Andrew F. Angelino
Chester W. Schmidt Jr.
Schizophrenia is a mental disorder, or group of disorders, for which the etiology is unknown. In the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV TR), the American Psychiatric Association lists the essential features of the disorder as the presence of certain psychotic features for a significant length of time (i.e., a 1-month period, with some signs persisting for at least 6 months); characteristic chronic symptoms involving multiple psychological processes; deterioration from a previous level of functioning; and median age at onset in the mid-twenties for men and late twenties for women. As noted later (see Diagnosis), none of these symptoms is pathognomonic for schizophrenia, and each is seen in other psychotic states.
Familiarity with schizophrenia is important to the generalist for three reasons: In the prodromal stage, the patient often presents first to a general physician; the interested generalist may provide much of the care for a patient with this lifelong disorder; and patients with schizophrenia have significant medical comorbidity as a result of diminished self-care and adverse effects of psychotropic medications.
Epidemiology
Schizophrenia has been found in all societies throughout the world. The distribution is similar throughout all populations. Epidemiologic studies in Western societies have found the lifetime prevalence of schizophrenia to be slightly less than 1 case per 100 persons. Lifetime incidence rates have been reported to range from 0.6% to 1.9% (1). Studies of incidence and prevalence in Europe using strict and somewhat narrow criteria for schizophrenia have produced case numbers and rates lower than similar studies done in the United States, which used broader criteria. In 1943, Lemkau et al. (2) determined that 15% to 25% of patients with schizophrenia never entered the hospital. Developments in psychopharmacology over the past three
P.350
decades and the wide availability of ambulatory treatment resources have expanded the number of patients who never enter the hospital and greatly reduced the duration of confinement for those who do require hospitalization.
Schizophrenia is equally common in men and women. Onset is usually during young adulthood, with the first hospitalization usually occurring between the ages of 25 and 34 years. Most schizophrenic patients are single and are members of lower socioeconomic groups. The proposed reason for the clustering of patients in the lower socioeconomic groups is a downward social drift resulting from deterioration of social and vocational function.
Causes
The cause or causes of schizophrenia remain unknown. Numerous constitutional, genetic, neurologic, anatomic, biochemical, nutritional, psychosocial, and psychoanalytic theories have been offered. Present evidence strongly suggests some genetic transmission, because schizophrenia has long been known to run in families. The increased risk ranges from 3% for second-degree relatives, to 7% to 15% for siblings and children of one schizophrenic parent, to 40% for children of two schizophrenic parents. Concordance rates are 10% to 15% in dizygotic twins and 45% in monozygotic twins (3). Children born of schizophrenic parents but raised in adoptive families also show a higher incidence of the disease. This evidence indicates that transmission of schizophrenia is not explained by simple mendelian inheritance. Current research is seeking a polygenic mechanism, possibly with incomplete penetrance. Further, the study of “biomarkers,” subtle neurologic signs and physical features, is emerging to help determine the precise genes involved.
In regard to the pathology of schizophrenia, many autopsy and neuroimaging efforts have played a significant role in the last decade. As the data emerge, it is becoming evident that schizophrenia is not a disease of one specific brain area but rather a functional disorder of brain systems that affects the developing brain of adolescents and young adults, causing several types of symptoms to emerge gradually. A significant research effort is now being directed at the heteromodal association cortex, a group of related brain structures thought to be involved in the higher, executive functions of the neocortex (4).
Neurochemical mechanisms involved in the production of symptoms of schizophrenia are still being investigated. An important clue emerged from studies of the pharmacologic effects of antipsychotic agents on schizophrenia. These medicines antagonize dopamine-mediated neurotransmission, leading to the speculation that excessive activity of the dopamine systems may be part of a biochemical defect in schizophrenic patients (5). Research has now shown that cortical serotoninergic systems modify the activity of the mesocortical and mesolimbic dopamine systems (6) and has led to the development of newer medicines that tend to have reduced rates of certain adverse effects.
