今日の臨床サポート

強迫性障害(強迫症)

著者: 松永寿人 兵庫医科大学 精神科

監修: 上島国利 昭和大学

著者校正/監修レビュー済:2022/10/12
患者向け説明資料

概要・推奨   

  1. SSRIの反応性を評価する際には、まずはこれを十分な量、そして十分な期間投与することが推奨される。反応性の評価には通常Y-BOCS総得点の変化、あるいはClinical Global Impressions-Improvement Scale(CGI-I)を用いる(推奨度2)
  1. SSRI抵抗性を疑う場合、その投与量、投与期間に加え、患者の薬物アドヒアランスが良好かを確認する事が推奨される(推奨度2)
  1. 抗不安薬はあくまでも、SSRIの効果発現までの間、あるいは急性期の不安制御のため、補助的に用いるべきであり、できるだけ限定的使用とすることが推奨される(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
松永寿人 : 未申告[2022年]
監修:上島国利 : 原稿料(大日本住友製薬)[2022年]

改訂のポイント:
  1. 定期レビューを行い、主に薬物療法において加筆・修正を行った。

病態・疫学・診察

疾患情報  
  1. 一般人口中の強迫性障害(強迫症)(obsessive-compulsive disorder:OCD)の生涯有病率は1~2%程度と考えられる。
  1. 通常は強迫観念と強迫行為からなる。
  1. 強迫観念とは、「自分の心の産物として認識されるもので、少なくとも経過中の一時期には、無意味ないし不適切、侵入的なものと体験され、無視や制御を試みても絶えず心を占める思考や衝動、イメージ」である。
  1. 強迫行為は、「主には観念に伴い高まる苦痛や不安を、予防・緩和したり、恐ろしい出来事を避けたりすることを目的とし、あるいは厳密に適用しなければならない規則に従って、そのばかばかしさや、過剰であることを自ら認識し止めたいと思いつつも、駆り立てられるように行う反復的行為や心の中の行為(祈る、呪文を唱える、数を数えるなど)」である。
  1. OCDと診断するには、以下を確認する必要がある。
  1. 強迫観念ないし強迫行為など、強迫症状が存在(多くの場合、両者が共存)。
  1. 経過中に強迫症状の過剰性や不合理性を認識したことがある(子どもには適用されない)。(注;DSM-5では、洞察の必要性に関する基準は削除されている。)
  1. 強迫症状が強い苦痛を生じ、時間を浪費(1日1時間以上)させ、日常や社会的、職業的機能に著しい障害を来している。
  1. 強迫症状の出現や内容が、他の精神障害や身体疾患、物質使用などによるものではない。
  1. OCDのサブタイプについて、DSM-IV-TRでは、経過中おおむね一貫し、症状の不合理性の「洞察に乏しいもの」を特定する必要がある。一方、2013年5月に改訂されたDSM-5では、チック症の生涯病歴を有する場合を「チック関連」と特定する。
  1. さらにDSM-5では、病識の程度を、「病識が十分、またはおおむね十分」、「病識が不十分」、「病識が欠如/妄想的な信念をともなう」のいずれに該当するか特定する必要がある。
問診・診察のポイント  
  1. 現存する強迫症状の内容や重症度の評価とともに、今までの既往、治療歴、家族歴を確認する。

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文献 

J A Eichstedt, S L Arnold
Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD?
Clin Psychol Rev. 2001 Feb;21(1):137-57.
Abstract/Text Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent obsessions or compulsions that cause significant impairment or distress. Although OCD was once perceived to be relatively rare in childhood, current estimates suggest that as many as half of all adult OCD cases may have their onset in childhood or adolescence. In general, there appears to be a great deal of continuity between the clinical presentation of OCD in children and that in adults. Yet, numerous differences have also been found between child and adult OCD, including differences in sex distribution, patterns of comorbidity, and degree of familial loading. These differences raise the issue of whether obsessive-compulsive symptoms that have their onset in childhood, but perhaps persist into adult life, are meaningfully different from those that emerge de novo in adulthood. In this article, current research on child- and adult-onset OCD is critically reviewed. It is proposed that child-onset OCD represents a phenomenologically and etiologically distinct subtype of OCD, bearing a close genetic relationship to tic-disorders and possibly sharing a common or similar pathogenesis. Clinical implications of the child- versus adult-onset OCD distinction are discussed.

PMID 11148894
Hisato Matsunaga, Toshihiko Nagata, Kazuhisa Hayashida, Kenzo Ohya, Nobuo Kiriike, Dan J Stein
A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder.
J Clin Psychiatry. 2009 Jun;70(6):863-8. doi: 10.4088/JCP.08m04369. Epub 2009 May 5.
Abstract/Text OBJECTIVE: Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short-term trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term.
METHOD: Subjects (N = 46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy (CBT) for 1 year. Subjects (N = 44) who failed to respond to SSRIs were randomly assigned to 1 of 3 atypical antipsychotics -- olanzapine, quetiapine, or risperidone -- and were consecutively treated using SSRI + atypical antipsychotics combined with CBT for 1 year. This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital, Japan.
RESULTS: Augmentation with atypical antipsychotics reduced mean +/- SD Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores in SSRI-refractory OCD patients (at initial assessment = 29.3 +/- 9.9, after 1 year = 19.3 +/- 6.8). However, compared to SSRI responders (at initial assessment = 25.8 +/- 11.4, after 1 year = 13.7 +/- 4.6), total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher, and they remained at higher levels than those of SRI responders after 1 year of the treatments.
CONCLUSIONS: Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients. Even though this approach seems useful for some types of OCD patients, such as those with symmetry/ordering and hoarding symptoms, these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD, and their chronic use raises a number of safety concerns.
TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier NCT00854919.

Copyright 2009 Physicians Postgraduate Press, Inc.
PMID 19422759
W K Goodman, L H Price, S A Rasmussen, C Mazure, R L Fleischmann, C L Hill, G R Heninger, D S Charney
The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.
Arch Gen Psychiatry. 1989 Nov;46(11):1006-11.
Abstract/Text The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

PMID 2684084
W K Goodman, L H Price, S A Rasmussen, C Mazure, P Delgado, G R Heninger, D S Charney
The Yale-Brown Obsessive Compulsive Scale. II. Validity.
Arch Gen Psychiatry. 1989 Nov;46(11):1012-6.
Abstract/Text The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.

