#56741: Dental Treatment of Patients with Mental Disorders

There is no current cure for bipolar disorder, and long-term treatment is designed to allow for better control of manic/depressive swings. Treatment plans generally consist of pharmacotherapy, psychotherapy, and lifestyle modification that can be encouraged with family and peer support.

Mood stabilizers have long been the first choice for the pharmacologic management of bipolar disorder. Among these medications, lithium is most frequently prescribed. This agent helps to prevent manic episodes and to decrease the risk of suicidal behavior [13]. However, it is not always effective and its side effects can preclude its use.

The long-term use of lithium can cause adverse cardiovascular, central nervous, endocrine, hematologic, and neuromuscular effects [13]. In oral health, perhaps the most significant adverse effect of long-term lithium use is xerostomia (dry mouth). Interventions for xerostomia (dry mouth) include artificial saliva substitutes, frequent sips of water, or cholinergic medications, such as pilocarpine. Immunoglobulins and other compounds present in saliva that support immune functions will have a decreased output and can subject patients to recurring opportunistic infections, such as oral candidiasis. Impaired salivary flow will also cause a decrease in saliva's cleansing action upon the teeth. Further, the ability of salivary components to maintain the pH of saliva as a mild base is altered, which causes the oral environment to become more acidic.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such ibuprofen and naproxen to manage dental or oral pain is common, but these medications can decrease the renal clearance of lithium and increase its serum concentration to toxic levels. As such, concurrent use of NSAIDs and lithium should be avoided in favor of acetaminophen-based analgesics, if appropriate. Patients taking lithium should also be cautioned to avoid over-the-counter NSAIDs [13].

The antibiotic metronidazole is occasionally used as a single agent or in conjunction with beta-lactam antibiotics (e.g., amoxicillin) to treat odontogenic infections. Metronidazole can also decrease the renal clearance of lithium and cause subsequent elevation in its plasma concentration, increasing the risk for lithium toxicity. As such, an antibiotic that is compatible with the patient's medical history should be used instead [13].

If lithium is ineffective or causes unacceptable side effects, valproic acid or carbamazepine may be used as a second-line option for patients with bipolar disorder. Valproic acid can potentiate central nervous system (CNS) depression seen with opioid analgesics and benzodiazepines (e.g., diazepam). Carbamazepine can decrease plasma concentrations of acetaminophen and tramadol and decrease their analgesic efficacy [14].

Macrolide antibiotics (e.g., erythromycin, azithromycin, clarithromycin) can increase the plasma concentration of valproic acid and carbamazepine, which can lead to systemic toxicity [13]. Alternative effective antibiotics should be used. Any other prescribed or over-the-counter medications that are used by the patient should be evaluated for potential adverse drug interactions with those used adjunctive to dental treatment.

As with any patient, dental treatment of a patient with bipolar disorder begins with a thorough review of the patient's current state and medical history. Patients experiencing a manic episode may display signs of hyperactivity, including grinding of teeth and excessive frequency and application of force during tooth brushing, which can lead to cervical abrasion and trauma to the gingival tissues. The subsequent sensitivity from the exposed dentin can discourage the patient from proper oral hygiene practices and increase the risk of caries and periodontal disease. Dental staff should provide the patient with a mirror view of any area of cervical abrasion and provide individualized oral hygiene instructions to maintain optimal oral hygiene without perpetuating the cycle of abrasion.

Patients experiencing a depressive episode may disregard oral hygiene. If this phase is extensive and oral hygiene is neglected for an extended period, caries and periodontal disease may develop or worsen. Patients with partial or complete dentures may neglect daily maintenance, with a consequent accumulation of food debris and micro-organisms that can cause inflammation of the underlying tissues and preclude the ability to wear the prostheses.

If possible, dental appointments should be scheduled between bipolar episodes, as patients who are in a manic or depressive phase may have difficulty enduring dental appointments or comprehending complex treatment plans, financial arrangements, and/or issues related to informed consent. The patient's physician should be contacted before initiation of treatment if there is any concern about the patient's ability to endure the proposed dental treatment plan.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) have advantages of low overdose lethality and better tolerability than first-generation antidepressants, which can improve adherence. SSRIs are particularly effective in patients with obsessive-compulsive symptoms, but may initially worsen anxiety or panic symptoms [22,23]. This class includes the agents fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), and vortioxetine (Brintellix). Citalopram may have fewer drug-drug interactions than other SSRIs, and fluoxetine may be a better choice in patients with poorer adherence due to its long half-life [22,23].

The most common side effects with SSRIs are gastrointestinal (nausea, vomiting, and diarrhea), activation/insomnia (restlessness, agitation, anxiety, akathisia, and sleep disturbances), sexual, headache, fatigue, and weight gain [22,23]. Xerostomia can also occur with the use of SSRIs. Many of these side effects dissipate over time.