Natural History of Schizophrenia
Although the first episode of acute psychosis usually occurs in late adolescence or early adulthood, prodromal manifestations of the disease are often present for years before the acute episode. During the prodromal phase, patients gradually withdraw from social relationships. They become indifferent to their grooming, ignore social graces and social rituals, and may develop suspicious attitudes about others. They appear different, peculiar, and sometimes bizarre. Timing of the onset of this phase plays a significant role in the achievement of social, educational, and occupational milestones. In some patients, the deterioration of social and vocational skills may be so striking that the patient seems to have a changed personality. In many cases of early onset schizophrenia, the patient has developed only marginal social and vocational skills, so his or her deterioration appears more insidious.
In one study of the prodromal stage of schizophrenia, many patients had some behavioral concern, most commonly depression or school or work decline, but the majority did not seek any health professional contact. Those patients that did seek out health care visited primary care physicians 35.7% of the time—at least twice as often as any other health care professional. Further, once psychotic symptoms began, the most frequent presentation site for patients became emergency departments, but family physicians were again more than twice as likely to be visited than any mental health care provider (7).
Psychiatrists classify psychotic symptoms into categories of positive, disorganized, and negative symptoms. Positive symptoms include delusions (fixed, false, idiosyncratic ideas) and hallucinations (perceptions without stimuli). Thought disorders—including loosening of associations, illogical or magical thinking, and inability to carry on discourse—and bizarre behavior and emotions make up the disorganized symptoms. The negative symptoms include apathy, preoccupation with fantasies and an inner psychological world (autism), inability to carry out goal-directed behavior because of preoccupation with consequences of alternatives (ambivalence), and anhedonia (loss of pleasure in activities). Occasionally, patients display catatonic symptoms, which include stereotypical movements, mutism, and sometimes rigid posturing.
Acute psychotic episodes are marked by the development or exacerbation of any of the positive or disorganized symptoms and are often brought on by stressful life events. Before antipsychotic medications were available,
P.351
these episodes could last from weeks to years. Currently, most episodes are brought under pharmacologic control within several weeks. After treatment, positive and disorganized psychotic symptoms subside and in some cases seem to disappear completely. Some patients, however, develop a more chronic course, with persistent positive and disorganized symptoms. Many patients also suffer from prominent negative symptoms, which may be evident only between acute exacerbations. With each subsequent psychotic episode, the patient may slip further into a dependent, regressed state in which he or she is unable to function and becomes entirely dependent on family or society. Scholastic and vocational ability often diminish. Fewer than 20% of patients work full-time; most are financially supported by welfare programs or federal disability programs. Institutionalization is required in some cases because the patients lose all ability to care for themselves.
Schizophrenia is a lifelong disease consisting of psychotic symptoms that periodically become intense and an arrest or deterioration of social and vocational functioning, probably caused by massive withdrawal of interest in the outside world. The devastation of the disease is supported by the fact that 30.6% of suicides by schizophrenics occur within the first 2 years after onset or first hospitalization, and overall lifetime prevalence of suicide in schizophrenic patients is 4.9% (8).
Diagnosis
The diagnosis of schizophrenia, especially during the initial episodes of acute psychosis, is based on clinical judgment and diagnostic criteria that, until recently, were unreliable. No pathognomonic symptoms, signs, or laboratory findings point to the diagnosis. The medical history of the patient does not contribute to the diagnosis, and, as discussed earlier, family history of the disease provides only partial information.
The diagnostic criteria for schizophrenia described in the DSM-IV TR are an excellent synthesis of several recognized diagnostic formulations (Table 25.1). Diagnosis rests on the findings of the symptoms of psychosis elicited by a mental status examination (see Chapter 19) and a history that documents the prodromal phase.
