今日の臨床サポート

うつ病

著者: 尾鷲登志美 牧田総合病院 精神科

監修: 上島国利 昭和大学

著者校正/監修レビュー済:2021/10/13
参考ガイドライン:
 
  1. 日本うつ病学会、気分障害の治療ガイドライン作成委員会 「日本うつ病学会治療ガイドライン Ⅱ.大うつ病性障害」
    (最新版:2016年7月31日) ※2019年7月24日 序文改訂
    https://www.secretariat.ne.jp/jsmd/iinkai/katsudou/data/20190724-02.pdf
  1. 日本うつ病学会、気分障害の治療ガイドライン検討委員会 「うつ病治療ガイドライン -高齢者のうつ病治療ガイドライン-」
    (最新版:2020年7月1日)
    https://www.secretariat.ne.jp/jsmd/iinkai/katsudou/data/guideline_20200713.pdf
  1. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders
https://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/WFSBP_TG_Unipolar_depressive_disorders_Bauer_et_al_2013.pdf
  1. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders. Part 2: Maintenance Treatment of Major Depressive Disorder-Update 2015
https://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bauer_et_al_2015.pdf
  1. Canadian Network for Mood and Anxiety Treatment (CANMAT)2016 Clinical Guidelines for the Management with Major Depressive Disorder
https://www.canmat.org/2019/03/17/2016-depression-guidelines/
  1. Clinical Practice Guideline for the Treatment of Depression Across Three Age Cohorts American Psychological Association Guideline Development Panel for the Treatment of Depressive Disorders Adopted as APA Policy Feb. 16, 2019 
https://www.apa.org/depression-guideline/guideline.pdf
 
 
患者向け説明資料

概要・推奨   

  1. うつ病を疑った場合には、睡眠障害についての評価も行うことが強く推奨される(推奨度1)。
  1. アルコール依存がうつ病発症の前か後か、併存かは判然としないこともあるが、アルコール乱用/依存はうつ病患者の自殺危険因子の1つであり、アルコールの問題を評価することが強く推奨される(推奨度1)。
  1. うつ病を疑った段階だけでなく、うつ病治療フォロー中も常に自殺リスクについて評価を行うことが強く推奨される(推奨度1)。
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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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
尾鷲登志美 : 特に申告事項無し[2021年]
監修:上島国利 : 原稿料(大日本住友製薬)[2021年]

改訂のポイント:
  1. rTMSの情報を加筆更新
  1. ボルチオキセチン(トリンテリックス)を「その他」から「セロトニン再取り込み阻害・セロトニン受容体調節剤」へ分類しなおした
  1. スルピリドを追加
  1. ルラシドンを追加
 

病態・疫学・診察

疾患情報(疫学・病態)  
  1. うつ病/大うつ病性障害の診断の際には、甲状腺機能障害などの身体疾患および薬剤や、アルコール誘発性によるうつ状態を除外する。
  1. 疾患の頻度は高く、厚生労働省が全国の医療施設に対して行っている「患者調査」によると、1996(平成8)年には43.3万人だったうつ病などの気分障害の総患者数は、2008年には104.1万人、2017年には127.6万人と、約20年間でおよそ3倍に増加した。
  1. 高齢者の場合には、認知症による自発性の低下や、低活動性せん妄との鑑別も重要である。また、うつ症状が認知症の前駆症状である、あるいは、抑うつエピソードが認知症リスクであるという指摘があり、認知症への移行に注意が必要である。
  1. 周産期~産後うつ病の罹患率は10~20%とほかの時期より高率にうつ病を発症する。
  1. 自殺既遂者に対する警視庁の調査によると、その動機である健康問題の4割以上がうつ病であった。
  1. うつ病は適応障害と異なるが、実際の診療上で両者の区別が困難な場合がある。
  1. うつ病の代表的な症状として、以下のものが挙げられる。
  1. ほとんど毎日の抑うつ気分
  1. 興味、喜びの著しい減退
  1. 著しい体重減少、あるいは体重増加
  1. 睡眠障害
  1. 精神運動性の焦燥または制止
  1. 易疲労性、気力の減退
  1. 無価値感、不適切な罪責感
  1. 思考力や集中力の減退
  1. 自殺念慮、自殺企図
  1. 米国精神医学会の診断マニュアル(DSM-5)によれば、これらのうち5つ以上が2週間以上存在し、そのうち少なくとも1つは、1)または2)である場合に、うつ病/大うつ病性障害と診断される。
 