PMID 2510699
Damiaan Denys
Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders.
Psychiatr Clin North Am. 2006 Jun;29(2):553-84, xi. doi: 10.1016/j.psc.2006.02.013.
Abstract/Text This article reviews new developments of pharmacotherapy in obsessive-compulsive disorder (OCD) and OC spectrum disorders of the past five years. New developments primarily involved the ex-tension of evidence of efficacy of serotonin reuptake inhibitors(SRIs), the use of atypical antipsychotics in addition to SRIs for treatment refractory patients, the combination of pharmacotherapy with behavior therapy, and studies assessing predictors of response. Today, frontline pharmacological treatment of OCD still consists of drugs with potent serotonin reuptake inhibition proper-ties. In case of non-response, treatment options comprise adding another drug, increasing the dose, switching drugs, or changing the mode of delivery.

PMID 16650723
P Alonso, J M Menchon, J Pifarre, D Mataix-Cols, L Torres, P Salgado, J Vallejo
Long-term follow-up and predictors of clinical outcome in obsessive-compulsive patients treated with serotonin reuptake inhibitors and behavioral therapy.
J Clin Psychiatry. 2001 Jul;62(7):535-40.
Abstract/Text BACKGROUND: The objective of this study was to examine the long-term course of obsessive-compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and behavioral therapy and to identify predictors of clinical outcome.
METHOD: Sixty outpatients meeting DSM-II-R or DSM-IV criteria for OCD were followed up for 1 to 5 years (mean = 2.5 years). All of them received prolonged pharmacologic therapy with an SRI.
RESULTS: Thirty-seven patients (61.7%) completed an adequate behavioral treatment. At long-term assessment, 22 patients (36.7%) exhibited a global Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score greater than 16 or a final reduction in Y-BOCS global score of less than 35% and were considered nonresponders. Patients who completed behavioral therapy showed a significant decrease in Y-BOCS compulsions subscale score (p = .01), whereas no significant differences in either Y-BOCS global or obsessions subscale scores between those who did and those who did not undergo behavioral therapy were detected. Obsessions of sexual/religious content were the unique factor related to a poorer long-term outcome.
CONCLUSION: A substantial number of OCD patients showed persistent disabling symptoms at the long-term follow-up in spite of combined pharmacologic and behavioral treatment. Major benefits from behavioral therapy appeared to be the improvement of ritualistic behaviors. Sexual/religious obsessions predicted poorer long-term outcome, whereas short-term response to SRI treatment failed to achieve predictive value in the long-term course of OCD.

PMID 11488364
Francesco Catapano, Francesco Perris, Mariangela Masella, Flavia Rossano, Marco Cigliano, Lorenza Magliano, Mario Maj
Obsessive-compulsive disorder: a 3-year prospective follow-up study of patients treated with serotonin reuptake inhibitors OCD follow-up study.
J Psychiatr Res. 2006 Sep;40(6):502-10. doi: 10.1016/j.jpsychires.2005.04.010.
Abstract/Text This study aimed to evaluate the long-term course of obsessive-compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving at least partial remission from obsessive-compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. For subjects who achieved at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state, and of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities. The development of alternative strategies is needed to improve the treatment approaches for treatment-resistant OCD patients.

PMID 16904424
Anish V Cherian, Suresh Bada Math, Thennarasu Kandavel, Y C Janardhan Reddy
A 5-year prospective follow-up study of patients with obsessive-compulsive disorder treated with serotonin reuptake inhibitors.
J Affect Disord. 2014 Jan;152-154:387-94. doi: 10.1016/j.jad.2013.09.042. Epub 2013 Oct 7.
Abstract/Text BACKGROUND: Although obsessive-compulsive disorder is usually regarded as a chronic illness, there is limited data on the naturalistic long-term outcome of the disorder and on predictors of remission and relapse. The study examines the 5-year course prospectively in outpatients with the primary diagnosis of DSM-IV OCD who were mostly treated with serotonin reuptake inhibitors (SRIs).
METHOD: 106 of 115 subjects recruited over a period of 2 years from the outpatient services of an OCD clinic in India were followed periodically up to 5 years.
RESULTS: Subjects were moderately ill, mostly self-referred (89%), and less than a half was treatment-naive. Cumulative probability of at least partial remission and full remission at 5 years was 93% and 65% respectively. Most achieved remission by 2 years. In those who achieved either partial or full remission, cumulative probability of relapse by 5 years was 36%. Percentage of time on treatment and treatment-naive status at intake predicted at least partial remission, whereas only percentage of time on treatment predicted full remission. Full remission and doubts/checking dimension predicted lesser likelihood of a relapse.
LIMITATIONS: Patients were recruited from a specialty OCD clinic and treatment was not controlled during the follow-up period.
CONCLUSIONS: The outcome of OCD seems to be better than generally assumed, at least in moderately ill outpatients. Regular treatment over extended period may enhance likelihood of remission. Full remission should be the goal of treatment since it is associated with lesser propensity for relapse. Most patients remit in the first 2 years of treatment; therefore, early detection and intervention may improve the outcome.

© 2013 Elsevier B.V. All rights reserved.
PMID 24157088
J L Eisen, W K Goodman, M B Keller, M G Warshaw, L M DeMarco, D D Luce, S A Rasmussen
Patterns of remission and relapse in obsessive-compulsive disorder: a 2-year prospective study.
J Clin Psychiatry. 1999 May;60(5):346-51; quiz 352.
Abstract/Text OBJECTIVE: This study examined the course of illness in patients with obsessive-compulsive disorder (OCD) over a 2-year period.
METHOD: Sixty-six patients with a primary diagnosis of DSM-III-R OCD were followed prospectively for 2 years. Baseline information was collected on demographic characteristics, Axis I and II diagnoses, and severity of OCD symptoms. Follow-up measures obtained at 3, 6, 12, and 24 months after baseline assessment included information on symptomatic and diagnostic status as well as behavioral and somatic treatments received.
RESULTS: The probability of full remission from OCD over the 2-year period was 12%. The probability of partial remission was 47%. After achieving remission from OCD, the probability of relapse was 48%. No factors were identified that significantly predicted full or partial remission. Seventy-seven percent (N = 51) of the subjects received a serotonin reuptake inhibitor (SRI) for > or =12 weeks, and 68% (N = 45) received medium-to-high doses of SRIs for > or =12 weeks. Only 18% received a full trial of behavior therapy.
CONCLUSION: Despite exposure to at least 1 adequate trial of an SRI, the likelihood of full remission of OCD in this study was low. Results of this study also suggest that behavior therapy may be under-utilized.

