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To safely and effectively treat patients with schizophrenia, clinicians first need to understand the nature and biology of the condition. The central nervous system is comprised of the brain and spinal cord and is the core structure involved in facilitating behavior. Schizophrenia is a psychiatric disorder characterized by psychosis leading to hallucinations and delusions. The major signs and symptoms of schizophrenia are listed in Table 1.1 Positive symptoms are due to characteristics of the disease itself, while negative symptoms refer to traits that are lacking or diminished in the person. Hallucinations and delusions are the hallmark symptoms of schizophrenia. Hallucinations are typically either visual or auditory disturbances (ie, false sensory perceptions); delusions are false beliefs (eg, someone is going to hurt them).
In the United States, 26.2% of the adult population experiences signs and symptoms of a recognized mental disorder each year, and serious mental illness is the leading cause of disability.1 An estimated 1.1% of the population has schizophrenia.2 Onset typically occurs during adolescence or young adulthood, roughly in the late teenaged years to early twenties.2 The long-term prognosis of patients with schizophrenia is variable and depends on many factors, such as the severity of the disease, access to care, compliance with medication and treatment, side effects of treatment, negative social stigma, and financial burden.2,3 While approximately 50% of these patients will have moderate to severe symptoms long term, about 25% have the potential for a full remission, and another 25% have the potential for a functional recovery (experiencing only mild or residual symptoms) with the ability to achieve adequate occupational and social functioning.2 Remission and/or functional recovery are important not only for those diagnosed with the illness, but also their families and healthcare professionals, including dentists.
Schizophrenia places a burden on families, healthcare systems, and society. The overall cost in Canada, for example, is an estimated CAN$6.9 billion, based on direct healthcare costs as well as indirect costs associated with unemployment and homelessness rates.4 However, the use of antipsychotic drugs has reduced the number of people needing to be housed in institutions.5
While there are many different theories about what causes schizophrenia, no single issue can be attributed to the diagnosis. Although the true cause is unknown, it is related to both a person's genes and his or her environmental experiences.2 Biologically speaking, schizophrenic patients have larger lateral brain ventricles and larger volumes of cerebral spinal fluid and are deficient in white and grey matter volumes.3 Genetic studies show that if one parent has schizophrenia there is a 13% chance of the offspring developing the disease.2 However, 89% of patients diagnosed with schizophrenia do not have a parent with the disease.2 If an identical twin has schizophrenia there is a 46% chance of the other twin developing it, but if a fraternal twin has the disease, the other twin has only a 14% chance of developing it.2
There are also several neurotransmitter theories, including dopamine, serotonin, and glutamate. The dopamine hypothesis states that some forms of schizophrenia may be associated with an increase in dopamine, increased post-synaptic response to dopamine, and/or prolonged activation of dopamine receptors.6 Drugs that act to increase dopamine release (eg, cocaine, amphetamines) or prevent its reuptake may cause schizophrenia-like symptoms. The typical antipsychotic drugs are based on this theory and work by blocking dopamine (D2) receptors.6 Drugs that are serotonin agonists, like lysergic acid diethylamide (LSD), can also cause hallucinations, which gives basis for the serotonin hypothesis.6 The atypical antipsychotics block the 5-HT2Aand 5-HT2C serotonin receptors.6 The glutamate hypothesis evolved based on evidence that drugs (like phencyclidine [PCP] or ketamine) that stimulate the N-methyl-D-aspartate (NMDA) receptor exacerbate cognitive impairment and psychosis in schizophrenic patients.6 Cannabis use has also been questioned as a possible cause, as it appears to be associated with a twofold risk of developing schizophrenia or schizophreniform disorders in susceptible people.7 Catechol-O-methyltransferase (COMT) gene may be associated with cannabis use in adolescence and the risk of developing psychosis later. Mutations in this gene cause a slower degradation of dopamine within the synapse.8
The goals of treating and managing schizophrenia are to reduce and eliminate the positive symptoms (hallucinations and delusions), prevent relapse of symptoms, reduce the risk of self-harm, and help these patients function within society. Use of medications is the predominant choice to treat acute psychotic episodes and also prevent relapse and future episodes.1 Treating the positive symptoms with medication is easier to do and offers better results than treating the negative symptoms in this manner.1 Other psychosocial treatments are also useful in educating these patients about their disease, providing support, and helping them to develop social skills they may lack.2
The drugs usually take a few weeks to become effective, however side effects may start immediately.2 This can lead to major compliance issues for these patients, because the side effects of the drugs typically outweigh the benefits. The side effects and adverse reactions are mainly related to the binding and blocking of other receptors such as alpha-adrenoreceptors, muscarinic receptors, and H1-histaminic receptors.6 Compliance also may become an issue when patients have been taking their medication for a long time and think they have been "cured." Patients may go off the medication at their own discretion and not their doctor's. Relapse within the first 5 years following a first psychotic episode are as high as 82%.3 Patients with other mood disorders such as depression are also more likely to be non-adherent with their medication.9 Schizophrenia can be very debilitating and, therefore, requires compliance not only with medication, but with psychological management through counseling as well.