  1. 気分障害と自殺の危険性は関連しており、単極性うつ病患者は、一般住民よりも自殺リスクが20倍高いといわれている。うつ病を疑った段階だけでなく、うつ病治療フォロー中も常に自殺リスクについて評価を行うことが強く推奨される(推奨度1)。治療においても、抗うつ薬が自殺関連行動に関係することが検討され、特に若年者では抗うつ薬処方による利点とリスクを十分に考慮することが必要である。年齢が上がるにつれて、抗うつ薬のリスクは減少し、利点が増加することが検討されている。気分障害における自殺予防効果はリチウムでよく検討されている。
  1. 自殺完遂者、自殺企図者とうつ病との関連を示す研究および調査が複数存在する。Qinは17年間にわたるデンマークの自殺者を調査した結果、反復性うつ病が男女ともに自殺リスクに最も強く関連していた[1]
  1. また、抗うつ薬投与後に特に若年者において自殺関連行動が増加したという研究が存在する。その1つである、2009年Stoneらの研究によると、抗うつ薬を用いた臨床試験では、精神病性特徴を伴わない場合の自殺行動および自殺念慮はまれであるが、精神病性特徴を伴う場合の自殺リスクは年齢と関連していたという。それぞれのオッズ比は、25歳未満では1.62(95%CI:0.97-2.71)と2.30(1.04 - 5.09)で、25-64歳では0.79(0.64 - 0.98)と0.87(0.58 - 1.29)、65歳以上では0.37(0.18 - 0.76)と0.06(0.01 - 0.58)であった。年齢を連続変数とした場合、自殺行動もしくは自殺念慮のオッズ比は、年齢とともに2.6%(-3.9%- -1.3%, P=0.0001)低下し、自殺行動のオッズ比は年齢とともに4.6%(-7.4% - -1.8%, P=0.001)低下していた[2]
  1. Leoらによる米国の27年間にわたる縦断的前方視的観察研究によれば、抗うつ薬の使用によって自殺リスクは有意に軽減していた(ハザード比0.80、95%CI: 0.68-0.95; z = -2.54; P = .011)[3]
  1. Ciprianiらによる48件の無作為化対照試験(6,674名)を対象にしたメタ解析によると、リチウムはプラセボに比して気分障害における自殺リスクを有意に低下させた[4]
病歴・診察のポイント  
  1. 現在のうつ症状評価と同時に、以前にも同様の症状がなかったか、既往・治療歴を確認する。

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文献 

著者: Ping Qin
雑誌名: J Psychiatr Res. 2011 Nov;45(11):1445-52. doi: 10.1016/j.jpsychires.2011.06.002. Epub 2011 Jun 30.
Abstract/Text People with a psychiatric illness are at high risk for suicide; however, variation of the risk by patients' sex and age and by specific diagnosis needs to be explored in a more detail. This large population study systematically assesses suicide incidence rate ratio (IRR) and population attributable risk (PAR) associated with various psychiatric disorders by comparing 21,169 suicides in Denmark over a 17-year period with sex-age-time-matched population controls. The study shows that suicide risk is significantly increased for persons with a hospitalized psychiatric disorder and the associated risk varies significantly by diagnosis and by sex and age of subjects. Further adjustment for personal socioeconomic differences eliminates the IRRs associated with various disorders only to a limited extend. Recurrent depression and borderline personality disorder increase suicide risk the strongest while dementia increases the risk the least for both males and females. The influence of various disorders generally weakens with increasing age; however, there are important exceptions. Schizophrenia affects people aged ≤35 years the strongest in terms of both IRR and PAR. Recurrent depression increases suicide risk particularly strong in all age groups and the associated PAR increases steadily with age. Borderline personality disorder has a strong effect in young people, especially those ≤35 years. Alcohol use disorder accounts the highest PAR of suicides in males of 36-60 years old. For the elderly above 60 years old, reaction to stress and adjustment disorder increases the risk for suicide the most in both sexes. These findings suggest that approaches to psychiatric suicide prevention should be varied according to diagnosis and sex and age of subjects.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21722920  J Psychiatr Res. 2011 Nov;45(11):1445-52. doi: 10.1016/・・・
著者: Marc Stone, Thomas Laughren, M Lisa Jones, Mark Levenson, P Chris Holland, Alice Hughes, Tarek A Hammad, Robert Temple, George Rochester
雑誌名: BMJ. 2009 Aug 11;339:b2880. Epub 2009 Aug 11.
Abstract/Text OBJECTIVE: To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults.
DESIGN: Meta-analysis of 372 double blind randomised placebo controlled trials.
SETTING: Drug development programmes for any indication in adults.
PARTICIPANTS: 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%).
MAIN OUTCOME MEASURES: Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation.
RESULTS: For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged >or=65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (-3.9% to -1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (-7.4% to -1.8%, P=0.001).
CONCLUSIONS: Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged >or=65.

