2013; Kisely, Forbes, Sawyer, Black, & Lalloo, 2016). Other common conditions associated with mouth pain are psychiatric disorders, xerostomia (from drugs, connective tissue disease, or aging), nutritional deficiencies (vitamin B12, iron, folate, zinc, vitamin B6), and allergic contact stomatitis (Sun, Wu, Wang, Lin, Chen, & Chiang, 2013). Functional magnetic resonance imaging studies suggest that stomatodynia patients may have impaired brain network dynamics essential for descending inhibition, leading to diminished inhibitory control of sensory experience; as a consequence they may experience intraoral proprioception as burning pain (Aravindhan et al., 2014). When primary stomatodynia persists despite the investigation and treatment of other common conditions associated with mouth pain (e.g., vitamin supplementation, zinc replacement, hormone replacement treatment), topical drug treatment with capsaicin, clonazepam, lidocaine, benzydamine hydrochlorate 0.15%, or aloe vera have been used with varying levels of success (Aravindhan et al., 2014; Sun et al., 2013; Thoppay, De Rossi, & Ciarrocca, 2013). Other neuropathic facial pain Other neuropathic pain in the facial region has been termed by the International Headache Society as persistent idiopathic facial pain and is described as persistent facial pain that does not have the characteristics of the cranial neuralgias and is not attributed to another disorder (International Headache Society, 2004; Benoliel, & Gaul, 2017). When medications of choice fail, a trial-and-error approach can be attempted with other drugs
Treatment algorithms with systemic medications for stomatodynia continue to rank tricyclic antidepressants as first-line agents, with either gabapentin or pregabalin as second choices (Table 4). Gabapentin or pregabalin may be considered as first-line agents in the elderly or when tricyclics are contraindicated. Opioids are considered third-line agents (Aravindhan et al., 2014; Sun et al., 2013; Thoppay et al., 2013). Alternative medications that have shown limited success in the treatment of stomatodynia include clonazepam and alpha-lipoic acid (Aravindhan et al., 2014; Sun et al., 2013; Thoppay et al., 2013). Clonazepam is a benzodiazepine-type drug and is started at 0.25 mg daily and increased by 0.25 mg weekly as needed. Doses of up to 20 mg daily have been used in epilepsy, but 3 to 6 mg daily (given in three divided doses) is more common when treating burning mouth syndrome (Sun et al., 2013; Ślebioda, Lukaszewska-Kuska & Dorocka- Bobkowska, 2020). Alpha-lipoic acid can be used at doses ranging from 20 mg to 1,800 mg daily. Most often it is given in the range of 200 mg to 600 mg daily in one or two divided doses. Doses higher than 600 mg per day are more likely to lead to adverse events (nausea, vomiting, vertigo; Thoppay et al., 2013). that have been used for neuropathic pain, including but not limited to, phenytoin, carbamazepine, clonazepam, valproate, phenothiazines, venlafaxine, mexiletine, and baclofen. Limited scientific evidence is available regarding these pharmacotherapy choices for neuropathic face pain and is based primarily on case reports in the literature (Costa, et al., 2021).
ADJUVANT PHARMACOTHERAPY FOR OROFACIAL PAIN: ANTIDEPRESSANTS, ANTICONVULSANTS, ANXIOLYTICS, AND MUSCLE RELAXANTS
This category of medications includes four major classes of medication: the antidepressants and anticonvulsants described in Table 4 and the anxiolytics and muscle relaxants described in Table 5. Anticonvulsant and antidepressant classes generally affect conductance of ions that reduce neuronal excitability (Na + , K + , Ca ++ , Cl-). Muscle relaxants are generally centrally
acting agents (i.e., not at the neuromuscular junction). For most chronic orofacial pain conditions, the use of these medications is considered off-label, although there is considerable biomedical literature in support of their use (Medical Letter, 2013; Nguyen & Wang, 2013; Smaïl-Faugeron, Courson, & Arrêto, 2013: Stern & Greenberg, 2013; Zakrzewska, 2009; Costa, et al., 2021).
Table 5: Anxiolytics and Muscle Relaxant Medications as Adjuvant Pharmacotherapy for Orofacial Pain Formulations Usual Daily Dosage
Anxiolytic Medications
Anxiolytic Medications Clonazepam (Klonopin, generics)
0.5, 1, 2 mg tablets
0.25 mg at bedtime for 1 week; increase dose by 0.25 mg every week (max dose: 1 mg tid)
Panic disorder Seizure disorder
Diazepam (Valium, generics)
2, 5, 10 mg tablets 1 mg/mL oral solution
2-10 mg 3-4 tid-qid
Acute ethanol withdrawal Anticonvulsant Anxiety Muscle spasticity Sedation
Doxepin (Silenor, generics)
10, 25, 50, 75, 100, 150 mg capsules 3, 6 mg ER tablets 10 mg/mL oral solution 50, 100, 150, 300 mg tablets 150, 300 mg ER tablets
10-50 mg qhs
Anxiety Depression Insomnia
Trazodone (Oleptro, generics)
50 mg tid
Depression
Muscle Relaxant Medications Baclofen (Lioresal, generics)
10, 20 mg tablets
5 mg tid, may increase 5 mg/dose every 3 days to a maximum of 80 mg/day
Muscle spasticity
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