Platelet aggregation can be impaired due to platelet serotonin depletion, which can interfere with the ability to achieve hemostasis during oral or periodontal surgery or root planing and curettage procedures. The concurrent use of NSAIDs or daily aspirin as a cardioprotective measure can exacerbate this problem and should be avoided, particularly if invasive dental procedures are planned. SSRI-induced bruxism (the involuntary grinding or clenching of the teeth) has been reported [13]. For patients prescribed SSRIs who have dental phobia or anxiety, anxiolytic medications should only be given following consultation with the patient's physician, as this combination can potentiate CNS depression and increase the risk for respiratory arrest.

If an SSRI or tricyclic antidepressant (TCA) is combined with tramadol (an analgesic used for moderate-to-severe pain), serotonin syndrome may develop. Mild cases of serotonin syndrome present with signs and symptoms such as anxiety, diaphoresis, and gastrointestinal complaints. Severe cases can present with confusion, hypertension, hyperthermia, hyper-reflexia, and seizures [24]. The serotonin toxidrome has a variable presentation and can be difficult to detect. The most distinguishing features are clonus, fever, and hyper-reflexia, but the most important diagnostic clue is a history of exposure to serotonergic drugs. Given the potentially serious and even deadly effects of combining these medications, tramadol should be avoided and another analgesic chosen for these patients.

SSRIs have also been associated with alteration in taste (dysgeusia), sialadenitis (inflammation of the salivary glands), stomatitis (inflammation of the mucosal lining of any of the structures of the mouth), and edema of the tongue. Patients who experience dysgeusia may use extra salt or sugar to compensate for the decreased ability to taste. These compensatory mechanisms are contrary to good general and oral health. The pain associated with stomatitis can discourage patients from maintaining optimal oral hygiene [13,25].

While these adverse oral effects will resolve upon cessation of SSRI use, halting the medication suddenly is dangerous. Titration or switching to another class of antidepressant should only be attempted by the patient's physician.

Serotonin-Norepinephrine Reuptake Inhibitors

Most serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine (Effexor), desvenlafaxine (Pristiq), levomilnacipran (Fetzima), and duloxetine (Cymbalta), are several-fold more selective for serotonin than norepinephrine. Safety, tolerability, and side effect profiles of SNRIs resemble SSRIs, with the exception that the SNRIs have been associated (rarely) with sustained elevated blood pressure [22,23]. As such, patients taking SNRIs are at risk for xerostomia, bruxism, and drug-drug interactions.

Tricyclic Antidepressants

TCAs are predominantly serotonin and/or norepinephrine reuptake inhibitors that act by blocking the serotonin transporter and the norepinephrine transporter, respectively, which results in an elevation of the extracellular concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. TCAs also have varying but typically high affinity for the H1 and H2 histamine receptors and muscarinic acetylcholine receptors. As a result, they also act as potent antihistamines and anticholinergics. These properties are generally undesirable in antidepressants, however, and likely contribute to their large side effect profiles [13,25].

TCAs are comparable in efficacy to SSRIs/SNRIs, but their side effect profile makes them seldom used as first-line therapy [22,23]. TCAs may initially worsen anxiety or panic symptoms. Due to side effect potential of cardiac arrhythmia, TCAs should be used very cautiously, if at all, in patients with heart problems. Issues with orthostatic hypotension and sedation, particularly in elderly patients, also arise and may be a concern following dental appointments.

Anticholinergic and antihistamine activity accounts for many side effects, including xerostomia, blurred vision, reduced gastrointestinal motility or constipation, urinary retention, cognitive and/or memory impairment, and increased body temperature [22,23]. Other side effects may include drowsiness, anxiety, emotional blunting (apathy/anhedonia), confusion, restlessness, dizziness, akathisia, hypotension, tachycardia, and arrhythmia. As with SSRIs, patients taking TCAs may develop dysgeusia, sialadenitis, stomatitis, and lingual edema. Tolerance to side effects often occurs if treatment is continued. Side effects may also be less troublesome if treatment is initiated with low doses and gradually increased [13,25].

The prolonged use of TCAs can cause suppression of the production of the formed elements of human blood, and this decreased production of platelets can result in coagulation problems after invasive dental procedures [14]. Similarly, decreased production of granular and agranular leukocytes can lead to an increased potential for opportunistic oral infections and delayed healing of intraoral surgical sites. A complete blood count (CBC) with differential and adjunctive laboratory tests (e.g., prothrombin time [PT], partial thromboplastin time [PTT]) are advisable prior to any dental procedure in which the ability to achieve hemostasis is required.

TCAs may also accentuate the effects of vasoconstrictors in local anesthetic solutions (e.g., epinephrine, levonordefrin), which can culminate in a rare but serious hypertensive crisis. This potential adverse effect is more pronounced when a TCA is combined with levonordefrin [28]. If appropriate, a local anesthetic solution without a vasoconstrictor (e.g., mepivacaine, prilocaine) should be used for these patients, keeping in mind that the duration and depth of anesthesia will be reduced. If a local anesthetic with a vasoconstrictor is used in a patient also taking a TCA, a cautious and conservative approach is mandatory.

