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| CECIL |
| TEXT BOOK of MEDICINE |
Section XXV Neurology
| 420 PSYCHIATRIC DISORDERS IN MEDICAL PRACTICE Randolph B. Schiffer • |
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▪BEHAVIORAL AND BEHAVIORALLY RELATED DISORDERS
As age-specific mortality decreases because of medical progress in treatment and prevention of infectious, nutritional, cardiovascular, and malignant disorders, the behavioral and behaviorally related disorders assume greater importance. According to the World Health Organization, 5 of the 10 leading causes of disability worldwide are psychiatric conditions: unipolar depression, substance abuse, bipolar disorder, schizophrenia, and obsessive-compulsive disorders.
Psychiatric morbidity is common among patients in ambulatory general medical settings, both in developed and in underdeveloped countries. General medical physicians can expect one in four of the patients whom they see to have active, diagnosable psychiatric disease. The most common diagnoses in medical settings are depression, generalized anxiety disorder, somatoform disorders, substance abuse, and personality disorders. These disorders are associated with substantial psychosocial morbidity and they are all treatable. Initial recognition and treatment of these disorders must occur in general medical settings because of shortages of psychiatrists and limitations in access to psychiatric expertise in managed care settings. Surveys indicate that less than 25% of patients with these mental illnesses are recognized and treated by primary care providers.
Psychiatric disorders are accompanied by a series of variable signs and symptoms, or syndromes, and diagnosis is still based on these clinical features despite increasing knowledge about the neurobiologic bases of these conditions. As yet, there are no reliable laboratory tests for diagnosis. All psychiatric diseases have a spectrum of severity, and available therapies probably work best during their milder phases. This chapter outlines the clinical features and therapeutics for the psychiatric syndromes that occur most frequently in general medical settings.
▪SYNDROMES
▪Depression and Risk of Suicide
▪Depression
Several depressive-spectrum disorders are included in the current edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Dysthymia is a syndrome of milder symptoms, but other patients have major depressive symptoms and can be suicidal.
When the pattern of recurrence is one of depressive syndromes only, the disorder is called a unipolar depressive disorder. When manic-like episodes are included (see later), the disorder is called a bipolar disorder.
Epidemiology
Lifetime prevalence rates for major depressive disorders are 15 to 20% in the United States. The exact prevalence is not known because of variable methods of ascertainment and diagnosis. Point prevalence rates for major depression in urban U.S. populations range from 2 to 4% for men and 4 to 6% for women.
Pathobiology
Several lines of evidence suggest that a genetic contribution exists for major depression. Occurrences of major depressive episodes clearly cluster in families. In general, increased rates of bipolar and unipolar disorders are present in first-degree relatives of patients with a bipolar disorder, and increased rates of unipolar depressive disorder are present in first-degree relatives of patients with unipolar disorders. These relatives have lifetime risks ranging from 10 to 20% for major depressive disorders, with perhaps a higher risk for depressive-spectrum disorders. This degree of increased risk is about three to five times that of the normal population. Twin and adoption studies are consistent with a genetic contribution to major depressive disorders, but studies suggest that other factors are also important. These life experience risk factors interact with the genetic constitution of each individual to determine the actual risk for depression. More recent techniques of molecular genetics, such as genomic mismatch scanning, repeat expansion detection, and mitochondrial DNA analysis, are beginning to contribute to our understanding of the genetics of affective disturbances, but as yet no discrete susceptibility genes for depression have been identified.
Neurochemical hypotheses for depression postulate that decreased availability of norepinephrine or serotonin at transmitter-specific synapses in the brain is associated with depression and that increased levels of these substances are associated with mania. Studies have generally supported the hypothesis that catecholamine and indolamine metabolism is important in mood states, although the relationships are complex. Almost all drugs with antidepressant properties affect catecholamine and indolamine availability at the synapse in the central nervous system.
Evidence also suggests that neuroendocrine function is altered in many people with major depressive disorders. Overactivity of the hypothalamic-pituitary-adrenocortical axis has been the most prominent of these neuroendocrine disturbances. This overactivity is reflected in higher levels of circulating cortisol in depressed patients than in controls, in addition to higher levels of cerebrospinal fluid (CSF) cortisol, increased excretion of urinary free cortisol, and cortisol resistance to dexamethasone suppression.
Clinical Manifestations and Diagnosis
The symptoms of depression are variable for each individual and are sometimes difficult to recognize. Behavior and cognition can be affected, as can mood and affect. Some people experience depression as a slowing of thought and movement. For some, forgetfulness and difficulty concentrating are prominent features. Other patients manifest agitation and even psychotic experiences when the disorder is severe. This variability in clinical features among patients can be used as a basis for classifying a major depressive episode into subtypes—agitated, psychotic, and others.
The core clinical features of the depressive disorders are included in the diagnostic criteria for a major depressive episode and for dysthymia (Table 420-1). These disorders tend to recur, and chronic, milder syndromes of depression, such as dysthymia, can evolve in time to the more severe major depressive disorder.
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Patients with affective disorders often have a disturbance in circadian rhythm reflected as abnormal sleep patterns. Complaints of difficulty falling asleep and early morning wakening are reliable clinical indicators of depression. Electroencephalographic studies show a relative absence of slow-wave sleep (stages 3 and 4) in depressed individuals and a shortened period between the onset of sleep and the first dreaming period (rapid eye movement [REM] latency). These disturbances in sleep improve when the mood disturbance improves.
