The first medications in my TMD toolbox

Temporomandibular disorders (TMDs) are a highly prevalent group of interrelated conditions affecting the temporomandibular joints, muscles of mastication, and intra-articular structures [1]. Understanding the pathophysiology of TMD and the nuances between subtypes is paramount in management, particularly when incorporating medications into care. Dentists expertly employ local anesthetics, analgesics, sedatives, and antibiotics in daily practice, but many feel less confident prescribing medications when treating TMD. This editorial will highlight medications I have found to be particularly useful, with an eye on optimal medication selection.

In contrast to many musculoskeletal pain conditions, the great majority of individuals with TMD improve over time without invasive therapy [2–5]. While the effectiveness of conservative therapy is encouraging, this also suggests the potential role that medications may play to improve quality of life when symptoms are present. Unfortunately, pharmacotherapy in TMD has not been rigorously studied in large randomized trials [6,7]. When scientific literature is less than ideal, we are left to make the best choices for our patients with the data available. I encourage each of you to explore the data and compare my experiences with those in your practice to determine if judicious use of medication could be beneficial as part of a comprehensive care protocol. In my practice, I have found three classes to be particularly useful: non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and tricyclic antidepressants. Understanding the indications for each, and the characteristics of drugs in each class, allows for application in a variety of circumstances.

The first consideration when prescribing is also the simplest: Why prescribe at all? Before “reaching for the prescription pad,” one must be able to clearly articulate the precise goals of therapy. What am I trying to accomplish with this drug? Are alternative therapies available? Would pharmacotherapy help to improve function or quality of life in a condition that cannot be cured? Answers vary in each individual circumstance.

Non-steroidal anti-inflammatory drugs are useful in treating many dental and orofacial conditions, due to their analgesic and anti-inflammatory properties. In TMD, they are the drugs of choice in treating acute (e.g., capsulitis) and chronic (e.g., degenerative joint disease) inflammatory conditions within the joint [6,8,9]. NSAIDs can provide acute pain relief in myalgia but are less effective in treating chronic myofascial pain, likely because most muscular pain is not caused by inflammation [10].

All NSAIDs inhibit cyclooxygenase 2 (COX-2), resulting in decreased synthesis of prostaglandin E2, a key mediator in inflammation and pain sensitization [11]. Unfortunately, most also block structurally similar COX-1, which negatively affects platelet aggregation, kidney function, and protection of gastrointestinal mucosa [12,13]. NSAIDs are cautioned in patients taking antiplatelet and anticoagulant drugs, due to increased bleeding risk, especially in the GI tract. Risk factors for GI bleeding include past history of GI bleeding, gastric and duodenal ulcers, H. pylori infection, alcohol and tobacco use, and age over 65 [13]. Short-term use is unlikely to produce GI symptoms de novo, with meta-analysis reporting 2–3 months of continuous therapy to induce symptoms when non-indomethacin NSAIDs are taken at recommended doses [14].

Ibuprofen is considered first-line therapy in temporomandibular joint (TMJ) arthralgia [15]. It is effective, inexpensive, and widely available [8,15,16]. The analgesic effect compares favorably to other NSAIDs [17]; however, higher doses (600 mg QID) are required to produce anti-inflammatory effects comparable to more potent NSAIDs [18,19]. The anti-inflammatory effect is important to consider, given the observation that pain relief in TMJ arthralgia may be due to decreased inflammation rather than direct pain relief [20,21]. Many patients struggle to be compliant with four-times-daily dosing.

Use of a once-daily medication can help alleviate this issue. In healthy individuals, I often begin with piroxicam 10 mg daily for 10–14 days. While it is an excellent anti-inflammatory, piroxicam has greater potential for GI side effects than many NSAIDs [16]. Celecoxib, a COX-2 selective inhibitor, is a well-tolerated alternative, which has shown a benefit in managing osteoarthritis in other areas of the body; however, the lone randomized trial evaluating celecoxib in TMD found no statistical benefit versus placebo [20]. This finding may be due to celecoxib’s slow absorption, which decreases effectiveness as an acute pain reliever [13]. The same study found naproxen (500 mg BID) to be effective in treating painful disc displacement with reduction [20]. While quite useful, naproxen’s longer half-life and greater tendency for GI effects make it slightly less adaptable than ibuprofen (400 mg TID) [13,16]. Weighing all factors, I often choose etodolac (200 mg BID-TID for 7–14 days), a prescription NSAID with high COX-2 selectivity, or combine acetaminophen with a lower dose of ibuprofen (a combination that has shown synergistic pain relief following dentoalveolar surgery) [9,22,23].

More than three-quarters of patients seeking treatment for TMD present with muscle pain [24,25]. Muscle relaxants are the principal class of medication in the treatment of muscle disorders and are a useful complement to other therapies designed to limit parafunctional behaviors. Medications differ in potency, duration of action, and drug interactions, allowing prescribers to tailor selection to an individual’s specific needs. For example, tizanidine has rapid time-to-peak and a short half-life, which makes it ideal for treating predictable episodic pain, such as stress-induced myalgia. Tizanidine’s direct action on alpha-2 adrenergic receptors is unique among commonly prescribed muscle relaxants. While this may allow use when other medications are not tolerated, it also carries a wider range of drug interactions (e.g., anti-hypertensives).

Sedation is the most common limiting side effect when using muscle relaxants. Medication lists must be reviewed to identify other central nervous system (CNS) depressants, and patients should be questioned regarding past responses to muscle relaxants and medications with similar chemical properties (e.g., selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs)). Drowsiness can often be mitigated by starting at a low dose and titrating slowly. A sedative effect may also be desirable. Cyclobenzaprine, the only muscle relaxant to show benefit in TMD in a randomized trial [26], improves sleep quality in patients with chronic pain [27,28]. I generally begin with 10 mg before bed, assess patient response, and titrate up or down, as needed. With treatment-naïve patients, it can be helpful to take the first dose on a weekend so the patient can gauge response before incorporating into his or her daily routine.

I have found tricyclic antidepressants to be some of the most effective medications in my TMD toolbox, despite their limited use in dentistry. Though they have fallen out of favor as antidepressants, TCAs are effective in managing TMD and other chronic pain conditions at lower doses than those required to produce an antidepressant effect [29–33]. Lower doses also help to reduce adverse effects. Though the exact mechanism in TMD is unknown, TCAs decrease pain signals from peripheral muscles and pain transmission within the spinal cord while simultaneously improving sleep quality [30,34]. Perhaps not surprisingly, I have found them to be most useful in individuals with parafunction-induced muscle pain and concurrent sleep dysfunction. TCAs increase synaptic concentration of serotonin and norepinephrine, so care must be taken when patients are taking medications with similar mechanisms (e.g., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or chemical structures (e.g., [tetracyclic] cyclobenzaprine) to avoid serious side effects, such as cardiac arrhythmia and serotonin [35]. Avoid amitriptyline in individuals over age 65, due to fall risk, anti-cholinergic effects, and potential cardiotoxicity [36]. Nortriptyline, which has no active metabolites, may be used as an alternative [37,38]. Thankfully, doses used in TMD (e.g., 10–30 mg amitriptyline, 25 mg nortriptyline) [39] are well below the 75 mg threshold for anticipated cardiotoxicity [40].

TMD represents a heterogeneous group of related disorders in which medications can play an important role. Optimal medication selection requires accurate diagnosis of a patient’s pain complaint and thorough review of health status. Non-steroidal anti-inflammatory drugs, muscle relaxants, and tricyclic antidepressants are effective tools in TMD management that can be used safely within dental practice.