The consequences of no treatment may be depression, homelessness, and suicide. Untreated psychosis is toxic to the brain causing structural changes and damaging neuronal connectivity.10 This can make future treatment more resistant.
Drugs used to treat schizophrenia are categorized into first-generation (typical) and second-generation (atypical) antipsychotics. Both work by blocking the dopamine D2 receptor to some extent, but the newer atypical antipsychotics have a strong affinity for the serotonin 5-HT2A receptor and only a weak affinity for D2.1 The more common antipsychotic drugs include chlorpromazine (eg, Thorazine®) and haloperidol (eg, Haldol®), which have a high affinity for post-synaptic dopamine D2 receptors, blocking its effects.6 The second-generation anti-psychotics commonly include aripiprazole (eg, Abilify®), clozapine (eg, Clozaril®), olanzapine (eg, Zyprexa®), and risperidone (eg, Risperdal®); these drugs have a weak affinity for D2 and a strong affinity for 5-HT2Areceptors. As a result, there are fewer motor deficits experienced with second-generation antipsychotics and they are more efficient at treating negative symptoms compared to the typical antipsychotics.2 All antipsychotics are highly lipid-soluble and protein-bound, and have large volumes of distribution and a long clinical duration.6 They are metabolized in the liver by P450 enzymes; of special relevance are CYP2D6 and CYP3A4.6
For 70% of patients, there is equal efficacy between typical and atypical antipsychotic drugs.6 However, atypical ones may be preferred because they yield fewer extrapyramidal motor symptoms, have less risk of tardive dyskinesia, are more effective at treating negative symptoms, and offer less risk of hyperprolactinemia. A summary of antipsychotic drugs is provided in Table 2.1,6
Effects on Oral Health
Antipsychotic drugs may cause agranulocytosis, leukopenia, or thrombocytopenia.2 Clozapine, in particular, carries a 3% and 0.8% risk of developing neutropenia or agranulocytosis, respectively.11 This condition may cause the patient to have more frequent infections, chronic infections, fever, or sores present in the mouth. Dentists should be aware of these possible complications and refer to the patient's physician upon any suspicion.
Other common side effects of antipsychotic drugs include spasms of lips, tongue, and facial muscles, as well as dysphasia.2 Patients with psychiatric conditions, including schizophrenia, may engage in self-harming behaviors such as tongue, lip, and/or cheek biting, burning of oral tissues, or other mucosal injuries.2 These lesions should be noted and monitored.
Schizophrenic patients may also lose all motivation for oral hygiene and thus have a poor oral health status. Drugs used to treat schizophrenia may cause xerostomia,6 and therefore these patients are at risk of developing associated dental diseases such as caries and fungal infections.
Establishing a good patient-practitioner relationship is key to treating patients with any psychological disorder. Many people may believe there is a negative stigma associated with a diagnosis of schizophrenia, and therefore patients may be reluctant to disclose this information to dentists. The dentist should have knowledge of the patient's current diagnosis, the treatment or medications the patient is receiving, and the stability and effectiveness of said treatment(s). By being aware of the various signs and symptoms associated with schizophrenia, the dentist may be better able to determine if the patient is being managed effectively, is compliant with his or her medication, and if further referral to the patient's physician is necessary.
Pharmacotherapy is a major contributor to xerostomia, and antipsychotic drugs are no exception.12 Dentists need to be aware of this adverse effect and manage it carefully. Ensuring adequate oral hygiene for caries control is crucial. Encouraging patients to manage their xerostomia with frequent sips of water or eating ice chips may provide relief. Patients might also consider chewing xylitol-containing candies or gum to increase salivary flow and reap an anticariogenic effect. Dentists may consider prescribing a sialagogue if local measures fail. Pilocarpine (3 mg to 5 mg three times per day) or cevimeline (30 mg three times per day) are examples of medications that may be used for systemic control of xerostomia.12
As mentioned earlier, antipsychotic drugs are metabolized by the P450 enzymes; of relevance to oral health are CYP2D6 and CYP3A4. As such, drug-drug interactions should be considered when prescribing certain medications to patients with schizophrenia (Table 3).2,6
The typical antipsychotic drugs have a high affinity for post-synaptic dopamine D2 receptors, and this may cause pseudoparkinsonism and impaired control of movement, which is a significant drawback of this class of drug. Another shortcoming of these drugs is an increased risk of the patient developing tardive dyskinesia. This is characterized by involuntary, persistent movement of the lips, jaws, face, and extremities and is caused by prolonged use of these antipsychotics over several years.1,2 It is estimated that 20% to 40% of people using this type of antipsychotic drug will develop this condition, with a higher incidence in older adults, in whom this occurs much quicker than in younger adults.6 There is no treatment or cure for tardive dyskinesia. The first sign of this condition is often a fine tremor of the tongue, and if the medication is stopped before other symptoms occur, then the full range of tardive dyskinesia may be arrested.1 Therefore, it is crucial that dentists are aware of this side effect, as they often are the first healthcare providers to see this symptom. Referral can then be made to the patient's physician to switch medications and possibly stop the progression to full-blown tardive dyskinesia. Any involuntary jaw movements the patient may have can also adversely affect at-home oral hygiene practices and could predispose the patient to temporomandibular joint disorders.