Differential Diagnosis
Any kind of psychotic state may resemble acute schizophrenia. However, differences in symptoms permit differentiation and diagnosis.Delirium, dementia, and amnestic and other cognitive disorders (see Chapter 26) are marked by disturbances in consciousness (delirium); by disorientation with respect to time, place, and person; and by
P.352
impairment in intellectual functions (e.g., memory, calculations). Additionally, especially in patients younger than 50 years of age, there is usually evidence from the history, physical examination, and laboratory tests of specific organic findings that are etiologically related to the mental condition. Single psychotic symptoms, such as persecutory delusions or auditory hallucinations, may occur de novo in elderly patients as symptoms of dementia or paraphrenia (see Chapter 26). Effects of illicit drugs, especially amphetamine and phencyclidine (seeChapter 29), may mimic the acute phase of schizophrenia. Additionally, a number of prescription drugs may occasionally produce hallucinations and other manifestations that suggest psychosis (Table 25.2). History of drug use and absence of the prodromal phase help differentiate these conditions from schizophrenia.
|
TABLE 25.1 Diagnostic Criteria for Schizophrenia |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
TABLE 25.2 Prescription Drugs That Have Been Reported Occasionally to Cause Hallucinations or Other Manifestations of Psychosis |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The psychotic symptoms of major affective episodes (both mania and depression; see Chapter 24) can also be similar to those seen during acute episodes in the course of schizophrenia. Affective disorders differ from schizophrenia in that psychotic symptoms (e.g., delusions, hallucinations) appear after the development of the affective disturbance (depression or mania) and generally remit when the affective disturbance remits. In schizophrenia, marked depression or mania may appear, but the affective disturbance occurs after the onset of the psychotic symptoms, which often exist as well in the complete absence of affective symptoms. These principles of differential diagnosis are far from perfect, and patients with both types of disorder have been mislabeled. Because the prognosis associated with schizophrenia is often worse than of affective disorders, mislabeling has significant consequences, including attitudes toward the patient and actual treatment provided.
Schizoid and schizotypal personality disorders, described in Chapter 23, are personality types that may share some of the features of withdrawal from society, but they are not accompanied by the psychotic features seen in schizophrenia (Table 25.1). There is some evidence that these personality types may comprise part of a spectrum of schizophrenic illness, including data showing higher rates of these personality types in families of patients with schizophrenia.
Treatment and Prognosis
Antipsychotic Drugs
The primary treatment of the acute and chronic psychotic manifestations of schizophrenia in ambulatory or hospitalized patients centers around the antipsychotic agents. There are several classes of antipsychotics, with numerous drugs in each class. Table 25.3 lists the common drugs, together with available strengths and potency equivalents to chlorpromazine.
Although the structures of the various antipsychotics are well known, the pharmacology is not. Dose–response relationships have not yet been worked out for humans. The drugs generally produce effects within 1 hour after oral administration and within 10 to 15 minutes after intramuscular injection. They are lipid soluble with a high affinity for cell membranes. The drugs and their metabolites are distributed generally throughout the central nervous system with no local or regional accumulation. Metabolites are partially excreted each day, with significant portions retained in lipid-rich tissues and connective tissues. As these tissues become saturated, the drugs undergo slow turnover. The drugs are detoxified and inactivated mainly through oxidation by hepatic microsomal enzymes, and they are excreted through both bile and urine.
There is no evidence that these agents are addicting, although tolerance to some of the side effects (sedation, hypotension, anticholinergic effects, parkinsonian
P.353
symptoms) has been reported. The drugs are fairly safe but may induce delirium if used in great excess. Further, antipsychotic drugs prolong the QTc interval (Q-T interval corrected for heart rate) to a varying degree depending on the specific agent, and care should be exercised when prescribing them to patients with cardiac conduction delays, because cases of sudden cardiac death have been reported. If patients are found to have a prolonged QTc interval (longer than 500 msec), the antipsychotic medicine should be evaluated for discontinuation, and consultation with a cardiologist should be obtained.
