以下、ご提出いただいたNEJM論文「Obsessive-Compulsive Disorder」（Michael A. Jenike, M.D., 2004）の本文をマークダウン書式で提示します。また、ご依頼の「分析」として、まずこの論文の特徴と、これまでの議論（フィードバックループ・症状停止のメカニズム）に関連するポイントを簡潔にまとめます。
論文の分析（簡潔な要点）
- 掲載誌と目的
New England Journal of Medicine の “Clinical Practice” 欄に掲載された総説。症例提示から始まり、診断・治療戦略・エビデンス・ガイドライン・著者の推奨までを実践的に解説。 - フィードバックループ／症状停止との関連
- 曝露と反応妨害法 (exposure and response prevention) のメカニズムとして、「habituation（慣れ）」を強調。繰り返し曝露することで不安が自然減少するプロセスは、OCDのループを「止める」ための体系的な方法である。
- 薬物療法（セロトニン再取り込み阻害薬）は、強迫的なループの駆動力を弱めるが、多くの場合「部分的効果」にとどまる。
- 著者は「OCDは寛解することは稀だが、症状は軽減できる」と述べており、完全な停止ではなく機能的な抑制が現実的目標であることを示唆。
- 家族による過度の確証求めへの応答がループを永続化させるため、それを控えるよう推奨 – これは社会的なネガティブ・フィードバックの操作に相当。
- 「疲弊による軽快」への言及
本文中に直接「疲弊」という用語はないが、治療なしでも症状が変動する（waxing and waning）という記載があり、自然経過での軽快の可能性を認めている。 - 臨床的意義
フィードバックモデルで言えば、曝露反応妨害法は「ループを意識的に断つ」介入であり、セロトニン再取り込み阻害薬は「ループのゲインを下げる」介入と解釈できる。
本文（マークダウン書式）
Obsessive-Compulsive Disorder
Michael A. Jenike, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.
A 33-year-old woman presents with a seven-year history of hand washing for two to six hours a day, as well as urges to check doors and stoves extensively before leaving her home. Her life is restricted, and her family members are upset about her behavior. How should she be evaluated and treated?
THE CLINICAL PROBLEM
This vignette describes a typical patient with an anxiety disorder called obsessive-compulsive disorder (OCD) (Table 1), which affects 2 to 3 percent of the world’s population. The patient has a general sense that something terrible may occur if a particular ritual is not performed, and the failure to perform a ritual may lead immediately to severe anxiety or a very uncomfortable, nagging feeling of incompleteness. In addition to checking and washing rituals, patients with OCD often present with persistent intrusive thoughts, extreme slowness or thoroughness, or doubts that lead to reassurance-seeking rituals. Patients with OCD commonly seek care from physicians other than psychiatrists. For example, in one study, 20 percent of patients who visited a dermatology clinic had OCD, which had been previously diagnosed in only 3 percent.
The mean age at the onset of OCD ranges from 22 to 36 years, with the disorder developing in only 15 percent of patients older than 35 years. Men tend to have an earlier age at onset than women, but women eventually catch up, and roughly 50 percent of adults with OCD are women. OCD is typically a chronic disorder with a waxing and waning course. With effective treatment, the severity of symptoms can be reduced, but typically some symptoms remain. On average, people with OCD see three to four doctors and spend more than nine years seeking treatment before they receive a correct diagnosis. It takes an average of 17 years from the onset of OCD to obtain appropriate treatment.
OCD tends to be underdiagnosed and undertreated. Patients may be secretive or lack insight about their illness. Many health care providers are not familiar with the symptoms or are not trained in providing treatment. Some people may not have access to treatment, and sometimes insurance plans do not cover behavioral therapy, although the situation is improving. This lack of access or coverage is unfortunate, since earlier diagnosis and proper treatment can help patients to avoid the suffering associated with OCD and lessen the risks of related problems, such as depression, marital difficulties, and problems related to employment.
