The influence of selective serotonin reuptake inhibitors on bruxism intensity: a narrative review

2.1. Central mechanisms

Bruxism is now understood to be primarily regulated by central nervous system mechanisms rather than peripheral occlusal factors [5]. Sleep bruxism is classified as a sleep-related movement disorder and is closely associated with micro-arousals during non-REM sleep [6]. The rhythmic masticatory muscle activity (RMMA) observed in SB episodes is generated by central pattern generators in the brainstem, which are modulated by cortical and subcortical inputs [7].

2.2. Role of neurotransmitters

The dopaminergic and serotonergic systems play critical roles in the regulation of motor activity, including the orofacial musculature. Dopamine, acting primarily through D1 and D2 receptors in the basal ganglia, modulates the inhibitory control of motor circuits. Studies using the D2 receptor agonist bromocriptine have shown reductions in SB episodes, supporting the role of the dopaminergic system [8]. Furthermore, pramipexole, another dopamine agonist, has shown efficacy in reducing SB in a randomized crossover study [9].

Serotonin (5-hydroxytryptamine, 5-HT) is a key modulator of mood, sleep architecture, and motor function. The serotonergic raphe nuclei project widely to cortical, limbic, and motor areas. Importantly, serotonin exerts an inhibitory influence on dopaminergic neurons in the mesocortical and nigrostriatal pathways. SSRIs, by blocking the serotonin transporter (SERT) and increasing synaptic 5-HT concentrations, may secondarily suppress dopaminergic transmission in the basal ganglia, thereby disinhibiting motor circuits and facilitating bruxism [10]. This serotonin-dopamine interaction is considered the principal neurobiological mechanism underlying SSRI-induced bruxism [11].

3.1. Case reports and case series

The earliest and most frequently cited evidence linking SSRIs to bruxism comes from case reports and case series. Ellison and Stanziani [4] described four patients who developed nocturnal bruxism within 3-4 weeks of initiating fluoxetine or sertraline therapy. Symptoms were characterized by tooth grinding, jaw pain upon awakening, and reports of grinding sounds by bed partners. In all cases, bruxism resolved upon drug discontinuation or addition of buspirone.

Wise [12] reported a case of citalopram-induced nocturnal bruxism with an onset of approximately two weeks after drug initiation. Milanlioglu [13] documented severe paroxetine-induced sleep bruxism that was successfully treated with buspirone 10 mg/day. Kuloglu et al. [14] reported three cases of venlafaxine-associated nocturnal bruxism (venlafaxine, an SNRI, shares the serotonergic mechanism), with symptom onset within 1-3 weeks. These reports consistently indicate a temporal relationship between SSRI initiation and bruxism onset, with resolution upon dose reduction, drug discontinuation, or the addition of adjunctive agents.

3.2. Systematic review evidence

Garrett and Hawley [15] conducted a systematic review of published case reports of SSRI-associated bruxism. Their analysis identified reports involving fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine, as well as SNRIs such as venlafaxine and duloxetine. The review found that sleep bruxism was the most commonly reported subtype, onset typically occurred within the first few weeks of treatment, and the most frequently employed management strategy was the addition of buspirone (a 5-HT1A partial agonist). The authors concluded that while the evidence is limited to case-level data, the consistent temporal associations and the pharmacological plausibility of the serotonin-dopamine mechanism strongly support a causal relationship.

3.3. Prevalence studies

Uca et al. [16] conducted a cross-sectional study investigating the prevalence of bruxism among patients receiving antidepressant therapy. Their findings indicated that patients on SSRIs had a significantly higher prevalence of bruxism compared to controls, with reported rates ranging from 24-25 % among SSRI users versus approximately 10 % in the general population. Importantly, the study also found a dose-dependent trend, suggesting that higher SSRI doses may be associated with more intense bruxism, though this finding requires confirmation in larger prospective studies.

4.1. Serotonin-dopamine imbalance

The most widely accepted mechanism for SSRI-induced bruxism involves the indirect suppression of dopaminergic neurotransmission via elevated serotonin levels. SSRIs increase synaptic 5-HT concentrations by blocking the serotonin transporter. The excess serotonin, acting through 5-HT2A and 5-HT2C receptors on dopaminergic neurons, exerts an inhibitory effect on dopamine release in the mesocortical and nigrostriatal pathways [10]. The resulting relative dopamine deficiency in the basal ganglia may disinhibit the trigeminal motor nucleus and central pattern generators, leading to increased rhythmic masticatory muscle activity and bruxism [17].

4.2. Effects on sleep architecture

SSRIs are known to alter sleep architecture, including suppression of REM sleep, increased sleep latency, and fragmentation of non-REM sleep with increased micro-arousals [18]. Since SB episodes are predominantly associated with micro-arousals during non-REM sleep transitions [6], SSRI-induced sleep fragmentation may represent an additional mechanism by which these drugs promote or intensify bruxism. The relationship between SSRI-induced sleep disruption and SB intensity warrants further investigation with polysomnographic studies.

4.3. 5-HT1A receptor involvement

The efficacy of buspirone, a 5-HT1A partial agonist, in managing SSRI-induced bruxism provides indirect evidence for the involvement of serotonin receptor subtypes in the pathogenesis of this adverse effect. The 5-HT1A receptor acts as both a presynaptic autoreceptor (reducing serotonin release) and a postsynaptic receptor modulating dopaminergic function. By activating presynaptic 5-HT1A autoreceptors, buspirone may reduce the excessive serotonergic tone induced by SSRIs, thereby restoring the serotonin–dopamine balance in motor circuits [19].

5.1. Dose reduction and drug substitution

When SSRI-associated bruxism is suspected, the initial approach should include a careful assessment of the temporal relationship between drug initiation (or dose escalation) and bruxism onset. Dose reduction may alleviate symptoms in some patients, though this must be balanced against the risk of psychiatric relapse [11]. Drug substitution to an antidepressant with a different mechanism of action (e.g., bupropion, mirtazapine, or agomelatine) may be considered, as these agents have not been consistently linked to bruxism and may in fact have a lower risk profile [17].

5.2. Buspirone

Buspirone, a 5-HT1A partial agonist, is the most frequently cited pharmacological antidote for SSRI-induced bruxism. Bostwick and Jaffee [20] first reported its efficacy in four patients with SSRI-associated bruxism at doses of 5-10 mg twice daily. Subsequent case reports have confirmed these findings [21]. Buspirone is hypothesized to counteract the excessive serotonergic stimulation by activating presynaptic 5-HT1A autoreceptors, thereby reducing serotonin release and partially restoring dopaminergic function in motor circuits. A recent systematic review by Chouinard et al. [19] supports the use of buspirone as a first-line adjunctive treatment for SSRI-induced bruxism.

5.3. Gabapentin

Gabapentin, a GABA analogue that modulates calcium channels and increases GABAergic inhibition, has been reported to alleviate SSRI-induced bruxism in isolated case reports. Soyata and Oflaz [22] described a patient with SSRI-induced sleep bruxism that was refractory to dose reduction but responded to gabapentin 300 mg at bedtime. Gabapentin’s mechanism in bruxism may involve stabilization of sleep architecture and enhancement of inhibitory neurotransmission in the central motor circuits. However, evidence remains limited to case-level data.

5.4. Intra-oral devices and non-pharmacological approaches

Intra-oral devices remain a cornerstone of symptomatic management for bruxism, regardless of etiology. While they do not address the underlying cause, they protect dental surfaces from attrition, reduce TMJ loading, and may decrease masticatory muscle hyperactivity. In the context of SSRI-induced bruxism, splints should be used as a complementary measure while pharmacological strategies are optimized [7].