|
TABLE 25.3 Available Strengths and Equivalent Doses of Commonly Used Neuroleptic Antipsychotic Agents |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The mechanisms of action of the antipsychotics are not fully understood. Although it has been speculated that specific antipsychotic activity may result from the dopamine-antagonist action of these agents, the drugs have a variety of effects on many metabolic processes. Newer, so-called atypical or second-generation, antipsychotics affect neurotransmitters other than dopamine, especially serotonin, and additional dopamine receptor types compared with the older agents. This is the proposed basis for their lower rates of certain side effects, such as extrapyramidal symptoms, and it may be the mechanism of action of their effect on negative symptoms. These atypicals include aripiprazole (Abilify), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
P.354
Treatment of Acute Psychotic Episodes
All antipsychotics are equally efficacious for controlling positive psychotic symptoms associated with schizophrenia, but only the atypical antipsychotics have been shown to have any efficacy in the treatment of negative symptoms. The choice of one drug over another depends on predicted differences in side effects, the history of a particular patient's response, and the clinician's familiarity with the agent. The treatment of acute psychotic episodes should begin with the equivalent of 300 to 1,000 mg of chlorpromazine (Thorazine) per day, in divided doses (usually three times daily). This dose range is equivalent to 6 to 20 mg of haloperidol (Haldol), which may be given as a single or divided dose. Only one antipsychotic should be given at a time, because administration of more than one agent increases the probability of side effects.
Combativeness, hyperactivity, and agitation are usually controlled within 24 to 48 hours after beginning treatment. If these symptoms are not modified within that period, the dosage should be increased, up to the equivalent of 800 to 2,000 mg of chlorpromazine, or 16 to 40 mg of haloperidol. It may be necessary to administer the drugs intramuscularly during the acute phase of agitation if the patient is unable to take oral medication. Haloperidol 2 to 5 mg is a good choice for intramuscular injection because of its minimal effects on circulatory regulation, but intramuscular preparations of the atypical agents ziprasidone and olanzapine are now available and becoming increasingly used because of lower incidence of acute dystonic reactions. For patients who do not respond to an adequate trial (4 to 6 weeks) of two or more antipsychotics, a trial of clozapine should be considered. Because clozapine causes fatal agranulocytosis in up to 1% of patients, a history of blood dyscrasias and poor compliance are contraindications. Clozapine trials should last at least 3 months at a dosage of 200 to 600 mg/day.
Delusions, hallucinations, associational defects, negativism, and withdrawal begin to subside within 1 to 2 weeks after treatment begins. Continued improvement of these symptoms may take place over an additional 4 to 8 weeks. If very high dosages of antipsychotic agents are initially required, the dosage should be cautiously reduced to the equivalent of 300 to 600 mg of chlorpromazine, because high doses of conventional antipsychotic agents can worsen apathy and negativism. This adjustment in dosage can usually begin 1 to 2 weeks after the peak dosage is reached.
Early Side Effects of Antipsychotics
Antipsychotic drugs with lower potency per milligram, such as chlorpromazine (Table 25.3), produce sedation, which can be a useful side effect in treating hyperactive or combative patients but is a disadvantage in regressed, withdrawn patients. The anticholinergic properties of all phenothiazines produces annoying symptoms of dry mouth, stuffy nose, blurred vision, and occasional urinary retention in older patients and delirium at high dosages. These side effects often abate or disappear within 2 to 4 weeks. A common worrisome side effect is drug-induced Parkinson syndrome, also called extrapyramidal symptoms. This occurs with greatest frequency in association with drugs of higher potency per milligram, such as haloperidol, the piperazine class of phenothiazines, thioxanthene, loxapine, and molindone (Table 25.3). The syndrome usually appears within 5 to 30 days after beginning treatment and includes tremor, rigidity, bradykinesia, fixed facies, drooling, and stooped posture. Because this problem commonly causes patients to discontinue antipsychotic treatment, it should be managed properly. In most cases reduction of dosage or addition of small amounts of an antiparkinsonism agent controls these side effects (seeChapter 90). The parkinsonian effects of antipsychotic drugs tend to decrease after 1 or 2 months. Therefore, withdrawal of antiparkinsonism drugs should be attempted after 6 to 12 weeks. Prophylactic treatment of all patients with antiparkinsonism drugs is generally discouraged because of the additional anticholinergic effects of these drugs.
The incidence of extrapyramidal symptoms is lower with the newer antipsychotic agents such as aripiprazole, olanzapine, quetiapine, and ziprasidone. Risperidone also shows a lower incidence at lower doses, but the symptoms appear at doses greater than 8 to 10 mg with the same regularity as with haloperidol or other potent agents.
