Medical management, orofacial findings, and dental care for the client with major depressive disorder

Abstract

Depression is a common mental illness affecting millions worldwide. It is characterised by several symptoms including persistent sadness, constant irritability, and the loss of interest in pleasurable activities. The medical management of depression includes psychotherapy and pharmacotherapy. Depression is associated with numerous oral findings such as diminished salivary flow, rampant dental decay, advanced periodontal disease, and oral dysesthesias. Many of the oral findings in clients with depression can be due to the disease itself or to the treatment used for the condition; it can be difficult to determine which came first. Dental practitioners need to be aware of these orofacial findings and to treat and manage these clients appropriately. This short communication reviews the pharmacotherapy of depression and the effects of the drugs commonly used. Necessary dental treatment modifications for clients with depression are discussed.

WHY THIS ARTICLE IS IMPORTANT TO DENTAL HYGIENISTS .

• Clients presenting for oral care may be taking medication to manage depressive disorders.

• Awareness of these medications and their side effects is essential in order to provide safe and appropriate clinical therapy.

• For clients on tricyclic antidepressants, local anesthesia with epinephrine or levonordefrin must be administered carefully, with regular monitoring of blood pressure and heart rate, to prevent potential complications.

INTRODUCTION AND EPIDEMIOLOGY

Depressive disorders are among the most common neuropsychiatric disorders across all ages. They have been associated with a substantial loss of quality of life and disability, not only for the individuals living with the disorder, but also for their family members who care for them. Moreover, depressive disorders are associated with significant economic and social burdens,^{1, 2} and have been associated with significant mortality from suicide.^{3, 4} Ranked by the World Health Organization as the first most common cause of disability and premature death in the world, depressive disorders are widespread in the United States.^{5, 6} Up to 6.7% of adults in the US suffer from depression, with 30% having severe depression.⁵ In Canada, a national mental health survey conducted in 2012 found that 5.4% of the population aged 15 years and over reported symptoms of a mood disorder.⁷

Multiple risk factors are associated with the development of depression. These may include positive or negative events in one’s life, such as the death of a loved one, diagnosis of a terminal illness or loss of work, as well as other neurological disorders like multiple sclerosis, Parkinson’s disease, stroke or head trauma.^5,8,9 Moreover, certain medications used alone or in combination can cause side effects much like the symptoms of depression.

The use of alcohol or other drugs can also lead to or worsen depression. Depression can, however, occur for no apparent reason. The symptoms of depression generally include depressed mood, persistent sadness, irritability, feeling of helplessness and guilt, fatigue or decreased energy, sleep difficulties (undersleeping or oversleeping), anxiety, poor concentration, poor memory, weight changes, thoughts of suicide and death or attempt suicide, and the loss of interest in people or activities (Table 1). This short communication reviews the pathophysiology of depression, as well as its medical management, oral manifestations, and the dental care for clients with depression.

PATHOPHYSIOLOGY OF DEPRESSION

While no single physiologic mechanism for mood disorders has been identified, considerable evidence suggests the involvement of several neurotransmitter systems. There are 2 main groups of neurotransmitters that contribute to depression: the monoamines (i.e., serotonin, dopamine, norepinephrine, and epinephrine) and the catecholamines (i.e., dopamine, norepinephrine, and epinephrine). Both monoamines and catecholamines are synthesized from tyrosine and phenylalanine, which are then converted to the aforementioned neurotransmitters. It has been postulated that depression decreases these neurotransmitters at the synaptic cleft between presynaptic neurons and postsynaptic neurons, thus reducing their ability to activate the postsynaptic receptors. This hypothesis, called the Amine Hypothesis, stems from studies in the early 1960s on the antihypertensive drug reserpine.^10,11 Reserpine induced depression in patients treated for hypertension as well as in normal subjects. Research demonstrated that the mechanism of action of reserpine was to inhibit the storage of serotonin and noradrenaline in the vesicles of presynaptic nerve endings and it was then concluded that depression is associated with decreased amine neurotransmission.^10,11 In addition to the Amine Hypothesis, depression is thought to be related to neuroendocrine abnormalities. Specifically, abnormalities in the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes have been identified. It has been suggested that the hyperactivity of the HPA axis alters levels of numerous endocrine gland hormones, leading to an increase in cortisol levels, which in turn produces depression symptoms.⁵

