"Disorganized" symptoms are inferred from the patient’s speech, which commonly manifests in rapid shifts between topics that either have only a loose logical association or are completely unrelated. Separate ideas are combined incomprehensibly and new words are created, but little information is imparted. People with schizophrenia also may exhibit disorganized and bizarre behaviors and inappropriate affects. The bizarre behaviors range from imitating others’ speech (echolalia) or movements and gestures (echopraxia) to repeating the same bodily movements (stereotyped) for short or extended periods. Inappropriate affect often manifests as childish silliness and unpredictable agitation.^2,3

The disorganized symptoms of schizophrenia also are associated with a range of neurocognitive impairments. These impairments affect areas such as memory, attention and executive functions. People with schizophrenia often will complain that they have difficulty with tasks that require sustained attention. Others report that they have difficulty reading or understanding conversations. Severe impairment in these areas often is associated with poor outcomes in vocational and social adjustments.⁴

Accompanying these symptoms are less dramatic but equally debilitating negative symptoms that represent a loss of normal functions and persist over time. Severely decreased are emotional responsiveness (flat affect), talkativeness and speech content. Also noted is an inability to plan, initiate and persist in goal-directed activities—known as "avolition"—necessary for completion of activities of daily living, such as meal preparation, washing and bathing. Also common are social withdrawal and loss of ability to experience pleasure in previously enjoyed activities, a condition called "anhedonia."^5,6

The diagnosis of schizophrenia is based on contemporaneous observations of behavior, findings on a mental status examination and psychiatric history. Prior to the onset of florid disease, the person often is described as being passive, introverted, excessively shy, having few friends, rarely dating, avoiding team sports, being suspicious and having peculiar ideas and behaviors. On physical examination, these people may have neurological abnormalities such as tics, an elevated blinking rate, impaired fine motor skills, left/right confusion and poor coordination.

Substance abuse frequently accompanies schizophrenia. The prevalence rate of alcohol abuse among people with schizophrenia ranges from 3 percent to 63 percent.⁷ Also commonly abused are marijuana (by about 15 to 25 percent of patients with schizophrenia) and cocaine (by about 5 to 10 percent of patients with schizophrenia). Abuse of these substances strongly correlates with medical and psychosocial problems (such as inadequate diet and homelessness), poor compliance with medication regimens and multiple acute episodes of the disorder.⁸ More than three-fourths of all people with schizophrenia smoke, and this frequently is associated with emphysema, lung cancer, cardiac disease and oral cancer.⁹

	EPIDEMIOLOGY

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While only 1 percent to 1.5 percent of Americans have schizophrenia or will develop it at some point in their lives, people with the disorder occupy 9 percent of all hospital beds, 11 percent of nursing home beds and 40 percent of mental health facility beds. In 1990, the illness cost American society $65 billion: $17.3 billion in direct care (inpatient and outpatient care) costs and the balance in the lost productivity of the patients and of their family members who served as their caretakers.^10–12 Schizophrenia runs in families, and studies of twins and adopted children indicate that this is accounted for largely by genetic factors.^13,14 Non-genetic factors, such as birth in an urban area, birth during the winter, maternal obstetrical complications, influenza infection during the mother’s pregnancy and low social class increase the relative risk for the disorder, but the reasons for these contributing factors remain unclear.¹⁵ The disorder is equally prevalent in men and women but typically strikes men between the ages of 15 to 25 years and women between the ages of 25 to 35 years. The majority of people with the disorder do not marry or have children.¹⁶

The prognosis for patients with the disorder was guarded through the 1980s. Data indicated that approximately 70 percent of patients with schizophrenia continued to suffer substantial functional impairment after the first episode of illness, and 20 percent required extended or repeated hospitalization; almost 40 percent of patients with schizophrenia attempted suicide, with 10 to 15 percent being successful.^17,18 However, there is wide variation in outcomes; many patients have relatively normal social and vocational adjustments in the community. The recent introduction of a new group of medications that often are more effective in controlling the full range of symptoms—that is, positive, disorganized and negative symptoms—has raised the possibility that the prognosis for schizophrenia may soon improve.¹⁹