Acute dystonias occur in some patients within 1 to 5 days after initiation of any antipsychotic; these effects are most often seen with haloperidol and the piperazine class of phenothiazines. The symptoms are sudden onset of severe, tonic contractions of the musculature of the neck (torticollis), the spine, the heels (opisthotonos), the extraocular muscles (oculogyric crises), the mouth, and the tongue. These symptoms remit promptly after intravenous or intramuscular injection of diphenhydramine (Benadryl, 25 to 50 mg) or benztropine (Cogentin, 1 to 2 mg). Antipsychotic treatment can be continued in these patients; an antiparkinsonism agent should be added for about 1 month to protect against recurrent dystonia. Akathisia may also occur early in treatment. This side effect is marked by motor restlessness with pacing, fidgeting, and restless legs. It does not resolve with treatment as predictably as the acute dystonias do. Treatment is the same as that prescribed for drug-induced parkinsonism. In a small, controlled trial the lipophilic β-blocker, propranolol, in daily doses of 20 to 60 mg, was shown to improve symptoms of akathisia in most patients (9).
P.355
A number of nonneurologic side effects can result from administration of the antipsychotics. Cardiovascular toxicity includes orthostatic hypotension; this problem is most commonly seen with the aliphatic and piperidine classes of phenothiazines and with chlorprothixene. Frank syncope may occur, rarely, after intramuscular administration of low-potency antipsychotics. Many agents have been shown to prolong the QTc to varying degrees. In particular, thioridazine and mesoridazine have been shown to cause significant QTc prolongation, and those drugs contain warnings in their prescription information mandated by the U.S. Food and Drug Administration (FDA). Torsades de pointes and ventricular tachycardia are rare side effects; there are no baseline characteristics that help one recognize patients at risk for this problem (see Chapter 64 for a discussion of cardiac arrhythmias). Reversible cholestatic jaundice can occur as an allergic response. Agranulocytosisis an exceedingly rare side effect.
The neuroleptic malignant syndrome is a rare, and occasionally lethal, idiosyncratic complication. It usually occurs within 1 month after the onset of treatment, when the dosage is increased, or when a second drug is introduced. Over 24 to 72 hours, the patient develops confusion, muscle rigidity, hypertension or severe orthostatic hypotension, and a high temperature (as high as 107.6°F [42°C]). Patients with this syndrome should be hospitalized immediately in an intensive care unit, because hypoventilation occurs as a consequence of the rigidity of the patient's chest wall muscles. The treatment involves discontinuation of all antipsychotic agents, aggressive intravenous hydration, and, in some cases, the administration of dantrolene or bromocriptine. Patients should remain off all antipsychotic drugs for a minimum of 2 weeks before reintroduction. In the interim period, acute exacerbations of symptoms are common, and patients may require inpatient psychiatric hospitalization.
Because older schizophrenic patients are more prone to the development of the common side effects, dosages should be lower for these patients, by the equivalent of 100 to 200 mg of chlorpromazine or 2 to 4 mg of haloperidol. The very high dosages described for treatment of combativeness and hyperactivity should be avoided in elderly patients.
Long-Term Drug Treatment of Schizophrenia
Interested generalists can assume responsibility for the long-term care of schizophrenic patients. Pharmacotherapy is the principal mode of long-term treatment. Many studies show that 60% to 70% of schizophrenic patients relapse within 1 year if they do not receive medication (10). A large meta-analysis of relapse demonstrated that patients withdrawn from antipsychotic therapy had a rate of relapse three times higher than those maintained on medication, with a mean follow up time of 9.7 months. However, almost half of the patients for whom antipsychotics were withdrawn remained stable without relapse during the followup period (11). These data support the conclusion that for most patients, antipsychotics should be maintained at the lowest level necessary to control symptoms and relapses, while minimizing risk of long-term side effects. Withdrawal of antipsychotics should be undertaken only in very stable situations, and for patients who have no history of violence, suicide attempts, or other serious consequences of relapse.