MEDICAL MANAGEMENT OF MAJOR DEPRESSION

The management of major depression in North America usually consists of the pharmacological administration of antidepressants. Antidepressants are the third most commonly prescribed class of medications in the United States for outpatient office visits, following analgesics and lipid lowering agents.¹² However, psychotherapy has also been used extensively and can help many people with depression understand themselves and cope with their problems. For instance, interpersonal therapy works to change relationships that affect depression.¹³ Similarly, cognitive–behavioural therapy helps people change negative thinking and behaviour patterns.^14,15 With respect to the pharmacotherapy of depression, 5 major categories of drugs have been used for the management of depression: tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, serotonin–norepinephrine reuptake inhibitors, and atypical antidepressants (Table 2).

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) include many drugs such as amitriptyline (Elavil), imipramine (Tofranil), trimipramine (Surmontil), nortriptyline (Aventyle), protriptyline (Vivactil), and desipramine (Pertofrane). So named because of their chemical 3-ring structure, these drugs exert their effect by blocking the presynaptic reuptake transporter for norepinephrine (NE) and/or serotonin, thus preventing presynaptic neurons from reabsorbing these neurotransmitters from the synaptic cleft for recycling.^5,16 Thus, the concentration of these 2 neurotransmitters is increased and neuronal activity is elevated. These drugs are not considered first-line agents and are administered to individuals who are not tolerant of SSRIs and suffer from moderate to severe depression. In addition to their desired effect (the blockade of the presynaptic reuptake transporter for norepinephrine and/or serotonin), these drugs also block the postsynaptic receptors for histamine, acetylcholine, and norepinephrine resulting in adverse effects. For instance, the blockade of postsynaptic receptors for histamine results in sedation. The blockade of acetylcholine may cause side effects such as confusion, memory and cognitive impairments as well as dry mouth. Lastly and most importantly, blocking the postsynaptic receptors for norepinephrine may cause a rapid drop in blood pressure and the clinician should be aware of the possibility of orthostatic hypotension, especially when dismissing clients from the dental chair after they have been supine for a period of time. ,Many geriatric patients with pre-existing medical conditions cannot tolerate the adverse side effects associated with TCAs.^5,17,18 Furthermore, overdose of these medications may be lethal and, as such, individuals who are considered suicidal should not be prescribed these drugs.

Table 1.

Symptoms of depression⁵

Persistent sadness, anxious or empty moods	Restlessness, irritability
Loss of pleasure in usual activities	Sleep disturbances
Feelings of helplessness, worthlessness or guilt	Change in appetite or weight
Crying, hopelessness or persistent pessimism	Physical symptoms that defy diagnosis and do not respond to treatment (especially pain or gastrointestinal complaints)
Fatigue or decreased energy	Thoughts of suicide or death, or suicide attempts
Loss of concentration, memory or decision-making capability	Poor self-image or self-esteem

Table 2.

Drugs used for the treatment of depression

Classification	Examples	Mechanism of action	Common adverse effects
Tricyclic antidepressants	amitriptyline imipramine nortriptyline protriptyline desipramine	Block the presynaptic reuptake transporter for norepinephrine, serotonin, histamine, and/or acetylcholine	Sedation, confusion, memory and cognitive impairments, dry mouth, orthostatic hypotension, constipation, dizziness, tachycardia, urinary retention, impaired sexual function
Selective serotonin reuptake inhibitors	fluoxetine sertraline paroxetine fluvoxamine citalopram	Selectively inhibit 5-HT uptake	Nausea, vomiting, dry mouth, insomnia & drowsiness, sexual dysfunction, weight loss
Monoamine oxidase (MAO) inhibitors	phenelzine tranylcypromine selegiline	Inhibition of intracellular enzyme MAO in central nervous system neurons	Insomnia, dizziness, blurred vision, sexual dysfunction, hypertensive crisis
Atypical antidepressants	venlafaxine bupropion trazodone	Various, depending on antidepressant	Various, depending on antidepressant