PMID 19671933  BMJ. 2009 Aug 11;339:b2880. Epub 2009 Aug 11.
著者: Andrew C Leon, David A Solomon, Chunshan Li, Jess G Fiedorowicz, W H Coryell, Jean Endicott, Martin B Keller
雑誌名: J Clin Psychiatry. 2011 May;72(5):580-6. doi: 10.4088/JCP.10m06552.
Abstract/Text OBJECTIVE: The 2007 revision of the black box warning for suicidality with antidepressants states that patients of all ages who initiate antidepressants should be monitored for clinical worsening or suicidality. The objective of this study was to examine the association of antidepressants with suicide attempts and with suicide deaths.
METHOD: A longitudinal, observational study of mood disorders with prospective assessments for up to 27 years was conducted at 5 US academic medical centers. The study sample included 757 participants who enrolled from 1979 to 1981 during an episode of mania, depression, or schizoaffective disorder, each based on Research Diagnostic Criteria. Unlike randomized controlled clinical trials of antidepressants, the analyses included participants with psychiatric and other medical comorbidity and those receiving acute or maintenance therapy, polypharmacy, or no psychopharmacologic treatment at all. Over follow-up, these participants had 6,716 time periods that were classified as either exposed to an antidepressant or not exposed. Propensity score-adjusted mixed-effects survival analyses were used to examine risk of suicide attempt or suicide, the primary outcome.
RESULTS: The propensity model showed that antidepressant therapy was significantly more likely when participants' symptom severity was greater (odds ratio [OR] = 1.16; 95% CI, 1.12-1.21; z = 8.22; P < .001) or when it was worsening (OR = 1.69; 95% CI, 1.50-1.89; z = 9.02; P < .001). Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68-0.95; z = -2.54; P = .011).
CONCLUSIONS: This longitudinal study of a broadly generalizable cohort found that, although those with more severe affective syndromes were more likely to initiate treatment, antidepressants were associated with a significant reduction in the risk of suicidal behavior. Nonetheless, we believe that clinicians must closely monitor patients when an antidepressant is initiated.

© Copyright 2011 Physicians Postgraduate Press, Inc.
PMID 21658345  J Clin Psychiatry. 2011 May;72(5):580-6. doi: 10.4088/J・・・
著者: Andrea Cipriani, Keith Hawton, Sarah Stockton, John R Geddes
雑誌名: BMJ. 2013 Jun 27;346:f3646. Epub 2013 Jun 27.
Abstract/Text OBJECTIVE: To assess whether lithium has a specific preventive effect for suicide and self harm in people with unipolar and bipolar mood disorders.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Medline, Embase, CINAHL, PsycINFO, CENTRAL, web based clinical trial registries, major textbooks, authors of important papers and other experts in the discipline, and websites of pharmaceutical companies that manufacture lithium or the comparator drugs (up to January 2013).
INCLUSION CRITERIA: Randomised controlled trials comparing lithium with placebo or active drugs in long term treatment for mood disorders.
REVIEW METHODS: Two reviewers assessed studies for inclusion and risk of bias and extracted data. The main outcomes were the number of people who completed suicide, engaged in deliberate self harm, and died from any cause.
RESULTS: 48 randomised controlled trials (6674 participants, 15 comparisons) were included. Lithium was more effective than placebo in reducing the number of suicides (odds ratio 0.13, 95% confidence interval 0.03 to 0.66) and deaths from any cause (0.38, 0.15 to 0.95). No clear benefits were observed for lithium compared with placebo in preventing deliberate self harm (0.60, 0.27 to 1.32). In unipolar depression, lithium was associated with a reduced risk of suicide (0.36, 0.13 to 0.98) and also the number of total deaths (0.13, 0.02 to 0.76) compared with placebo. When lithium was compared with each active individual treatment a statistically significant difference was found only with carbamazepine for deliberate self harm. Lithium tended to be generally better than the other active comparators, with small statistical variation between the results.
CONCLUSIONS: Lithium is an effective treatment for reducing the risk of suicide in people with mood disorders. Lithium may exert its antisuicidal effects by reducing relapse of mood disorder, but additional mechanisms should also be considered because there is some evidence that lithium decreases aggression and possibly impulsivity, which might be another mechanism mediating the antisuicidal effect.

PMID 23814104  BMJ. 2013 Jun 27;346:f3646. Epub 2013 Jun 27.
著者: D E Ford, D B Kamerow
雑誌名: JAMA. 1989 Sep 15;262(11):1479-84.
Abstract/Text As part of the National Institute of Mental Health Epidemiologic Catchment Area study, 7954 respondents were questioned at baseline and 1 year later about sleep complaints and psychiatric symptoms using the Diagnostic Interview Schedule. Of this community sample, 10.2% and 3.2% noted insomnia and hypersomnia, respectively, at the first interview. Forty percent of those with insomnia and 46.5% of those with hypersomnia had a psychiatric disorder compared with 16.4% of those with no sleep complaints. The risk of developing new major depression was much higher in those who had insomnia at both interviews compared with those without insomnia (odds ratio, 39.8; 95% confidence interval, 19.8 to 80.0). The risk of developing new major depression was much less for those who had insomnia that had resolved by the second visit (odds ratio, 1.6; 95% confidence interval, 0.5 to 5.3). Further research is needed to determine if early recognition and treatment of sleep disturbances can prevent future psychiatric disorders.

