Obsessive-Compulsive Mark Zetin, M.D. Meagan A. Kramer,

M.S.W.

Obsessive-compulsive disorder is a well-defined clinical syndrome that has been difficult to treat with standardpsychotberapies and med. ications. Data accumulated over the last decade have demonstrated that the disorder is relatively common and frequently coexists with phobia, depression, and alcohol abuse. The authors review current studies oftbe spectrum of obsessivecompulsive disorder and related disorders that respond to the new serotonergic antidepressants and behavioral therapy. Differential diagnosis, epidemiology and comorbidity, etiology, evaluation, and psychologic and pharmacologic treatments are discussed. Most patients with obsessive-compulsive disorder require long-term treatment with drugs, but behavioral therapy has also been used successfully. Serotonin reuptake inhibitors used in the treatment of depression have been found effective; clomipramine has produced the best results in large-scale tests. The fswt that serotonin reuptake inhibitors are effective as both antidepressants and antiobsessional agents suggests common biological factors in disorders that respond to these drugs.

Dr. Zetin is associate adjunct professor ofpsychiatry in the Department of Psychiatry, University of California, 101

City

Irvine,

Drive

Orange,

California

Kramer

is a recent

Medical

South,

Center,

Route 92668.

graduate

88, Ms. of the

University of Southern School of Social Work.

California

Hospital

Psychiatry

and

Community

Disorder

Older psychiatric textbooks described obsessive-compulsive disorder as both rare and difficult to treat. Neither description now appears to

Definition

designed to produce or prevent some future event or situation. The act is not realistically connected to the event or situation. It is typically viewed by the patient as excessive, senseless, and unpleasurable despite its tension-relieving properties (2). Many other disorders have syrnptorns closely related to those of obsessive-cornpulsive disorder, and they may ultimately be considered as disorders on the obsessive-compulsive spectrum. Body-dysmorphic disorder, also known as atypical sornatoform disorder or monosymptomatic hypochondriasis, involves preoccupation with a supposed bodily defect. It responds to antiobsessional drugs (3-5). Trichotillomania involves compulsive hair pulling that often leads to large bald spots on the scalp. It primarily affects females, usually beginning at puberty, and often takes a chronic course (6). Trichotillomania, religious scrupulosity, urinary obsessions, cornpulsive facial picking, hoarding, and paraphilias share many features of obsessive-compulsive disorder, including pharmacologic responsiveness (7-12). Unwanted erections may be a presenting symptom of ohsessive-compulsive disorder (13). Some authors debate whether the preoccupation with food, weight, and body image of anorexia nervosa represents a variant of obsessivecompulsive disorder (14-16).

Obsessive-compulsive disorder is defined by the presence ofeither obsessions or compulsions (2). Typically both are present. An obsession is an intrusive or recurrent thought, image, or impulse that is senseless or repugnant and that the person attempts to ignore or suppress. A cornpulsion is a need to perform a task or ritual in a repetitive, seemingly purposeful, stereotyped way that is

Case examples The following cases illustrate the suffering that make aggressive treatment of obsessive-compulsive disorder essential. Mr. G was a 48-year-old married self-employed man who came for his ninth psychiatric consultation. He had been in and out of therapy since age 14. He indicated that his symp-

be accurate. In this paper trum of obsessive-compulsive

the

spec-

disorder and related disorders that respond to the new serotonergic antidepressants and behavioral therapy are discussed. Jenike (1 ) has described obsessivecompulsive disorder as a hidden epidemic” affecting approximately 4 million people in the United States. Most suffer silently in their homes, sadly missing out on life’s enjoyable experiences. They imprison their families in their orderly and ritualistic life-style. As media reports on effective therapies increase, consumer demand for treatment will predictably rise. Treating clinicians must be aware of highly specific serotonin reuptake inhibitors and behavioral therapies, as well as nonspecific supportive treatments. Treatments for obsessive-compulsive disorder will require us to reconceptualize serotonin reuptake inhibitors as more than antidepressants. The central role of serotoni n in obsessive-compulsive disorder, depression, bulimia, impulsive aggressive behavior, and suicide is emerging as a major theme in biological psychiatry. “

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Table 1 Frequency of obsessive and compulsive symptoms among 70 children and adolescents with obsessive-compulsive disorder1 Symptom

%

Obsession Dirt, germs, or toxins Something terrible happening Symmetry, order, exactness

40 24 17

Religious

scrupulosity

13

Compulsions Hand washing, showering, bathing, tooth brushing, grooming Repeating rituals (in and out door, up or down from chair) Checking (doors, locks, stove, appliances, etc.) Rituals to remove contact with contaminants Touching 1 Based

on data from

Rapoport

85 51 46 23 20

(17)

ily dinner and made spaghetti sauce. She was washing the floor with ammonia while cooking and became worried that she had poured the dirty water into the spaghetti sauce. When Mrs. 0 looked at a crucifix, she thought obscene thoughts about God. She stopped taking communion because she had to shake hands at church and then touch the communion

wafer

before

putting

it

in her mouth. She felt out of control and unable to resist her rituals. Obsessive-compulsive disorder may be a secretive, controlling, and socially debilitating disease, the symptoms of which are manifest primarily at home. Many sufferers seek treatment only when they can no longer hide the embarrassing symptoms in public or when the family insists that the rituals have become intolerable. Other motivating factors include a loss of self-esteem, friendships, and job effectiveness.