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). These drugs are considered first-line treatment for individuals with mild to moderate depression.^15,19-21 These agents exert their antidepressant effect by preventing the reuptake of serotonin by presynaptic neurons in the synaptic cleft, resulting in increased concentration of serotonin and thus enhanced neuronal activity.^5,21 As opposed to the TCAs, these agents have no effect on NE uptake and have little affinity for muscarinic receptors, as well as many other neuroreceptors.¹⁵ This increased selectivity results in fewer adverse effects compared to TCAs. However, adverse effects remain, including nausea, vomiting, dry mouth, insomnia, drowsiness, sexual dysfunction, and weight loss.^22,23

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) include phenelzine (Nardil), tranylcypromine (Parnate) and selegiline (Eldepryl). Monoamine oxidase is an enzyme that is responsible for the degradation of catecholamines and serotonin; inhibition of this intracellular enzyme in the central nervous system will potentiate monoaminergic neurotransmission by augmenting NE, serotonin, and dopamine in nerve terminals.²³ These drugs are typically reserved for individuals who are unable to tolerate other antidepressants and are not considered a first-line treatment.²⁴ Adverse effects associated with the use of MAOIs may include dizziness, orthostatic hypotension, insomnia, central nervous system stimulation, weight gain, and edema.⁵

Serotonin–norepinephrine reuptake inhibitors

Serotonin–norepinephrine reuptake inhibitors (SNRIs) include venlafaxine (Effexor), desvenlafaxine (Pristiq), and duloxetine (Cymbalta). Venlafaxine is a drug used to treat depression and depression with anxiety, generalized anxiety disorders, social phobias, and neuropathic pain.^25,26 Its pharmacodynamics are similar to the TCAs and it has an improved profile of adverse reactions. Adverse effects may include nausea, vertigo (both frequent and may improve), hypertension, and manic reactions.^23,27 The SNRIs tend to be prescribed for individuals with major depressive disorder, as well as those with combined depression and anxiety disorders, and certain chronic pain conditions.

Atypical antidepressants

The atypical antidepressants are used to treat depression where comorbidity exists. Bupropion (Wellbutrin; Zyban), for example, is a noradrenaline and dopamine reuptake inhibitor (NDRI) commonly used for severe depression but is also used as a smoking cessation treatment.^28,29 Adverse reactions include insomnia, excitation, restlessness, and seizures. Another example is trazodone, a serotonin antagonist/reuptake inhibitor (SARI) that is used primarily to treat depression with significant anxiety and sleep disturbances. Side effects include severe sedation and moderate sexual dysfunction.

ORAL MANIFESTATIONS AND DENTAL MANAGEMENT

For the dental professional, orofacial manifestations of depression as well as the effects of the pharmacological management of depression warrant consideration. Dentally, clients with depression have higher incidences of tooth loss and non-use of oral health services, and may have poorer oral hygiene resulting in increased incidence of caries and periodontal diseases.^29,30 The combination of neglect and disinterest, in conjunction with adverse effects from their medications, may result in rampant caries. Those presenting to the practice may also have craniofacial pain conditions including atypical facial pain (“neuralgia”), burning sensation of the oral mucosa (often on the tongue) or some temporomandibular joint disorder. ,Whether the onset of these conditions resulted in depression or whether clients without depression more readily develop these conditions is unclear. It has been suggested that the pain may arise from stress-induced disruption of the HPA axis, a mechanism previously implicated as the cause of both depression and inflammatory joint disease.^5,31-34 Other oral findings include dysgeusia, stomatitis, and glossitis.