The goal of long-term pharmacotherapy is to minimize psychotic symptoms with the lowest dosage of antipsychotic possible. Moderate maintenance dosages appear to be as effective as, and safer than, the larger dosages that have been popular in the United States (12). For most patients a low to moderate dosage is the equivalent of 200 to 400 mg of chlorpromazine (or 4 to 8 mg of haloperidol) daily. Patients receiving this dosage often continue to have psychotic symptoms but do not seem to be disturbed by them (e.g., “I still hear the voices, but they don't bother me”).
Compliance Problems
Some patients temporarily have difficulty maintaining a regular medication schedule because of psychotic disorganization, negativism, or fear of medication. Inability to comply with the medication regimen may signal the onset of an acute episode. With the first indication of a disruption in medication schedule, the patient should be evaluated, the frequency of visits increased to at least once a week, and the medication dosage increased if warranted. If the patient remains unable to comply, a long-acting intramuscular agent, such as fluphenazine decanoate (Prolixin Decanoate, available in doses of 25 mg/mL), 1 to 2 mL every 2 weeks, haloperidol decanoate (Haldol Decanoate, available in doses of 50 mg/mL), 2 to 4 mL every 4 weeks, or risperidone (Risperdal Consta, available in doses of 25 mg/mL) 1 to 2 mL every 2 weeks should be used. The patient can be returned to an oral medication when symptom control is reestablished. Long-acting intramuscular agents are also useful for new patients for whom no information is available on compliance in aftercare or ambulatory programs. Evidence suggests that family therapy and cognitive behavioral therapy improve compliance with medication regimens (13). Patients having difficulty with medication compliance should be referred for one of these types of therapy in addition to the previously described measures.
Nonresponders
Between 5% and 25% of schizophrenic patients do not respond to antipsychotics, and a similar number are
P.356
intolerant of the side effects. Both groups of patients are candidates for treatment with clozapine (Clozaril) (14), a tricyclic dibenzodiazepine. The recommended starting dosage is 25 mg once or twice per day, to be increased by 25 mg every other day to 100 mg per dose, then increased by 50 mg every other day to 300 to 450 mg per day by 2 weeks. Clozapine is available in 25- and 100-mg tablets. The risk of agranulocytosis is 1% to 2% and necessitates initial weekly blood monitoring. Because of dose-related incidence of seizures, the dosage should not exceed 600 mg. Common side effects are weight gain, sedation, drooling, and dizziness. There are reports of increased incidence of type 2 diabetes mellitus (DM) in patients treated with clozapine.
Late Side Effects of Antipsychotics
Onset of the early type side effects is uncommon in patients taking maintenance dosages of antipsychotics (see Treatment of Acute Psychotic Episodes discussed earlier). When an increase in medication is necessary, drug-induced parkinsonism may appear. Patients who experience symptoms of parkinsonism over a long period should try other antipsychotic medications until one is found that does not produce the side effect. As noted previously, long-term use of antiparkinsonism medication is to be avoided if possible (see Chapter 90).
Tardive dyskinesia is an extrapyramidal syndrome that occurs in patients after prolonged (months to years) moderate- to high-dosage antipsychotic treatment. The cumulative prevalence is approximately 24% to 27% in women and 22% in men—but is much lower with the newer, atypical antipsychotic agents and is nonexistent for clozapine. The prevalence reaches its peak in men between 50 and 70 years of age but continues to rise after age 70 years in women. Asians have lower prevalence than North Americans, Europeans, or Africans (15). The disorder has been reported in association with long-term treatment with anticonvulsants, and there is a very small incidence among untreated schizophrenic patients. Up to 25% of patients treated with antipsychotics who are evaluated for drug-induced tardive dyskinesia are found to have another disorder causing their dyskinesia. The most common of these is the oral-buccal-lingual dyskinesia that arises in 10% of edentulous patients.