toms included checking things and fearing that he would not say just the right thing. He rewrote letters 1 5 or 20 times trying to correct imperfections. He rearranged furniture in spite ofsevere back pain. He got special color-coded note pads to organize his lists and “master lists.” He feared misplacing things, doing things out of sequence, and germs. He avoided situations that might trigger checking behavior. He felt that everything he did resulted in an unpleasurable experience. He spent his second appointment categorizing his lengthy list of symptoms to determine which were indicative of ohsessive-compulsive disorder or depression and which were nonspecific. Mrs. 0, a 59-year-old married homemaker, presented with the complaint that “I have always been a compulsive person, and recently I have had a phobia ofdiseases.” She visited an emergency room weekly for throat cultures to rule out strep and feared developing shingles after seeing her mother suffer from it two years earlier. She was afraid of giving germs to family members and would not kiss them. She would not eat at a buffet because other people had touched the utensils. Two weeks before her evaluation, she had a fam-

Most patients with obsessive-cornpulsive disorder have both obsessions and compulsions. These symptoms are generally ego-dystonic and thus anxiety producing. As shown in Table 1 the most common symptoms among children are concern about dirt or germs, worry about something terrible happening, excessive hand washing and grooming, and repeating and checking behaviors (17). Table 2 lists the most common symptoms among adults, which are worry about contamination, excessive doubt, and somatic concerns. Compulsions include checking, washing, counting, and a need to ask or confess (18). The premorbid antecedents of adult obsessive-compulsive disorder most often include separation anxiety, resistance to change or novelty, risk aversion, ambivalence, excessive devotion to work, magical thinking, hypermorality, and perfectionism (18). The most common coexisting disorders in adults seeking treatment include major depression, simple or social phobia, separation anxiety, eating disorders, alcohol abuse or dependence, panic disorder, and Tourette’s

syndrome

690

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Symptomatic

profiles

,

(18).

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typical

pa-

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tient has suffered an average of seven and a halfyears between the onset of symptoms and first psychiatric contact (19). Differential diagnosis Disorders such as obsessive-compulsive personality disorder, depression, schizophrenia, and phobias share some clinical features of obsessivecompulsive disorder. These other disorders

must

be considered

in the

differential diagnosis because their treatment differs from that of obsessive-compulsive disorder. In contrast to obsessive-compulsive disorder, obsessive-compulsive personality disorder is characterized by long-standing perfectionism and inflexibility. Perfectionism interferes with task completion by focusing attention on details rather than the main point ofan activity. Such a person is often controlling, indecisive, stingy, overly conscientious, restricted in emotional expression, and excessively devoted to work; he or she may hoard objects (2). This set of personality traits does not create discomfort or internal conflict. On the contrary,

the

person

others should share and values. Such a person

expects

that

his or her outlook is likely

to seek

Frequency of obsessive and compulsive symptoms among 200 adults with obsessive-compulsive disorder1 Symptom Obsessions Contamination Pathologic doubt Somatic concerns Need ftr symmetry Aggressive

45 42 36 31

impulse

28

Sexual impulse Other Multiple obsessions

26 13 60

Compulsions

Checking Washing Counting Need to ask or confess Symmetry and precision Hoarding Multiple compulsions I

Based

on data

from

Rasmussen

63 50 36 31 28 18 48 and Eisen

(18)

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and Community

Psychiatry

treatment when facing upsetting life events such as the loss ofa job or relationship. He or she is likely to benefit from traditional psychotherapy rather than treatments specific to ohsessive-compulsive disorder. The advantages of group therapy in confronting the character defenses of such individuals have been elaborated by Wells and associates (20). The relationship of obsessivecompulsive personality disorder to obsessive-compulsive disorder is not simple or causal, as evidenced by the numerous other personality disorders that are found in patients with obsessive-compulsive disorder. In treatment samples of patients with obsessive-compulsive disorder, the most common personality disorders include avoidant, histrionic, dependent, and mixed (21-23). Major depression and obsessivecompulsive disorder respond somewhat similarly to medication and share some biological markers. They may be genetically related. Major depression is characterized by changes in mood; loss of interest or pleasure; changes in weight, appetite, or sleep; psychomotor agitation or retardation; fatigue; feelings of worthlessness or guilt; difficulties with thinking, concentrating, or making decisions; and thoughts ofdeath (2). All drugs effective in treating ohsessive-compulsive disorder are also effective in treating depression, but the converse is not true. The biologic basis for this fact is unknown. Seventeen to 70 percent ofpatients with obsessive-compulsive disorder are significantly depressed. About onethird of patients with psychotic depression have obsessional thoughts. Patients with obsessive-compulsive disorder may share many of the

obsessive-compulsive disorder (27). Interestingly, obsessional features in the course of depressive psychosis may confer a protective effect against suicide attempts (28). Schizophrenia is most readily distinguished from obsessive-compulsive disorder by lack of insight, disorganized thinking, and deterioration of social functioning. Schizophrenia is also characterized by hal-

Data

the

accumulated

last

over

decade

demonstrated

have that

obsessive-compulsive disorder

is relatively

common and frequently coexists with other psychiatric disorders.