Dopamine receptor blockade may also cause an increased risk of developing hyperprolactinemia, leading to infertility, impotence, galactorrhea, and/or amenorrhea.6 Neuroleptic malignant syndrome (NMS) is also a rare side effect but may become lethal. It is caused by excessive blockade of post-synaptic D2 receptors in people who are sensitive to these effects.2,6 Symptoms include muscle rigidity, fluctuating consciousness, hyperthermia, tachycardia, sweating, pallor, and hypo- or hypertension.2 Treatment involves anti-Parkinson's drugs to increase dopamine and muscle relaxants, such as diazepam.6 There is a higher risk of developing NMS associated with haloperidol compared to the other antipsychotics.13
The second-generation antipsychotics have a stronger affinity for serotonin 5-HT2A receptors than their first-generation counterparts. As a result, fewer motor deficits are experienced. Excess serotonin may contribute to hallucinations; therefore, blocking 5-HT2A can also be an effective treatment.5 Two drugs in particular, clozapine and olanzapine, are associated with increased blood glucose levels predisposing schizophrenia patients to developing type 2 diabetes; in general, patients on antipsychotics are 14% more likely to develop type 2 diabetes.14 Clozapine and olanzapine also have been associated with an elevation in blood cholesterol.14 In light of these findings, these patients should have regular glucose monitoring and be made aware of high cholesterol, as both of these consequences-type 2 diabetes and high cholesterol-are associated with greater health problems. Care also should be taken when prescribing medications to these patients, as much like antipsychotics, macrolide antibiotics and azole antifungals also may cause QT prolongation, which can lead to an increased risk of developing arrhythmias.6
Preventive dental care is extremely important in this population and is often difficult to accomplish if the patient is not well controlled. Adequate oral hygiene instructions, modeled demonstrations, and use of diagrams may aid in conveying proper brushing and flossing. For patients who lack motivation or are unable to perform proper oral hygiene measures themselves, a family member may be able to assist in performing these tasks. Alternatively, dentists may consider prescribing other aids such as chlorhexidine and/or fluoride rinses to help the patient with oral hygiene and reduce the risk of developing dental diseases. If dental treatment at recall appointments is too difficult or unsafe to perform due to tardive dyskinesia and its associated excessive movements, a mild sedative such as diazepam may be considered after consultation with the physician.2 However, extreme caution should be taken due to potentiation of sedative effects with the concurrent use of an antipsychotic drug, which may lead to excessive central nervous system depression, hypotension, and/or respiratory depression.2 In Table 4 the authors provide an overview of suggested dental management of patients with schizophrenia.
Schizophrenia is a neurodevelopmental disorder, meaning it has both structural and functional brain changes that can either occur while a person is a fetus or develop later in life, or both.6 The cause of this disorder is unknown but is related to both a person's genes and their environment. If left untreated, it is highly debilitating and toxic to the brain.
Schizophrenia is treated with anti-psychotic drugs that have various orofacial side effects, including xerostomia, dysphasia, and dysgeusia. These drugs may also cause more serious side effects, such as tardive dyskinesia and neuroleptic malignant syndrome. Antipsychotics have many drug interactions with medications commonly prescribed by dentists, including macrolide antibiotics, azole antifungals, and opioids, as well as interactions with epinephrine.
After treatment half of patients diagnosed with schizophrenia have either a full remission of symptoms or mild residual symptoms. Subsequently, dentists may be treating these patients in private dental practices and need to be cognizant of their proper management and how to best provide safe and effective dental care.
About the Authors
Fourth-year Dental Student, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
Aviv Ouanounou, DDS, MSc
Assistant Professor, Department of Clinical Sciences (Pharmacology and Preventive Dentistry), Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Private Practice, Toronto, Ontario, Canada
Queries to the author regarding this course may be submitted to firstname.lastname@example.org.
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