PMID 2769898  JAMA. 1989 Sep 15;262(11):1479-84.
著者: Chiara Baglioni, Gemma Battagliese, Bernd Feige, Kai Spiegelhalder, Christoph Nissen, Ulrich Voderholzer, Caterina Lombardo, Dieter Riemann
雑誌名: J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011. Epub 2011 Feb 5.
Abstract/Text BACKGROUND: In many patients with depression, symptoms of insomnia herald the onset of the disorder and may persist into remission or recovery, even after adequate treatment. Several studies have raised the question whether insomniac symptoms may constitute an independent clinical predictor of depression. This meta-analysis is aimed at evaluating quantitatively if insomnia constitutes a predictor of depression.
METHODS: PubMed, Medline, PsycInfo, and PsycArticles databases were searched from 1980 until 2010 to identify longitudinal epidemiological studies simultaneously investigating insomniac complaints and depressed psychopathology. Effects were summarized using the logarithms of the odds ratios for insomnia at baseline to predict depression at follow-up. Studies were pooled with both fixed- and random-effects meta-analytic models in order to evaluate the concordance. Heterogeneity test and sensitivity analysis were computed.
RESULTS: Twenty-one studies met inclusion criteria. Considering all studies together, heterogeneity was found. The random-effects model showed an overall odds ratio for insomnia to predict depression of 2.60 (confidence interval [CI]: 1.98-3.42). When the analysis was adjusted for outliers, the studies were not longer heterogeneous. The fixed-effects model showed an overall odds ratio of 2.10 (CI: 1.86-2.38).
LIMITATIONS: The main limit is that included studies did not always consider the role of other intervening variables.
CONCLUSIONS: Non-depressed people with insomnia have a twofold risk to develop depression, compared to people with no sleep difficulties. Thus, early treatment programs for insomnia might reduce the risk for developing depression in the general population and be considered a helpful general preventive strategy in the area of mental health care.

Copyright © 2011 Elsevier B.V. All rights reserved.
PMID 21300408  J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j・・・
著者: N Breslau, T Roth, L Rosenthal, P Andreski
雑誌名: Biol Psychiatry. 1996 Mar 15;39(6):411-8.
Abstract/Text In a longitudinal epidemiological study of young adults, we estimated the association between sleep disturbance and psychiatric disorders, cross-sectionally and prospectively. A random sample of 1200 was drawn from all 21-30-year-old members of a large health maintenance organization (HMO) in Michigan; 1007 were interviewed in 1989 and 979 were reinterviewed in 1992. Lifetime prevalence of insomnia alone was 16.6%, of hypersomnia alone, 8.2%, and of insomnia plus hypersomnia, 8%. The gender-adjusted relative risk for new onset of major depression during the follow-up period in persons with history of insomnia at baseline was 4.0 (95% confidence interval [CI] 2.2-7.0) and in persons with baseline history of hypersomnia, 2.9 (95% CI 1.5-5.6). When history of other prior depressive symptoms (e.g., psychomotor retardation or agitation, suicidal ideation) was controlled for, prior insomnia remained a significant predictor of subsequent major depression. Complaints of 2 weeks or more of insomnia nearly every night might be a useful marker of subsequent onset of major depression.

PMID 8679786  Biol Psychiatry. 1996 Mar 15;39(6):411-8.
著者: W Vaughn McCall, Jill N Blocker, Ralph D'Agostino, James Kimball, Niki Boggs, Barbara Lasater, Peter B Rosenquist
雑誌名: Sleep Med. 2010 Oct;11(9):822-7. doi: 10.1016/j.sleep.2010.04.004. Epub 2010 May 15.
Abstract/Text OBJECTIVE: Insomnia has been linked to suicidal ideas and suicide death in cross-sectional and longitudinal population-based studies. A link between insomnia and suicide has not been previously examined in the setting of a clinical trial. Herein we describe the relationship between insomnia and suicidal thinking during the course of a clinical trial for depression with insomnia.
METHODS: Sixty patients aged 41.5±12.5 years (2/3 women) with major depressive episode and symptoms of insomnia received open-label fluoxetine for 9 weeks and also received blinded, randomized eszopiclone 3mg or placebo at bedtime after the first week of fluoxetine. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI), and suicidal ideation was assessed with The Scale for Suicide Ideation (SSI). Depression symptoms were assessed with the depressed mood item and the anhedonia item from the Hamilton Rating Scale for Depression-24 (HRSD24), as well as a sum score for all non-sleep and non-suicide items from the HRSD (HRSD20). Measurements were taken at baseline and weeks 1, 2, 4, 6, and 8. SSI was examined by generalized linear mixed models for repeated measures as the outcome of interest for all 60 participants with ISI and various mood symptoms as independent variables, with adjustment for age, gender, treatment assignment, and baseline SSI.
RESULTS: Higher levels of insomnia corresponded to significantly greater intensity of suicidal thinking (p<0.01). The depressed mood item of the HRSD, and the sum of the HRSD20, both corresponded to greater suicidal thinking (p<0.001). The anhedonia item did not correspond with suicidal thinking. When both ISI and the depressed mood item, or ISI and the anhedonia item, were included together in the same model, the ISI remained an independent predictor of suicidal thinking.
CONCLUSIONS: The results support the concept that insomnia may be a useful indicator for suicidal ideation and now extend this idea into clinical trials. Insomnia remains an independent indicator of suicidal ideation, even taking into account the core symptoms of depression such as depressed mood and anhedonia. The complaint of insomnia during a depression clinical trial might indicate that more direct questioning about suicide is warranted.