blunted growth hormone response to intravenous clonidine and a nonsuppressing response to the dexamethasone suppression test. Abnormal sleep patterns may include short REM latency, decreased total sleep time, decreased stage 4 sleep, decreased sleep efficiency, and increased awakenings (24-26). Two of three studies reported an increased prevalence of affective disorders in first-degree relatives of patients with

lucinations, delusions, and thought disorder. A patient with schizophrenia typically states his or her delusions with a greater sense of conviction, a less plausible explanation, and less questioning than does a patient with obsessive-compulsive disorder. The magical thinking and rituals in schizophrenia may at times resemble those in obsessive-compulsive disorder. In the majority of long-term studies of obsessive-compulsive disorder, less than 3 percent of patients develop schizophrenia (28). Schizophrenic patients with obsessivecompulsive symptoms may have less personality disintegration (28). The biologic treatment of schizophrenia rarely involves antidepressants. Some patients may have obsessive-compulsive disorder with psychotic features, which usually represents a transient reactive psychosis with loss of insight. Accompanying psychotic features may predict poor long-term outcome without specific aggressive treatment (29,30). A simple phobia is a persistent fear of a circumscribed object or situational stimulus. It is anxiety provoking to an excessive or unreasonable extent. Avoidance of the phobic stimulus interferes with normal activities and relationships. This

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avoidance contrasts with the ritualizing response to an anxiety-provoking stimulus in obsessive-compulsive disorder (2). The phobic stimulus is unrelated to the obsessional content of obsessive-compulsive disorder. Behavioral desensitization may be helpful in treating phobias, and medication is seldom required. Tourette’s syndrome involves chronic and frequent motor and vocal tics. In Trimble’s sample (3 1 ) of 90 Tourette’s patients, 33 had symptoms of obsessive-compulsive disorder. These symptoms were often more disabling than the tics. Diagnostic evaluations of first-degree relatives of patients with Tourette’s syndrome have indicated a genetic link with obsessive-compulsive disorder (32,33). Hoarding is a nonspecific symptom that may be present in obsessive-compulsive disorder, paranoid delusional disorders, or organic mental disorders (34). Other disorders with symptoms similar to those of obsessive-compulsive disorder indude epilepsy, Sydenham’s chorea, postencephalitic Parkinson’s disease, and toxic lesions ofthe basal ganglia. Epidemiology

and

comorbidity Data accumulated over the last decade have demonstrated that obsessive-compulsive disorder is relatively common and frequently coexists with other psychiatric disorders. A 1984 review ofthe epidemiology of obsessive-compulsive disorder by Rasmussen and Tsuang (35) found widely divergent estimates of its incidence in adult psychiatric patients, ranging from 1 to 4 percent of inpatients and .6 to 2 percent of outpatients. The authors noted a male-female patient ratio in the literature of 1 to 1 1 among adults and contrasted it with findings of other studies in which 76 percent of children with obsessive-compulsive disorder were male. Among high school students, the cumulative prevalence of obsessive-compulsive disorder is about 1 percent (17). Rasmussen and Tsuang also reviewed studies of intelligence in ohsessive-compulsive patients as measured by the Wechsler Adult Intelligence Scale (WAIS). The reported .

.

691

mean WAIS full-scale values of 99, 106, and 1 13 contradict the general impression that patients with obsessive-compulsive disorder are highly intelligent. Family and twin studies of patients with the disorder were complicated by the presence of depression and anxiety, and results were considered inconclusive Premorbid obsessional traits were cornmon but were not specific for development ofobsessive-compulsive disorder. Rasmussen and Tsuang also found that marital maladjustment might not be syndrome specific. Black’s 1974 review (28) of studies of obsessive-compulsive disorder indicated that 49 percent of patients were male. Celibacy and marital conflict were common. The major epidemiologic study of obsessive-compulsive disorder in the United States was part of the 1988 National Institute of Mental Health (NIMH) Epidemiologic Catchment Area program. In five major cities, structured interviews using the Diagnostic Interview Schedule were conducted with 18,000 adults living in the community and 2,500 adults in institutional settings. A strict DSM-III lifetime diagnosis of obsessive-compulsive disorder was found in 1.2 to 2.4 percent ofadults (36). Without the DSM-III exclusion criteria, the estimate of lifetime prevalence rose to 1 .9 to 3.3 percent of the adult population. As with other psychiatric disorders, lifetime diagnosis of obsessivecompulsive disorder was associated with risk of divorce or separation. The mean age of onset was 22.7 years. Age ofonset and lifetime preyalence were essentially the same for men and women. Several comorbid disorders were found in the five-city sample. The strongest associations included ohsessive-compulsive disorder and phobia (46.5 percent), a major depressive episode (3 1 .7 percent), and alcohol abuse or dependence (24.1 percent). Among those diagnosed with obsessive-compulsive disorder, 43.7 percent were receiving mental health care, compared with 61.8 percent of those with panic disorder and 23.9 percent of those with phobic disorder (36). The lifetime preva-