OCD may have a genetic basis. Concordance for OCD is greater among pairs of monozygotic twins (80 to 87 percent) than among pairs of dizygotic twins (47 to 50 percent). The prevalence of OCD is increased among the first-degree relatives of patients with OCD, as compared with the relatives of control subjects, and the age at onset in the proband is inversely related to the risk of OCD among the relatives. There is evidence of a dominant or codominant mode of transmission of OCD.
Table 1. DSM-IV Diagnostic Criteria for OCD.
Either obsessions or compulsions
Obsessions are defined by the following:
- 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
- Thoughts, impulses, or images that are not simply excessive worries about real-life problems
- The effort by the affected person to ignore or suppress such thoughts, impulses, or images, or to neutralize them with some other thought or action
- Recognition by the affected person that the obsessional thoughts, impulses, or images are a product of his or her own mind rather than imposed from without
Compulsions are defined by the following:
- Repetitive activities (e.g., hand washing, 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
- Behavior or mental acts aimed at preventing or reducing distress or preventing some dreaded event or situation but either clearly excessive or not connected in a realistic way with what they are designed to neutralize or prevent
Recognition, by the affected person (unless he or she is a child), at some point during the course of the disorder, that the obsessions or compulsions are excessive or unreasonable
Obsessions or compulsions that cause marked distress, are time consuming (take more than 1 hr/day), or interfere substantially with the person’s normal routine, occupational or academic functioning, or usual social activities or relationships
Content of the obsessions or compulsions not restricted to any other Axis I disorder, such as an obsession with food in the context of an eating disorder, that is present
Disturbance not due to the direct physiological effects of a substance or a general medical condition
Specified as OCD 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
Consistent differences in regional brain activity between patients with OCD and control subjects, and the abnormal activity in patients with OCD shifts toward normal after either successful treatment with serotonin-reuptake inhibitors or effective behavioral therapy.
STRATEGIES AND EVIDENCE
DIAGNOSIS
The diagnosis of OCD is based on the clinical picture. Unlike patients with psychotic illnesses, patients with OCD usually exhibit insight and realize that their behavior is extreme or illogical. Often embarrassed by the symptoms, patients may go to extreme lengths to hide them. In severe cases, insight can become tenuous, and patients may truly believe that their obsessional concerns are justified; such cases are designated as “OCD with poor insight” according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).
Since patients are often reluctant to volunteer the information that they have symptoms of OCD, three routine screening questions can greatly increase the likelihood of diagnosis: “Do you have repetitive thoughts that make you anxious and that you cannot get rid of regardless of how hard you try?” “Do you keep things extremely clean or wash your hands frequently?” And “Do you check things to excess?” An affirmative answer to any of these questions strongly suggests a diagnosis of OCD, indicating the need for further investigation to determine whether the diagnostic criteria are met.
TREATMENT
Approaches to treatment that help patients with OCD include behavioral therapy (involving exposure to feared situations and the prevention of compulsive behavior), cognitive therapy (in which maladaptive thoughts — such as an exaggerated sense of risk, an enhanced sense of personal responsibility for events, or excessive doubt — are challenged), and specific medications. For most patients, combining cognitive-behavioral therapy with the use of medication is the most effective approach. Used alone, serotonin-reuptake inhibitors (Table 2) have a generally moderate, but occasionally dramatic, effect. When first-line medications fail, the augmentation of serotonin-reuptake-inhibitor therapy with an additional drug and trials of alternative medications are indicated. Neurosurgery should be reserved as the treatment of last resort.
Table 2. Recommended Treatments for OCD.
| Treatment | Initial Daily Dose | Target Daily Dose | Common Side Effects |
|---|---|---|---|
| Selective serotonin-reuptake inhibitors | Anxiety, decreased libido, sexual dysfunction, diarrhea, sedation, headache, insomnia, dizziness, nausea | ||
| Fluoxetine (Prozac) | 20 | 80 | |
| Fluvoxamine (Luvox) | 50 | 300 | |
| Sertraline (Zoloft) | 50 | 200 | |
| Paroxetine (Paxil) | 20 | 60 | |
| Citalopram (Celexa) | 20 | 60 | |
| Escitalopram (Lexapro) | 10 | Unknown | |
| Clomipramine (Anafranil, tricyclic antidepressant) | 25–50 | 250 | Dizziness, sedation, dry mouth, weight gain, sexual dysfunction |
| Venlafaxine (Effexor) | 75 | 375 | Accommodation disorder, blurred vision, headache, sexual dysfunction, paresthesias, nausea, weight loss, withdrawal syndrome (dizziness, nausea, weakness) |
Note: OCD denotes obsessive-compulsive disorder. All selective serotonin-reuptake inhibitors except escitalopram have been formally studied in patients with OCD. Side-effect profiles may vary among these agents; an alternative agent in this class should be tried if one agent proves to be ineffective or is associated with substantial side effects.
