Obsessive Compulsive Disorder: A Clinical Update
Authors: Jerald Kay, MD, Professor and Chair of Psychiatry, Wright State University School of Medicine, Dayton, OH; and Deborah Y. Liggan, MD, Psychiatry Resident, Wright State University School of Medicine.
Peer Reviewer: Julia K. Warnock, MD, PhD, Associate Professor of Psychiatry; Director, Clinical Research, University of Oklahoma Health Science Center, Tulsa.
Editor's Note-Obsessive-compulsive disorder (OCD) is characterized by recurrent, persistent, intrusive, often repugnant obsessions and/or compulsions performed by the patient to allay overwhelming anxiety. Obsessions are unwanted, repetitive, irresistible thoughts or urges. In spite of their senseless and repugnant qualities, attempts to banish them are to no avail. Compulsions are stereotyped repetitive behaviors designed to produce or prevent some feeling magically connected to the behavior. There is a subjective sense of being compelled-often associated with a simultaneous desire to resist. Insight into the perverse and senseless nature of these frequently bizarre rituals is usually preserved. Evidence exists that early detection and assertive treatment are important for minimizing the impairment experienced. However, OCD is often called a silent epidemic in that patients underreport symptoms or complain of depression or nonspecific anxiety instead of obsessions and compulsions. The primary care physician might be the only health professional who has regular contact with a patient who has this debilitating disorder. Diagnosis is not difficult if the clinician is aware of its prevalence and the different ways it is expressed.
Definition
As many as 5 million Americans may be suffering from serious functional impairment due to this chronic anxiety disorder. Many of these patients initially present to primary care physicians where they go undiagnosed. Often, patients are hesitant to reveal what they consider to be "crazy" or "odd" symptoms to physicians. Their obsessions are intense, intrusive, unwanted thoughts, such as concerns about bodily wastes and secretions, unfounded fears, need for exactness, symmetry, neatness, excessive religious concerns, perverse sexual thoughts, and intrusions of words, phrases, or music. Usually, the person attempts to ignore or suppress such thoughts or to neutralize them with some other thought or action. Compulsions consist of the subjective urge to repeat meaningless and irrational rituals, such as checking, counting, cleaning, washing, touching, smelling, hoarding, and rearranging. The person feels driven to perform compulsions in response to an obsession or according to rules that must be rigidly applied. Compulsions are excessively time consuming-taking more than an hour a day-or cause marked distress or significant impairment. The patient is aware of the irrationality of his or her behavior but feels compelled to continue nevertheless. The reluctance of patients to divulge their obsessive-compulsive symptoms is compounded by the fact that many physicians were trained in an era when OCD was thought to be a rare condition and fail to ask routine screening questions for obsessions and compulsions.
Epidemiology
Until the mid 1980s, OCD was considered extremely rare. However, the results of the Epidemiological Catchment Area Study (ECA) conducted in 1984 revealed that OCD is the fourth most common psychiatric disorder (after the phobias, substance use disorders, and major depressive disorder). OCD has a six-month prevalence of 1.6% and a life-time prevalence of 2.5%. Age of onset has a bimodal distribution, with one peak in childhood and another peak in adulthood. The disorder begins most often in adolescence and early adulthood. The disabling condition afflicts more than 1% of children and adolescents.1,2 Thirty-one percent of first episodes occur between ages 10 and 15, with 75% developing by age 30.3 Early onset tends to be associated more frequently with tics and male gender, whereas those whose symptoms emerge later in life are more likely to be female and associated with eating disorders or depression. The overall gender ratio is approximately 1:1. However, higher frequency of cleaning rituals, fear of contamination, and avoidant behavior has been found in women, whereas primary obsessive slowness, sexual obsessions, and fear of social situations are prevalent in men.4,5
Etiology
At least some predisposition to obsessional behavior is inherited. However, most cases have no single precipitating event or stressor. A model based on the psychological concept of conditioning has been used to understand the development of obsessions and compulsions.6 If a person is preoccupied with fears of contamination from germs, repetitive hand washing usually decreases the anxiety caused by these fears. The compulsion becomes a conditioned response to anxiety. Because of the tension-reducing aspect of the compulsion, this learned behavior becomes reinforced and eventually fixed.7 By performing a compulsion, contact with the fear-evoking stimulus (i.e., dirt) is not maintained, and the cycle linking obsessions and compulsions is maintained.