lence rates reported in the Epidemiologic Catchment Area study were about 25 to 60 times higher than had been estimated based on studies of clinical populations. The report suggested that “although not conclusive, the evidence is strong that obsessive-compulsive disorder is a common mental disorder that, like other stigmatized disorders in the past, may be ready for discovery and demands for treatment on a large scale” (36). Comorbidity of obsessive-compulsive disorder and panic and phobic disorders is common (37). Comorbid personality traits of patients in treatment samples have been evaluated using the Tridimensional Personality Questionnaire (38). Patients with obsessive-compulsive disorder were significantly more likely to have the trait of harm avoidance than control subjects without the disorder (38). The Personality Diagnostic Questionnaire indicated that the most common personality disorders among patients with obsessive-compulsive disorder were avoidant (30 percent), histrionic (26 percent), and dependent (19 percent) (2 1 ,22). Patients with personality disorders significantly improved during treatment (21,22). Using the Structured Interview for the DSM-III Personality Disorders, Baer and associates (23) found the most common personality disorders among patients with obsessivecompulsive disorder were mixed (15 percent), dependent (12 percent), and histrionic (9 percent). Compulsive personality disorder was found in only 6 percent of patients. The presence of a personality disorder may be relevant to pharmacotherapy outcome (39). Etiology There are many psychological and biological approaches to understanding obsessive-compulsive disorder. Older psychodynamic formulations have given way to newer behavioral approaches. Neurobiologic findings have consistently pointed toward an underlying brain dysfunction in obsessive-compulsive disorder. Psychological theories. The classical psychoanalytic approach to oh-

sessive-compulsive disorder follows Freud’s concept that obsessions are a defensive response. They begin as unconscious hostile impulses toward the parents and surface at the time of toilet training when control, autonomy, and aggression issues emerge. Anal-sadistic regressive impulses are defended by isolation, undoing, and reaction formation. This anal-sadistic phase involves ambivalence, magical thinking, and an archaic harsh punitive conscience. Modern analysts view the conflict as one of obedience versus defiance, fear ofbeing caught and punished for naughtiness, and rage at relinquishing one’s own desires and submitting to authority (40-42). Esman (42) quotes Salzman’s summary: “The ohsessive compulsive dynamism is a device for preventing any feeling or thought that might produce shame, loss ofpride or status or a feeling of weakness or deficiency whether such feelings are aggressive, sexual, or otherwise.” The richness ofthe psychoanalytic formulation lies in its elaboration of the conflictual struggle, with its ambivalence, need for control, forbidden wishes, rigid prohibitions, magical thinking, and confusion of thought and action. Unfortunately, Esman concludes, “The therapeutic efficacy of the application of those constructions has been less than dramatic. Were demonstrated therapeutic success a test of construct validity, psychoanalysis would not fare well with obsessive-compulsive neurosis.” Behaviorists view compulsive behavioral symptoms as maladaptive attempts to reduce anxiety. The psychological view elaborated by Carr, as quoted by Esman (42), indicates that “in all situations [the obsessivecompulsive patient] has an abnormally high subjective estimate of the probability of occurrence of the unfavorable outcome. All situations will generate a relatively high level of threat with its consequent anxiety. [Compulsive behaviors are] regarded as the person’s best attempt to reduce threats where no appropriate threat-reducing action can be taken.” Biological theories. Biological

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.

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.

.

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studies have focused on the biochemistry ofserotonin and other neurotransmitter

systems.

Brain-imaging

studies have used functional activity and anatomical methods. Neuropsychological tests and lesions induced by naturally occurring diseases or by neurosurgery

have

also

been

studied.

Neurotransmitter studies. The central focus of neurotransmitter studies is the fact that antidepressants that are highly specific serotonin reuptake inhibitors are effective in treating obsessive-compulsive disorder. These antidepressants indude clomipramine, fluoxetine, fluvoxamine, and sertraline (43,44). It is possible that obsessive-compulsive disorder is associated with upregulated postsynaptic serotonin receptors and that chronic serotonergic antidepressant treatment downregulates these receptors (24,45,46). There is some evidence for dopaminergic involvement in patients with obsessive-compulsive disorder who have tic spectrum disorders (47). It is important to emphasize that pharmacologic response does not imply etiology or pathogenesis. Changes in any neurotransmitter system associated with pharmacologic response may be directly or indirectly related to the primary cause ofthe disorder. Brain-imagingstudies. Positron emission tomography (PET) studies can be used to determine glucose metabolism in different regions of the brain. Baxter and associates’ work (48) with patients with obsessivecompulsive disorder has demonstrated increased activity bilaterally in the caudate nuclei and in the left orbital gyrus. Rapoport’s study (17) showed increased frontal and cingulate activity. Increased orbital frontal cortex activity is a consistent finding in PET studies of obsessive-compulsive disorder, but it is not yet known whether this finding represents trait or state abnormalities (49). Nuclear magnetic resonance and computerized axial tomography demonstrate orbital frontal cortex, caudate, and ventricle-brain ratio changes, though some findings have not yet been replicated (50-53). Neuropsychological studies. Frontal lobe dysfunction is suspected

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based on detailed neuropsychological, electroencephalogram, and imaging studies. Some suggest changes in normal brain laterality (54). Adolescents with obsessive-compulsive disorder were found to have spatialperceptual deficits similar to those of patients with frontal lobe lesions, age-inappropriate synkinesias, and left hemibody signs (52). Medication-free patients with ohsessive-compulsive disorder showed more abnormalities in fine motor coordination, involuntary and mirror movements, and visuospatial function than matched controls (5 5). Excessive neurologic soft signs on the left side of the body and abnormalities in cube drawing suggest right hemispheric dysfunction. These neurological soft signs correlated with severity ofobsessions (5 5). Lesion studies. Patients with rheumatic fever may develop Sydenham’s chorea, probably as a result of an autoimmune response to the basal ganglia. Obsessional symptoms and obsessive-compulsive disorder are more common in those who develop chorea than in those who do not (17). Neurosurgical lesions have been used in the treatment of refractory obsessive-compulsive disorder. Areas where lesions are especially useful in reducing symptoms include the cmgulum and anterior capsule (56).