The rate of suicide is significantly higher among persons with a mood disorder than the general population. One long-term study found that 12% to 20% of individuals diagnosed with a major mood disorder (including schizophrenia, anxiety, depression, dementia, and/or substance abuse), ultimately died by suicide. The first three months after diagnosis is the period of highest risk for a first attempt, with the three months following the first attempt being the highest risk period for a second attempt [26].

Most people who are suicidal exhibit warning signs, whether or not they are in an acute suicide crisis. These warning signs should be taken seriously and include observable signs of serious depression; withdrawal from friends and/or social activities; sleep problems; and loss of interest in personal appearance, hobbies, work, and/or school [27]. Although dental professionals may feel uncomfortable with suicidal patients, it is essential not to ignore or deny the suspicion of suicide risk. The first and most immediate step is to allocate adequate time to the patient, even though many others may be scheduled, in order to show empathy and build rapport. Patients at risk for suicide should be referred to a behavioral health provider and provided the National Suicide and Crisis Lifeline phone number, 988. If suicide is an imminent risk, contacting emergency medical services may be warranted.

As discussed, the oral health of patients with major depressive disorder can be compromised by the direct and indirect effects of the medications that are used in its treatment and by the manner in which this disorder affects the patient's motivation to maintain optimal oral hygiene and attend periodic dental recall appointments. However, there are no universal modifications that apply to the dental treatment for these patients. Motivation of the patient to maintain optimal oral hygiene at home and to continue attendance at periodic recall appointments is a challenge, although this is an issue for many patients without depression as well. The length of a dental appointment should reflect the patient's ability to withstand dental treatment. Longer appointments and more complex dental procedures should only be scheduled if necessary. If there is any doubt about the degree to which major depressive disorder affects a patient's ability to commit to a treatment plan, withstand dental treatment, or tolerate medications, consultation with the patient's physician or psychiatrist is recommended.

The primary goals of generalized anxiety disorder treatment are reduction of anxiety symptoms and reduction or elimination of disability. Pharmacotherapy and CBT or cognitive therapy are equal as first-line options.

The Anxiety Disorders Association of Canada and the Anxiety and Depression Association of America have created guidelines for the selection of appropriate pharmacotherapy in the treatment of generalized anxiety disorder with differing recommendations regarding first- and second-line medications [33,34]. The Anxiety Disorders Association of Canada recommends agomelatine, pregabalin, venlafaxine XR, duloxetine, escitalopram, paroxetine, or sertraline as first-line options, while the Anxiety and Depression Association of America suggests venlafaxine XR, duloxetine, paroxetine, escitalopram, sertraline, or fluoxetine [33,34].

As discussed, depression of the respiratory system and the CNS can occur with the use of benzodiazepines, especially in conjunction with alcohol or opioid analgesics. Dental clinicians should use non-opioid analgesics to treat pain if a patient is being treated with a benzodiazepine. Some dental practices use benzodiazepines to help calm apprehensive patients so they may receive treatment (marketed as "sleep dentistry"). Patients who are already taking a benzodiazepine to treat generalized anxiety disorder should not take an additional dose of any other benzodiazepine medication as an anxiolytic before dental treatment, as this combination can also potentiate respiratory and CNS depression.

Macrolide antibiotics (e.g., erythromycin, clarithromycin, azithromycin) used to treat odontogenic infections can increase blood plasma levels of alprazolam, with the potential for systemic toxicity. So, the simultaneous use of these medications is contraindicated [14]. Instead, alternative antibiotics (e.g., penicillin, amoxicillin, clindamycin) compatible with the patient's medical history should be used.

The pharmacokinetics of benzodiazepines should also be considered when medications are used adjunctive to dental treatment. Specifically, the half-life (i.e., the interval of time required to achieve a 50% reduction in blood plasma concentration) of benzodiazepines can be affected by drug interactions. An extended half-life results in a lingering drug effect [13].

Diazepam (via its active metabolite desmethyldiazepam) has a half-life that can range from 50 to 100 hours, compared with 40 hours for lorazepam and 11.2 hours for alprazolam [13]. Thus, the adverse interactions between diazepam and opioids can occur for approximately four days after the last dose of diazepam is taken. Although the half-lives of lorazepam and alprazolam are considerably less than that of diazepam, precaution for the expected half-lives of those drugs is also recommended.

Dental treatment modifications for patients with generalized anxiety disorder should be customized to reflect the degree to which the disorder affects their lives. Whether patients with generalized anxiety disorder have anxiety or phobias about dental treatment or not, dental treatment should progress at a pace and for a duration that does not challenge their emotional endurance. Oral manifestations of long-term anxiety can include destructive parafunctional habits such as bruxism, which can cause excessive wear of the teeth, fractures of existing restorations, temporomandibular joint disorders, and a decrease in the vertical dimension of occlusion. The fabrication of splints or night guards may be required to address these issues.