Environmental causes may also play a role in the cause of OCD or may affect symptom severity. Environmental factors, such as postinfectious antineuronal cross-reactivity in a small number of patients recovering from a course of streptococcal infection with Group A beta-hemolytic streptococci (GABHS) may play a role in OCD etiology. Some children may develop a predisposition to OCD after experiencing a streptococcal infection. A biological marker for a variant of rheumatic fever may identify children at risk of developing OCD after an untreated streptococcal infection. Researchers from Rockefeller University and the National Institutes of Mental Health suggest that OCD may be triggered by an abnormal reaction to streptococcal bacteria by the immune system.8,9 Antibodies may go to the healthy brain and attack the caudate and subthalamic nuclei, causing a variant of rheumatic fever. In this process, the antibodies alert white blood cells to attack the healthy brain tissue, mistaking it for bacteria.
In contrast to childhood-onset OCD, an adult-onset neurobiologic subtype of OCD has also been proposed for some cases of OCD. Pregnancy and childbirth are particularly strong risk factors for new onset OCD. Recent reports suggest that women may have an increased risk for the onset of OCD during pregnancy and the puerperium.10-12 Oxytocin, a nonapeptide produced in the hypothalamus, mediates several systemic functions (e.g., uterine contractions and the milk let-down reflex) and several CNS-related functions, such as attachment. In this subgroup of patients, CSF oxytocin has been correlated with OCD severity.
Pathophysiology
Serotonin dysfunction and certain neurocircuits are thought to be involved in OCD behavior.
Although OCD is hypothesized to be a manifestation of primary serotonin dysregulation, multiple neurotransmitters with serotonergic and dopaminergic activity are most likely involved in the cause of OCD. Serotonin has been implicated in mediating impulsivity, suicidality, aggression, and anxiety. Dysregulation of this behaviorally inhihibitory neurotransmitter could possibly contribute to the repetitive obsessions and ritualistic behaviors seen in OCD patients.
Functional neuroimaging studies of patients with OCD are consistent with right frontal lobe dysfunction. The neurobiological basis for OCD is suggested by: 1) OCD symptoms are found in conjunction with selected neurologic disorders; 2) Neuropsychological abnormalities are found in patients with OCD; 3) There are beneficial effects of psychosurgical procedures for some patients; and 4) There are consistent abnormalities found with structural and functional brain imaging in patients with OCD.13
Clinical Features
OCD encompasses a broad range of symptoms that clinically can be grouped into four symptom categories:14 1) Cleanliness and washing-consistently paired washing and cleaning compulsions with contamination obsessions; 2) Aggression and checking-aggressive, sexual, and religious obsessions and checking compulsions; 3) Symmetry and ordering-combined compulsions of ordering and arranging, counting compulsions, and repeating rituals with obsessions of symmetry; and 4) Hoarding-hoarding obsessions correlated with hoarding behaviors and other collecting compulsions. The Diagnostic and Statistical Manual of Mental Disorders' criteria for OCD is depicted in Table 1.15
Table 1. DSM-IV Diagnostic Criteria for Obsessive-Compulsive Disorder
A. Either obsessions or compulsions:
Obsessions as defined by (1), (2), (3), and (4):
1. Recurrent and persistent thoughts, impulses, or images that are experienced, at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress.
2. The thoughts, impulses, or images are not simply excessive worries about real-life problems.
3. The person attempts to ignore or suppress such thoughts, impulses, or images or to neutralize them with some other thought or action.
4. The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind (not imposed from without as in thought insertion).
Compulsions as defined by (1) and (2):
1. Repetitive behaviors (e.g., handwashing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly.
2. The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts are either not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive.
B. At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable. Note: This does not apply to children.
C. The obsessions or compulsions cause marked distress, are time consuming (take more than 1 hour a day), or significantly interfere with the person's normal routing, occupational (or academic) functioning, or usual social activities or relationships.