Natural

history

The long-term course of obsessivecompulsive disorder is remarkably variable and unpredictable. One review estimated that in 30 percent of persons with the disorder, the onset occurred between the ages offive and 1 5 years (27); in 60 to 68 percent, the onset was before age 25 (19,27). Another review indicated that in half the cases, the disorder began in childhood, with peak incidence in the early 20s, and that in less than 10 to 1 5 percent of patients did the onset occur after age 35 (35). The initial symptoms may indude pain, hypochondriasis, neurasthenia, anxiety, and depressive leatures (28). The most common precipitating factors have been found to be sexual and marital difficulties, pregnancy and delivery, and illness or death of a near relative (19,28). Among Chinese patients, frustration

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and overwork were common precipitants (28). In 50 percent of patients, the course of illness may be chronic and unremitting (19). It may also fluctuate over time, with episodes of illness typically lasting less than one year (19). Only about 3 1 to 38 percent of patients seek treatment in their first year of illness (12). Most patients seek treatment in their 20s; however, the average age of patients at hospital admission for the disorder is 33 to 36 years (28). Rasmussen and Tsuang (35) reviewed follow-up studies of patients in nine different samples. Follow-up periods ranged from three to 1 7 years after treatment. Nine to 32 percent of patients improved greatly, 22 to 56 percent showed some improvement, and 22 to 61 percent were unchanged. Long-term treatment outcome was worse with electroconvulsive therapy than with psychodynamic or supportive psychological therapies or no treatment (35). The role of life stress in the longterm course of obsessive-compulsive disorder has been noted by several authors. Improvement may occur when tension is reduced or when the patient has to deal with new external difficulties (28). Wartime service and religious pilgrimages may dramatically decrease symptoms. Increased responsibility, fatigue, recurrence of the original precipitating situations, and increased tension may

worsen

symptoms

(28).

Most

patients with obsessive-compulsive disorder are able to work; however, a minority are severely impaired (28). Prognostic factors are not clearly delineated, but in some studies good prognosis is associated with normal premorbid personality, episodic course, precipitating factors, and a shorter period of illness before first treatment (28). Poor prognostic factors may include obsessional premorbid personality, severe clinical picture on admission, unmarried status, and childhood nervousness (28). Evaluation and psychological treatments The extent of suffering of patients with obsessive-compulsive disorder justifies detailed assessment, education, and psychological and medical

693

interventions. The initial phase of assessment consists of elaborating symptoms. The Yale-Brown Obsessive Compulsive Symptom Checklist is an extremely useful probe for symptoms that may not be mentioned spontaneously (18,57). The Yale-Brown Obsessive Compulsive Scale was developed as a reliable, specific, sensitive, and valid indicator of severity of symptoms that is not influenced by the type of obsessions or compulsions present (58,59). It is very useftil in assessing change in response to treatment. At the time of initial evaluation, differential diagnosis of obsessivecompulsive disorder and other comorbid disorders is necessary. Detailed historical inquiry about personal and family history of mood, anxiety, and substance use disorders is an essential part ofgetting to know the patient. The initial supportive and educational psychotherapy of obsessivecompulsive disorder must take into account several factors. The disorder has probably caused the patient to struggle with his or her thoughts and impulses for a very long time before treatment is sought (19). Predictable issues at the time of presentation indude demoralization resulting from an inability to control symptoms despite many self-help efforts. Guilt, helplessness, and loss of self-esteem are inherent in having struggled to keep the disease a secret. The patient may fear being forced to give up certam thoughts or actions (60). The social impact of the disease may involve celibacy or a broken marriage. If the patient is living with family members, they may report more about the symptom severity and its impact on the patient’s life and lamadmit. The impact of the disorder on the patient’s functioning at work may involve inefficiency and slowness, with decreased productivity. A great deal of time may be spent secretly in the bathroom washing or in the work area arranging objects perfectly before beginning to work. Perfectionism and obsessional slowness may be viewed by others as passiveaggressive behaviors rather than

symptoms of obsessive-compulsive disorder. Psychotherapy should begin with an educational and supportive stance toward both the patient and the lamily. The usual psychoanalytic approach is notoriously ineffective in resolving the symptoms of obsessivecompulsive disorder and may needlessly prolong the patient’s suffering. Simple relaxation techniques are ineffective Behavioral treatment or medications or both are usually mdicated. Behavioral treatment of compulsions involves working with exposure to a progressive hierarchy of evoking stimuli. Exposure in vivo with response prevention is the treatment of choice for compulsions. Exposure in imagination with thought stopping appears to be the treatment ofchoice for obsessions. The latter may be somewhat less effective than the treatment for compulsions. Nonresponders to behavioral therapies may have overvalued ideation-bordering on a delusional belief that their fears are realisticor severe depression. They may be taking high doses of anxiolytics. Some may be unwilling to comply with the time-consuming and anxiety-provoking homework required for behavioral treatment. These issues must be addressed psychologically or biologically before therapy may progress (27). An interesting variant of behavioral therapy was reported by Mehta (6 1), who compared 1 5 patients treated individually with 1 5 patients treated with a family member acting as cotherapist for support in homework assignments. Both at completion of therapy and at follow-up, the symptoms were reduced in the group in which a family member assisted with treatment. Undoubtedly the issue of behavioral therapy versus pharmacotherapy for obsessive-compulsive disorder will remain as controversial as it is for patients with depression and panic disorders. Marks and O’Sullivan (62) and Christensen and associates (63) reviewed the literature and concluded that both modalities are effective. The investigators agreed that exposure is an essential