Treatment
Diagnosis of a depressive disorder is the beginning of therapy. Depressed patients are usually relieved when their suffering is recognized and they are permitted to discuss it. The treatment plan must be individualized. A psychotherapeutic strategy (discussed later) should be considered for each patient before a drug is selected. Emerging clinical trials indicate that the combination of antidepressant medication and psychotherapy (see later) is superior to either alone in the treatment of depression.1 These treatments should generally be initiated in primary care settings, followed by psychiatric consultation for nonresponders. Treatments should be continued for 6 to 12 months, with the goal of resolution of the depressive syndrome rather than just improvement.
Medical Therapy
Antidepressant drugs available in the United States (Table 420-2) vary in their structure and function. Second-generation medications (selective serotonin re-uptake inhibitors [SSRIs], bupropion, duloxetine, mirtazapine, and venlafaxine) are generally equivalent to each other therapeutically2 and have fewer side effects than tricyclic antidepressants do.
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Selective Serotonin Re-uptake Inhibitors
SSRIs are the initial therapy for depressive illness. They block the re-uptake of serotonin at presynaptic membranes, with relatively little effect on noradrenergic, cholinergic, histaminergic, or other neurochemical systems. As a result, they are associated with fewer side effects than the tricyclic antidepressants are. Additional advantages of SSRIs over the older tricyclic antidepressants include once-daily dosing and the ability to initiate treatment at the target dose for most patients. For sertraline, the dose is 50 mg once daily for almost all patients. The dosage can be increased to 100 mg/day after 3 weeks if there is no evidence of improvement. For nonresponders, the dose can be increased to 150 or 200 mg/day. Paroxetine can be started at 20 mg once daily and increased at similar intervals to 50 mg. Escitalopram may be taken on a once-daily schedule, beginning at 10 mg/day and increased after 4 to 6 weeks to 20 mg. Although plasma levels of these drugs and their metabolites are available in some laboratories, large clinical trials suggest that measurement of plasma levels is not a useful guide to clinical response.
Concerns about SSRIs include their adverse effects on sexual function and not as well established efficacy late in life. The greatest concern, however, is the occasional association of these drugs with impulsive self-destructive or violent behavior; this concern has resulted in a Food and Drug Administration warning.
Atypical Antidepressants
Amoxapine is an antidepressant with some dopamine-blocking properties. It is associated with extrapyramidal side effects. This drug has a theoretical advantage in depressed patients with psychotic features.
Trazodone and nefazodone inhibit the re-uptake of serotonin (5-HT) at the synapse and exhibit antagonism for a serotonin receptor subtype (5-HT2). The absence of prominent anticholinergic side effects is a specific advantage for nefazodone. Trazodone has some sedating properties, which makes it useful in agitated patients with disturbed sleep, particularly elderly persons.
Venlafaxine is a phenylethylamine antidepressant that inhibits the re-uptake of serotonin and norepinephrine. It is selective for these two neurochemical systems and shows little in vitro binding to cholinergic, histaminergic, or dopaminergic receptors.
Bupropion is a novel monocyclic compound that inhibits the re-uptake of dopamine but has little effect on other adrenergic systems. Mirtazapine, a tetracyclic piperazinoazepine that is an analogue of mianserin, is an antidepressant that has been available in Europe. It is a presynaptic α2-blocker that increases the release of norepinephrine and serotonin. It also blocks 5-HT2 and 5-HT3 receptors and histamine H1 receptors. Common side effects include weight gain, dizziness, dry mouth, and constipation. It is a reasonable alternative for patients who do not respond to SSRIs.
Duloxetine combines SSRI-like pharmacologic properties with inhibition of norepinephrine re-uptake. This agent is also approved for the treatment of pain syndromes associated with peripheral neuropathy.
Tricyclic Antidepressants
The tricyclic antidepressants are thought to affect depressed mood by inhibiting synaptic re-uptake of norepinephrine and serotonin. Some of these agents, such as desipramine and nortriptyline, have a relatively greater effect on norepinephrine re-uptake systems. Others, such as amitriptyline, have a broader effect on serotonin systems. As a group, however, the tricyclic antidepressants have the disadvantage that they affect neurochemical systems that are not thought to be essential for antidepressant efficacy, including the histaminergic, adrenergic, and acetylcholinergic systems. Tricyclic antidepressants have a wide range of side effects such as postural hypotension, cardiac tachyarrhythmias, urinary retention, and constipation. These drugs are considered second-line agents for the treatment of depression, to be used in patients in whom treatment with SSRIs fails or in patients who have special complicating medical conditions, such as spastic bladder or parkinsonism. In these latter situations, the side effects of the tricyclic agents may be beneficial.
Monoamine Oxidase Inhibitors
The monoamine oxidase inhibitors used in psychiatric practice are irreversible inhibitors of both forms (A and B) of brain monoamine oxidase. These drugs are rarely used now because of their potentially dangerous interactions with dietary tyramine and other agents that have sympathomimetic or serotoninergic properties.
Prognosis
Depressive disorders should generally be considered to be chronic and recurring. Up to 70% of patients who have one major depression episode will have another. When antidepressant medications are discontinued, clinical surveillance should be continued according to the individual circumstances of each patient.
Risk of Suicide
Suicide is a uniquely human behavior for which we have only a limited psychobiologic understanding. Completed suicides are common in the United States and account for some 30,000 deaths each year. A much greater number of people attempt suicide, with variable degrees of intentionality. The most powerful associated features for completed suicide are current depression, alcohol abuse, and chronic medical illness. Suicide rates are highest for men older than 69 years, and rates are higher in whites and Native Americans than in other racial groups.