D. If another Axis I disorder is present, the content of the obsessions or compulsions is not restricted to it (e.g., preoccupation with food in the presence of an eating disorder; hair pulling in the presence of trichotillomania; concern with appearance in the presence of body dysmorphic disorder; preoccupation with drugs in the presence of a substance use disorder; preoccupation with having a serious illness in the presence of hypochondriasis; preoccupation with sexual urges or fantasies in the presence of a paraphilia; or guilty ruminations in the presence of major depressive disorder).
E. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition.
Specify if:
With poor insight: if, for most of the time during the current episode, the person does not recognize that the obsessions and compulsions are excessive or unreasonable.
The most common obsession is concerned with contamination by dirt or germs; the accompanying compulsion is washing. Patients may spend several hours daily washing their hands, showering, or cleaning. They typically try to avoid sources of contamination, such as doorknobs, electrical switches, and newspapers. While they recognize that nothing will happen if they resist washing, they refuse to touch even their own bodies, knowing that if they do, they will not be at ease unless they perform extensive washing rituals.
Checkers are obsessed with doubt, usually tinged with guilt, and are frequently concerned that if they do not check carefully enough they will harm others. However, their checking often contributes to even greater doubt, which leads to further checking. Often, these patients will enlist the help of family and friends to ensure that they have checked enough or correctly. The checker ultimately resolves a particular doubt, only to have it replaced by a new one. Resistance, which, in this case, is the attempt to refrain from checking, leads to difficulty in concentrating and to exhaustion from the endless intrusion of nagging uncertainties. Common examples of such doubts are a fear of causing a fire, leading to checking the stove, to the extent that the patient cannot leave home; or a fear of hurting someone while driving, leading to repetitive driving back over the same spot after hitting a bump in the road. Hoarding behaviors can be seen as a corollary to checking behavior. Patients may refuse to throw out junk mail, old newspapers, or used tissues, for example, because they fear throwing away something important in the process.
Table 2. Screening Questions for OCD
· Do you have to wash your hands over and over?
· Do you have to check things repeatedly?
· Do you have thoughts that come into your mind that cause distress and that you can't stop thinking about?
· Do you need to complete actions over and over until they are just right or in a certain way before you can move on to the next thing?
Obsessional impulses may be aggressive or sexual, such as intrusive impulses of stabbing one's spouse or raping one's child. When the obsession is an aggressive impulse, it is most often directed at the one person most valuable to the patient. Often, there are subtle rituals around these obsessive thoughts. For example, a mother who is afraid she will stab her daughter might struggle with this impulse by avoiding sharp objects, then by avoiding touching her daughter, and ultimately, by leaving the house altogether. Sexual obsessions include forbidden sexual thoughts, images, or impulses that may involve children, animals, incest, homosexuality, etc.
Obsessional slowness involves the need to have objects or events in a certain order or position, to do and undo certain motor actions in an exact way, or to have things perfectly symmetrical. Such patients require an inordinate amount of time to complete even the simplest of tasks. Getting dressed may take a couple of hours. Unlike most obsessive-compulsive patients, these patients do not resist their symptoms. Instead, they seem to be consumed with completing their routine precisely.
Although OCD affects children, adolescents, and adults, whether it's juvenile and adult forms are part of a developmental continuum or different subtypes of a disorder that share phenotypic features remains unknown. OCD symptoms in younger children may not be identified readily. This may be due to parents misinterpreting OCD symptoms as developmental problems-that is, that the child would grow out of them-or to younger children not being able to communicate the severity of their symptoms as effectively as older ones. Children tend to have less insight regarding their illness than their adult counterparts.16
Dermatological manifestations of OCD consist of skin lesions resulting from scratching, picking, and other self-injurious behaviors. It is important to recognize that excoriations, dermatitis, acne, and other skin disorders may be manifestations of underlying neuropsychiatric conditions and often present only to the primary care physician.