Pharmacotherapy The pharmacotherapy of obsessivecompulsive disorder may be divided into modalities that are nonspecific and those that appear to be highly specific. Small, open-label, case report series exemplify nonspecific drug treatments. Medications that appear to be highly specific are demonstrated effective by double-blind placebo-controlled studies. The clinician should warn the patient that significant response may take four to eight weeks while side effects appear relatively quickly. Dcpression at baseline is not required to achieve treatment efficacy with serotonin reuptake inhibitors, according to numerous studies. Demographic variables are not predictive ofclomipramine response (66). Nonspecific medications. Many medications have been reported eflective in small samples of patients. These include L-tryptophan, neuroleptics, benzodiazepines, tricyclics, trazodone, clonidine, and lithium. It now appears that neuroleptics are useful primarily for treating patients with obsessive-compulsive disorder who have schizotypal personality or tic spectrum disorder. Monoamine oxidase (MAO) inhibitors are useful for treating patients with comorbid

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part of psychological therapies. Marks stated that antidepressants are worth trying “when patients refuse or fail with exposure therapy, or are dysphoric.” Behavioral therapies may have long-term impact that drugs do not have. Without specific behavioral treatments, the relapse rate for patients discontinued from clomipramine is high (64). In a six-year follow-up (65), patients were treated with 36 weeks of placebo or clomipramine and three or six weeks of inpatient exposure therapy. A better long-term outcome was correlated with more exposure therapy and better compliance with homework assigned during exposure therapy. Drug treatment during the first year had no impact on long-term outcome. This finding argues strongly for the use of behavioral therapy as part of the long-term treatment of even those patients who benefit greatly from medications (62-65).

and Community

Psychiatry

panic disorder (27,43-45,67-71). Specific medications. The response of obsessive-compulsive disorder to medications is unusual for two reasons. Insel and colleagues (72) stated that “from a neuropharmacologic perspective, the most remarkable aspect of obsessive-compulsive disorder is its high selectivity for drug response. Mavissakalian and associates (73) noted the other lascinating pharmacologic fact about obsessive-compulsive disorder: its lack of response to placebos, compared with other anxiety disorders. Long-term treatment with mcdications appears to be required for most patients with obsessive-cornpulsive disorder. Response begins over a period of one to two months after treatment is initiated. Relapse is likely when medications are discontinued. Clomipramine is a new tricyclic drug in the United States, but it has been used in Europe since 1966(74). Its efficacy in treating depression is greater than or equal to that of serotonin-specific reuptake inhibitors. It has significant efficacy in resistant depression, panic disorder, and chronic pain. Like other antidepres“

ed that the onset ofaction of clomipramine at 150 mg per day was clearcut at five weeks of treatment. The response was not predictable from demographic data on the presence or absence of secondary depression. They found nortniptyline no better than placebo. Half of the nortniptyline-treated patients benefited when crossed over to nonblind administration of clomipramine at the

Long-term with

treatment

(78).

medications

obsessive-compulsive Response

begins over a period one to two months.

of

(79)

with unipolar depression to become manic; older patients may be at increased risk ofbecoming manic (75). The efficacy of clomipramine for the treatment of obsessive-compulsive disorder is established more definitively than that ofany other drug. It has been proved to be superior to nortriptyline, clorgiline, and desipramine in numerous studies. The usual dose range for clomipramine is 100 mg to 250 mg per day. The seizure risk during acute treatment tnals in the United States was found to be .48 percent at daily doses of 250 mg or less and 2 1 percent at doses of 300 mg on more (69). Its side effects are those typical of most tnicyclics, including increased pulse rate, constipation, difficulty urinating, dry mouth, delayed ejaculation, drowsiness, hypotension, nausea, dizziness, and tremor. Lithium or L-tryptophan (the latter is not available in the U.S.) may potentiate response to clomipramine in partial responders. Thoren and associates (76) report-

end of the study. Using a doubleblind crossover format, Leonard and colleagues (77) effectively treated children and adolescents with a mean dose of 1 50 mg per day. When crossed over to desipramine, 64 pencent relapsed. Jenike and associates (7 1) also observed clomipramine’s superiority to placebo after five weeks of treatment. The multicenten trials of clomipramine sponsored by Ciba-Geigy in the U.S. have been summarized by DeVeaugh-Geiss and associates (66, 68-70). Patients who failed to improve during a two-week placebo washout were randomly assigned to receive placebo on clomipramine at 100 to 300 mg per day. Only 10 percent ofpatients improved during the washout period, leaving 384 patients in the preliminary analysis. Response to placebo over the ten-week medication trial was minimal (73). Response to clomipramine was statistically significant beginning at week 2. Patients’ scores on the YaleBrown Obsessive Compulsive Scale improved an average of4O to 45 pencent by week 10. Improvement continued throughout the drug administration period; no plateau was apparent by week 10 (69). The results indicate a partial response; however,