Most people who commit suicide have seen a physician within the previous month. Analysis of these physician visits suggests that clinical clues were probably conveyed but not adequately appreciated by the treating clinicians, in part because of the difficulty of recognizing depression in ambulatory general medical settings. When there is any suspicion about potential suicide, it is important to ask patients directly. When depressive symptoms are more severe or when they include features of agitation or delusional ideas, the risk for suicide is greater (Fig. 420-1). Older age, male gender, and intercurrent alcohol abuse are also risk factors. Social isolation is a powerful risk factor, as is chronic painful medical illness. Consultation with a psychiatrist is essential for high-risk patients.
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| FIGURE 420-1 Approach to a depressed patient at potential risk for suicide. |
▪Bipolar Disorders
Definition
Bipolar disorders (previously called manic-depressive disorders) are characterized by swings in mood from depressive episodes to manic episodes. Normal behavior is usually seen between episodes. Psychotic features may accompany the manic phases of these disorders. There is little difficulty in recognizing the illness over a longitudinal course. If patients are examined only briefly at a particular moment in time, however, manic excitement can be confused with schizophrenic psychosis. The severe depressive phase of bipolar illness can also be misconstrued as a catatonic state. During the acute phases, bipolar disorders should be managed by psychiatrists.
Epidemiology
The lifetime risk for the development of bipolar illness ranges from 0.6 to 0.9%. The annual new-case incidence is 9 to 15 per 100,000 in men and 7.4 to 32 per 100,000 in women. The average age at onset of bipolar disorder is about 30 years, but about 20% of patients have an onset before 20 years of age. In women, onset of the condition has a bimodal distribution, with one peak falling between 20 and 30 years and the other far earlier, but the age at onset of bipolar illness overlaps enough that the differential diagnosis of a psychotic illness in a young person is difficult and may change as the clinical picture evolves over time.
Pathobiology
There is familial risk for bipolar illness, with 72% concordance in monozygotic twins and 19% concordance in same-sex dizygotic twins. The genetic loci associated with risk for bipolar disorder are not yet known and may vary with the phenotypic subtypes of the syndrome. The underlying neuropathophysiology of bipolar illness may differ somewhat from that of the major depressive disorders and may overlap with other psychiatric disorders, including the schizophrenias.
Clinical Manifestations and Diagnosis
The manic phase of bipolar disorder is characterized by an expansive, euphoric mood in which the patient is subject to grandiose plans and ideas (Table 420-3). Despite this expansiveness and grandiosity, patients who are frustrated or confronted often become irritable and sometimes aggressive. The patient can be psychotic in the manic phase, with delusions and hallucinations consistent with grandiosity; persecutory delusions (i.e., feelings of being controlled) may also be present. At times, it is difficult to distinguish an excited schizophrenic patient from a manic patient until either a depressive episode occurs or the course deteriorates into a schizophrenic process. In all instances, it is crucial to exclude metabolic and other medical disorders, particularly in older patients.
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Almost half of patients with bipolar disorder have at least two or three episodes of illness, and a third experience seven or more episodes after the pattern has started. Each episode of illness, whether manic or depressive, can last 4 to 13 months; some become chronic, and some cease much sooner. Shorter durations are usually related to the effectiveness of treatment. Although some patients rapidly alternate between extremes over a period of 2 to 4 days, most episodes have a longer duration, and a manic phase frequently follows a depressive phase.
Treatment
Treatment of bipolar disorder has to approach two phases of the disease: the acute relapse, which may be mania, depression, or both, and long-term prevention of relapse. Treatment of an acute relapse is usually undertaken in the hospital, especially for patients who have manic features or severe depressive symptoms. Psychotropic drugs are the mainstay of this phase of treatment, and a combination of lithium and an antipsychotic drug such as olanzapine is most commonly used.3 Antiepileptic drugs such as valproate or carbamazepine can be substituted for lithium in the treatment of acute manic and mixed phases of bipolar disorder.
Treatment to prevent relapse has historically relied on lithium or an antiepileptic drug. Olanzapine is associated with a substantial risk for adverse effects on various cardiovascular risk factors, including glucose tolerance, cholesterol levels, and blood pressure (Chapter 460). Integration of a psychotherapy, either cognitive or supportive (see later), with medications is optimal for preventing relapses.
Before lithium therapy is begun, a complete blood cell count, urinalysis, electrolytes, creatinine level, blood urea nitrogen level, thyroid function studies, and a baseline electrocardiogram should be obtained. Chronic medical illnesses, especially renal insufficiency, can be contraindications to lithium therapy. Lithium carbonate is available in 300-mg tablets or capsules, and a 300-mg slow-release tablet is available. The starting dose of lithium carbonate for acute mania is generally 300 mg three or four times per day. Lithium has a half-life of 24 to 36 hours, and it takes at least 4 days to achieve a steady state. Its specific therapeutic effectiveness is not evident until at least 4 to 10 days after the institution of therapy. The serum level of lithium should be monitored and the dose adjusted accordingly. The dosage should be adjusted upward by a full or half tablet after the serum level is checked during this time. Adequate levels for acute illness are 0.8 to 1.4 mEq/L. For maintenance therapy, blood levels of about 0.4 mEq/L are desirable. The dose and blood level should be titrated, however, against clinical effectiveness for each patient. Doses are usually given twice daily because absorption from the gastrointestinal tract is rapid and serum drug levels peak within 1 to 2 hours. Elevation of serum lithium levels to more than 2 mEq/L is toxic and a medical emergency requiring immediate hospitalization and possibly hemodialysis (Chapter 133). Side effects of the long-term use of lithium include the development of mild leukocytosis, hypothyroidism, diabetes insipidus, and renal tubular damage. Many patients have a tremor that can be embarrassing and occasionally interferes with activities.