PMID 10362449
Jane L Eisen, Nicholas J Sibrava, Christina L Boisseau, Maria C Mancebo, Robert L Stout, Anthony Pinto, Steven A Rasmussen
Five-year course of obsessive-compulsive disorder: predictors of remission and relapse.
J Clin Psychiatry. 2013 Mar;74(3):233-9. doi: 10.4088/JCP.12m07657.
Abstract/Text BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous and disabling condition; however, no studies have examined symptom categories or subtypes as predictors of long-term clinical course in adults with primary OCD.
METHOD: A total of 213 adults with DSM-IV OCD were recruited from several mental health treatment sites between July 2001 and February 2006 as part of the Brown Longitudinal Obsessive Compulsive Study, a prospective, naturalistic study of treatment-seeking adults with primary OCD. OCD symptoms were assessed annually over the 5-year follow-up period using the Longitudinal Interval Follow-Up Evaluation.
RESULTS: Thirty-nine percent of participants experienced either a partial (22.1%) or a full (16.9%) remission. Two OCD symptom dimensions impacted remission. Participants with primary obsessions regarding overresponsibility for harm were nearly twice as likely to experience a remission (P < .05), whereas only 2 of 21 participants (9.5%) with primary hoarding achieved remission. Other predictors of increased remission were lower OCD severity (P < .0001) and shorter duration of illness (P < .0001). Fifty-nine percent of participants who remitted subsequently relapsed. Participants with obsessive-compulsive personality disorder were more than twice as likely to relapse (P < .005). Participants were also particularly vulnerable to relapse if they experienced partial remission versus full remission (70% vs 45%; P < .05).
CONCLUSIONS: The contributions of OCD symptom categories and comorbid obsessive-compulsive personality disorder are critically important to advancing our understanding of the prognosis and ultimately the successful treatment of OCD. Longer duration of illness was also found to be a significant predictor of course, highlighting the critical importance of early detection and treatment of OCD. Furthermore, having full remission as a treatment target is an important consideration for the prevention of relapse in this disorder.

© Copyright 2013 Physicians Postgraduate Press, Inc.
PMID 23561228
Eric Hollander, Dan J Stein, Naomi A Fineberg, Florence Marteau, Mark Legault
Quality of life outcomes in patients with obsessive-compulsive disorder: relationship to treatment response and symptom relapse.
J Clin Psychiatry. 2010 Jun;71(6):784-92. doi: 10.4088/JCP.09m05911blu. Epub 2010 May 4.
Abstract/Text OBJECTIVE: Data were analyzed from 2 prospective, double-blind, placebo-controlled trials of escitalopram in obsessive-compulsive disorder (OCD) to characterize the baseline levels of functional disability and impairment in health-related quality of life (HRQoL) and to assess the relationship between treatment outcomes (response or relapse) and disability or HRQoL.
METHOD: Data from a 24-week, placebo-controlled, fixed-dose trial (N = 466) of escitalopram (10-20 mg/d) or paroxetine (40 mg/d) and from a 40-week, flexible-dose (escitalopram 10-20 mg/d), placebo-controlled relapse-prevention trial (N = 468) were analyzed. Obsessive-compulsive disorder symptoms (DSM-IV criteria) were assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS), functioning was assessed using the Sheehan Disability Scale (SDS), and HRQoL was assessed using the Medical Outcomes Study Short Form (SF-36). Baseline data were pooled for patients across both studies. For patients in the fixed-dose study, SDS and SF-36 scores were compared across treatment groups and for responders versus nonresponders. In the relapse-prevention trial, SDS and SF-36 scores were compared for relapsed versus nonrelapsed patients.
RESULTS: Patients with more severe baseline symptoms (YBOCS > or = 27) reported significantly greater impairment on the SDS (P < .001) and SF-36 (except for bodily pain). Patients receiving escitalopram or paroxetine reported significant improvements on most SF-36 dimensions and on the SDS compared to placebo; however, improvements in work-related functioning were seen earlier for patients receiving escitalopram (20 mg/d). At the study endpoints, SDS and SF-36 scores were significantly better for patients who were responders (versus nonresponders) and for patients who did not relapse (versus relapsers).
CONCLUSIONS: Obsessive-compulsive disorder is associated with significant impairment in functioning and HRQoL. Significant differences in disability and HRQoL between responders and nonresponders or relapsers and nonrelapsers suggest a relationship between symptomatic and functional outcomes.
TRIAL REGISTRATION: lundbecktrials.com Identifiers: 10205 and 10193.

2010 Physicians Postgraduate Press, Inc.
PMID 20492845
G O'Sullivan, H Noshirvani, I Marks, W Monteiro, P Lelliott
Six-year follow-up after exposure and clomipramine therapy for obsessive compulsive disorder.
J Clin Psychiatry. 1991 Apr;52(4):150-5.
Abstract/Text To determine whether gains from exposure therapy are lasting in patients with chronic obsessive compulsive disorder, the authors followed up 34 (85%) of 40 such patients who had been treated 6 years earlier with exposure therapy for 3 or 6 weeks and with clomipramine or placebo for 36 weeks. Severity of obsessive compulsive disorder was assessed by rating the discomfort caused by the time devoted to four target rituals, the Behavioral Avoidance Test, and the Compulsion Checklist. Mood was assessed by the 17-item Hamilton Rating Scale for Depression, the Wakefield Self-Assessment Depression Inventory, and the Anxiety scale. In addition, the patients' general adjustment was assessed. The authors found that the group as a whole remained significantly improved on obsessive compulsive symptoms, work and social adjustment, and depression; however, the group returned to pretreatment levels (slight to moderate) of general anxiety. They found that neither clomipramine nor placebo affected long-term outcome and that the majority of patients who were taking clomipramine or other antidepressants at follow-up were no more improved that those who were not taking antidepressants. Better long-term outcome correlated with more exposure therapy (6 weeks of therapy vs. 3 weeks) and with better compliance with the exposure therapy homework. The best predictor of long-term outcome was improvement at the end of treatment. Subjects who had initially been most depressed were more likely to receive psychotropic medication during follow-up. Initial severity of illness did not preclude benefit from exposure therapy.

