Very Low Dose Aripiprazole (2 mg/d) for Venlafaxine-Induced Bruxism: A Case Report

The association of bruxism with selective serotonin reuptake inhibitors/serotonin norepinephrine reuptake inhibitors (SSRI/SNRI) has been noted for a long time.^{1, 2} Here we report a case of venlafaxine-induced sleep bruxism and its successful management with very low dose aripiprazole.

Case Report

Mr U, a 21 years old male, presented with four months’ history of a severe depressive episode without psychotic symptoms. An adequate trial of escitalopram failed, and he was initiated on venlafaxine. The dose was gradually increased to 225 mg/d over a period of three weeks. His depressive symptoms improved partially over four weeks (40% reduction in the Hamilton Depression Rating Scale, i.e., from 42 to 25). After four weeks, the dose of venlafaxine was increased to 300 mg/d. In the following 4–5 days, the patient’s caregivers, who had stayed throughout this period with him, noticed the sound of teeth grinding and clinching when the patient was asleep in the night. The frequency of night bruxism increased in the next few days, occurring for 3–4 minutes every hour. Mr U reported discomfort in his jaws after waking up in the morning, but there was no history of awake bruxism, and the patient neither remembered sleep bruxism nor complained of sleep disturbance. Because of an increase in the frequency of suicidal ideas, the patient was offered inpatient care. By this time, he had received Cap venlafaxine 300 mg/d for about ten days. Diagnostic possibility of venlafaxine-induced bruxism was considered, and aripiprazole 2 mg/d was added to venlafaxine 300 mg/d on the second day of inpatient care. The frequency of sleep bruxism decreased from the first day of adding aripiprazole and it completely stopped. As depressive symptoms were persisting, the clinical history was reclarified, and an episode suggestive of hypomania in the past was noted. The primary psychiatry diagnosis was revised to bipolar affective disorder (BPAD) current episode severe depressive episode without psychotic symptoms. Lithium carbonate (1050 mg/d) was added to venlafaxine (300 mg/d) and aripiprazole (2 mg/d) after about a week of IP care. On this treatment, his depressive symptoms improved completely in three weeks, and he was discharged. Mr U was continued on the same medications for two months after discharge, and he did not have any recurrence of sleep bruxism during this period. Later, venlafaxine dose was decreased to 225 mg/d, and aripiprazole was stopped after a week of decreasing the venlafaxine dose. It has been two months since stopping aripiprazole. Mr. U did not have a relapse of sleep bruxism, and he has been maintaining well on venlafaxine 225 mg/d and lithium 1050 mg/d. We intend to taper off venlafaxine in the follow-up. Score on Naranjo Adverse Drug Reaction Probability Scale was 4, which suggest probable role of venlafaxine in the occurrence of bruxism.

Discussion

Our report highlights the utility of very low dose aripiprazole (2 mg/d) in the management of venlafaxine-induced bruxism. More commonly, buspirone, by virtue of its partial agonism of 5HT1A receptors, has been used in the management of SSRI/SNRI-induced bruxism. ¹ There are also reports of antipsychotics being used in the management of the same ( Table 1 ). Oulis et al. reported, for the first time, the utility of aripiprazole (10 mg/d) for the management of SSRI (fluoxetine and escitalopram)-induced bruxism. ³ Aripiprazole is a partial agonist of dopamine receptors (D2 and D3), with 30%–40% intrinsic dopamine agonistic activity. ⁴ So, our report suggests that aripiprazole at the dose of 2 mg/d may have sufficient dopamine agonistic activity to be effective for the management of venlafaxine-induced bruxism. Aripiprazole blocks about 70% of the postsynaptic D2 receptors at about 2 mg, and the proportion increases to 90%–94% at the dose of 30 mg. ⁵ SSRI-induced bruxism is due to the decreased prefrontal dopaminergic tone. ⁶ It may be that 2 mg/d of aripiprazole leaves adequate postsynaptic dopamine receptors for the available endogenous dopamine to act upon; the endogenous dopamine, together with the partial agonistic activity of aripiprazole, may overall enhance the dopaminergic activity in the prefrontal cortex. This may be the reason for the improvement it produces in SSRI-induced bruxism. At higher dose, aripiprazole may compete with the available endogenous dopamine and occupy higher percentage of the postsynaptic dopamine receptors. The overall effect may be dopamine antagonism in the prefrontal cortex and inducing bruxism as noted in an earlier case report. Lithium carbonate has been reported to increase serum aripiprazole levels by 43%, and the combination of lithium 1200 mg/d and aripiprazole 15 mg/d was reported to be associated with bruxism and extrapyramidal symptoms in a patient with BPAD.^{7, 8} It may be due to the dopamine antagonistic activity of the aripiprazole at that dose when given in combination with lithium. In our patient, complete improvement in bruxism had been noted before adding lithium, and there were no extrapyramidal symptoms after adding lithium. The current report also suggests that venlafaxine-induced bruxism is dose-dependent and that, if clinically advisable, dose reduction may be used as a measure to relieve bruxism. This is in line with earlier reports of dose reduction being helpful in the management of SSRI-associated bruxism.^{2, 9} In other available reports of venlafaxine-induced bruxism, either venlafaxine was stopped or add-on treatment with other agents was considered. ¹ Though anecdotal, our report suggests the need for further systematic studies to explore the role of very low dose aripiprazole in the management of antidepressants-induced bruxism.

Table 1.

Antipsychotics for the Management of SSRI/SNRI-Induced Bruxism

Age (Years), Sex (M/F)	Diagnosis	SSRI/SNRI and Dose (mg/d)	Antipsychotic Agent and Dose (mg/d)
67, F12	Nonaffective psychosis with depressive disorder	Paroxetine, 20	Chlorpromazine, 50
63, F8	OCD	Escitalopram, 60	Aripiprazole, 10
28, F13 35, M 18, F 45, F 32, F	MDD MDD MDD MDD MDD	Sertraline, 75 Sertraline, 50 Fluoxetine, 20 Sertraline, 50 Citalopram, 10	Quetiapine, 25 Quetiapine, 25 Quetiapine, 37.5 Quetiapine, 37.5 Quetiapine, 25
21, M*	Bipolar affective disorder	Venlafaxine, 300	Aripiprazole, 2

SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor; OCD = obsessive compulsive disorder; MDD = major depressive disorder; *current report.