Olanzapine is administered once daily, starting at 10 mg and increasing in 5-mg steps to 20 mg/day, if necessary. Monitoring for drug-induced change in weight, total cholesterol, triglycerides, and serum glucose should be performed at initiation of treatment and at 3-month intervals thereafter. Management of these cardiovascular risk factors should be carried out as for the population at large if in the judgment of the treating clinician the olanzapine is of substantial benefit for the patient. Valproate is initiated at 750 mg/day in divided doses, with increases every 3 to 4 days until a serum trough concentration greater than 50 μg/mL is achieved. Most patients require 1000 to 2500 mg/kg/day in divided doses two or three times per day.
Prognosis
Relapse episodes of bipolar disorder produce major disruptions in psychological, social, and vocational function. Divorce and job loss are common. Long-term, residual symptoms are more common. Most bipolar patients will face one or more relapses during the course of what must be considered a lifelong disease. Their long-term functional outcome depends on the frequency and severity of the affective episodes, response to treatment, and the care and quality with which that treatment is applied. Mortality with bipolar illness averages 2 to 2.5 times the age-expected rate; 8 to 10% of patients commit suicide.
▪Anxiety Disorders
Definition
The anxiety disorders, which occur across the entire lifespan, are accompanied by an array of neuropsychiatric symptoms, including nervousness, fearfulness, sleeplessness, dyspnea, chest pain, gastrointestinal distress, and others. These disorders generally occur in two patterns: (1) chronic, generalized anxiety and (2) episodic, panic-like anxiety. Episodic anxiety is often context dependent, such as the performance anxiety of a musician before an audience. When panic attacks occur, however, they are qualitatively different from generalized anxiety. The patient typically experiences a sudden onset of intense fear, arousal, and somatic symptoms without provocation. Panic attacks are often confused with systemic medical illnesses such as angina pectoris or epilepsy. A spectrum of related psychiatric disorders often coexists with the anxiety disorders, including post-traumatic stress disorder, substance abuse, and depression.
Epidemiology
Lifetime prevalence rates for DSM diagnosable anxiety disorders are 30% in women and 19% in men. Point prevalence rates in general U.S. populations are 2 to 6% for generalized anxiety and 1% for panic disorder. The anxiety disorders may be the most common psychiatric disorders in general medical practice.
Pathobiology
Anxiety disorders cluster in families, and there is often an overlap with depressive disorders. Twin studies more clearly indicate a shared familial risk for panic disorder than for generalized anxiety. The underlying neurophysiology and neurochemistry of the anxiety disorders are thought to involve increased activity or sensitivity of noradrenergic systems projecting from the locus ceruleus into frontal and temporal forebrain regions.
Clinical Manifestations and Diagnosis
Diagnostic criteria for generalized anxiety disorder (DSM-IV) emphasize the presence of unrealistic or excessive worry and apprehension about two or more life circumstances for a period of 6 months or longer, during which time the person has been bothered more days than not by these concerns. At least six symptoms from Table 420-4 must be present during these periods.
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Panic attacks are characterized by the sudden onset of intense apprehension, fear, or a sense of impending doom. These attacks are often spontaneous and may overlap with the more generalized anxiety disorder described earlier (Table 420-5).
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Treatment
In acute anxiety or panic disorder, the short-term efficacy of pharmacologic agents as measured by panic-free rates is high, with success rates of 50 to 70%. Four classes of medications have been shown to be effective in reducing recurrent panic attacks: SSRIs, tricyclic antidepressants, benzodiazepines, and monoamine oxidase inhibitors. Drugs from all four classes have roughly comparable efficacy. Treatment is generally initiated with either SSRIs or benzodiazepines. All the available SSRIs in the United States have support from clinical trials to justify their use in the treatment of panic disorder. The doses of SSRIs for panic disorder should be at the high end of the ranges presented in Table 420-2. Alprazolam has been studied more extensively than other benzodiazepines for the treatment of panic disorder. Typically, its dosing is initiated at 0.5 mg twice daily and increased to 6 to 8 mg/day if clinically necessary to control symptoms. Many patients require ongoing pharmacotherapy, and others have symptoms despite treatment.
For generalized or chronic anxiety, the antidepressants are much less efficacious. The short-term relief afforded by almost any benzodiazepine is dramatic in generalized anxiety, but habituation and addiction are common, so caution should be exercised. If the generalized anxiety symptoms have any situational quality, other therapeutic measures should be considered before benzodiazepines are prescribed. Variations of cognitive behavioral psychotherapy should be tried, including reassurance, education, relaxation exercises, hypnosis, and other psychotherapies. Environmental alterations may be considered at home or at work, depending on the individual's specific anxiety symptoms. When a psychopharmacologic intervention is prescribed, it should be given for a defined period of 1 to 4 weeks while the situation is reassessed by the physician. Antihistamines such as diphenhydramine, 25 mg three times a day, can be tried in some patients. Buspirone is a nonbenzodiazepine antianxiety agent that sometimes provides relief at doses of 5 mg twice a day initially. The benzodiazepines presented in Table 420-6 are effective in many patients. Lorazepam is often the first used because it is relatively short acting (half-life of 10 to 15 hours) and easier to titrate in elderly or medically ill patients. Because its half-life is shorter than that of drugs such as diazepam, lorazepam must be taken at least twice and often three times per day. A dosage of 0.5 mg twice daily is the initial regimen for most patients. The dose should be increased by 0.5 mg/day at 3-day intervals until the target symptoms resolve or sedative side effects supervene. Elderly patients should always be watched carefully for an ataxic gait. For all patients, opportunities to taper or reduce the drug dose should be sought.