PMID 2016246
Petros Skapinakis, Deborah M Caldwell, William Hollingworth, Peter Bryden, Naomi A Fineberg, Paul Salkovskis, Nicky J Welton, Helen Baxter, David Kessler, Rachel Churchill, Glyn Lewis
Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis.
Lancet Psychiatry. 2016 Aug;3(8):730-739. doi: 10.1016/S2215-0366(16)30069-4. Epub 2016 Jun 16.
Abstract/Text BACKGROUND: Several interventions are available for management of obsessive-compulsive disorder in adults, but few studies have compared their relative efficacy in a single analysis. We aimed to simultaneously compare all available treatments using both direct and indirect data.
METHODS: In this systematic review and network meta-analysis, we searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group for trials published up to Feb 16, 2016. We selected randomised controlled trials in which an active psychotherapeutic or pharmacological intervention had been used in adults with obsessive-compulsive disorder. We allowed all comorbidities except for schizophrenia or bipolar disorder. We excluded studies that focused exclusively on treatment-resistant patient populations defined within the same study. We extracted data from published reports. The primary outcome was symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. We report mean differences with 95% credible intervals compared with placebo. This study is registered with PROSPERO, number CRD42012002441.
FINDINGS: We identified 1480 articles in our search and included 53 articles (54 trials; 6652 participants) in the network meta-analysis. Behavioural therapy (mean difference -14·48 [95% credible interval -18·61 to -10·23]; 11 trials and 287 patients), cognitive therapy (-13·36 [-18·40 to -8·21]; six trials and 172 patients), behavioural therapy and clomipramine (-12·97 [-19·18 to -6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (-7·50 [-13·89 to -1·17]; one trial and six patients), cognitive behavioural therapy (-5·37 [-9·10 to -1·63]; nine trials and 231 patients), clomipramine (-4·72 [-6·85 to -2·60]; 13 trials and 831 patients), and all SSRIs (class effect -3·49 [95% credible interval -5·12 to -1·81]; 37 trials and 3158 patients) had greater effects than did drug placebo. Clomipramine was not better than were SSRIs (-1·23 [-3·41 to 0·94]). Psychotherapeutic interventions had a greater effect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants).
INTERPRETATION: A range of interventions is effective in the management of obsessive-compulsive disorder, but considerable uncertainty and limitations exist regarding their relative efficacy. Taking all the evidence into account, the combination of psychotherapeutic and psychopharmacological interventions is likely to be more effective than are psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder.
FUNDING: National Institute for Health Research.

Copyright © 2016 Skapinakis et al. Open Access article published under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
PMID 27318812
Dong-Dong Zhou, Xiao-Xin Zhou, Yao Li, Kai-Fu Zhang, Zhen Lv, Xiao-Rong Chen, Li-Yang Wan, Wo Wang, Gao-Mao Wang, Da-Qi Li, Ming Ai, Li Kuang
Augmentation agents to serotonin reuptake inhibitors for treatment-resistant obsessive-compulsive disorder: A network meta-analysis.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 2;90:277-287. doi: 10.1016/j.pnpbp.2018.12.009. Epub 2018 Dec 18.
Abstract/Text BACKGROUND: Various agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults.
METHODS: PubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs).
RESULTS: Thirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, -8.94; 95% CI, -14.42 to -3.42), risperidone (-4.47, -8.75 to -0.17), topiramate (-6.05, -10.89 to -1.20), lamotrigine (-6.07, -11.61 to -0.50), and aripiprazole (-5.14, -9.95 to -0.28) were significantly superior to placebo. Antipsychotic (-4.09, -6.22 to -1.93) and glutamatergic (-5.22, -7.53 to -2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (-5.00, -8.59 to -1.29) and olanzapine (-8.28, -15.34 to -1.13) became significantly superior to placebo.
CONCLUSIONS: Our study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.

Copyright © 2018 Elsevier Inc. All rights reserved.
PMID 30576763
Lorrin M Koran, Gregory L Hanna, Eric Hollander, Gerald Nestadt, Helen Blair Simpson, American Psychiatric Association
Practice guideline for the treatment of patients with obsessive-compulsive disorder.
Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53.
Abstract/Text
PMID 17849776
Eric Hollander, Andrea Allen, Martin Steiner, David E Wheadon, Rosemary Oakes, Daniel B Burnham, Paroxetine OCD Study Group
Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine.
J Clin Psychiatry. 2003 Sep;64(9):1113-21.
Abstract/Text BACKGROUND: Limited information is available regarding optimal dosing or long-term pharmacotherapy with serotonin reuptake inhibitors in obsessive-compulsive disorder. This study evaluated the acute safety and efficacy and long-term efficacy, safety, and impact on relapse prevention of paroxetine in obsessive-compulsive disorder.
METHOD: We enrolled 348 outpatients with DSM-III-R obsessive-compulsive disorder in phase 1, a 12-week randomized, double-blind, parallel study of fixed doses of paroxetine (20 mg/day, 40 mg/day, or 60 mg/day) and placebo. In phase 2, 263 phase 1 completers were enrolled in 6 months of flexibly dosed open-label paroxetine treatment. In phase 3, 105 responders to open-label paroxetine were randomized to 6-month double-blind, fixed-dose, parallel paroxetine/placebo treatment to evaluate long-term efficacy, safety, and impact on relapse prevention. The study was conducted from July 1991 to February 1994.
RESULTS: Patients in phase 1 acute treatment receiving 40 mg/day or 60 mg/day of paroxetine improved significantly (p < .05) more than those receiving placebo; the mean reduction in Yale-Brown Obsessive-Compulsive Scale score was 25% on 40 mg/day of paroxetine and 29% on 60 mg/day compared with 13% on placebo. During phase 3, long-term treatment, a greater proportion of placebo- (59%) than paroxetine-treated (38%) patients relapsed. Paroxetine was well tolerated at all doses, with no significant increase in frequency of adverse events during long-term compared with short-term therapy. Greater adverse events in the placebo than in the paroxetine group in phase 3 probably represent a discontinuation effect.
CONCLUSION: Paroxetine doses of 40 mg/day and 60 mg/day (but not 20 mg/day) are effective in treating acute obsessive-compulsive disorder. Long-term treatment with paroxetine is effective and safe, decreases the rate of relapse, and lengthens the time to relapse.