Anxiety can detract from the patient's desire and ability to maintain optimal oral hygiene. Dental staff should be supportive and use a non-judgmental motivational approach to encourage the patient to maintain an appropriate oral hygiene regimen that may include more frequent recall appointments. Alcohol, prescription drug, and/or illicit drug use may co-occur in patients with generalized anxiety disorder, which can lead to worsening symptoms and a high degree of morbidity and even mortality if left untreated. It is incumbent that dental clinicians discuss their concerns with the patient in an appropriate way and make referrals to mental health care.

Combined treatment is superior in panic disorder, with effects of combined psycho- and pharmacotherapy treatment versus placebo about twice as large as pharmacotherapy alone versus placebo [40]. The first-line drugs recommended for the treatment of panic disorder are SSRIs or venlafaxine XR [33]. Research suggests that the largest effect size is found with clonazepam, followed by venlafaxine and fluoxetine [41].

The use of medications can only reduce the frequency and intensity of a panic attack but cannot eliminate the situations or places that precipitated the attack. The goal of psychotherapy such as cognitive therapy is to discern the patient's beliefs and perceptions that may serve as the trigger for a panic attack and eliminate them as a source of the heightened anxiety from which a panic attack evolves [42]. The use and duration of medications and psychotherapy will vary according to individual needs.

As discussed, the drugs used to treat panic disorder, specifically antidepressants and benzodiazepines, can interact with other drugs used in dental treatment and result in adverse or unintended effects. These potential interactions should be considered whenever prescribing or administering a medication to these patients.

Dental treatment of patients with panic disorder should begin with a discussion of the patient's medical history that includes the details of the places or situations that have served as triggers for panic attacks. It is also possible that a patient may be unaware that he or she is experiencing what might be a first panic attack. Further complicating the matter, the signs and symptoms can resemble those of serious medical emergencies, including myocardial infarction (heart attack), acute asthmatic attack, or hypoglycemic crisis. In these situations, emergency medical services should be summoned; distinguishing between a panic attack and a medical emergency is beyond the ability of dental professionals.

Conversely, patients with a known history of panic disorder may develop a medical emergency that mimics a panic attack. Patients believed to be experiencing a panic attack should never be left alone, and if there is any doubt as to the origin of the acute symptomatology, emergency medical services should be called.

Patients who experience a panic attack in a dental setting may defer or avoid dental treatment completely and increase their risk of the development of carious lesions and periodontal disease. These patients should be encouraged to continue to seek dental care, with the reassurance that steps can be taken to make the experience less triggering.

Patients with specific phobias generally do not consult medical professionals when able to avoid the specific feared situations or objects. Exposure therapy is effective in treating specific phobia and is the favored approach. For blood-injection-injury phobias, an effective approach is combining exposure therapy with muscle tension exercises (applied tension) designed to prevent fainting. Using stress-reducing medical devices, such as decorated butterfly needles and syringes, has significantly reduced needle phobia and stress in pediatric and adult patients. With dental phobias, use of cognitive-behavioral therapy can reduce avoidance of oral injections and decrease patient anxiety [42,47].

It is essential that a discussion that is based on empathy and compassion reveals situations within the dental setting that cause anxiety of such a magnitude that they have precipitated phobia and/or a panic attack in the past for the patient and have the potential to do so in subsequent dental appointments. As noted, modifying treatment and/or devises to reduce stress is recommended to allow dental treatment to proceed.

Pain disorder is considered a somatic disorder characterized by pain for which no organic or physical etiology can be identified. In patients with this disorder, psychologic factors such as stress, anxiety, and depression usually precede the onset of pain and can influence its severity and duration. The perception of pain can occur anywhere, including the oral and maxillofacial complex. Patients may complain of odontogenic pain even after a complete radiographic survey and clinical examination rules out dental caries, endodontic pathology, and defective restorations.

Atypical facial pain can be of varying durations and can occur in varying locations. Common oral manifestations of pain disorder include atypical facial pain and oral dysesthesia [64]. The pain may be described as burning or tingling, sharp, dull, or as a sensation of pressure or crushing [65]. Other conditions that can cause an oral burning sensation (e.g., vitamin B12 deficiency, erythematous candidiasis) should be ruled out before a somatic disorder is considered.

It is important not to equate the absence of obvious oral or odontogenic pathology with a somatic disorder. Likewise, providing dental treatment and/or analgesic prescriptions is not recommended without knowledge of the underlying cause of pain. When there is no apparent etiology for expressed pain, referral to another healthcare professional (e.g., an oral surgeon, primary care physician, neurologist) should be given to determine if the pain has an etiology beyond the oral and maxillofacial complex.

Hypochondriasis is a somatic disorder in which the patient is convinced that his/her physical symptoms are indicative of a life-threatening medical condition. Hypochondriasis affects 1% to 8% of the population, and its diagnosis is made if the patient maintains a nondelusional preoccupation with the symptoms for at least six months [63]. In the dental setting, a patient who has pain in the oral-pharyngeal area may be convinced the pain originates from malignancy.