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Somatoform Disorders
Definition
The somatoform disorders (Table 420-7) are a heterogeneous group of psychiatric disorders that share the common feature of mimicking medical or neurologic disease; their categorization may undergo revision in the future. The mimicry may involve an exaggeration of the severity or disability of an actual medical illness, or it may consist entirely of simulating a medical illness that is not present. In the lexicon of general medicine, some of these disorders are called “functional,” some are called “pain syndromes,” and some are called “conversion” or “Munchausen” syndromes. These disorders are quite common in general medical settings, where they account for as many as 25% of cases seen in primary and secondary care settings.
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Epidemiology
Good epidemiologic data about the somatoform disorders are lacking. Cross-sectional studies of patients attending general neurology practices indicate prevalence rates of 15 to 20% in these populations. Disor-der-specific and population-based studies are not available for these disorders.
Pathobiology
There are as yet no credible neurobiologic explanations for the somatoform disorders. Freud and colleagues believed that the symptoms were produced by a process of primary gain in which the expressed somatoform disorder provided a partial solution to an intrapsychic problem or conflict. The primary gain is not usually readily discernible because the patient is almost always unaware of it.
The secondary gain associated with a conversion illness refers to the clearly visible financial gain or relief from responsibility conferred by the sick role. These gains may be seen in many guises, such as disability pensions, relief from work, enhanced attention from family and physicians, and litigation payouts.
Clinical Manifestations and Diagnosis
▪Conversion Disorder
The essential feature of a conversion disorder is the mimicry of a discrete general medical or neurologic syndrome by a psychiatric process. Conversions typically do not conform to known anatomic systems but instead follow the individual's unconscious conceptualization of neurologic function. Conversion disorders may be episodic, as in conversion seizures, or chronic and persistent, as in the case of sensory loss or weakness. To make a valid diagnosis of conversion disorder, two features should be established: failure of the disorder to respect known neuroanatomy and neurophysiology and some positive association with unintentional psychological motivation.
▪Factitious Disorder
In a factitious disorder, the motivation for production of the symptom or sign must be more deliberate than in a conversion disorder but still not fully conscious. The individual may self-administer a drug or other material to create physical signs. Generally, these patients are aware of the behavior that constitutes the factitious syndrome, but they are not aware of why they are doing it.
Munchausen's syndrome, which is perhaps the best known of the factitious disorders, is defined as a repetitious pattern of medical attention–seeking behavior in which the individual has dramatic but untruthful complaints. The somatic complaints typically involve organ systems, such as abdominal pain, and tend to generate painful or invasive medical interventions.
▪Malingering
Malingering refers to the deliberate production of false or grossly exaggerated physical or psychological symptoms to achieve some obvious reinforcement. The secondary gain for malingering syndromes is usually obvious, such as an insurance settlement or relief from arduous duty or responsibility.
▪Hypochondriasis
In hypochondriasis, patients have an abnormal and emotionally heightened relationship with their medical symptoms. The symptoms may be related to an actual neuromedical disorder, or they may occur within the spectrum of normal physiology. A hypochondriacal individual fears the symptoms but is preoccupied with them at the same time. Social or vocational impairment occurs and is poorly responsive to reassurance from physicians.
Pain Disorder
In somatoform pain disorder, chronic and persistent pain has no neuromedical explanation nor objective manifestations. Pain clinics generally classify these disorders as “complex regional pain syndrome” (Chapter 28), but the results of physical treatments are often disappointing. Analgesic addiction is all too often the final, common psychiatric pathway for these patients.
Treatment
The long-term goal of treatment of somatoform disorders is to enable the patient to convert from a medical to a psychiatric patient. Cognitive behavioral therapy can improve hypochrondriachal manifestations and improve functioning.4 This process requires patience and flexibility on the part of the physician. General medical interventions may be invoked initially, including biologic tests, medical rehabilitation, and pharmacotherapy. These interventions may make sense if an underlying medical disease is present or the patient adamantly views the illness as a physical one. The danger of biologic interventions is that they may strengthen the patient's conviction that the illness is physical.
If a pharmacologically accessible psychiatric symptom complex such as anxiety or depression accompanies the somatoform disorder, it may be helpful to initiate psychopharmacologic treatment. For the pain syndromes that represent masked addictions (Chapter 32), opportunities should be sought to promote the patient's entry into a drug treatment program.
▪Character Disorders
Definition
Behavior includes more than cognition and emotion; action and style are additional dimensions that are essential to success and satisfaction in life. Sustained dysfunctional patterns of coping with the world that involve dysfunctional patterns of action and style are called character disorders or personality disorders.
Pathobiology
All individuals have an enduring set of behavioral traits with which they faces life's challenges. These predispositions for the most part do not depend on context, and they are not easily changed from one time to another. These traits manifest themselves in style and action, especially in relationships with others. An individual is typically unaware of these qualities because they are formed in childhood as enduring aspects of personality. Qualities of character include honesty, timeliness, reliability, aggressiveness, and submissiveness.