	ETIOLOGY

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The exact cause of schizophrenia is not yet known; however, there are strong indications that it results from abnormalities in brain development and maturation that adversely affect neural circuits and neurotransmitter systems. The delusions and hallucinations may result from excess dopamine activity in limbic areas of the brain. Decreased emotional responsiveness, paucity of speech content and a lack of goal-initiated behaviors may result from dopamine deficiency in pre-frontal areas. Aberrant levels of the neurotransmitter serotonin also have been implicated as a possible cause of both negative and positive symptoms. Structural imaging studies have shown that patients with schizophrenia have reduced whole-brain volume and specific reductions in cortical gray and white matter, frontal lobes, thalamus and limbic system structures (amygdala, hippocampus, parahippocampal gyrus).²⁰ Functional imaging studies such as regional cerebral blood flow and positron emission tomography have demonstrated that the prefrontal cortex suffers impaired blood flow, as well as inadequate oxygen use and glucose metabolism, when a patient with the disorder performs problem-solving tasks.^21,22

	PSYCHIATRIC TREATMENT

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Comprehensive care of the patient requires antipsychotic medication and psychosocial interventions such as family therapy and social skills training.

Medications. The choice of medication usually is based on its side-effect profile, its cost and the patient’s tolerance of and history of responsiveness to it.

Conventional antipsychotic medications. "Conventional" antipsychotic medications, initially derived from phenothiazines (such as chlorpromazine) and later somewhat structurally altered (such as butyrophenones), were introduced in the 1950s and still are commonly prescribed today.²³ These medications derive their antipsychotic properties by blocking dopamine D₂ receptors in the mesolimbic system of the brain, thereby affecting mood and the thought process. These medications are very effective in curtailing delusions, hallucinations, assaultive behavior and severe agitation. However, these agents have only limited effectiveness in treating the disorganized and negative symptoms.

The adverse side effects of these medications are significant, especially the development of movement disorders that mimic neurological diseases. These movement disorders frequently have an orofacial component and develop in a time-dependent fashion (Box). They arise because of the conventional medication’s blockade of basal ganglia dopamine D₂ receptors in the extrapyramidal system.²⁴

– Acute dystonia manifests itself as sustained muscle spasms of the back, neck, eyes, face and throat. It usually develops within the first three to five days of therapy and occurs in 2 percent to 10 percent of patients. The mandible may be locked in either the open position with the tongue protruded or in the closed position with the tongue retruded. Compromise of the airway can occur when this is accompanied by swelling of the tongue and laryngospasm. The muscle spasms are treated by the administration of anti-cholinergic medication or benzodiazepines; the laryngospasm is treated with intravenous or intramuscular administration of benztropine mesylate.

– Akathisia manifests as subjective inner feelings of restlessness, anxiety and the need to move (inability to sit still, pacing, crossing and uncrossing of legs, rocking back and forth). It usually develops within days to weeks after therapy has begun and occurs in 20 percent to 40 percent of patients. Treatment consists of lowering the dosage of antipsychotic medication; of administering a ß-blocker, an anticholinergic medication or a benzodiazepine; or both.

– Pseudoparkinsonism presents as a generalized slowing of voluntary movements and consists of a masklike face; drooling; soft and monotonous speech; tremor; and rigidity of the extremities, neck or trunk. It usually develops one to three months after therapy has begun and occurs in 10 percent to 40 percent of patients.²⁴ Treatment consists of lowering the dosage of the antipsychotic medication if feasible, and administering anticholinergic medication or the dopaminergic drug amantadine. To avoid the development of acute dystonias, akathisia and pseudoparkinsonism, some clinicians prophylactically administer anticholinergic medications (benztropine mesylate or trihexyphenidyl hydrochloride) when starting a patient on a regimen of potent conventional antipsychotic medication such as haloperidol or fluphenazine. However, anticholinergic medications can cause their own side effects, including impaired memory, dry mouth and constipation.