PMID 20478741  Sleep Med. 2010 Oct;11(9):822-7. doi: 10.1016/j.sleep.2・・・
著者: Anders F Thomsen, Tine K Kvist, Per K Andersen, Lars V Kessing
雑誌名: Thyroid. 2005 Jul;15(7):700-7. doi: 10.1089/thy.2005.15.700.
Abstract/Text BACKGROUND: Links between thyroid function and depression have been noted in many contexts. We assessed whether hospitalization with hypothyroidism was a risk factor for developing affective disorder.
METHODS: We conducted a prospective cohort study using historical data from Danish registers. The observational period was 1977-1999. Three study cohorts were identified: all patients with a first hospital admittance with the resulting index discharge diagnoses hypothyroidism, osteoarthritis, or nontoxic goiter. A later hospitalization with a resulting discharge diagnosis of affective disorder was used as event of interest, and rates of readmission were estimated and compared using competing risk models in survival analyses.
FINDINGS: We identified 165,307 patients discharged with an index diagnosis. In the observational period, 1041 events occurred. An index diagnosis of hypothyroidism was associated with an increased risk of hospitalization with affective disorder when compared to the control diseases. The risk of hospitalization with affective disorder was greatest in the first year after index hospitalization.
CONCLUSION: Patients hospitalized with hypothyroidism have a greater risk of readmission with depression or bipolar disorder than control patients. This renders epidemiologic support to theories linking thyroid dysfunction with mood disturbances.

PMID 16053387  Thyroid. 2005 Jul;15(7):700-7. doi: 10.1089/thy.2005.15・・・
著者: Anne Farmer, Ania Korszun, Michael J Owen, Nick Craddock, Lisa Jones, Ian Jones, Jo Gray, Richard J Williamson, Peter McGuffin
雑誌名: Br J Psychiatry. 2008 May;192(5):351-5. doi: 10.1192/bjp.bp.107.038380.
Abstract/Text BACKGROUND: Few studies have examined the rates of physical disorders in those with recurrent depression.
AIMS: To examine self-reported physical disorders in people with recurrent depression compared with a psychiatrically healthy control group.
METHOD: As part of a genetic case-control association study, 1546 participants with recurrent depression and 884 controls were interviewed about lifetime ever treatment for 16 different physical health disorders.
RESULTS: The cases group had a significantly higher frequency of 14 physical disorders and more obesity than the control group. After controlling for age, gender, body mass index (BMI) and multiple testing, those in the cases group had significantly higher rates of gastric ulcer, rhinitis/hay fever, osteoarthritis, thyroid disease, hypertension and asthma.
CONCLUSIONS: People with recurrent depression show high rates of many common physical disorders. Although this can be partly explained by BMI, shared aetiological pathways such as dysfunction of the hypothalamic-pituitary axis may have a role.

PMID 18450658  Br J Psychiatry. 2008 May;192(5):351-5. doi: 10.1192/bj・・・
著者: J F Goldberg, T M Singer, J L Garno
雑誌名: J Clin Psychiatry. 2001;62 Suppl 25:35-43.
Abstract/Text The relationship between suicidality and substance abuse has long been recognized, although studies have only fairly recently begun to identify factors that may help clarify how alcohol or other drug abuse increases the susceptibility to suicidal behavior in vulnerable populations. In particular, alcohol and other psychoactive substance misuse has been linked with mood destabilization and the induction of manic or depressive episodes in affectively ill individuals, while also demarcating groups with heightened tendencies toward impulsivity, aggression, and sensitivity to interpersonal loss. Serotonergic mechanisms have been implicated in each of these clinical settings, along with possible dysregulation of other neurotransmitter systems. Psychosocial aspects of alcohol or drug abuse relevant to suicide may involve a heightened sensitivity to interpersonal loss, poor coping skills in response to adverse life events, and affective dysregulation induced by circadian and psychosocial stresses. Consequently, self-destructive behaviors with relatively little premeditation may arise during periods of increased stress, intoxication, depression, or other psychopathology. Early detection of substance abuse followed by appropriate pharmacologic and/or psychotherapeutic interventions may greatly help to minimize the formation of complex comorbid psychiatric conditions and reduce the potential for suicidal acts among high-risk populations.