Clinical Manifestations and Diagnosis
Some individuals have clusters of maladaptive traits that cause recurrent psychosocial difficulties (Table 420-8). In DSM-IV, these disorders are classified as Axis II disorders as opposed to the Axis I classification of the more overt major psychiatric disorders. The personality disorders have a spectrum of severity with poorly specified boundaries and thresholds. It makes clinical sense to think of “personality styles” when the maladaptive traits are less severe. The personality disorders also differ from the Axis I disorders in that they are mostly manifested in interpersonal relationships. It is difficult to imagine the diagnosis of a passive-aggressive personality style in a setting that did not include other people. Often the best clue to the diagnosis of character pathology is the pattern of behavior that the patient shows in relating to the physician. Personality disorders are difficult to recognize. Patients are not consciously aware of the data that validate their diagnoses, and they are typically sensitive when dysfunctional patterns of behavior are clarified. Physicians often do not “see” the personality disorders unless such patients provoke their physicians to feel angry or rejected.
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Treatment
Psychopharmacology is of limited value for the interpersonal dimensions of these disorders. The goal of management is to help patients increase their awareness of the dysfunctional interpersonal traits so that they become more self-conscious about how others are affected by their behavior. Although longer-term psychotherapies must be performed by psychiatric clinicians, general medical physicians can often provide the initial clarifying interventions. Variants of the psychotherapy type described as “interpersonal” (see later) are the most effective approach to patients who show character disorder behavior patterns in practice settings.
▪Schizophrenic Disorders
Definition
Schizophrenia is the “heart of madness” and is still the archetypal psychotic mental disorder. Psychosis is defined as a psychiatric disorder that disrupts reality testing or thought processes. Schizophrenia most often starts in late adolescence.
Epidemiology
The prevalence of schizophrenia in the general population is about 1%, with an incidence of about 0.5 per 1000 person years. The prevalence rate is eight times as great in the lower as in the higher socioeconomic groups. Because the parents of schizophrenics have a social class distribution similar to that of the general population, the lower position of the patients seems to be a result of the illness rather than the cause of it.
Of schizophrenics, 70% become ill between the ages of 15 and 35. The illness affects men and women in equal proportion over the entire lifespan. The age of peak onset risk is 15 to 24 years in men and 25 to 34 years in women. There are slight ethnic differences, with a higher incidence in Scandinavian countries and in nonwhites.
Pathobiology
Schizophrenia is a neuropsychiatric disorder with both structural and functional deficits in a variety of neural circuits interconnecting the prefrontal cortex, striatum, thalamus, and brain stem. It is not yet known to what extent these neurobiologic substrates are determined by genetics and to what extent they are determined by early developmental experiences. The evidence for genetic facilitation in schizophrenia is strong, but as in other psychiatric disorders, no single gene seems to be involved, and concordance in monozygotic twins is only 50 to 60%. The onset of clinical symptoms is often precipitated by adverse psychosocial events in early adult life. The emotional structures and patterns in families are also thought to be important in generating or maintaining some of the schizophrenic symptoms.
Clinical Manifestations and Diagnosis
The characteristic symptoms of schizophrenia fall into two broad categories described as positive and negative symptoms. Positive features include behavior such as delusions and hallucinations. Negative features include symptoms such as restricted affect, anhedonia, and apathy. When a thought process disturbance is the predominant clinical feature, the schizophrenic disorder is described as disorganized. The course of schizophrenia is usually marked by a decline in psychosocial functioning, with a tendency for the patient to become downwardly mobile in social strata. For most patients it becomes a chronic illness characterized by relapses.
Schizophrenia is defined as a long-term mental illness because psychotic features are required to persist for 6 months (Table 420-9). Psychosocial deterioration from a previous level of functioning is also required as part of the definition of schizophrenia. When a psychotic mental illness has persisted for less than 6 months, it is inadvisable to use the diagnosis of schizophrenia. Schizophrenia also tends to be characterized by acute relapses of psychotic features over time. With the first episode of any psychotic illness, an affective disorder or a systemic medical illness should be considered; psychotic episodes secondary to toxic drug reactions, sleep deprivation, and medical causes invariably persist for less than 6 months.
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Subtypes of schizophrenia are defined by the predominant symptoms at the time of the most recent clinical evaluation. Subtypes include the paranoid type, the disorganized type, the catatonic type, and an undifferentiated type. Catatonic symptoms involve either markedly retarded motor behavior (often to the point of no voluntary movement; patients retain any posture into which they are passively placed) or markedly agitated motor behavior. In the paranoid forms of schizophrenia, the paranoid delusions are often the only major symptoms and tend to remain stable over time. The term schizophrenia, residual type is used when positive symptoms of psychosis have abated but the patient continues to have poor psychosocial function.
Treatment and Prognosis
During a 25- to 30-year period, about a third of patients with schizophrenia show some recovery or remission, but the remaining patients have major residual symptoms or require long-term hospitalization. Management requires the establishment of a long-term psychotherapeutic relationship with the patient or the patient's family system, which can facilitate monitoring of the clinical course, recognition of early signs of decompensation, and enhanced compliance with psychopharmacologic treatments. Psychotherapy for schizophrenia is supportive (see later), educational, and rehabilitative in an attempt to prevent or minimize the chronic psychosocial deterioration that can occur in the course of the disease. Protected vocational and living situations are often important constituents of long-term treatment plans.
Long-term antipsychotic medication is essential to reduce relapses (Table 420-10). The initial pharmacologic therapy for psychosis should begin with the administration of one of the newer, “atypical” antipsychotic drugs. This group of drugs includes olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, and clozapine. Clozapine cannot be considered first-line therapy because of its hematopoietic and hepatic side effects (Chapter 460). These agents are termed atypical because of their side effect spectrum, which differs significantly from that of the older, traditional antipsychotic agents such as haloperidol and chlorpromazine. As a group, the newer drugs cause less acute motor system side effects than the older drugs do and may have a lower long-term risk for tardive dyskinesias.