PMID 14628989
David Healy, Chris Whitaker
Antidepressants and suicide: risk-benefit conundrums.
J Psychiatry Neurosci. 2003 Sep;28(5):331-7.
Abstract/Text There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. To shed light on this issue, this paper reviews available randomized controlled trials (RCTs), meta-analyses of clinical trials and epidemiological studies that have been undertaken to investigate the issue further. The original clinical studies raising concerns about SSRIs and suicide induction produced evidence of a dose-dependent link on a challenge-dechallenge and rechallenge basis between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicated that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, revealed an excess of suicidal acts on active treatments compared with placebo, with an odds ratio of 2.4 (95; confidence interval 1.6-3.7). This excess of suicidal acts also appears in epidemiological studies. The data reviewed here make it difficult to sustain a null hypothesis that SSRIs do not cause problems in some individuals. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.

PMID 14517576
Abstract/Text The selective serotonin reuptake inhibitors (SSRIs) may occasionally induce extrapyramidal side-effects (EPS) and/or akathisia. This may be a consequence of serotonergically-mediated inhibition of the dopaminergic system. Manifestations of these effects in patients may depend on predisposing factors such as the presence of psychomotor disturbance, a previous history of drug-induced akathisia and/or EPS, concurrent antidopaminergic and/or serotonergic therapy, recent monoamine oxidase inhibitor discontinuation, comorbid Parkinson's disease and possibly deficient cytochrome P450 (CYP) isoenzyme status. There is increasing awareness that there may be a distinct form of melancholic or endogenous depression with neurobiological underpinnings similar to those of disorders of the basal ganglia such as Parkinson's disease. Thus, it is not surprising that some individuals with depressive disorders appear to be susceptible to developing drug-induced EPS and/or akathisia. In addition, the propensity for the SSRIs to induce these effects in individual patients may vary within the drug class depending, for example, on their selectivity for serotonin relative to other monoamines, affinity for the 5-HT2C receptor, pharmacokinetic drug interaction potential with concomitantly administered neuroleptics and potential for accumulation due to a long half-life. The relative risk of EPS and akathisia associated with SSRIs have yet to be clearly established. The potential risks may be reduced by avoiding rapid and unnecessary dose titration. Furthermore, early recognition and appropriate management of EPS and/or akathisia is required to prevent the impact of these effects on patient compliance and subjective well-being. It is important that the rare occurrence of EPS in patients receiving SSRIs does not preclude their use in Parkinson's disease where their potentially significant role requires more systematic evaluation.

PMID 9694033
Stefano Pallanti, Leonardo Quercioli
Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 May;30(3):400-12. doi: 10.1016/j.pnpbp.2005.11.028. Epub 2006 Feb 28.
Abstract/Text While controlled trials with SRIs have demonstrated a selective efficacy in obsessive-compulsive disorder (OCD), up to 40-60% of patients do not have a satisfactory outcome. Non-response to treatment in OCD is associated with serious social disability. There are a large number of non-responsive patients, and they are difficult to cluster due to ambiguities in diagnostic criteria, possibility of subtypes and a high rate of comorbidity. Moreover, the findings of current studies of "so-called" non-responsive cases are currently non-generalizable because of the lack of an operational definition of non-response. The result has been that a cumulative body of data on a reasonably homogeneous sample of non-responders has not been developed. The aims of the research in this area are to clarify some of the obstacles in defining stages of response and levels of non-response and, through a comprehensive analysis, to propose a systematic nosology for this rather common condition. Better characterization of which patients respond and do not respond to various treatments will enable more accurate clustering of patients, and help facilitate multisite data collection for future research trials. The authors reviewed also the more recent therapeutic pharmacological and psychological lines for the treatment of refractoriness in OCD.

PMID 16503369
Eric Hollander, Carol A Bienstock, Lorrin M Koran, Stefano Pallanti, Donatella Marazziti, Steven A Rasmussen, Luigi Ravizza, Chawkie Benkelfat, Sanjaya Saxena, Benjamin D Greenberg, Yehuda Sasson, Joseph Zohar
Refractory obsessive-compulsive disorder: state-of-the-art treatment.
J Clin Psychiatry. 2002;63 Suppl 6:20-9.
Abstract/Text Nonresponse to treatment in obsessive-compulsive disorder is common, associated with substantial impairment, and understudied. Little practical advice is available to clinicians on next-step treatment strategies for patients who have not responded well to 2 trials of selective serotonin reuptake inhibitors (SSRIs). Available options include continuation of SSRI treatment, switching to another SSRI or selective serotonin-norepinephrine reuptake inhibitor, augmenting with atypical neuroleptics or cognitive-behavioral therapy, or utilizing novel treatment approaches. The authors synthesize state-of-the-art treatment and give practical advice for clinicians.

PMID 12027116
Barbara A Crockett, Erik Churchill, Jonathan R T Davidson
A double-blind combination study of clonazepam with sertraline in obsessive-compulsive disorder.
Ann Clin Psychiatry. 2004 Jul-Sep;16(3):127-32.
Abstract/Text This double blind, randomized, parallel, placebo-controlled study investigates whether clonazepam accelerates and/ or increases the overall response in patients with obsessive compulsive disorder (OCD) who are treated with sertraline. Thirty-seven patients were randomized with 20 in the sertraline and clonazepam group and 17 in the sertraline and placebo groups. Male and female outpatients, age 18-65 years, met criteria for a primary diagnosis of obsessive compulsive disorder according to DSM-IV, as determined by the structured clinical MINI interview. Appropriate safety and efficacy parameters were measured throughout the study. The determination of efficacy was based primarily on changes from baseline to the last observation taken through week 12. Analysis revealed no significant difference between groups at endpoint on the main scale.

PMID 15517844
Umberto Albert, Eugenio Aguglia, Giuseppe Maina, Filippo Bogetto
Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study.
J Clin Psychiatry. 2002 Nov;63(11):1004-9.
Abstract/Text BACKGROUND: The objective of this study was to investigate, in a single-blind manner over a period of 12 weeks, the efficacy and tolerability of venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder (OCD).
METHOD: Patients with a DSM-IV diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score >/= 16 were randomly assigned to receive venlafaxine, 225 to 350 mg/day (26 patients), or clomipramine, 150 to 225 mg/day (47 patients), for 12 weeks, with dosage adjustments according to tolerability and response to treatment. All patients were medication-free from at least 2 months prior to study enrollment. Efficacy measures were the YBOCS and the Clinical Global Impressions scale (CGI), which were completed at baseline and every 4 weeks. We defined responders as patients who had an improvement from baseline in YBOCS score of >/= 35% and a CGI score RESULTS: Twenty-five patients in the venlafaxine group and 40 in the clomipramine group completed the 12-week trial. Responder rates at the end of the 12 weeks were 36% for venlafaxine (9/25) versus 50% for clomipramine (20/40) according to the visitwise analysis and 34.6% (9/26) for venlafaxine versus 42.6% (20/47) for clomipramine according to the last-observation-carried-forward analysis, with no statistically significant difference between the 2 drugs. Adverse experiences were reported by 61.5% of patients receiving venlafaxine (16/26) and by 91.5% of those receiving clomipramine (43/47).
CONCLUSION: Our results indicate that venlafaxine might be as efficacious as clomipramine in the acute treatment of OCD, with fewer side effects.