Diagnostic Studies
Although a variety of biological and neuropsychiatric markers have been associated with OCD, the diagnosis rests on the psychiatric examination and history. Routine inquiry during the review of systems regarding recurrent, intrusive thoughts or repetitive rituals can increase detection. Likewise, any complaint of anxiety or panic should be carefully investigated using a similar inquiry to rule out OCD. (See Table 2.) The four screening questions in Table 2 have an 85% sensitivity for OCD patients. If the answer to one of these questions is positive, the patient should be screened more fully with the symptom checklist and 10-item severity rating scale of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Table 3. Yale-Brown Obsessive-Compulsive Scale Symptom Checklist
Aggressive Obsessions Fear might harm others Fear might harm self Violent or horrific images Fear of blurting out obsessions or insults Fear of doing something embarrassing Fear of acting on other impulses (e.g., robbing a bank, stealing groceries, overeating) Fear of being responsible for things going wrong (e.g., others will lose their job because of patient) Fear something terrible might happen (e.g., fire, burglary) Other
Contamination Obsessions Concerns or disgust with bodily waste (e.g., urine, feces, saliva) Concern with dirt or germs Excessive concern with environmental contaminants (e.g., asbestos, radiation, toxic wastes) Excessive concern with household items (e.g., cleansers, solvents, pets) Concerned will become ill Concerned will become ill (aggressive) Other
Sexual Obsessions Forbidden or perverse sexual thoughts, images, or impulses Content involves children Content involves animals Content involves incest Content involves homosexuality Sexual behavior toward others (aggressive) Other
Hoarding or Collecting Obsessions
Religious Obsessions
Obsession with Need for Symmetry or Exactness
Miscellaneous Obsessions Need to know or remember Fear of saying certain things Fear of not saying things just right Intrusive (neutral) images Intrusive nonsense sounds, words, or music Other
Somatic Obsession-Compulsion
Cleaning or Washing Compulsions Excessive or ritualized hand washing Excessive or ritualized showering, bathing, brushing the teeth, or grooming Involves cleaning of household items or inanimate objects Other measures to prevent contact with contaminants
Counting Compulsions
Checking Compulsions Checking that did not or will not harm others Checking that did not or will not harm self Checking that nothing terrible did or will happen Checking for contaminants Other
Repeating Rituals
Ordering or Arranging Compulsions
Miscellaneous Compulsions Mental rituals (other than checking or counting) Need to tell, ask, or confess Need to touch Measures to prevent Harm to self Harm to others Terrible consequences Other
Reprinted with permission of WB Saunders Company from: Tasman, Kay, Lieberman. Psychiatry. WB Saunders Co;. 1996:1062.
Differential Diagnosis
The differential diagnosis of OCD can be challenging. Many patients prefer to keep their symptoms private from others and seek help for conditions caused by the OCD symptoms without identifying OCD as the problem. For example, studies have reported high frequency of medical patients in dermatology clinics who exhibited contamination obsessions and washing compulsions that produced dermatitis. In children, careful evaluation is needed to rule out normal developmental variations, depression, and autistic disorders.
A number of issues may be raised regarding the differential diagnosis of OCD. First, there may be some similarities in the diagnosis of OCD and obsessive-compulsive personality disorder. Both disorders reveal a preoccupation with aggression and control; however, OCD symptoms cause great distress to the patient, whereas the patient with personality disorder rarely resists his or her compulsive character and seldom has a sense of compulsion. Second, it may be difficult to distinguish between an obsession, such as contamination, and a delusion, such as being poisoned. The difference here is that an obsession is resisted and recognized as having an internal origin. A delusion is not resisted and is believed to be external. The schizophrenic is also distinguished by disorganized thinking and poor social functioning. If a schizophrenic patient has rituals, they are usually not purposeful and are in response to a threatening external force perceived by the patient.
Another important diagnostic issue concerns depression, the most common complication of OCD. At the clinical level, these illnesses often seem inseparable-one worsening or improving in synchronicity with the other. However, in other clinical cases, OCD symptoms may remain in remission while depression recurs. Depression can express itself through ruminations, but these are generally negative appraisals of the patient's self or life situation rather than the typical OCD patient's obsessions regarding contamination, symmetry, blasphemy, etc. It is important to note that in a study of 100 patients with OCD, 67% had a lifetime history of major depression. Some patients with OCD view their depressive symptoms as occurring secondary to the demoralization and hopelessness accompanying their symptoms of OCD, and report that they would not be depressed if they did not have OCD. Other patients view their major depressive symptoms as occurring independently of the symptoms of OCD. Symptoms of OCD in some patients intensify during depressive episodes, while other patients report that their OCD symptoms are less intense during depression because they feel too apathetic to be as concerned with their obsessions and too fatigued to perform compulsions.