PMID 11765095  J Clin Psychiatry. 2001;62 Suppl 25:35-43.
著者: Ulrich W Preuss, Gabriele Koller, Sven Barnow, Markus Eikmeier, Michael Soyka
雑誌名: Alcohol Clin Exp Res. 2006 May;30(5):866-77. doi: 10.1111/j.1530-0277.2006.00073.x.
Abstract/Text BACKGROUND: Comobidity of personality disorders (PDs) and alcohol dependence are considered to increase the risk for suicidal behavior. The aim of this study is to assess the influence of Diagnostic and Statistical Manual of Mental Disorder-fourth edition (DSM-IV) personality characteristics and comorbid axis I disorders on suicidal behavior in alcohol-dependent inpatients.
METHODS: Characteristics of alcohol dependence and suicidal behavior were obtained using the Semi-Structured Assessment on Genetics in Alcoholism (SSAGA). Personality disorder characteristics were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders.
RESULTS: Three-hundred seventy-six treatment-seeking alcohol-dependent subjects, of whom 55% were diagnosed to have a PD and approximately 25% had a history of at least 1 suicide attempt, were enrolled into the study. Subjects with PDs in all clusters reported a higher rate of suicide attempt history, depression episodes, and depression during the most serious attempt. As indicated by univariate and multivarate analysis, this pattern of suicide attempt characteristics was most pronounced in borderline disordered subjects and alcoholic individuals who live alone.
CONCLUSION: Subjects with alcohol dependence who have various comorbid PDs and depression deserve special attention in psychiatric care to prevent suicide. Psychotherapeutic strategies may have to be adapted to treat this high-risk population.

PMID 16634856  Alcohol Clin Exp Res. 2006 May;30(5):866-77. doi: 10.11・・・
著者: S P Roose, A H Glassman, B T Walsh, S Woodring, J Vital-Herne
雑誌名: Am J Psychiatry. 1983 Sep;140(9):1159-62.
Abstract/Text A retrospective analysis of all the suicides at the New York State Psychiatric Institute over a 25-year period was carried out. The authors retrospectively assigned diagnoses according to Research Diagnostic Criteria and DSM-III and found that among the patients who committed suicide there were 14 with unipolar endogenous depression. Of those 14 patients, 10 were considered delusional or probably delusional. In comparison, a control group of similarly diagnosed depressed patients taken from the same institution over the same time period included far fewer delusional depressions. Thus, there was a significant association between delusions and suicide: A delusionally depressed patient was five times more likely to commit suicide than a nondelusional one.

PMID 6614220  Am J Psychiatry. 1983 Sep;140(9):1159-62.
著者: Andrea Cipriani, Toshi A Furukawa, Georgia Salanti, Anna Chaimani, Lauren Z Atkinson, Yusuke Ogawa, Stefan Leucht, Henricus G Ruhe, Erick H Turner, Julian P T Higgins, Matthias Egger, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aran Tajika, John P A Ioannidis, John R Geddes
雑誌名: Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. Epub 2018 Feb 21.
Abstract/Text BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
METHODS: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
FINDINGS: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
INTERPRETATION: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
FUNDING: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 29477251  Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S・・・
著者: George I Papakostas, Michael E Thase, Maurizio Fava, J Craig Nelson, Richard C Shelton
雑誌名: Biol Psychiatry. 2007 Dec 1;62(11):1217-27. doi: 10.1016/j.biopsych.2007.03.027. Epub 2007 Jun 22.
Abstract/Text BACKGROUND: Recent studies suggest that the treatment of major depressive disorder (MDD) with newer antidepressant drugs that simultaneously enhance norepinephrine and serotonin neurotransmission might result in higher response and remission rates than the selective serotonin reuptake inhibitors (SSRIs). The goal of our work was to compare response rates among patients with MDD treated with either of these two broad categories of antidepressant drugs.
METHODS: Medline/Pubmed, EMBase, clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies were searched for double-blind, randomized trials comparing a newer serotonergic-noradrenergic antidepressant drug (venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, or moclobemide) with an SSRI for MDD.
RESULTS: Ninety-three trials (n = 17,036) were combined using a random-effects model. Treatment with serotonergic + noradrenergic antidepressant drugs was more likely to result in clinical response than the SSRIs (risk ratio [RR] = 1.059; response rates 63.6% versus 59.3%; p = .003). There was no evidence for heterogeneity among studies combined (p = 1.0). Excluding each individual agent did not significantly alter the pooled RR. With the exception of duloxetine (.985), RRs for response for each individual serotonergic + noradrenergic antidepressant drug were within the 95% confidence interval of the pooled RR (1.019-1.101).
CONCLUSIONS: Serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared with SSRIs in MDD. With the Number Needed to Treat (NNT) statistic as one indicator of clinical significance, nearly 24 patients would need to be treated with dual-action antidepressant drugs instead of SSRIs in order to obtain one additional responder. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom's National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of depressed patients treated with SSRI /serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant drugs. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms.

