomena of
tardive and oral dyskinesia. Accordingly, drugs stimulating
dopaminergic transmission such as such as L-DOPA and
DA receptor agonists suppress bruxism. On the other
hand, phenomena of sensitization in the mesocortical path-
way caused by psychostimulants may produce the opposite
effect as a result of a hypersensitization of the presynaptic
D2 receptor in the prefrontal cortex, which reduces the
mesocortical tract dopaminergic innervation [53]. This mech-
anism has been hypothesized in the study by Chen et al. [53]
and has been supported by the notion that recreational
drugs, which act on the so-called reward system (notably
the mesolimbic and mesocortical pathways), induce rather
than suppress bruxism. Altogether, these studies suggest
that regional differences in DA receptor pharmacology
may be the cause of the confusion generated by the occur-
rence of bruxism in both hyper- and hypo-dopaminergic
states. A tentative mechanism of psychotropic drugs on
bruxism is shown in Figure 1.
Important information also arises from studies on drugs
acting on the 5-HT neurotransmission. A close relationship
between DA and 5-HT transmission in the regulation of
motor pathways may exist, as demonstrated by the fact that
patients with L-DOPA-induced dyskinesia show compensa-
tive upregulation of 5-HT2 receptors [56]. Drugs such SSRIs,
which block the reuptake of 5-HT, may induce bruxism by
increasing the inhibitory action of serotonergic neurons
of the raphe nucleus on the mesocortical dopaminergic path-
way, thereby resulting in a diminution of dopaminergic
5
 G. Falisi et al.

Table 2. Effects of different classes of psychotropic drugs on bruxism.

Psychotropic drugs Effects Ref.

Sleep bruxism Awake bruxism

Dopamine agonists # $ [20,23,26,27]

Psychostimulants " " [18,31-35]
Dopamine antagonists
Typical antipsychotics $ " [40-42]
Atypical antipsychotics $ # [40,42,44,45]
Serotonin antagonists (SSRIs) " $ [47-53]
Serotonin agonists (Buspirone) # $ [48,51,54,55]
Histamine antagonists " $ [56-58]

#: Decrease; ": Increase; $: No effect; SSRIs: Selective serotonin reuptake inhibitors.

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Dopamine Serotonin

Agonists Antagonists Psychostimulants Reuptake inhibitors Antagonists

Activation of DA receptors Repression of DA receptors Hypersensitization of DA receptors Increased serotonin Repression of

5-HT receptors
For personal use only.

Basal ganglia Frontal cortex Raphe nucleus

Potentiation of Downregulation of Dysregulation of Potentiation of

nigrostriatal pathway nigrostriatal pathway mesocortical pathway mesocortical pathway

Normalization of motor control Loss of motor control Hyperactivation of motor control Normalization of motor control

Bruxism suppression Bruxism Bruxism suppression

Figure 1. Schematic representation of putative mechanism(s) of psychotropic drugs on bruxism. DA agonists such as L-DOPA,
stimulate DA receptors in the basal ganglia, thus increasing DA control on motor functions by the nigrostriatal pathways.
Selective DA antagonists, such as typical antipsychotics, antagonize the DA receptors in the same DA pathway causing
dysfunction of motor control and phenomena of tardive dyskinesia and bruxism. Psychostimulants cause a sensitization of DA
receptors in the frontal cortex and a reduced functionality of the mesocortical pathway and less inhibition of motor control is
exerted. Serotonin reuptake inhibitors alter serotonin control of the raphe nucleus on the mesocortical pathway, resulting in
a similar effect. Drugs inhibiting the serotonergic neurotransmission, such as atypical antipsychotics, suppress bruxism by the
inverse mechanism, normalizing the activity of the mesocortical pathway.
DA: Dopamine.

transmission (Figure 1). Nonetheless, although these studies antihistaminergic drugs such as ketotifen, which may also
bring light to the pathogenesis of psychotropic drug-centrally induce bruxism as a consequence of their disinhibitory effect
mediated bruxism, other mechanism involving other to the serotonergic system, thus resembling the pharmacolog-
neurotransmitters are emerging. This is the case of ical condition caused by administration of SSRIs.

6 Expert Opin. Drug Saf. (2014) 13(10)


Declaration of interest
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial interest
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Affiliation
Giovanni Falisi†1 DDS PhD,
Claudio Rastelli1 MD, Fabrizio Panti2 MD,
Horacio Maglione3 MD &
Raul Quezada Arcega4 MD
†
Author for correspondence
1
University of L’Aquila, School of Dentistry,
Department of Life, Health, and Environmental
Sciences, Piazzale Salvatore Tommasi 1,
67100 Coppito (AQ), L’Aquila, Italy
Tel: +39 0862433202;
Fax: +39 08624332;
E-mail: g.falisi@tiscali.it
2
Sapienza University of Rome, Department of
Oral and Maxillo-Facial Sciences, Rome, Italy
3
"Maimonides" University, School of Dentistry,
Buenos Aires, Argentina
4
Manuel Acuna 1775 (Gua Jal)
44650 Guadalajara, Jalisco, Mexico