Table 4. Considerations in Patients with Obsessive-Compulsive Disorder in Whom Initial Treatment Fails
· Was the diagnosis correct?
· Is there an Axis II disorder, especially schizotypal or obsessive-compulsive personality disorder?
· Are there comorbid diagnoses that could interfere with treatment response?
· Is there a major depressive disorder?
· Are there obsessive thoughts, overvalued ideas, or delusions?
· Was the pharmacotherapy trial adequate?
· Was a known effective agent used?
· Was the dose adequate?
· Was the duration of treatment long enough?
· Was behavioral therapy performed?
· Were an adequate number of sessions attended?
· Did the patient comply with homework assignments?
· Was there cognitive impairment inhibiting the ability to implement treatment?
· Was there concurrent use of central nervous system depressants that affected ability to attend to evoked anxiety?
Management
The goals of treatment are to reduce both the frequency and intensity of symptoms, although few patients experience a cure. Treatment response is generally considered to constitute at least a 25% reduction in OCD symptoms as measured by the Y-BOS score. It is misleading to assume that the drastic changes in the management of OCD in the last 10 years have simplified the management of this disorder. With the development of new selective serotonin reuptake inhibitors (SSRIs), attention has now focused on the need for long-term maintenance, on safety and efficacy in the pediatric ages, and on applicability in compulsive-like spectrum disorders. To optimally treat patients suffering from OCD, the clinician needs to integrate various approaches. A combination of pharmacotherapy and behavior therapy is the treatment of choice for OCD.17 It is unusual for OCD patients to respond fully to either psychotherapeutic or pharmacologic interventions alone.
The SSRIs differ among themselves, just as they do when compared with clomipramine, on specific pharmacokinetic properties, which affect dosage issues, therapeutic monitoring, side effect profile, and drug-drug interaction. The prescribing physician is left with choosing from the SRI/SSRI family, which includes clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine. Although clomipramine has been the most extensively studied, it has the greatest anticholinergic side effect profile of the agents. This may be desirable for patients who require a more sedating medication at bedtime or during the day. In patients with a high risk of suicide, clomipramine would not be the first choice of agents since it can be toxic in overdoses. In contrast, the SSRIs offer a less anticholinergic side effect profile but may be associated with more complaints of headaches, nausea, insomnia, and agitation. Generally, if an individual has had no response to the SSRI at 10-12 weeks, another SSRI may be attempted. Failure to respond to one SSRI does not necessarily predict failure to respond to another SSRI. With aggressive treatment, 80-90% of patients experience some improvement in their symptoms, although few patients become symptom free.
Behavior techniques most consistently effective in reducing compulsive rituals and obsessive thoughts are exposure to the feared situation or object, and response prevention in which the patient resists the urge to perform the compulsion after exposure. Exposure consists of asking the patient to interact with stimuli that result in the obsession or ritualistic behavior. Response prevention consists of delaying, diminishing, or discontinuing anxiety-reducing rituals. Behavior therapy produces the largest changes in rituals, such as compulsive cleaning or checking, whereas changes in obsessive thoughts are less predictable. However, 15-25% of patients refuse to engage in behavioral treatment or drop out early in treatment because it is so anxiety provoking. Family members need to help patients by not participating in the compulsive behavior and by supporting treatment compliance.
If a patient does not respond to a full dose of SSRI for at least 12 weeks and systematic behavior therapy has already been tried, consider other selective serotonin reuptake inhibitors. If the patient still does not respond after an adequate trial, consider augmenting the SSRI with buspirone (15-60 mg/d), trazodone (100-200 mg/d), lithium (300-600 mg/d), or L-tryptophan (2-4 mg/d), each for approximately one month. It is advisable to refer the patient for pharmacological consultation. (See Table 4.) Severe refractory obsessive-compulsive patients may benefit from neurosurgery, which disconnects the outflow pathways from the orbitofrontal cortex.18
Disposition
In most cases, no particular stress or event precipitates the onset of OCD symptoms, and following an insidious onset there is a chronic and often progressive course. The natural history of OCD may be characterized by waxing and waning symptoms, but more than half of patients have chronic courses. Without treatment, symptoms usually remain constant or worsen. The disorder has a major impact on daily functioning, with some patients spending all their waking hours consumed with their obsessions and rituals. Patients are often socially isolated, marry at an older age, and have high celibacy rates (particularly in males) and a low fertility rate. Early age of onset is predictive of poor prognosis and multiple obsessions and compulsions.17 OCD symptoms are often exacerbated by depression. Moreover, persons with OCD and comorbid psychiatric illness have a significantly higher rate of suicide attempts.