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A 40

percent

dose

reduction,

from a mean dose of 270 mg per day to 165 mg per day, was possible without clinical deterioration. High doses of fluoxetine and domipramine appear to be equally effective in treating obsessive-compulsive disorder. Turner and colleagues

appears to be required for most patients with disorder.

patients and clinicians reported very significant symptomatic improvement. The presence of panic or phobia with obsessive-compulsive disorder is a positive predictor of response to clomipramine (37). When clomipramine is used in long-term treatment of obsessivecompulsive disorder, the dose may be gradually lowered. Patients who were good initial responders and who had deteriorated when the drug was discontinued were followed up for 17 to 22 months after restabilization

No.

7

made

an

early

report

on

flu-

oxetine’s efficacy in obsessive-compulsive disorder. They treated ten patients with 20 to 80 mg daily. No improvement was evident during the initial two-week placebo washout, but some significant benefit occurred during treatment with fluoxetine. Fluoxetine has been demonstrated to be equally effective in treating patients with obsessivecompulsive disorder in a crossover from clomipramine to fluoxetine at 60 to 90 mg per day (80). Fontaine and associates (8 1) carned out a high-dose open-label study offluoxetine at 60 to 100 mg per day and found a six-week response rate of 86 percent. Side effects included insomnia (18 percent), tremor (16 percent), inhibited ejaculation (7 percent), and nausea (6 percent). Several patients were treated for one year on a mean dose of 78 mg per day. Only 23 percent had a liii! relapse of symptoms of obsessive-compulsive disorden after being taken off medication for one year. Jenike and associates (82) treated 61 patients in a 1 2-week open-label study offluoxetine with a mean dose of 75 mg per day. They found significant improvement in symptoms rated on the Yale-Brown Obsessive Compulsive Scale and the Beck Dcpression Inventory beginning at week 4. Side effects included fatigue

695

(N = 6), sexual dysfunction (N = 5), tremor (N=5), insomnia (N=5), and nausea (N= 3). They pointed out that symptoms of obsessive-compulsive disorder improved equally in depressed and nondepressed patients. Levine and colleagues (83) treated 75 outpatients for up to five months; almost all patients received a dose of 80 mg of fluoxetine daily. Improvement in symptoms was seen after one month of treatment, and patients steadily progressed. This finding led the investigators to recommend a medication trial of several months for patients who fiuil to respond mitially. In an open trial of three to eight months, fluoxetine at a dose of 20 to 40 mg per day was shown to be effective in treating patients with obsessive-compulsive disorder who had Tourette’s syndrome (84). A cautionary note was raised by Hoehn-Saric and associates’ case report (85) of a 23-year-old male treated with fluoxetine at 100 mg per day. Symptoms of obsessivecompulsive disorder successfully resolved, but the patient developed apathy, poor attention and concentration, indifference, perseveration, and forgetfulness consistent with a frontal lobe syndrome. Jenike and colleagues (86) indirectly compared the efficacy and side effects of clomipramine and fluoxetine across different studies. Their conclusions suggest that domipramine is slightly more effective but causes more side effects than fluoxetine. An 1 1-patient randomized double-blind crossover study by NIMH and a subsequent 21-patient clomipramine-to-fluoxetine substitution study (87,88) demonstrated equal efficacy of the two drugs. However, there was a significant lag time in response to the second drug used in both studies. Some adolescent patients did not tolerate clomipramine or improve adequately while taking it(89). They tolerated the combination of low doses of clomipramine (25 to 50 mg per day) with fluoxetine (20 to 40 mg per day). Fluvoxamine is an investigational drug known to be effective in treating obsessive-compulsive disorder. In one study, nine of 21 patients re-

696

sponded to the drug and none of 21 patients to placebo (90). It was unclear why a relatively small proportion of patients responded to the drug. In Perse and associates’ double-blind crossover study (90) of 16 patients for eight weeks and Goodman and associates’ double-blind parallel-group study (91,92) of 42 patients, fluvoxamine was more effective than placebo in the treatment of obsessive-compulsive disorder. Sertraline shows possible efficacy in the treatment of obsessive-cornpulsive disorder and has recently been marketed in the United States (93,94). Buspirone is a specific 5-hydroxytryptaminelA receptor agonist with unknown effects on human cerebrospinal fluid serotonin metabolite levels (95). It is closely related to ipsapirone, which has been used as a serotonergic probe in patients with obsessive-compulsive disorder (95). Buspirone has been reported effective in one case (96), ineffective in a an open trial with 14 patients (97), and effective in a recent NIMH double-blind trial comparing it with clomipramine (87,98). Choice of medication. In the United States, 80 mg of fluoxetine per day costs approximately twice the average wholesale pharmacy price of225 mg ofclomipramine per day. Only clomipramine is approved by the Food and Drug Administration for the treatment of obsessivecompulsive disorder. Although the two drugs are about equally effective, their side effects differ significantly. Clomipramine is associated with sedation, weight gain, tremor, dizziness, sexual dysfunction, and anticholinergic effects. Fluoxetine has the side effect spectrum ofgastrointestinal upset, anxiety, and insomnia. The clinical setting offers more choice than a research protocol. Thus the clinician may choose to instruct the patient to try each drug for a few days at a low dose to establish which is more tolerable before committing to a two-month trial of escalating dosage to determine effectiveness. If neither drug is tolerable to the patient, buspirone is a reasonable third alternative.