All the antidepressants discussed above have the potential to cause xerostomia. The majority of SSRIs, TCAs, and some atypical antidepressants have xerostomia listed as a side effect.^5,35-37 Xerostomia provides a breeding ground for oral biofilm, particularly when oral hygiene is neglected. Furthermore, long-term use of TCAs is associated with an increase in dental decay because these medications induce a craving for carbohydrates.³⁸ In addition, the long-term use of antidepressants has been linked with the development of diabetes mellitus, which has been shown to be a risk factor for periodontal disease.³⁹

The effective management of a client with depression begins with a thorough medical history to ascertain the presence of depression, whether the depression is being treated and managed, and what medications the client may be taking. ,Due to stigma, some clients may be reluctant to disclose their medical history of depression but may report the medications they are taking; the prudent dental professional should be able to recognize which medications are commonly associated with this condition. In reconciling the medication list, however, it is important to understand where a medication may be used for purposes other than the management of depression. Bupropion, as previously mentioned, may be used for smoking cessation; venlafaxine is often used for the management of post-herpetic neuralgia. An open discussion with the client to understand the indication for the medication is critical. One should not assume that an antidepressant is only being used to treat depression. When there is doubt, contact should be made with the client’s family physician or psychiatrist.

A preventive approach should be taken with these clients, given their propensity for oral diseases. Involving the family whenever possible is advisable as having a support network may improve oral health outcomes. Salivary substitutes or stimulants (e.g., pilocarpine) should be considered if xerostomia is noted.

Pharmacological agents employed by dentists to control disease, pain or anxiety (e.g., antibiotics, analgesics, and sedatives, respectively) must be carefully selected to avoid potential interactions with the medications being used to manage the depression. For example, SSRIs are known to inhibit cytochrome P450.⁴⁰ Codeine, an analgesic commonly used in dentistry, is a weak opioid that has no analgesic effect on its own but is converted to morphine by the liver enzyme CYP2D6. However, some people lack the ability to make this conversion because of low CYP2D6 enzyme levels. Moreover, the conversion can be inhibited by antidepressant medications such as the SSRIs (e.g., fluoxetine, paroxetine, and sertraline).^41,42 In addition, MAOIs can increase the potency of other narcotics and TCAs may potentiate other sedatives resulting in respiratory depression.⁵ In many cases, pharmacists can be of assistance in selecting medications that will produce the least interactions and should be consulted.

The administration of local anesthesia with epinephrine or levonordefrin to facilitate treatment must be done following common principles (minimum dosage, aspiration, etc.) to prevent potential complications. TCAs inhibit the reuptake of these vasoconstrictive agents and can result in increases in systolic blood pressure as well as cardiac dysrhythmias.¹² This appears to be more relevant for levonordefrin than epinephrine; thus, the dental practitioner should consider the use of epinephrine with careful aspiration to avoid introducing epinephrine intravascularly., It is therefore our recommendation that, for clients taking TCAs, the dose of epinephrine contained in anesthetics be limited to a maximum of 0.04 mg, which translates into 2 carpules of 1:100,000 epinephrine or 4 carpules of 1:200,000 epinephrine. Moreover, monitoring blood pressure and heart rate is advised when considering multiple administrations of epinephrine-containing local anesthetic. Finally, where possible, epinephrine-containing local anesthetics should be given slowly over time to help limit systemic absorption.¹² The usage of epinephrine- or levonordefrin-containing local anesthetics is of little concern with MAOIs.⁴³ In summary, the prudent clinician should consider monitoring blood pressure and heart rate when multiple administrations of epinephrine-containing local anesthetic are used.

CONCLUSION

Depression is a common medical condition and thus will be seen in many clients presenting for dental care. Since dental disease tends to be more prevalent in this population group compared to the wider client population, it is crucial that these clients be appropriately managed and provided with effective treatment.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.