If a thorough clinical and radiographic exam detects pathology (e.g., caries, periodontal disease, oral lesions, endodontic pathology), these issues should be treated first. If a patient's symptoms persist upon the successful resolution of these problems and in the absence of any other evident pathology, the patient should be referred to a specialist. Patients with hypochondriasis may not be reassured even if clinical examinations and tests do not reveal any further pathology.

Opioids have been the mainstay of pain treatment for thousands of years, exerting their effects by mimicking naturally occurring endogenous opioid peptides or endorphins [67]. Although many new opioids have been developed with pharmacologic properties similar to morphine, morphine remains the standard against which new analgesics are measured [67].

Endogenous Opioid Peptides

The endogenous opioid system is complex and subtle, with diverse functions. The system plays a sensory role, which is prominent in inhibiting response to painful stimuli; a modulatory role in gastrointestinal, endocrine, and autonomic functions; an emotional role evidenced by the powerful rewarding and addicting properties of opioids; and a cognitive role involving modulation of learning and memory [67].

There are three distinct families of classical opioid peptides: enkephalins, endorphins, and dynorphins. Each of these families is derived from a distinct precursor protein and has a characteristic anatomical distribution. The precursor proteins, preproenkephalin, pro-opiomelanocortin (POMC), and preprodynorphin are encoded by three corresponding genes. The primary opioid peptide derived from POMC is beta-endorphin. The POMC precursor is also processed into the non-opioid peptides adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone (alpha-MSH), and beta-lipotropin (beta-LPH), suggesting a common precursor for the stress hormone ACTH and the opioid peptide beta-endorphin. This association indicates a shared physiologic linkage between the stress axis and opioid systems, which has been validated by the observation of stress-induced analgesia [67].

Opioid Receptors

Opioids produce their effects through activity at three major receptor subtypes: mu, kappa, and delta. These G-protein-coupled receptors are linked to adenylate cyclase. The endogenous ligands for these receptors, beta-endorphin, enkephalin, and dynorphin, are expressed heterogeneously throughout the central and peripheral nervous systems, with a distribution pattern parallel with that of opioid receptors. Opioid receptors are also found in the central respiratory centers. Functional studies have revealed substantial parallels between mu and delta receptors and dramatic contrasts between mu/delta and kappa receptors [71].

Most opioid therapeutics, and all opioids with abuse potential, are selective for mu receptors, reflecting their similarity to morphine. However, drugs that are relatively selective at standard doses can interact with additional receptor subtypes at higher doses, resulting in divergent pharmacologic profiles [67]. A large number of endogenous ligands activate a small number of opioid receptors, a pattern strikingly different from most other neurotransmitter systems, in which a single ligand interacts with a large number of receptors that have different structures and second messengers [67].

Absorption, Distribution, Metabolism, and Elimination

Typically, opioids are readily absorbed from the gastrointestinal tract. The more lipophilic opioids are easily absorbed through the nasal or buccal mucosa. The most lipophilic opioids can be absorbed transdermally [67]. Most opioids, including morphine, undergo variable but significant hepatic first-pass metabolism, limiting oral bioavailability relative to parenteral administration. Most opioids act quickly when given intravenously. Compared with more lipid-soluble opioids, such as codeine, heroin, and methadone, morphine crosses the blood-brain barrier at a considerably lower rate [67].

Persons at heightened risk for opioid misuse or dependence include those who have a current or past history of substance misuse/abuse, individuals with untreated psychiatric disorders, and those with social or family environments that facilitate or encourage misuse [72]. It is estimated that approximately 6.7 to 7.6 million adolescents and adults in the United States are living with opioid use disorder at any given time [73].

The expected drug effect and the setting of use (context of administration) play important roles in the social learning of drug use. Because opioids, like other drugs that increase dopamine turnover, lead to conditional responses, the use of opioids may become conditioned to the activities of daily living. As a result, environmental stimuli become powerfully associated with opioid use, which can trigger cravings for the drug. The visibility of pharmaceutical marketing and advertising of medications may also play a role by changing the attitudes towards ingestion of these agents.

For youth, a social learning aspect to drug use is likely, based on the modeling of drug use by adults in their families and social networks [72]. Studies have found that 15% of high school students reported having ever used select illicit or injection drugs (i.e., cocaine, inhalants, heroin, methamphetamines, hallucinogens, or ecstasy); in addition, 14% of students reported misusing prescription opioids [74]. Individuals who use nonmedical prescription opioids before 13 years of age are more likely to become addicts than those who initiated use at 21 years of age or older. The odds of becoming an addict are reduced 5% each year after 13 years of age [75]. Additionally, it is a commonly held view among adolescents (27%) that prescription drugs are "much safer" than street drugs [76]. This belief is undoubtedly shared with much of the adult population and has led to the extraordinary rise in recreational prescription drug users.