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The relative effectiveness of these second-generation (atypical) antipsychotic drugs may not fully justify their widespread use. For example, a large randomized trial found that the efficacy of the first-generation antipsychotic drug perphenazine was equal to that of a series of second-generation drugs, including olanzapine, quetiapine, risperidone, and ziprasidone.5 Of note was that 74% of patients in this study were unable to take their medication for the full 18-month target duration because of side effects.
As a group, the newer antipsychotic agents exacerbate cardiovascular disease risk factors such as hypertension, glucose tolerance, and hyperlipidemia. These adverse effects are significant for many patients and require continuous monitoring, usually on an every-3-month schedule (Chapter 460). The decision whether to manage such cardiovascular risk factors as in the general population while continuing the drug or to substitute an antipsychotic agent from another class must be based on the clinician's judgment of the substantive value of an individual drug for an individual patient.
Typical initial regimens include risperidone, 2 mg twice daily, with an increase to a total dose of 6 to 10 mg/day after 1 week if tolerated. Antipsychotic efficacy is usually seen in this target dose range for risperidone, with a 4- to 6-week delay for some effects. An alternative is olanzapine, which can be administered once daily. A starting dose for olanzapine is 5 mg daily, with 5-mg increases at weekly intervals to the 15- to 20-mg range if symptoms do not improve and side effects are tolerable. The aggressiveness of the dosing regimen is dictated to some extent by the quality and severity of the psychotic symptoms. The antipsychotic benefit from these drugs may be immediate, occur gradually over a period of weeks, or be delayed for 4 to 6 weeks. Additional psychotropic agents are sometimes added during the early days of treatment. A benzodiazepine (e.g., alprazolam, 0.25 mg three times daily) may be added when agitation and sleep disturbance are severe. The most frequent limiting factor in the dosing of antipsychotic drugs is the appearance of extrapyramidal side effects, including dystonia, akathisia (restlessness), and parkinsonism.
An additional risk with the use of antipsychotic drugs is the development of tardive dyskinesia. Tardive dyskinesia (Chapter 434) is a syndrome of involuntary movements, usually choreoathetoid, that can affect the mouth, lips, tongue, extremities, or trunk. Though generally associated with use of neuroleptics for 6 months or more, tardive dyskinesia can occur with shorter administration. Patients receiving neuroleptics should be evaluated periodically for these abnormal movements. Rates of tardive dyskinesia with the atypical antipsychotic medications are considerably lower than with the traditional ones but are not zero. The cause of tardive dyskinesia is not known, but it is believed to represent the development of dopaminergic hypersensitivity in extrapyramidal motor systems.
Drugs for Psychosis
Drugs that affect dopaminergic function by blocking mesolimbic dopamine receptors have the demonstrated ability to improve a variety of psychotic symptoms. The older antipsychotic drugs show broad-spectrum dopamine receptor–blocking properties; they affect all receptor subtypes, as well as nigrostriatal neurons (substantia nigra pars compacta, A9) and limbic dopaminergic neurons (ventral tegmental area, A10). Consequently, these drugs have many motor system side effects. The newer antipsychotic agents have variable effects on dopamine receptor subtypes and other neurochemical systems such as serotonin.
Risperidone
Concomitant blockade of D2 receptors in the basal ganglia has been presumed to underlie the production of extrapyramidal syndromes by traditional antipsychotic drugs. More recently, psychopharmacologic research has turned to agents that simultaneously block D2 and serotonin (5-HT2) receptors. These agents have fewer extrapyramidal side effects and may be more broadly effective for the negative symptoms of schizophrenia than the traditional antipsychotic drugs are. In vitro evidence indicates that risperidone has 20-fold higher affinity for 5-HT2A receptors than for D2 receptors.
Clozapine
Clozapine was developed in Austria and Germany in the 1960s. Because of its tricyclic-like structure, it was hoped that it might be an antidepressant. Instead, it turned out to be an antipsychotic drug with no extrapyramidal side effects. Clozapine is a dibenzodiazepine with atypical properties and side effects. It possesses strong anticholinergic properties in addition to serotonin-blocking properties. It produces proportionally greater suppression of mesolimbic as opposed to striatal dopamine systems. Clozapine blocks D2 receptors, as do other antipsychotic drugs, but it also produces a relatively greater blockade of D1 systems, which may account for its altered pattern of efficacy and the absence of tardive dyskinesia as a side effect.
Clozapine can cause fatal agranulocytosis. An overview of available reports indicates that agranulocytosis occurs in 0.05 to 2% of patients given clozapine, a rate higher than that found in patients given other antipsychotic drugs. The agranulocytosis does not seem to be dose related. In most cases there is a several-week prodrome with a declining peripheral white blood cell count, but this prodrome is not always seen. Discontinuation of the medication does not consistently prevent progression to agranulocytosis. Most cases occur within 3 months after initiating treatment. Weekly monitoring of hematologic function is indicated for all patients receiving clozapine.
Olanzapine
Olanzapine blocks 5-HT2 receptors in addition to a spectrum of dopamine receptor subtypes, including D1, D2, and D4. It also has some anticholinergic and α1-blocking properties. This spectrum of pharmacologic properties generates fewer extrapyramidal side effects than most older antipsychotic drugs do.
Quetiapine
Quetiapine has actions and uses similar to clozapine. It is associated with a lower incidence of agranulocytosis. Because of reports of cataracts with prolonged use, semiannual slit lamp examinations are recommended for patients taking quetiapine.