PMID 12444814
Damiaan Denys, Nic van der Wee, Harold J G M van Megen, Herman G M Westenberg
A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder.
J Clin Psychopharmacol. 2003 Dec;23(6):568-75. doi: 10.1097/01.jcp.0000095342.32154.54.
Abstract/Text SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.

PMID 14624187
Lorrin M Koran, Nona N Gamel, Helen W Choung, Emily H Smith, Elias N Aboujaoude
Mirtazapine for obsessive-compulsive disorder: an open trial followed by double-blind discontinuation.
J Clin Psychiatry. 2005 Apr;66(4):515-20.
Abstract/Text BACKGROUND: Many patients with obsessive-compulsive disorder (OCD) experience little response to standard treatment with serotonin reuptake inhibitors. Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition. Because a pilot study suggested effectiveness of mirtazapine in OCD, we conducted a controlled trial.
METHOD: We recruited 30 subjects, 15 treatmentnaive and 15 treatment-experienced, with DSM-IV OCD of > or =1 year's duration and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of > or =20. In the 12-week, open-label phase, subjects received mirtazapine starting at 30 mg/day and titrated over 2 weeks as tolerated to 60 mg/day. At week 12, responders (YBOCS score decrease > 25%) were randomly assigned, double-blind, to continue mirtazapine or switch to placebo for 8 weeks, including a 1-week, double-blind taper week for placebo subjects.
RESULTS: In the open-label phase, the mean +/-SD YBOCS score fell from 28.3 +/-3.7 to 20.3 +/-8.5 (paired samples t = 4.81, p < .0001). Four subjects (13.3%) discontinued for side effects. Sixteen subjects (53.3%) (8 treatmentnaive, 8 treatment-experienced) were responders and 15 agreed to randomization. Response was independent of comorbid mood disorders. In the 8-week, double-blind, placebo-controlled discontinuation phase, the mirtazapine group's mean YBOCS score fell a mean +/-SD of 2.6 +/-8.7 points while the placebo group's mean score rose a mean +/-SD of 9.1 +/-7.5 points (Mann Whitney U = 6.5, p = .005, 1-tailed). All other outcome measures were consistent with mirtazapine's superiority versus placebo.
CONCLUSION: Mirtazapine may be an effective pharmacotherapy for OCD. If our results are replicated, larger double-blind studies would be indicated.

PMID 15816795
Abstract/Text BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone.
METHOD: Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003.
RESULTS: The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a "much improved" or "very much improved" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment.
CONCLUSIONS: We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.

PMID 15491244
Narendra Nath Samantaray, Suprakash Chaudhury, Preeti Singh
Efficacy of inhibitory learning theory-based exposure and response prevention and selective serotonin reuptake inhibitor in obsessive-compulsive disorder management: A treatment comparison.
Ind Psychiatry J. 2018 Jan-Jun;27(1):53-60. doi: 10.4103/ipj.ipj_35_18.
Abstract/Text BACKGROUND: The majority of treatment research on obsessive-compulsive disorder (OCD) has focused on emotional processing theory (EPT)-based exposure-based interventions. Despite the outcomes of EPT-based exposure and response prevention (ERP), a sizeable percentage of patients do not respond whereas 50%-60% of those who respond experience at least partial relapse at follow-up assessments. Inhibitory learning theory (ILT) provides a novel foundation for understanding how exposure therapy can be maximized to overcome such deficits but has not been adequately studied and compared to other evidence-based management in OCD.
AIM: The aim of this study was to compare ILT-based ERP plus selective serotonin reuptake inhibitor (SSRI) with only SSRI treatment in OCD patients.
MATERIALS AND METHODS: The present study is pretest/posttest control group design with single masking, where participants (n = 32) diagnosed with OCD were randomly assigned into two treatment groups, namely ILT-based ERP plus SSRI and SSRI alone. Yale-Brown obsessive-compulsive scale was primary outcome measure. Intervention was done for 3 months. Thereafter, the participants were followed up for 6 months.
RESULTS: ILT-based ERP and SSRI are both effective treatments. There was no significant difference in treatment effects between combined treatments of SSRI plus ILT-based ERP and SSRI alone in immediate post assessment. However, combined treatment of SSRI plus ILT-based ERP had significantly better treatment effects on follow-ups than SSRI alone.
CONCLUSIONS: SSRI combined with ILT-based strategies to maximize ERP is significantly better than SSRI alone in the treatment of OCD.

PMID 30416292
Naomi A Fineberg, David S Baldwin, Lynne M Drummond, Solange Wyatt, Jasmine Hanson, Srinivas Gopi, Sukhwinder Kaur, Jemma Reid, Virender Marwah, Ricky A Sachdev, Ilenia Pampaloni, Sonia Shahper, Yana Varlakova, Davis Mpavaenda, Christopher Manson, Cliodhna O'Leary, Karen Irvine, Deela Monji-Patel, Ayotunde Shodunke, Tony Dyer, Amy Dymond, Garry Barton, David Wellsted
Optimal treatment for obsessive compulsive disorder: a randomized controlled feasibility study of the clinical-effectiveness and cost-effectiveness of cognitive-behavioural therapy, selective serotonin reuptake inhibitors and their combination in the management of obsessive compulsive disorder.
Int Clin Psychopharmacol. 2018 Nov;33(6):334-348. doi: 10.1097/YIC.0000000000000237.
Abstract/Text Established treatments for obsessive compulsive disorder (OCD) include cognitive behaviour therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication. Combined treatment may outperform monotherapy, but few studies have investigated this. A total of 49 community-based adults with OCD were randomly assigned to CBT, SSRI, or SSRI+CBT. Sertraline (50-200 mg/day) was given as the SSRI for 52 weeks. A 16-h-manualized individual CBT was delivered over 8 weeks with four follow-up sessions. Assessors were 'blinded' to treatment allocation. A preliminary health economic evaluation was conducted. At week 16, combined treatment (n=13) was associated with the largest improvement, sertraline (n=7) the next largest and CBT (n=9) the smallest on the observed case analysis. The effect size (Cohen's d) comparing the improvement in Yale Brown Obsessive Compulsive Scale on CBT versus combined treatment was -0.39 and versus sertraline was -0.27. Between 16 and 52 weeks, the greatest clinical improvement was seen with sertraline, but participant discontinuation prevented reliable analysis. Compared with sertraline, the mean costs were higher for CBT and for combined treatment. The mean Quality Adjusted Life Year scores for sertraline were 0.1823 (95% confidence interval: 0.0447-0.3199) greater than for CBT and 0.1135 (95% confidence interval: -0.0290-0.2560), greater than for combined treatment. Combined treatment appeared the most clinically effective option, especially over CBT, but the advantages over SSRI monotherapy were not sustained beyond 16 weeks. SSRI monotherapy was the most cost-effective. A definitive study can and should be conducted.