Responsible prescribing of opioids is an essential measure to avoid contributing to and escalating the opioid crisis in the United States. Opioid analgesics are generally not used as first-line analgesic therapy; non-drug and non-opioid drug alternatives should be considered first. Opioids may be initiated when benefits are likely to outweigh risks, when other approaches to analgesia are ineffective or unlikely to be effective, and with a treatment plan designed to mitigate the risks of addiction, toxicity, and other adverse effects.

Dental pain after oral or periodontal surgery is caused by the release of prostaglandins from injured tissues. This type of pain is generally best managed by nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin formation. NSAIDs act locally while opioids act centrally, which results in greater and more dangerous side effects. Several controlled studies have concluded that NSAIDs, with or without adjunctive acetaminophen, provide equivalent or superior dental pain relief when compared to opioids [77]. The recommended dose of ibuprofen for mild post-procedural dental pain is 200–400 mg every four to six hours; alternatively, 400–600 mg ibuprofen combined with 500 mg acetaminophen every six hours may be used. If severe pain develops and an opioid analgesic is indicated, it is vital to start with the lowest possible dose for three days, after which the patient can be switched to ibuprofen with or without acetaminophen [78]. The American Dental Association supports statutory limits on the dosage and duration of opioid analgesics of no more than seven days for the treatment of acute dental pain [79]. Dental clinicians can also use techniques, including atraumatic surgical technique and long-lasting local anesthetics (e.g. bupivacaine), to minimize postprocedural pain and the need for analgesia.

If an opioid use disorder is disclosed or suspected, steps should be taken to increase patient safety and minimize the risk of misuse and dependence. In patients with opioid use disorder, nitrous oxide inhalation analgesia should be avoided, as it creates a similar pleasurable effect to opioids and can increase cravings. Benzodiazepines have become a popular adjunct medication to reduce dental-related anxiety ("sleep dentistry"), but coingestion of opioids and this class of medications elevates the risk of pronounced respiratory depression and fatality [80].

Patients with opioid use disorder are more prone to the development of xerostomia, caries, periodontal disease, and oral infections [61]. As discussed, the decreased flow and volume of saliva associated with xerostomia reduces the self-cleaning action of the teeth, increasing the risk of dental caries and periodontal disease.

Although the patient's medical history is reviewed prior to any dental treatment, he or she may not disclose current or historical opioid misuse or addiction. If a patient has a suspected opioid use disorder, the clinician should initiate an open, judgement-free discussion that focuses on the long-term well-being of the patient. Through responsible prescribing practices and patient referral, if appropriate, dental clinicians can help address the opioid crisis and provide the best level of patient care.

If a dental patient is known to be on long-term benzodiazepine therapy, consultation with the individual's physician or psychiatrist may be required to ensure that the medication can be safely continued or halted. As discussed, opioid analgesics should be avoided if possible in these patients. Similarly, nitrous oxide inhalation sedation can enhance the CNS depressant effects of benzodiazepines and should be avoided.

Withdrawal from benzodiazepines must be done under medical supervision and usually features a gradually decreasing dose. The expected severity of withdrawal from benzodiazepines can be assessed using the Clinical Institute Withdrawal Assessment—Benzodiazepines (CIWA-B) tool, which consists of 22 items. Higher scores indicate increasing difficulty and morbidity with the withdrawal symptoms [85].

Although there are no oral lesions specific to benzodiazepine use, xerostomia is a potential adverse oral effect. Personalized oral hygiene instructions and a more frequent recall schedule can promote optimal oral health for patients who experience this adverse effect. Consultation with the patient's physician should be sought if there is any concern about the patient's ability to withstand dental treatment.

Alcohol consumption can affect a variety of physiologic and psychologic processes, and persons who are currently inebriated should have dental treatment deferred. Although alcohol use disorder is not associated with any specific oral lesions, there are several areas of oral involvement that may be associated with excessive and/or long-term alcohol consumption. Excessive drinking may interfere with the absorption, digestion, metabolism, and utilization of nutrients, particularly vitamins. Individuals with alcohol use disorder often use alcohol as a source of calories to the exclusion of other food sources, which may also lead to a nutrient deficiency and malnutrition. In the late stage of the disease, patients may develop anorexia or severe loss of appetite, and refuse to eat. Persons with alcohol use disorder account for a significant proportion of patients hospitalized for malnutrition [89].

Direct toxic effects of alcohol on the small bowel causes a decrease in the absorption of water-soluble vitamins (e.g., thiamine, folate, B6). Studies have suggested that alcoholism is the most common cause of vitamin and trace-element deficiency in adults in the United States. Alcohol's effects are dose dependent and the result of malnutrition, malabsorption, and ethanol toxicity [90]. Vitamins A, C, D, E, K, and the B vitamins are deficient in some individuals with alcohol use disorder. All of these vitamins are involved in wound healing and cell maintenance. Because vitamin K is necessary for blood clotting, deficiencies can cause delayed clotting and result in excess bleeding. Vitamin A deficiency can be associated with night blindness, and vitamin D deficiency is associated with softening of the bones. Deficiencies of other vitamins involved in brain function can cause severe neurologic damage (e.g., deficiencies of folic acid, pyridoxine, thiamine, iron, zinc). Thiamine deficiency from chronic heavy alcohol consumption can lead to devastating neurologic complications, including Wernicke-Korsakoff syndrome, cerebellar degeneration, dementia, and peripheral neuropathy [91].