– Tardive dyskinesia, or TD, manifests as involuntary movements that are either slow and rhythmic or choreatic, as evidenced by lip smacking and tongue protrusion. It usually develops within seven years after therapy has begun and occurs in approximately 25 percent of patients.²⁴ There are no specific treatments for patients who have developed TD. However, there is evidence that newer or "atypical" antipsychotic drugs (described below) are associated with a lower risk of developing TD. The development of medication-induced movement disorders—particularly akathisia—is so unpleasant that approximately 40 percent of patients stop taking the drugs and experience a relapse of the disease symptoms.²⁵

Other major adverse side effects of these medications include electrocardiographic changes (that is, prolongation of QT and PR intervals, blunting of T waves and depression of the ST segment), orthostatic hypotension, obstructive jaundice, impotence, irregular menstrual cycles, and anti-cholinergic effects (constipation, dry mouth, nasal stuffiness, blurred vision, urinary hesitancy).^26,27

Atypical antipsychotic medications and associated adverse effects. The first "atypical" antipsychotic medication, clozapine was approved for use in the United States in 1989. The term "atypical" has been used to describe this class of medications because they rarely cause movement disorders. The most likely explanation is that all of these agents have a relatively high ratio of 5HT_2A, or serotonin, to D₂ activity. This property has led some authorities to refer to these drugs as "serotonin-dopamine antagonists," whereas the conventional agents are called "dopamine antagonists."

Clozapine, the first of the atypical agents, has been demonstrated as particularly effective in patients whose disease had been unresponsive to other medications.²⁸ Clozapine also is uniquely effective in reducing the cravings for alcohol and illicit drugs that often complicate the management of patients with both schizophrenia and a substance abuse disorder.²⁹ Less than one-half of 1 percent of patients treated with clozapine develop bone marrow suppression (independent of dosage and duration of therapy), which manifests as agranulocytosis or granulopenia.³⁰ However, this reaction, which on occasion has been fatal, may not be evident for 12 to 24 weeks and has led to the drugs’ being restricted to people with psychosis who have failed to respond to other agents.³⁰ Patients who receive clozapine are required to have white blood cell, or WBC, counts, obtained weekly for the first six months of therapy and, if the count is stable (> 3,000 per cubic millimeter), then every other week thereafter.³¹ Hypotension, sedation, constipation, seizures and tachycardia also may develop, but these adverse side effects tend to subside with continued drug use.

Since 1994, three other "atypical" antipsychotic medications (risperidone, olanzapine and quetiapine) have been approved for use in the United States. These medications are classified as first-line agents and can be used for initial therapy. The pharmacological mechanism of each is somewhat different, but they all may have greater effectiveness than the conventional agents in treating negative symptoms.^32,33 These medications also appear to improve neural function in the prefrontal cortex of the brain, thereby rectifying some of the disorganized symptoms and neurocognitive deficits and permitting acquisition of some psychosocial, vocational and problem-solving skills necessary for successful functioning in the community.^34,35 The use of these medications, however, is associated with minor degrees of sedation, cardiovascular effects, weight gain (possibly leading to type 2 diabetes mellitus), sexual dysfunction and anticholinergic effects.³⁶ However, none of these medications causes agranulocytosis. Furthermore, their milder benign side effects lead to improved compliance and a more favorable clinical course—improved quality of life, as well as a decreased likelihood of relapse and a consequent reduction in utilization of health services—than that seen with conventional medications.^37–39

Psychosocial interventions. A host of psychosocial interventions has been shown to enhance patients’ compliance with medication regimens, assist in their social reintegration and reduce their relapse rate.

– Individual supportive therapy enables the patient to develop a therapeutic relationship with a clinician who serves as an empathetic listener, offers practical advice about everyday problems and provides information about the illness and the need for adherence to medication regimens.

– Family therapy addresses the stresses that the patient and the family experience as a result of the illness. The therapist educates the family about the illness and its treatment and attempts to assist the family in decreasing behavior that is critical of the patient. This form of therapy has been shown to reduce the patient’s level of stress and enhance his or her coping capabilities, thereby decreasing the required dosage of medication and reducing the relapse rate.^40,41

– Social skills training also increases the patient’s self-confidence by providing him or her with the skills necessary for successful interpersonal interactions—such as how to express affection, how to deal with friction and how to groom oneself and care for one’s own physical needs. The acquisition of these skills reduces the patient’s stress, isolation and risk of relapse.^42,43

	OROFACIAL EFFECTS OF SCHIZOPHRENIA

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There are several aspects of schizophrenia and its treatment that can affect the patient’s orofacial complex.