The syndrome of tardive dyskinesia consists of involuntary or semivoluntary movements of a choreiform, tic-like nature, sometimes associated with a dystonic component that classically involves the tongue, facial, and neck muscles. Early manifestations include fine, worm-like movements of the tongue at rest, facial tics, and jaw movements. Later symptoms are bucco-lingual-masticatory movements, chewing motions, lip smacking, puffing of cheeks, blinking of eyes, and choreoathetoid movements of the extremities. Younger patients often have significant involvement of the extremities and trunk. Although the syndrome is painless, it can be socially embarrassing and can interfere with patients’ ability to feed and care for themselves.
The prognosis for remission of tardive dyskinesia is poor, regardless of treatment, and symptoms last for years if not indefinitely. The emphasis of antipsychotic use should therefore be on prevention of tardive dyskinesia, by careful selection of patients for long-term antipsychotic treatment, trials of atypical agents first, and use of the lowest possible dosage. At the first sign of the disorder, antipsychotics should be tapered and discontinued if possible. Symptoms gradually diminish or disappear over several months in approximately one third of patients who can be taken off drugs early.
Because there is no satisfactory treatment for tardive dyskinesia, understanding support by the physician and family members is especially important in long-term care of the patient. Antiparkinsonism medications usually worsen the symptoms. One short-term effective treatment is the use of more potent antipsychotics to suppress the symptoms, but this usually requires increasing dosages of the suppressing agent, and subsequent withdrawal of antipsychotics often leads to worsening of the symptoms for a period of time. In case reports, benzodiazepines, pure lecithin, lithium, sodium valproate, and vitamin E have been reported to be useful, but there are no well-delineated guidelines for selecting one of these agents. Another strategy is to switch the patient to clozapine, so that antipsychotic therapy is continued with a medication that does not cause tardive dyskinesia; this strategy is best done in consultation with a psychiatrist.
Overall Psychiatric Treatment of the Patient
The schizophrenic patient is sensitive to change or instability in any aspect of his or her life. Whenever possible, a single practitioner should provide continuous care, so that that practitioner becomes a predictable resource for helping the patient to maintain his or her role in the community. Although few schizophrenic patients work full time, patients should be referred for vocational rehabilitation (see Chapter 9) or for sheltered workshops when requested. Most patients determine their own levels of social activity and may not change despite encouragement, but offers and suggestions should be made. The clinician should be available to the patient's family or to foster care providers for periodic review of the patient's progress and expectations. The book, Surviving Schizophrenia, should be recommended to the patient's family (see http://www.hopkinsbayview.org/PAMreferences).
Ideally, residential facilities are available when there is no family with whom the patient may live or when the family is a harmful influence. However, in many communities, such facilities do not exist. For some patients, the clinician
P.357
and the ambulatory center itself become the sources of the few social contacts that the patient has outside his or her home and inner psychological world.
Regular office visits should be scheduled. Frequency of visits should be determined on the basis of current status of the patient, history of the course of the patient's illness, reliability of the patient in taking medication, and the patient's ability to recognize early signs of onset of acute episodes. Routine office visits need last only 15 to 20 minutes and should include an interim history, a brief mental status examination, a review of the effectiveness of medications and of significant side effects, and provision of support or advice regarding the ways in which the patient is dealing with day-to-day matters. In other words, these office visits may be defined as supportive therapy, as described in Chapter 20.
In addition to individual office visits, a family management approach may be useful for patients who are having difficulties with their families (16). The method involves a two-step process:
Management is enhanced if the clinician has ready access to social services, emergency mental health services, and psychiatric day care and inpatient services. Social services, especially for financial support (e.g., welfare, food stamps, disability payments), are important in the treatment of schizophrenic patients because of their usual dependent status. Many acute episodes of psychosis are precipitated by threatened or actual withdrawal of welfare and disability payments.
The generalist caring for a schizophrenic patient may need to consult with a psychiatrist for confirmation of the initial diagnosis, decisions regarding hospitalization, or treatment recommendations when symptoms respond poorly to antipsychotics or when side effects are intolerable.
Medical Comorbidity in Patients with Schizophrenia
Patients who suffer from schizophrenia may have little contact with primary care physicians unless they are part of a program that mandates medical visits or have family members dedicated to keeping up with general health issues. The number one cause of death for schizophrenic patients is heart disease, and the patients have several risk factors.