Alcohol abuse is a major risk factor for many infectious diseases. While respiratory infections are the most common, opportunistic oral infections may also occur, including candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, and recurrent herpes labialis. Odontogenic infections of pulpal and/or periodontal origin are more virulent in persons with compromised immune systems and can have an aggressive extension into deeper fascial and muscle layers, with the potential for serious morbidity. Infections of rapid onset and regional dissemination require intravenous antibiotics and may require hospital admission. Dental clinicians who observe these opportunistic oral infections should discuss the finding with the patient.

Chronic alcohol abuse can also have an adverse effect on the salivary glands. In some cases, this manifests as bilateral enlargement of the parotid glands, known as sialosis. Sialosis is the result of peripheral neuropathy induced by chronic exposure to ethanol and reduced salivary flow [61].

A decrease in the buffering ability of the saliva results in a more acidic environment and proliferation of caries and Candida albicans. Prescription-strength fluoride toothpaste or gels can help reduce this risk.

The teeth of an individual with alcohol use disorder may be eroded due to the repetitive chemical (acidic) exposure to alcoholic drinks or vomit, resulting in perimolysis. The process of dental erosion can affect any tooth but the palatal surfaces of the maxillary teeth are most frequently affected. The classic presentation of an eroded tooth surface is smooth and shiny surface dentin. This exposed dentin can be sensitive to thermal changes and sweets. Erosive wear can undermine dental restorations and lead to a progressive loss of the vertical dimension of occlusion. Teeth with extensive loss of enamel can be difficult to restore.

The long-term abuse of alcohol has been shown to cause bone marrow suppression [93]. This can lead to a diminished number of neutrophils, which have a critical role in phagocytize bacteria associated with periodontal disease. This deficiency can predispose individuals with alcohol use disorder to opportunistic infections and more severe periodontal disease.

A deficiency in the quantity or the quality of platelets can impair the ability to obtain hemostasis after oral surgery, periodontal surgery, or root planing and curettage. Conducting a complete blood count (CBC) with differential can determine if platelet levels are sufficient to obtain hemostasis. However, these tests are not easily accessible for many dental practices. Patients should be asked if they bruise easily, if they experience problems with postprocedural bleeding after other invasive procedures, if they have a history of spontaneous nose bleeds, or if a small cut requires an extended time to coagulate. A positive response to any of these questions could indicate a problem with coagulation/healing and should prompt referral to a physician for further testing. Any invasive dental procedures should be deferred.

The liver is a particularly vulnerable organ to alcohol consumption, in large part because it is where alcohol is metabolized prior to elimination from the body. The most common manifestation among persons with alcohol use disorder is called "fatty liver." Among heavy drinkers, the incidence of fatty liver is almost universal. For some, a fatty liver may precede the onset of alcoholic cirrhosis.

The liver is the most critical organ for the metabolism of medications most commonly used in dental treatment, including analgesics, antibiotics, and local anesthetics. Amide-type local anesthetics (e.g., lidocaine, mepivacaine, prilocaine bupivacaine) are metabolized in the liver, and compromised hepatic function can cause plasma levels of local anesthetic to increase to toxic levels. As such, the lowest dose of local anesthetics should be used for these patients. Articaine is technically classified as an amide, but approximately 90% to 95% is metabolized by plasma esterases [13]. So, articaine is preferred for patients with compromised hepatic function, if appropriate.

Chronic heavy drinking appears to activate the enzyme CYP2E1, which may be responsible for transforming the over-the-counter pain reliever acetaminophen into toxic metabolites that can cause liver damage. Even when acetaminophen is taken in standard therapeutic doses, liver damage has been reported in this population [94]. A review of studies of liver damage resulting from acetaminophen-alcohol interaction reported that, in individuals with alcohol use disorder, these effects may occur with as little as 2.6 grams of acetaminophen (four to five "extra-strength" pills) taken over the course of the day by persons consuming varying amounts of alcohol [95]. The damage caused by alcohol-acetaminophen interaction is more likely to occur when acetaminophen is taken after, rather than before, the alcohol has been metabolized [94]. Moderate drinkers should also be made aware of this potential for interaction. There is now a warning label on the bottle that states, "If you consume three or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers." Further, in 2014, the FDA issued a statement that combination prescription pain relievers containing more than 325 mg acetaminophen per dosage unit should no longer be prescribed due to reported severe liver injury with acetaminophen in patients who took more than the prescribed dose in a 24-hour period; took more than one acetaminophen-containing product at the same time; or drank alcohol while taking acetaminophen products [96].