Psychosocial factors. Patients with schizophrenia are likely to face a unique set of factors that lead to the development of advanced oral diseases. The disorder often is associated with a disinterest in performing appropriate preventive oral hygiene techniques.^44,45 Compounding the issue is access to care that is often limited because of these patients’ prolonged hospitalizations and impaired finances, as well as the paucity of clinicians who are knowledgeable and comfortable in caring for these people.

Adverse effects of antipsychotic medications. The low-potency conventional antipsychotic medications—particularly chlorpromazine and thioridazine—cause a profound hyposalivation by blocking (through anticholinergic action) parasympathetic stimulation of the salivary glands.⁴⁶ The incidence and severity of this effect often is increased by the concomitant administration of anticholinergic antiparkinsonism agents, which are prescribed with high-potency agents such as fluphenazine and haloperidol. The resultant hyposalivation causes an intensification of periodontal disease, and of rapid caries progression, because of adverse changes in the oral environment.⁴⁷ These factors are responsible for the fact that the majority of people with schizophrenia have extremely high requirements for periodontal treatment, dental restorations and dental extractions.⁴⁸

Conventional antipsychotic medication–induced movement disorders are associated with spasms of the jaw muscles that can cause dislocation of the temporomandibular joint, an impaired gag reflex and an increased incidence of death from obstructive asphyxia.^49,50 The unceasing mandibular movements associated with TD can cause the dislodging of complete removable prostheses, orofacial pain from mucosal ulcers and fatigue of the masticatory muscles.⁵¹ These medications also may induce agranulocytosis and leukopenia, which manifests as buccomucosal ulcerations and candida infections of the mouth.⁵² The official U.S. Food and Drug Administration, or FDA, product label that accompanies each of these medications, is reprinted in the Physicians’ Desk Reference and identifies other, less frequently encountered, adverse orofacial reactions (Table 1).⁵³

	DENTAL MANAGEMENT CONSIDERATIONS

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Adverse interactions between medications used in dentistry and the conventional antipsychotic drugs may produce morbid reactions. These antipsychotic medications may add to or potentiate the action of other central nervous system, or CNS, depressants, such as narcotic analgesics, barbiturates and general anesthetic agents. When these agents are prescribed concurrently, caution must be exercised to avoid excessive CNS depression, hypotension, orthostatic hypotension and respiratory depression.⁵⁶

Patients being treated with clozapine need to have their most recent WBC count evaluated for adverse drug-related changes. Dental treatment cannot begin if there are any signs of significant bone marrow suppression—that is, a total WBC count of less than 3,000 per mm³.

Preventive dental education for this unique group of patients is paramount. Hygiene instruction sessions are best conducted before a large mirror. Oral instructions, modeled demonstrations (in which the dental hygienist brushes and flosses his or her own teeth) and colorful posters are effective in describing the proper tooth brushing and flossing techniques and the use of artificial saliva products, antimicrobial agents (for example, chlorhexidine gluconate), and fluoride mouth rinses. Patients should be rescheduled at three-month intervals for a clinical examination, oral prophylaxis, acid rinse and application of a fluoride gel. Unfortunately, a significant number of patients lack the ability or motivation to independently perform oral hygiene procedures. Thus, maximal effectiveness is achieved by also educating a family member who can serve as the patient’s primary caregiver.

Dental treatment may be performed using local anesthesia.⁵⁷ Subgingival scaling, root planing and curettage, dental restorations and extractions can be performed for all patients. Fixed prosthodontic prostheses, even in those patients with compromised oral hygiene, have a respectable life span and are preferable to removable appliances, which may be misplaced or even occasionally ingested.^58,59 During the treatment, the airway should be assiduously protected because of the patient’s propensity to have an impaired gag reflex.

	CONCLUSION

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Dental disease and psychiatric disease are the most prevalent health problems in the United States. Dentists should be prepared to treat patients with psychiatric disorders, even if the experience is time-consuming and stressful. Assistance by the patient’s psychiatrist can alleviate much of the doubt and anxiety associated with providing dental care to these patients. As health care professionals, we must be able to recognize patients with the initial signs and symptoms of schizophrenia and provide them with appropriate referral sources for definitive diagnosis and treatment.