First, there is a growing body of evidence that patients with schizophrenia are frequently comorbid with obesity (17). It is as yet unclear how much of this problem is caused by the lifestyle of the diseased patient and how much by side effects of medications used to treat the disorder. In fact, most antipsychotic agents are associated with weight gain, the notable exceptions being pimozide and molindone, two older typical antipsychotics and ziprasidone, a second-generation agent. The mechanism for this effect is still unclear but may involve several factors, including sedation, rigidity side effects of medications, increased appetite caused by antihistamine properties of some medications, or other metabolic changes resulting in increased fat storage. In general, weight issues and diet should be addressed in all patients with schizophrenia, and attempts should be made to help obese and overweight patients reduce weight. Attention should be given to possible medication effects, and attempts to alleviate sedation and/or rigidity should be actively pursued. If necessary, patients may try switching to antipsychotics associated with less weight gain, under careful supervision for recurrence of psychotic symptoms.
Second, there is a high rate of comorbidity between schizophrenia and nicotine addiction. Although there are theories about the specific effects of nicotine on schizophrenic brains, suggesting a self-medication model for this behavior, the untoward effects of smoking on the cardiopulmonary system run rampant. Generally, although efforts to force schizophrenic patients to quit smoking may be fruitless, all attempts should be made to reduce smoking to the lowest level possible, offering nicotine replacement as necessary and behavioral therapy to address cravings.
Third, there is evidence that diabetes is a more common problem in schizophrenia than in the general population (18). The possible mechanisms are that diabetes and schizophrenia are in some way genetically linked, so that risk genes may be transmitted together because of their proximity on chromosomes, and that antipsychotic medications may cause diabetes by directly impairing glucose handling and by causing obesity, which may impair insulin responsiveness. Diabetes complications arise as the disease takes its toll on the body, and schizophrenics may be poorly compliant with diet and hypoglycemic or insulin regimens. All schizophrenic patients should be regularly screened for diabetes on routine examinations.
In addition to heart, lung, and endocrine diseases, patients with schizophrenia are at increased risk for certain infectious diseases. Tuberculosis is associated with homelessness, a far-too-frequent sad consequence of chronic mental illness. The rates of human immunodeficiency virus infection and viral hepatitis in patients with schizophrenia are frighteningly high. Sexual transmission of these viruses may be related to the smaller sample of the population with whom patients with schizophrenia have the opportunity for intercourse. There are data to suggest
P.358
that schizophrenic patients choose sexual partners most often from among other patients in the psychiatric clinic. Further, there is a profound comorbidity of substance use disorders in schizophrenia. The possible mechanisms for this are (a) as a method of self-medication for positive or negative symptoms, (b) as a means of increasing social interaction via a fairly scripted set of rules that patients with schizophrenia can follow, and (c) as a result of increased availability in impoverished areas, to which schizophrenic patients tend to “drift” due to social disenfranchisement. In any case, intravenous drug use may lead directly to infection, and because many schizophrenic patients do not see internists or family practitioners regularly, the illnesses may be overlooked until later stages of infection, when treatment is more difficult and possibly less efficacious. Patients with schizophrenia should be routinely asked about sexual practices and intravenous drug use, and appropriate serologic testing should be performed.
Prognosis for the Treated Patient
Schizophrenia is a lifelong disease that requires an open-ended commitment by the clinician. The patient's life is disrupted by periodic psychosis, sometimes necessitating hospitalization, and by an arrest or deterioration of social function. Some patients are able to work and maintain satisfying interpersonal relationships. Many lead lonely, withdrawn, socially marginal existences. Psychopharmacologic treatment is effective for controlling the symptoms of acute psychosis and suppressing the intensity of psychotic symptoms over long periods. Suppression of psychosis may permit the patient to use his or her intellectual and social talents more effectively in developing and maintaining some role in the community. The atypical antipsychotics (Table 25.3) are reported to have efficacy in the treatment of the negative symptoms that may impair social function.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.