In addition to the many deleterious systemic effects of nicotine and smoking, tobacco can have serious adverse effects on oral health as well. Some are reversible and relatively mild, such as teeth staining, while others can result in serious morbidity and mortality, including oral and oropharyngeal squamous cell carcinoma.

The American Dental Association asserts potentially malignant disorders can be diagnosed clinically as leukoplakia, erythroplakia, erythroleukoplakia, or submucous fibrosis, and these lesions may occur among heavy tobacco and alcohol users.

(https://jada.ada.org/article/S0002-8177(17)30701-8/fulltext?dgcid=PromoSpots_EBDsite_Oralcancer Last Accessed: February 19, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

Tobacco residue leaves a sticky film on the teeth, which causes staining but also can retain bacterial plaque and increase the risk of caries and periodontal disease. Composite restorations can also be stained by tobacco, especially if there are surface porosities and/or irregularities. Depending on the depth and extent of staining, it may be necessary to replace restorations. Smokers should be advised to adhere to strict oral hygiene practices and recall schedule.

The soft tissues of the oral cavity and throat are also affected by prolonged exposure to tobacco via smoking or chewing. Some of the most common adverse effects associated with tobacco use are gingival recession, mucosal lesions (e.g., leukoplakia), delayed healing of surgical sites, and discoloration of the dorsum of the tongue [15]. Nicotine stomatitis (a widespread palatal keratosis) is most common among heavy pipe and cigar smokers and is a chronic inflammatory response of the palatal minor salivary glands.

Of course, the most dire oral consequence of tobacco use is oral cavity squamous cell carcinoma (OCSCC). Each year, there are more than 58,450 new cases and 12,230 deaths from OCSCC or related complications [18]. Many cases of OCSCC are diagnosed at advanced stages with significant local and regional metastases, and the related surgical resection and radiation therapy necessary for advanced-stage OCSCC are associated with a high degree of morbidity and mortality. Tobacco use is the most commonly identified risk factor for the development of OCSCC, and tobacco users have a 5- to 25-fold higher risk of the development of these malignancies compared with nonusers [19]. While both smoking and chewing tobacco increase the risk for oral malignancy, the sustained direct exposure seen with smokeless tobacco use is a greater risk. This risk is increased with concurrent alcohol consumption, as alcohol desiccates the mucosal surface and allows the carcinogens in tobacco to have an extended contact time with the tissues.

Early identification of the lesions of OCSCC is essential. Dental clinicians should provide thorough oral cancer screenings on all of their patients, and lesions that have not healed within two weeks after discovery or those that are highly suspicious should be biopsied. Unfortunately, the lesions of OCSCC can present in a variety of ways—there is no characteristic or diagnostic lesion. Leukoplakic (white) lesions are more common than the erythroplakic (red) lesions, but the latter has a much higher potential for malignant transformation.

Other possible adverse oral effects of smokeless tobacco use include gingival recession, halitosis, enamel erosion, damage to the alveolar bone, and periodontal disease. There is also an increased risk for coronal and root surface dental caries, because sugar is added to smokeless tobacco products [20].

Given the extensive potentially detrimental effects of tobacco use, all healthcare professionals, including dental professionals, should counsel their patients to stop tobacco use. U.S. Public Health Service guidelines recommend that all patients be asked [20]:

If a patient wants to quit, draw upon the same armament of strategies used to help motivate other health behavior change, such as brushing, flossing, and attending recall appointments. In addition, tobacco cessation programs and pharmacologic agents are often effective. For patients who are not ready to quit, employ the strategies for people in the precontemplative stage of change—remain nonjudgmental and find neutral ways to raise awareness of the problem.

Nicotine replacement therapy is effective in helping people stop tobacco use. This includes patches, gum, lozenges, inhalers, and nasal spray. Bupropion was the first non-nicotine pharmacotherapy for the treatment of tobacco dependence with proven efficacy [21]. Cessation rates have been reported to improve when drug therapy combines nicotine replacement with the antidepressant bupropion [32,35]. However, in its 2020 guideline for initiating pharmacologic treatment of tobacco-dependent adults, the American Thoracic Society (ATS) recommends varenicline over both bupropion and a nicotine patch for tobacco-dependent adults. In adults who are not ready to discontinue tobacco use, the ATS recommends beginning treatment with varenicline rather than waiting until patients are ready to stop tobacco use [21]. It is important to note that these medications have been associated with adverse effects, including an increased risk for depression and suicide [13].

Not surprisingly, tobacco cessation has high rates of relapse, and most people require multiple quit attempts to remain permanently tobacco-free. After 12 weeks of abstinence, about 43% of people return to regular use. However, longer periods of abstinence increase long-term success rates. After five years of abstinence, relapse rates drop to about 7% [43]. This presents an opportunity to help patients understand that tobacco cessation is a long-term process and previous attempts provide learning opportunities for the next attempt.