Bipolar disorder, also known as manic depressive disorder, is a mood disorder that affects approximately 2.8% of the adult population, without a statistically significant difference of occurrence between men and women [3]. Bipolar disorder I features alternation of major depressive episodes with full manic episodes; bipolar disorder II is characterized by major depressive episodes and manic episodes that are less severe than those seen in bipolar I disorder [4]. A manic episode is defined in the revised fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) with the following criteria[5]:

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.

The DSM-5-TR diagnostic criteria for MDD also include several specifiers to further describe the nature of the current episode of MDD. These specifiers include [5]:

Anxious distress

Mixed features

Melancholic features

Atypical features

Mood-congruent psychotic features

Mood-incongruent psychotic features

Catatonic features

Peripartum onset

Seasonal pattern

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.

Generalized anxiety disorder is characterized by excessive and inappropriate worrying that is persistent and not restricted to particular circumstances. Patients have physical anxiety symptoms and key psychologic symptoms. Generalized anxiety disorder is often comorbid with major depressive disorder, panic disorder, phobia, health anxiety, and obsessive-compulsive disorder [31]. The diagnostic criteria for generalized anxiety disorder are [5]:

Excessive anxiety and worry (apprehensive expectation) over a number of everyday concerns (e.g., school/work performance)

Individual finds it difficult to control the worry

Excessive anxiety and worry are associated with three or more of the following six symptoms, with at least some occurring more days than not for at least six months:

Restlessness, feeling "on edge"

Easily fatigued

Difficulty concentrating

Irritability

Muscle tension

Sleep disturbance (difficulty falling or staying asleep, restless sleep)

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.

Specific, simple, or isolated phobia is the excessive or unreasonable fear of (and is restricted to) animals, objects, or specific situations (e.g., dentists, spiders, elevators, flying, seeing blood) [31]. Intense anxiety or unexpected panic responses in the presence of specific objects or situations can mark phobia onset but are not the sole causal route. Disgust, either alone or combined with fear, may trigger the onset and maintenance of animal (particularly spiders, snakes, and worms) or blood-injection-injury phobias. This is the most common type of anxiety disorder, with a lifetime prevalence of 15.6% and a past-year prevalence of 12.1% [36].

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].

Post-traumatic stress disorder (PTSD) is a severe, potentially chronic and disabling disorder that develops in some persons following exposure to a traumatic event involving actual or threatened death, serious injury, or sexual assault [49]. Some common symptoms include intrusive thoughts, nightmares and flashbacks of traumatic events, avoidance of trauma reminders, hypervigilance, and sleep disturbance. These symptoms can be highly distressing and substantially impair social, occupational, and interpersonal functioning. The intensely distressing and impairing symptoms of traumatic stress are highly prevalent immediately following traumatic exposure and dissipate over the following days and weeks in most people. Persistence beyond one month post-trauma suggests PTSD [49].

Dental clinicians should be aware of these potential adverse drug interactions and side effects of the medications used to treat PTSD when they perform dental procedures and prescribe medications adjunctive to dental treatment. Paroxetine is an SSRI that has been found effective in the short-term treatment of PTSD; however, it has been associated with xerostomia. Normal salivary flow resumes upon discontinuation. The concurrent use of paroxetine and NSAIDs (e.g., ibuprofen, naproxen) can decrease platelet aggregation, and should be avoided if possible. Opioid analgesics may potentiate the effect and toxicity of paroxetine, so their concurrent use should be minimized or avoided [13].

Positive symptoms include auditory (most common), olfactory, visual, or tactile hallucinations. Paranoid delusions, delusions of persecution, and grandiose delusions also occur. Thought disorders, characterized by a dysfunctional pattern of thinking, are another type of positive symptom. Finally, movement disorders commonly occur and tend to feature exaggerated and/or agitated body movements.

Negative symptoms are disruptions in normal emotions and behaviors. This may manifest in a variety of emotional issues and behaviors such as flat affect, anhedonia (i.e., a loss of pleasure in the activities of daily life), and difficulty initiating and sustaining activities. Less commonly, patients may display catatonia, with markedly depressed or absent movement and responses.

Cognitive symptoms tend to be more difficult to discern and include poor executive functioning (i.e., ability to understand information and use it to make decisions), difficulty concentrating, and memory issues [54]. A diagnosis of schizophrenia is made when a patient has two or more of the following symptoms for at least one month [5]:

Hallucinations

Catatonic movements

Delusions

Disorganized speech patterns

Flattened affect

Alogia (restricted amount and/or content of speech)

Disruptions in social or occupational abilities

A more pronounced adverse effect of typical antipsychotic medications is tardive dyskinesia— involuntary movements of the tongue, lips, facial muscles, limbs, and trunk of the body [57]. This adverse effect can take months or years to develop and although it occurs predominantly with the use of the typical antipsychotics, it can also occur with the use of atypical agents.

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.

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.

Substance use disorder (SUD) is considered a mental illness and can undermine individuals' physical, psychologic, social, and emotional health and safety. The DSM-5-TR identifies 10 classes of drugs that may be linked to an SUD: alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants, and nicotine (tobacco) [5]. Although they are outlined individually, individuals may have more than one SUD concurrently.

Tolerance refers to the diminishing effect of a substance over time. A patient has developed tolerance if it takes an increased dose of the drug to illicit the same effects. The term dependence has replaced the term "addiction" in some contexts. Substance dependence refers to both psychologic dependence (or addiction) and physical dependence. Physical dependence consists of neurobiologic adaptation (development of tolerance) from chronic exposure.

Morphine and most other opioid agonists share in common the following physiologic effects [67]:

Analgesia

Changes in mood and reward behavior

Disruption of neuroendocrine function

Alteration of respiration

Changes in gastrointestinal and cardiovascular function

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].

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.

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.

The ideal anxiolytic medication for dental appointments would provide adequate sedation with a short half-life. As such, triazolam is a better option, with a plasma half-life of two to three hours and rapid clearance that allows the patient to resume regular activities quickly [83]. Patients should be advised to refrain from alcohol while taking benzodiazepines because of the risk for CNS depression.

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.

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.

Patients are unlikely to volunteer use of cocaine during a dental appointment. However, if any common signs or symptoms of cocaine use or cocaine withdrawal are observed, clinicians should have an open, nonjudgmental discussion focusing on the patient's well-being. If appropriate, referral information should be provided.

In patients who may be taking cocaine, local anesthetics with a vasoconstrictor (e.g., 1:100,000 epinephrine) should be avoided. Concurrent use within 24 hours of last cocaine dose potentiates the stimulant effects and can lead to a hypertensive crisis, cerebrovascular accident (stroke), or myocardial infarction (heart attack) [61].

"Meth mouth" is widespread among certain populations of methamphetamine users, particularly those incarcerated for methamphetamine-related offenses. "Meth mouth" (dental deterioration) is a constellation of signs and symptoms associated with chronic use of methamphetamine and is caused by methamphetamine-induced vasoconstriction and reduced salivary flow, methamphetamine-induced vomiting, jaw clenching, the high intake of sugary beverages often seen with methamphetamine users, and abandonment of oral hygiene. This condition is characterized by widespread tooth decay and tooth loss, advanced tooth wear and fracture, and oral soft tissue inflammation and breakdown [117].