Medications that may contribute to TMD and orofacial pain

Persistent jaw pain may be linked to more than temporomandibular disorders alone. Donald R. Tanenbaum, DDS, MPH, is a board-certified orofacial pain specialist and he examines how common medications can contribute to orofacial pain, bruxism, and muscle dysfunction, helping clinicians improve diagnosis and patient care.

Not every patient assessment is straightforward. In fact, figuring out why a patient has persistent jaw symptoms is not always clear-cut. Over the last few years, while searching for answers, I’ve begun to look a bit more carefully at the medications my patients are taking. What I have found is that there is a repetitive list of medications that continue to be part of the medical histories in a surprising number of patients.

As many of these medications have been identified as potential contributors to musculoskeletal pain in the orofacial region due to an impact on muscle physiology, pain modulation, electrolyte balance, sleep, or parafunctional activities, a careful review of a patient’s medication history deserves consideration whenever the clinical picture seems more complicated than expected.

Levothyroxine and Synthroid

Levothyroxine and Synthroid are prescribed to replace thyroid hormone that the gland can no longer produce adequately, most commonly in patients with Hashimoto’s thyroiditis. When dosed appropriately, these medications restore euthyroid function and should improve rather than worsen musculoskeletal symptoms.

At times, however, underdosing may present a different picture. Patients may report persistent jaw muscle pain, poor sleep, fatigue, and generalized muscle discomfort that does not fit the mechanical pattern of a simple TMD problem. Their levothyroxine dose may be considered adequate by laboratory standards yet still be insufficient for that individual’s tissue needs.

Overdosing can create the opposite problem. Excess thyroid hormone may produce sympathetic nervous system activation, elevated resting muscle tension, anxiety, and disrupted sleep, all of which may contribute to persistent masticatory muscle pain.

When a patient has remained on thyroid replacement therapy for an extended period without periodic reassessment, collaboration with the prescribing physician has often proven worthwhile.

Statins

Cholesterol-lowering statin medications produce muscle aching and fatigue in a meaningful number of patients. It is estimated that this occurs in approximately 5%–10% of patients worldwide.1 The underlying mechanism is believed to involve impaired energy production within skeletal muscle.

Jaw and facial muscle pain developing after initiation of statin therapy, following a dosage adjustment, or after switching from one statin to another may reflect statin-associated myopathy rather than primary TMD.

Although the masticatory muscles are not commonly discussed in the statin literature, the possibility should be considered when muscle pain appears without another satisfactory explanation. Communication with the prescribing physician is certainly justified in these scenarios.

ACE inhibitors and ARBs: Lisinopril and losartan

ACE inhibitors such as lisinopril and ARBs such as losartan are among the most commonly prescribed antihypertensive medications because, beyond lowering blood pressure, they provide well-documented protective effects on the kidneys and cardiovascular system.

Musculoskeletal complaints including myalgia and arthralgia have been described with losartan, while lisinopril has been associated with arthritis, arthralgia, neck pain, and generalized joint pain. However, there is no published literature specifically examining ACE inhibitor- or ARB-related musculoskeletal pain involving the TMJ or masticatory system.

So, what would the connection potentially be?

ACE inhibitors increase circulating bradykinin, a peptide that has been shown to influence pain hypersensitivity following tissue injury. ARBs do not increase bradykinin to the same degree and therefore may not contribute to chronic pain through this same mechanism.

Theoretically, if circulating bradykinin levels rise in a patient who already has inflamed or sensitized masticatory tissues, those elevated levels may amplify the pain signals those tissues are generating.

In practical terms, this means that a patient taking lisinopril or another ACE inhibitor who has even modest TMJ inflammation or masticatory muscle involvement may experience pain that appears disproportionate to the degree of tissue injury present.

Therefore, in the patient whose pain seems inconsistent with the clinical findings, investigation into this possibility may be justified. I have pursued this line of thinking in a number of patients, collaborating with cardiologists who have been receptive to considering medication changes when clinically appropriate.

Omeprazole and proton pump inhibitors

Long-term proton pump inhibitor (PPI) therapy has been associated with impaired intestinal magnesium absorption. Magnesium deficiency is a well-established cause of muscle cramping, myalgia, and neuromuscular irritability.

PPIs may also impair the long-term absorption of vitamin D and vitamin B12. In patients receiving chronic PPI therapy who present with unexplained jaw muscle cramping, diffuse myalgia, or persistent muscle tenderness, evaluation of magnesium, vitamin D, and vitamin B12 levels is often a simple and productive step.

Spironolactone

Spironolactone has become one of the most commonly prescribed medications seen in women presenting for consultation. Its most widespread modern application has been in the management of hormonal acne.

The musculoskeletal consequences of spironolactone may operate through two intersecting pathways. By blocking androgen receptors, spironolactone may reduce endogenous pain-inhibitory mechanisms, shifting the nervous system toward greater pain sensitivity at precisely the time when the jaw may be under increased functional stress.

The second pathway is electrolyte-mediated. Long-term spironolactone therapy may contribute to magnesium depletion. When magnesium levels fall, the threshold for pain amplification may decrease, leaving the masticatory system less protected against the development or persistence of chronic pain.

Though this relationship may be more theoretical than predictable, there are so many women in my practice taking this medication that I believe it deserves consideration and should at least prompt discussion and collaboration with the prescribing physician when appropriate.

Amphetamines for ADHD

Stimulant medications prescribed for attention-deficit/hyperactivity disorder activate the sympathetic nervous system, increasing resting muscle tone and potentially promoting both awake and sleep bruxism.

When jaw symptoms begin or worsen following initiation of stimulant therapy, this relationship deserves careful consideration. The combination of stimulant-induced sympathetic activation and preexisting jaw loading habits may place these patients at increased risk for the development or exacerbation of TMD symptoms.

SSRIs and SNRIs

Serotonergic antidepressants, including sertraline, fluoxetine, escitalopram, and venlafaxine, have the potential to produce sleep bruxism by altering dopamine pathways that normally suppress masticatory muscle activity during sleep.

The onset or worsening of jaw symptoms within weeks to months of initiating therapy, or following an increase in dosage, is a pattern that, when encountered in this practice, consistently prompts further discussion.

Although medication-induced bruxism is not universally recognized, increasing attention has been given to this phenomenon in both the psychiatric and dental literature and should remain part of the differential diagnosis when evaluating persistent jaw pain.