PMID 30113928
J H Greist, J W Jefferson, K A Kobak, D J Katzelnick, R C Serlin
Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis.
Arch Gen Psychiatry. 1995 Jan;52(1):53-60.
Abstract/Text BACKGROUND: Questions have been raised regarding the relative efficacy and tolerability of the different serotonin transport inhibitors in the treatment of obsessive-compulsive disorder. We compared the results from four large multicenter placebo-controlled trials of the serotonin transport inhibitors clomipramine hydrochloride (N = 520), fluoxetine hydrochloride (N = 355), fluvoxamine maleate (N = 320), and sertraline hydrochloride (N = 325) for the treatment of obsessive-compulsive disorder.
METHODS: Effect size was calculated by subtracting the end-point drug treatment mean change from the end-point placebo mean change and dividing by the end-point pooled change standard deviation. A test for overall differences between effect sizes was conducted, followed by all possible pairwise comparisons. The Yale-Brown Obsessive Compulsive Scale was the primary outcome measure for all four studies.
RESULTS: All four agents were significantly more effective than placebo, with clomipramine significantly more effective than the other three treatments, which did not differ in effect size. A significantly greater percentage of patients treated with clomipramine were rated much or very much improved than were patients treated with fluoxetine, fluvoxamine, or sertraline.
CONCLUSION: While the results of this meta-analysis support the superiority of clomipramine, head-to-head, double-blind comparisons of these compounds would be the best test of comparative efficacy and tolerability.

PMID 7811162
Nienke H Tenneij, Harold J G M van Megen, Damiaan A J P Denys, Herman G M Westenberg
Behavior therapy augments response of patients with obsessive-compulsive disorder responding to drug treatment.
J Clin Psychiatry. 2005 Sep;66(9):1169-75.
Abstract/Text OBJECTIVE: In many patients with obsessive-compulsive disorder (OCD), residual symptoms persist despite a clinically meaningful response. The objective of this study was to examine whether addition of behavior therapy would augment treatment outcome in these patients.
METHOD: Ninety-six patients with DSM-IV OCD who had responded to 3 months of drug treatment were randomly assigned to either receive addition of behavior therapy or continue on drug treatment alone for 6 months. Patients who continued on drug treatment alone eventually received addition of behavior therapy for 6 months. Data were gathered from October 1998 to June 2002.
RESULTS: OCD patients who received addition of behavior therapy showed a greater improvement in obsessive-compulsive symptoms (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score change = -3.9 in the completers sample) than those who continued on drug treatment alone (Y-BOCS score change = +3.9 for completers). Significantly more patients who received addition of behavior therapy were in remission compared with those who continued on drug treatment alone (p < .0001 for completers). Patients who received behavior therapy after 6 months of drug treatment alone showed a nonsignificant decline in obsessive-compulsive symptoms (Y-BOCS score change = -2.7 for completers); however, the remission rate found in this group was comparable to the remission rate found in the group of patients receiving addition of behavior therapy directly after responding to drug treatment.
CONCLUSION: The results indicate that addition of behavior therapy is beneficial for patients who have responded to drug treatment. The data also suggest that the effect is greater when behavior therapy is added immediately after attainment of the drug response.

PMID 16187776
Mark Zimmerman, Iwona Chelminski
Clinician recognition of anxiety disorders in depressed outpatients.
J Psychiatr Res. 2003 Jul-Aug;37(4):325-33.
Abstract/Text The recognition of anxiety disorders in depressed patients has potential clinical significance because their presence predicts poorer outcome and may influence treatment selection. In routine clinical settings, an unstructured diagnostic interview is typically used to assess patients at the initiation of treatment. Unstructured interviews, however, may result in missed diagnoses, with potential negative clinical consequences. The goals of the present study were to examine whether anxiety disorders are less frequently identified using a routine unstructured clinical evaluation than a semi-structured diagnostic interview in patients with a principal diagnosis of major depressive disorder (MDD), and to determine patients' desire for treatment for comorbid anxiety disorders. Psychiatric outpatients with MDD were evaluated with either a semi-structured or an unstructured diagnostic interview. Current DSM-IV anxiety disorder diagnoses were compared in the two, nonoverlapping, groups of depressed psychiatric outpatients seen in the same practice setting. Patients with comorbid anxiety disorders who were interviewed with the semi-structured interview were asked if they wanted treatment to address their anxiety symptoms. Individuals interviewed with the semi-structured interview were diagnosed with significantly more current anxiety disorders than individuals who were assessed with an unstructured interview. There was variability in patients' desire for treatment of the different anxiety disorders, though for each disorder the majority of patients wanted treatment to address the anxiety symptoms. In psychiatric outpatients with a principal diagnosis of MDD psychiatrists underrecognize anxiety disorder comorbidity for which patients want treatment.