Cognitive-Behavioral Therapy
The gold standard for behavioral therapy for OCD involves exposure and the prevention of rituals; in such therapy, the patient repeatedly exposes himself or herself to provocative stimuli (e.g., touching a “contaminated” object) and refrains from compulsions (e.g., hand washing). Most therapists now combine cognitive therapy, in which faulty beliefs are challenged, with the standard therapy known as exposure and response prevention to help reduce the feeling of impending catastrophe and the exaggerated sense of responsibility often seen in patients with OCD. Behavioral therapy begins with the patient’s making a complete list of obsessions, compulsions, and things that he or she avoids. This list is then arranged in a hierarchy from least anxiety-provoking to most anxiety-provoking. The patient then starts with a moderately anxiety-provoking stimulus and repeatedly exposes himself or herself to it until the situation produces minimal anxiety (i.e., habituation). The next (more anxiety-provoking) stimulus in the hierarchy is then tackled, and then the next, until the most feared situation generates little or no anxiety.
Relaxation techniques alone are not helpful in the treatment of OCD and are often used as a control form of therapy in studies. Patients who have only obsessive thoughts and no compulsions are taught not to resist the thoughts but just to let them pass naturally. Doing so requires considerable practice. For patients who report repulsive, sacrilegious, or intrusive sexual thoughts that are repugnant to them, audio-loop tapes are often made of the patient voicing the thoughts; then, the patient listens to the tape for extended periods until the thoughts lose their power to be upsetting.
More than 30 open and controlled trials have consistently shown that behavioral therapy is very effective in controlling obsessions, with some studies demonstrating that the approach of exposure and response prevention is more effective than medication. In numerous studies involving 10 to 20 treatment sessions, symptoms of OCD were at least “improved” in 85 percent of patients immediately after treatment, and in about 55 percent, target symptoms were “much improved” or “very much improved” — that is, improved by more than 50 percent. At follow-up, the rates of improvement remained high, averaging about 75 percent for “much improved” and 50 percent for “very much improved,” although some patients required additional therapy.
A combined analysis of multiple randomized studies comparing treatments (medications, psychodynamic psychotherapy, behavioral therapy consisting of exposure and response prevention, or cognitive-behavioral therapy) indicated that behavioral therapy alone or in combination with medication was significantly more effective than medication alone, which was more effective than placebo. Cognitive-behavioral therapy has been shown to be effective even when delivered in a group format, by a computer, or by telephone.
Pharmacotherapy
Selective serotonin-reuptake inhibitors (SSRIs) are the medications of first choice for OCD. Clomipramine, a nonselective serotonin-reuptake inhibitor, also has proven efficacy, but it is less well tolerated because of its anticholinergic, antiadrenergic, and antihistaminergic effects. Studies of SSRIs consistently show efficacy, with a 20 to 40 percent reduction in the severity of symptoms (compared with a 0 to 10 percent reduction with placebo). On average, the effect is moderate, but 10 to 20 percent of patients have dramatic improvement. Higher doses are often required for OCD than for depression, and a longer period (8 to 12 weeks, rather than 4 to 6 weeks) may be needed to observe an initial response. Once a response is achieved, medication should be continued for at least 1 to 2 years; longer treatment is often needed. Relapse is common after discontinuation. Some patients may benefit from long-term maintenance therapy.