Ziprasidone
Ziprasidone is a newly approved antipsychotic drug that favorably affects positive and negative symptoms in schizophrenia. It has low rates of extrapyramidal side effects but can cause akathisia. It has been associated with a prolonged QT interval on the electrocardiogram.
Aripiprazole
Aripiprazole is the newest of the atypical antipsychotic drugs available in the United States. It is a mixed agonist/antagonist across several subtypes of dopamine and serotonin receptors.
PSYCHOPHARMACOLOGY AND PSYCHOTHERAPY
General Approach to Psychopharmacology
Some general clinical guidelines should be followed in the use of all psychotropic drugs. The physician should select in advance the symptoms that are targets for therapy, such as agitation, sleep disturbance, or depression. In addition, the clinician should establish clinical guideposts to judge the efficacy of the therapy. If the targeted symptoms fail to improve after some defined period, the therapy should be stopped or changed, or consultation should be sought.
Dosing and Timing
The two most common errors made by nonpsychiatrists who use psychopharmacologic agents are inadequate dosing and not waiting long enough to observe the expected effect. For all agents, the first approach to a suboptimal response should be to increase the dose of the selected drug either to a predetermined total daily target or to a maximal tolerated dose. Second, the physician must wait for a predetermined time, usually 4 to 6 weeks for antidepressant and antipsychotic drugs, to allow evidence of clinical efficacy to emerge.
Clinical Familiarity
Effective use of these drugs, as with other pharmacologic agents, requires practical expertise that comes only from experience. Clinicians should not attempt to become familiar with all psychopharmacologic drugs equally but should develop experience-based familiarity with one or two agents from each category.
General Approach to Psychotherapy
Of the total scope of ambulatory psychiatric morbidity, 90% is treated by primary care and other nonpsychiatric physicians. Restriction of these general medical therapies to psychopharmacology is too narrow in view of increasingly persuasive evidence of the efficacy of psychotherapies for neurotic psychiatric illness. At present, however, there is no generally accepted model by which to bring psychotherapeutic skills into the general medical setting. It has been argued persuasively for decades that nonpsychiatric physicians perform various forms of psychotherapy on a regular basis through the relationships that they already have with their patients. These practitioners can work to improve their psychotherapeutic effectiveness.
Theory of the Therapeutic Relationship
The patient comes to the physician because of an experienced need. There is almost always a perceived need for help that may be more or less developed and conceptualized, depending on the individual patient. It is from this fundamental need for assistance that the possibility of a therapeutic relationship arises. Nonpsychiatric physicians may underestimate the emotional depth and potential psychotherapeutic power of this therapeutic relationship. This relationship already exists in nascent form with many of their patients and is an underused therapeutic tool.
Psychotherapeutic Strategies
The fundamental skills of psychotherapy are largely generic and independent of technical expertise. These skills include empathy, sensitivity to emotional cues, the capacity to listen actively, and the ability to intervene with corrective information at acceptable time points as patients talk. When psychopharmacologic agents are prescribed, clinicians should generally craft some complementary psychotherapy in parallel. Several general approaches can be used.
Cognitive Behavioral Therapy
Behavioral therapy is a psychotherapy based on the general principle that interventions should be focused on behavior, thoughts, and emotions that are present at a given time. Such a hypothesis underlies most of our educational endeavors and is readily understandable to most physicians. Key elements of this psychotherapeutic technique are clarification, education, and emotional support. This strategy is commendable as a first-line therapeutic strategy for most mild psychiatric problems. This approach is similar to the approach that physicians use for other clinical problems.
Psychodynamic Therapy
Psychodynamic psychotherapy refers to more time-limited versions of psychotherapy that derive from psychoanalytic theory. One of the basic tenets of such therapies is that we do not fully understand ourselves, our motivations, our feelings, the ways in which we affect others, and the ways in which we are affected by important experiences earlier in life. The healing process of the dynamic or insight-oriented therapies is to increase this self-understanding. Freud allowed his patients to think and speak freely during his sessions with them while he listened intently for clues about meanings and motivations that were not quite consciously understood by the patients. He described resistances that patients showed to keep painful feelings and conflicts from emerging into conscious life, and he wrote about transference, or the application to the physician of emotional attachment behavior that derives from other areas of the patient's life experience. One of the major advantages of this perspective is that it permits the clinician to take full account of the strengths of individuals as they have expressed themselves across their entire life course. The technical skills most important in this technique include active listening, empathic connections with the patient, and the ability to make interpretive connections to previous life events.
Interpersonal Therapy
The interpersonal approach to psychotherapy is directed explicitly at the group system in which a patient lives or works, as opposed to the patient as an individual. It is a relationship-oriented psychotherapy. An approach to the family is a variation of interpersonal therapy and is performed whenever the physician brings family members into the examination room. Couples therapy is also a form of interpersonal psychotherapy and is the most common type of family therapy performed by nonpsychiatric clinicians. In these therapies, the physician addresses some difficulty in the interpersonal system. The relationship patterns of the system must be considered, and the positive strengths must be identified. The problem must be amenable to definition within such a relationship system. The simplest metaphor to use for interpersonal therapy in medical settings is the system-wide impact of the medical illness being experienced by the identified patient.
Guideline
A rough guideline to set a work plan for a medical psychotherapy might consider the following technical points:
Diagnosis: Define the problem in psychosocial terms in a way that makes sense to the patient and family.
Work plan: Set an initial number of talking visits and specify the frequency and duration of each visit.
Strategy: Consider the overview strategies outlined here, and consider which strategies might be best applicable to the situation at hand.
Consultation: Be prepared to request a psychiatric consultation.
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