PMID 12765855
Damiaan Denys, Nienke Tenney, Harold J G M van Megen, Femke de Geus, Herman G M Westenberg
Axis I and II comorbidity in a large sample of patients with obsessive-compulsive disorder.
J Affect Disord. 2004 Jun;80(2-3):155-62. doi: 10.1016/S0165-0327(03)00056-9.
Abstract/Text BACKGROUND: No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms.
OBJECTIVE: To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD).
METHOD: 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics.
RESULTS: Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder.
LIMITATIONS: A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses.
CONCLUSION: Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Copyright 2003 Elsevier B.V.
PMID 15207928
A M Ruscio, D J Stein, W T Chiu, R C Kessler
The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication.
Mol Psychiatry. 2010 Jan;15(1):53-63. doi: 10.1038/mp.2008.94. Epub 2008 Aug 26.
Abstract/Text Despite significant advances in the study of obsessive-compulsive disorder (OCD), important questions remain about the disorder's public health significance, appropriate diagnostic classification, and clinical heterogeneity. These issues were explored using data from the National Comorbidity Survey Replication, a nationally representative survey of US adults. A subsample of 2073 respondents was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing obsessions or compulsions at some time in their lives. While conditional probability of OCD was strongly associated with the number of obsessions and compulsions reported, only small proportions of respondents met full DSM-IV criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with substantial comorbidity, not only with anxiety and mood disorders but also with impulse-control and substance use disorders. Severity of OCD, assessed by an adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with poor insight, high comorbidity, high role impairment, and high probability of seeking treatment. The high prevalence of subthreshold OCD symptoms may help explain past inconsistencies in prevalence estimates across surveys and suggests that the public health burden of OCD may be greater than its low prevalence implies. Evidence of a preponderance of early onset cases in men, high comorbidity with a wide range of disorders, and reliable associations between disorder severity and key outcomes may have implications for how OCD is classified in DSM-V.

PMID 18725912
Abstract/Text This study examined 49 in-patients with obsessive-compulsive disorder who were treated over three years. The patients had failed to respond to previous treatment. Treatment consisted of in-patient exposure, occasionally combined with other interventions individually tailored to the patient's specific difficulties. This resulted in significant clinical improvements and an average 40% reduction in rituals in 31 (63.3%) of these chronic patients. These gains were maintained at an average 19-month follow-up. Checking rituals were more likely to be associated with good outcome. Women had a later onset of the disorder and a slight tendency to better prognosis. No other predictors of outcome were found.

PMID 8075915
David Mataix-Cols, Isaac M Marks, John H Greist, Kenneth A Kobak, Lee Baer
Obsessive-compulsive symptom dimensions as predictors of compliance with and response to behaviour therapy: results from a controlled trial.
Psychother Psychosom. 2002 Sep-Oct;71(5):255-62.
Abstract/Text BACKGROUND: Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions comes from studies of psychiatric comorbidity, functional brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD.
METHODS: One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer- versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation.
RESULTS: The patients studied were phenomenologically comparable (including the presence of 'pure' obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the 'hoarding' dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the 'sexual/religious obsessions' factor predicted poorer outcome with BT, especially when computer-guided.
CONCLUSIONS: BT is especially indicated for OCD patients with aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients' adherence and response to treatment.

Copyright 2002 S. Karger AG, Basel
PMID 12207105
David Veale, Sarah Miles, Nicola Smallcombe, Haben Ghezai, Ben Goldacre, John Hodsoll
Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis.
BMC Psychiatry. 2014 Nov 29;14:317. doi: 10.1186/s12888-014-0317-5. Epub 2014 Nov 29.
Abstract/Text BACKGROUND: In 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI.
METHODS: Studies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS.
RESULTS: Two studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.
CONCLUSIONS: Risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

PMID 25432131
Petros Skapinakis, Tzeni Papatheodorou, Venetsanos Mavreas
Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials.
Eur Neuropsychopharmacol. 2007 Jan 15;17(2):79-93. doi: 10.1016/j.euroneuro.2006.07.002. Epub 2006 Aug 10.
Abstract/Text This study aimed to determine the effectiveness of antipsychotic augmentation of serotonergic antidepressants in the management of treatment-resistant obsessive compulsive disorder by carrying out a meta-analysis of all randomized controlled trials. Studies selected through a literature search conducted in March 2006. Ten trials comparing antipsychotic drugs versus placebo met inclusion criteria (haloperidol [n=1], risperidone [n=3], olanzapine [n=2], quetiapine [n=4]). A total of 157 patients were randomized to study drug and 148 were randomized to placebo. Response occurred more often among patients randomized to antipsychotic drugs. The weighted combined response rate ratio by random effects meta-analysis was 3.31 (95% CI 1.40-7.84). Significant between studies heterogeneity was partly explained by the definition of refractoriness, the type and dose of the drug used and the inclusion or exclusion of patients with tic disorders. The study supports the use of antipsychotic drugs as an augmentation strategy but more and larger trials are needed.

PMID 16904298
Gabriele Masi, Chiara Pfanner, Stefania Millepiedi, Stefano Berloffa
Aripiprazole augmentation in 39 adolescents with medication-resistant obsessive-compulsive disorder.
J Clin Psychopharmacol. 2010 Dec;30(6):688-93.
Abstract/Text The aim of this study was to assess efficacy of aripiprazole augmentation of serotonin reuptake inhibitor (SRI) treatment in adolescents with obsessive-compulsive disorder (OCD) who did not respond to 2 initial trials with SRI monotherapy. A consecutive series of 39 adolescents (28 males and 11 females; age range, 12 to 18 years; mean age, 14.6 ± 1.2 years), with OCD diagnosed based on a clinical interview and according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were included. The mean final aripiprazole dosage was 12.2 ± 3.4 mg/d. At the endpoint, 27 patients (59.0%) had a Clinical Global Impression (CGI)-Improvement score 1 or 2 (very much or much improved) and a Clinical Global Impression-Severity (CGI-S) score 3 or below and were thus considered responders. The CGI-S improved from 6.0 ± 0.9 at the baseline (severely to extremely severely ill) to 3.5 ± 1.0 (mild to moderately ill) at the end of the follow-up (P < 0.0001), whereas the Children's Global Assessment Scale improved from 39.2 ± 5.8 to 49.8 ± 9.0 (P < 0.0001). Compared with nonresponders, responders were less impaired at the baseline in functional impairment (Children's Global Assessment Scale; P = 0.004) but not in clinical severity (CGI-S). Subtypes of OCD comorbidity and absence of insight did not affect clinical response. Mild transitory agitation (10.3%), mild sedation (10.3%), and sleep disorders (7.7%) were reported, but any of the patients discontinued medication because of adverse effects.In these severely impaired adolescents, aripiprazole augmentation of SRIs was well tolerated and effective in more than half of the patients.

PMID 21105283

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