When a patient does not have a satisfactory response to an adequate trial of an SSRI (i.e., 12 weeks at the maximum tolerated dose), several strategies are available. These include switching to another SSRI, adding an atypical antipsychotic (e.g., risperidone, olanzapine, quetiapine), or adding a medication such as clonazepam, buspirone, or a monoamine oxidase inhibitor. The evidence for augmentation with antipsychotics is strongest, with several controlled trials showing benefit.
Neurosurgery
Despite the lack of data from controlled trials, several types of operations for severe, treatment-refractory OCD are performed around the world: anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. These operations all have the common objective of severing connections between dorsolateral and the orbitomedial areas of the frontal lobes and limbic and thalamic structures. In observational, prospective trials of cingulotomy and capsulotomy, approximately 45 percent of patients had a reduction of at least 35 percent in the severity of symptoms. Adverse effects included seizure, weight gain, and transient headache. Negative effects on cognition or personality were rare.
Deep brain stimulation, which involves surgically implanted electrodes that can be turned on and off to stimulate or inhibit activity in surrounding brain tissue, has been used for the treatment of Parkinson’s disease and intractable pain; preliminary data from uncontrolled trials suggest that it also has efficacy in OCD. In addition, transcranial magnetic stimulation, whereby pulses of magnetic energy are intermittently administered to surface regions of the brain through the skull, appeared to be effective in one preliminary study.
AREAS OF UNCERTAINTY
A small number of patients fail to become habituated to anxiety-provoking stimuli, despite repeated exposure. There are limited data with which to predict responsiveness to cognitive-behavioral therapy or medication, but the expression of negative emotions — for example, by family members who are overtly highly critical of the patient — can have a negative effect on the outcome of treatment.
Further research is warranted regarding the role of autoimmunity induced by streptococcal infection in the pathogenesis of OCD. Small, uncontrolled, preliminary studies in selected patients have shown encouraging results with the use of plasmapheresis to clear autoantibodies, as well as with the use of prophylactic antibiotic treatment for the prevention of subsequent infections and further damage, but more data are needed for the accurate evaluation of the efficacy of such therapies.
Although published outcome data are not available, three residential facilities for the treatment of OCD in patients with very severe symptoms that have proved to be unresponsive to outpatient treatment are now operating in the United States (further information is available at http://www.ocfoundation.org/1003/index.html).
There have been no studies directly comparing the relative efficacy and safety of the different neurosurgical procedures. With the advent of innovative surgical devices that permit neurosurgery without requiring craniotomy (e.g., the gamma knife), it is now feasible to conduct ethical double-blind, sham-surgery-controlled trials.
GUIDELINES
Expert consensus guidelines issued in 1997 (http://www.psychguides.com/gl-treatment_of_obsessive-compulsive_disorder.html) ranked the effectiveness of all treatment options on the basis of published data and expert opinion. According to the guidelines, cognitive-behavioral therapy should be the first-line treatment. For severely ill patients (those who are unable to function in a job or socially because of the symptoms of OCD), it is recommended that medication be introduced first, before the addition of cognitive-behavioral therapy. The guidelines recommend that cognitive-behavioral therapy begin with weekly sessions, with homework assignments or therapist-assisted, out-of-office therapy. For most patients, 13 to 20 sessions of cognitive-behavioral therapy are adequate, although some patients require more, and some fewer. The guidelines indicate that serotonin-reuptake inhibitors are the most effective medications for OCD and recommend beginning with selective serotonin-reuptake inhibitors, with a trial of clomipramine if two or three selective serotonin-reuptake inhibitors have failed.
CONCLUSIONS AND RECOMMENDATIONS
If OCD is not adequately treated, most patients have clinically significant disability, with symptoms that wax and wane over time. Even with effective treatment, OCD rarely remits, but symptoms do diminish so that patients can work, raise a family, and have an active social life. For a patient such as the one in the vignette, I would start with a serotonin-reuptake inhibitor and, if it is available, behavioral therapy at the same time. (The Obsessive Compulsive Foundation
REFERENCES
(References omitted here for brevity; full list appears in the original PDF, including items 1–55 covering DSM-IV, epidemiological studies, treatment trials, and neurosurgery.)