PMID 17588546  Biol Psychiatry. 2007 Dec 1;62(11):1217-27. doi: 10.101・・・
著者: Andrea Cipriani, Toshiaki A Furukawa, John R Geddes, Lara Malvini, Alessandra Signoretti, Hugh McGuire, Rachel Churchill, Atsuo Nakagawa, Corrado Barbui, MANGA Study Group
雑誌名: J Clin Psychiatry. 2008 Nov;69(11):1732-42. Epub 2008 Nov 4.
Abstract/Text OBJECTIVE: Preliminary evidence suggested that sertraline might be slightly superior to other antidepressant medications in terms of efficacy. The aim of this study was to carry out a systematic review and meta-analysis to compare sertraline with any other antidepressant in the acute phase treatment of major depression at 8 weeks.
DATA SOURCES: MEDLINE; EMBASE; the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register; and the Cochrane Central Register of Controlled Trials up to August 2007. No language restriction. The following search strategy was used: diagnosis = depress* or dysthymi* or adjustment disorder* or mood disorder* or affective disorder or affective symptoms, and intervention (or free text) = sertraline. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
STUDY SELECTION: Only randomized controlled trials allocating patients with major depression to sertraline versus any other antidepressant agent.
DATA EXTRACTION: Three reviewers independently extracted data. A double-entry procedure was employed by 2 reviewers. To analyze data, a very conservative approach with a 99% confidence interval (CI) and a random effects model was used. Information extracted included study characteristics, participant characteristics, intervention details, and outcome measures, such as the number of patients who responded to treatment and the number of patients who failed to complete the study by any cause at 8 weeks.
DATA SYNTHESIS: This systematic review and meta-analysis found that sertraline is statistically significantly better than fluoxetine (relative risk [RR] = 0.85, 99% CI = 0.74 to 0.98; number needed to treat [NNT] = 12) and other SSRIs as a class (RR = 0.88, 99% CI = 0.78 to 0.99; NNT = 17) and highlighted a consistent even though not statistically significant trend in favor of sertraline over many other antidepressants both in terms of efficacy and acceptability in a homogeneous and clinically relevant time frame of 8 weeks.
CONCLUSIONS: The results of this review suggest that sertraline may be a candidate as the initial choice of antidepressant for people with major depression.

Copyright 2008 Physicians Postgraduate Press, Inc.
PMID 19026250  J Clin Psychiatry. 2008 Nov;69(11):1732-42. Epub 2008 N・・・
著者: F Petty, M H Trivedi, M Fulton, A J Rush
雑誌名: Biol Psychiatry. 1995 Nov 1;38(9):578-91.
Abstract/Text Benzodiazepines, the most widely prescribed psychotropic drugs, are often used in patients with depressive disorders, either alone or in combination with standard antidepressants. This review evaluates the efficacy of benzodiazepines (alprazolam, diazepam, chlordiazepoxide) as established in acute-phase, randomized controlled trials (RCTs) in major depressive disorder. Metaanalyses using intent-to-treat, as well as adequate treatment exposure samples, revealed an overall efficacy of 47-63% and a drug-placebo difference of 0-27% for all benzodiazepines. Alprazolam, the best studied of the benzodiazepines, had a 27.1% (sd = 6.1%) greater response than placebo, which is comparable to standard antidepressants. Alprazolam, in particular, may be a useful treatment option for patients in whom standard antidepressant medications are contraindicated, poorly tolerated, or possibly ineffective. Alprazolam may have a more rapid onset of action for some patients. Benzodiazepines do not primarily affect biogenic amine uptake or metabolism, although they do augment gamma-amino butyric acid (GABA) activity. The antidepressant efficacy of benzodiazepines, which are GABAA receptor agonists, is consistent with the GABA theory of depression.

PMID 8573660  Biol Psychiatry. 1995 Nov 1;38(9):578-91.
著者: T A Furukawa, D L Streiner, L T Young
雑誌名: Cochrane Database Syst Rev. 2002;(1):CD001026. doi: 10.1002/14651858.CD001026.
Abstract/Text BACKGROUND: Anxiety frequently coexists with depression. Adding benzodiazepines to antidepressants is commonly used to treat people with depression, although there has been no convincing evidence to show that such a combination is more effective than antidepressants alone and that there are suggestions that benzodiazepines may lose their efficacy with long-term administration and that their chronic use carries risks of dependence.
OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone.
SEARCH STRATEGY: We searched MEDLINE (1972 to September 1997), EMBASE (1980 to September 1997), International Pharmaceutical Abstracts (1972 to September 1997), Biological Abstracts (1984 to September 1997), LILACS (1980 to September 1997), PsycLIT (1974 to September 1997), the Cochrane Library (issue 3, 1997) and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (last searched March 1999), combined with hand searching, reference searching, SciSearch and personal contacts.
SELECTION CRITERIA: All randomised controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression. Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than four weeks.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favourable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the type.
MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was less likely to drop out than the antidepressant alone group (relative risk 0.63, 95% confidence interval 0.49 to 0.81). The intention-to-treat analysis (with people dropping out assigned the least favourable outcome) showed that the combination group was more likely to show improvement in their depression (defined as 50% or greater reduction in the depression scale from baseline) (relative risk 1.63, 95% confidence interval 1.18 to 2.27 at one week and relative risk 1.38, 95% confidence interval 1.15 to 1.66 at four weeks). The difference was no longer significant at six to eight weeks. None of the included RCTs lasted longer than eight weeks. The patients allocated to the combination therapy were less likely to drop out from the treatment due to side effects than those receiving antidepressants alone (relative risk 0.53, 95% confidence interval 0.32 to 0.86). However, these two groups of patients were equally likely to report at least one side effect (relative risk 0.99, 95% confidence interval 0.92 to 1.07).
REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