July

1992

Vol. 43

No.

7

Augmenting strategies. Partial responders to maximal tolerated doses of clomipramine or fluoxetine during a two-month trial may benefit from a planned series ofdrug augmentation trials. Lithium, buspirone, fenfluramine, and neuroleptics have all been found useful for this purpose (99). Buspirone may be more beneficial in augmentation treatment of patients taking fluoxetine than of those taking clomipramine (87). In an open comparison, ten patients with obsessivecompulsive disorder were treated for 20 weeks with fluoxetine, and ten patients were treated with fluoxetine alone for 1 2 weeks and then fluoxetine plus buspirone for eight weeks (100). The latter group reported significantly greater improvement in obsessive-compulsive symptoms than the group treated with fluoxetine alone; however, selfratings ofdepression did not differ between the groups. Markovitz and associates (101) reported on 1 1 patients with obsessivecompulsive disorder receiving fluoxetine at 80 mg per day for seven to 48 weeks; the patients’ regimen then was augmented with buspirone, 10 mg three times daily with meals. More than half the patients taking the combined drugs showed clear gains compared with their earlier response to fluoxetine alone. One patient who had been treated with fluoxetine (20 mg per day) and lorazepam showed improvement of depression but not of obsessive-cornpulsive symptoms; when buspirone was added obsessive-compulsive symptoms worsened (102). This result may have been related to the relatively low dose of fluoxetine that was used. Fenfluramine at 20 to 60 mg per day may work as an augmenting agent in patients nonresponsive to serotonin reuptake inhibitors (103). Neuroleptics are best reserved for patients with obsessive-compulsive disorder who also have tic spectrum disorder or schizotypal personality; these patients are more likely to respond (104). Neuroleptics carry risks of extrapyramidal side effects, tardive dyskinesia, and neuroleptic malignant syndrome. Both fluvox,

Hospital

and

Community

Psychiatry

amine and pimozide were necessary for treatment of a patient with Tourette’s disorder and obsessivecompulsive disorder (105). MAO inhibitors may be useful for treating patients with obsessivecompulsive disorder who also have panic disorder. However, combining MAO inhibitors with fluoxetine or clomipramine may cause death (99). Psychosurgery Some patients fail to respond to lengthy trials ofboth behavioral psychotherapy and specific medications. For these unfortunate few, psychosurgery may offer a last-chance treatment worthy of consideration (56). Long-term follow-up of refractory patients treated with cingulotomy has indicated that seizures and transient mania are rare complications. At least 25 to 30 percent of patients receive substantial benefit (106). Research questions Evidence suggests that serotonergic abnormalities are present in numerous conditions, including aggressive impulsive violence, fire setting, suicide, depression, and obsessive-cornpulsive disorder. The serotonin reuptake inhibitors discussed above are clearly effective antidepressants and antiobsessional agents. What is their true range of efficacy? Are there other disorders sharing a common psychopharmacologic response? Rapoport (17) has raised the question of whether other disorders involving undesirable compelling behaviors will respond to antiobsessional drugs (17). These disorders indude nail biting, kleptomania, gambling, paraphilias, bowel and urinary obsessions, compulsive sexual behaviors, and others that appear to respond as well to antiobsessional drugs as does obsessive-compulsive disorder. Trichotillomania, monosymptomatic hypochondriasis, religious scrupulosity, compulsive nail biting, and bulimia nervosa respond very specifically to serotonin reuptake inhibitors (3,7). Only well-controlled experiments with these drugs will demonstrate their true spectrum of action. Perhaps a common psychological factor will be found to be related to a neurotransmitter system abnormality.

Hospital

and Community

Psychiatry

Such factors as pathological uncertainty, compulsivity, impulsivity, or abnormal submission-dominance behavior may be among the contenders. Conclusions Greater public and professional awareness of the prevalence and treatability of obsessive-compulsive disorder will lead to greater demands on the clinician. These demands indude development of expertise in the use ofserotonin-specific reuptake inhibitor drugs and behavioral therapies for exposure and response prevention. With appropriate treatment, the quality of life of patients with obsessive-compulsive disorder may be dramatically improved.

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7

Universal access to health care, geriatric psychiatry, the mental health care system in Canada, and managed care are among the issues that will be explored in depth at all-day or halfday sessions at the 1992 Institute on Hospital and Community Psychiatry, to be held October 23-27 at the Westin Harbour Castle in Toronto, Ontario, Canada. “Partnerships for Mental Health: Access, Quality, Cost” is the theme of the meeting, which will feature more than 200 educational sessions, including a videofest and poster sessions. David A. Olenik, M.D., of San Diego is chairman of the institute program committee. For more information, see the preliminary program in the June issue or contact Sandra Hass, H&CP Institute, American Psychiatric Association, 1400 K Street, N.W., Washington, D.C. 20005; telephone, 202-682-6174.

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