Summary
OCD is a common but underrecognized disorder, characterized by repetitive thoughts and behaviors that cause significant functional impairment. Diagnosis is not difficult if one is aware of its prevalence and the different ways it is expressed. Because OCD patients often attempt to conceal their symptoms, it is incumbent on clinicians to screen for OCD, since appropriate treatment can often result in improved quality of life. There have been many new developments in the management of obsessive-compulsive disorder during the past decade. Only the selective serotonin reuptake inhibitors (SSRIs) and clomipramine are consistent in controlling obsessive-compulsive symptoms. To maximize recovery, patients must undergo behavioral therapy along with drug therapy. In many communities, self-help groups exist for OCD. As in other self-help groups, OCD group members share their experiences, educate one another, provide mutual support, and reduce the individual's sense of being alone with this disorder.
References
1. Flament M, et al. Obsessive-compulsive disorder in adolescence: An epidemiologic study. J Am Acad Child Adolesc Psychiatry 1988;27:764-771.
2. Valleni-Basile LA, et al. Frequency of obsessive-compulsive disorder in a community sample of adolescents. J Am Acad Child Adolesc Psychiatry 1994;33:782-791.
3. Black JL. Obsessive-compulsive disorder: A clinical update. Mayo Clin Proc 1992;67:266-275.
4. Marks IM. Fears, Phobias and Rituals. Oxford: Oxford University Press; 1987.
5. Roy A. Obsessive-compulsive phenomenology. Outcome and comparison with hysterical neurosis. Compr Psychiatry 1979;20:528-531.
6. Minichiello WE, et al. Age of onset of major subtypes of obsessive-compulsive disorder. J Anxiety Disord 1990;4:147-150.
7. Rachman SL, Hodgson RJ. Obsessions and Compulsions. Englewood Cliffs, NJ: Prentice Hall; 1980.
8. Swedo S. Sydenham's chorea: A model for childhood autoimmune neuropsychiatric disorders. JAMA 1994;272:1788-1791.
9. Swedo S, et al. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry 1997;154:110-112.
10. Buttolph ML, Holland A. Obsessive-compulsive disorders in pregnancy and childbirth. In: Jenike M, Baer L, Minichiello WE, eds. Obsessive Compulsive Disorders, Theory and Management. Chicago, IL: Yearbook Medical Publishers; 1990.
11. Neziroglu F, et al. Onset of obsessive-compulsive disorder in pregnancy. Am J Psychiatry 1992;149:947-950.
12. Sichel DA, et al. Postpartum obsessive compulsive disorder: A case series. J Clin Psychiatry 1993;54:156-159.
13. Trivedi M. Functional neuroanatomy of obsessive-compulsive disorder. J Clin Psychiatry 1996;57(suppl):26-35.
14. Leckman JF, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997;154:911-917.
15. Diagnostic and Statistical Manual of Mental Disorders. DSM-IV. 4th ed. Washington, DC: American Psychiatric Press; 1994.
16. Foa EB, Kozak MJ. The DSM-IV field trial: Obsessive-compulsive disorder. Am J Psychiatry 1995;152:90-96.
17. Griest JH, et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder: A meta-analysis. Arch Gen Psychiatry 1995;52:53-60.
18. Mindus P, Jenike M. Neurosurgical treatment of malignant obsessive-compulsive disorder. Psychiatr Clin North Am 1992;15:921-938.
19. Ackerman DL, et al. Predictors of treatment response in obsessive-compulsive disorder: Multivariate analyses from a multicenter trial of clomipramine. J Clin Psychopharmacol 1994;14:247-254.
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