PMID 11869584  Cochrane Database Syst Rev. 2002;(1):CD001026. doi: 10.・・・
著者: Yi-Yung Hung, Tiao-Lai Huang
雑誌名: Clin Neuropharmacol. 2006 May-Jun;29(3):144-7. doi: 10.1097/01.WNF.0000221908.56361.C7.
Abstract/Text We have proved that a modified strategy (ie, lorazepam intramuscular injection [IMI] or diazepam intravenous drip [IVD] if lorazepam IMI fails) can rapidly relieve catatonic features in patients with schizophrenia. During a period of 3 years, we identified 7 major depressive patients with catatonic features in the emergency unit of a general hospital. The patients were treated with lorazepam IMI (dose, 2 mg/mL.per ampule) once or twice during the first 2 hours. If lorazepam IMI failed, diazepam IVD (dose, 10 mg/2 mL.per ampule) in 500 mL normal saline every 8 hours for 1 day would be administered. The total complete remission rate to lorazepam IMI within 2 hours was 6 (85.7%) per 7 patients, and the total complete remission rate to benzodiazepines (lorazepam IMI and diazepam IVD) within 1 day was 7 (100%) of all 7 patients. These results highly suggest that this modified strategy can also rapidly relieve catatonic features in major depression within 1 day and attain a high complete remission rate, even without electroconvulsive therapy.

PMID 16772813  Clin Neuropharmacol. 2006 May-Jun;29(3):144-7. doi: 10.・・・
著者: Frank Schneider, Martin Härter, Silke Brand, Petra Sitta, Ralph Menke, Ursula Hammer-Filipiak, Ralf Kudling, Andrea Heindl, Kurt Herold, Ulrich Frommberger, Olivier Elmer, Günter Hetzel, Gabriele Witt, Manfred Wolfersdorf, Mathias Berger, Wolfgang Gaebel
雑誌名: Br J Psychiatry. 2005 Nov;187:462-9. doi: 10.1192/bjp.187.5.462.
Abstract/Text BACKGROUND: Adherence to treatment guidelines enhances treatment outcome. However, in clinical practice many patients with depression do not receive appropriate treatment.
AIMS: To evaluate the treatment of depression in in-patients of German psychiatric hospitals with respect to treatment outcome and adherence to guidelines.
METHOD: We recruited 1202 in-patients with depression from ten different hospitals. Quality data concerning treatment were collected at admission, during the treatment course and at discharge.
RESULTS: The level of depression was significantly decreased and most patients were satisfied with treatment. Many aspects of the treatment routine adhered to guideline recommendations. Adherence to guidelines could be improved with respect to adjustment of antidepressant dosage, reduction of benzodiazepine prescription, enhanced use of electroconvulsive therapy and wider use of interpersonal therapy.
CONCLUSIONS: The study reveals a high standard of psychiatric treatment of in-patients with depression. Nevertheless there is still room for improvement. Differences between hospitals in adherence to guidelines indicates the need for individual application of quality management tools.

PMID 16260823  Br J Psychiatry. 2005 Nov;187:462-9. doi: 10.1192/bjp.1・・・
著者: UK ECT Review Group
雑誌名: Lancet. 2003 Mar 8;361(9360):799-808. doi: 10.1016/S0140-6736(03)12705-5.
Abstract/Text BACKGROUND: We aimed to review published work for the efficacy and safety of electroconvulsive therapy (ECT) with simulated ECT, ECT versus pharmacotherapy, and different forms of ECT for patients with depressive illness.
METHODS: We designed a systematic overview and meta-analysis of randomised controlled trials and observational studies. We obtained data from the Cochrane Collaboration Depressive Anxiety and Neurosis and Schizophrenia Group Controlled trial registers, Cochrane Controlled Trials register, Biological Abstracts, CINAHL, EMBASE, LILACS, MEDLINE, PsycINFO, and SIGLE, reference lists, and specialist textbooks. Our main outcome measures were depressive symptoms, measures of cognitive function, and mortality.
FINDINGS: Meta-analysis of data of short-term efficacy from randomised controlled trials was possible. Real ECT was significantly more effective than simulated ECT (six trials, 256 patients, standardised effect size [SES] -0.91, 95% CI -1.27 to -0.54). Treatment with ECT was significantly more effective than pharmacotherapy (18 trials, 1144 participants, SES -0.80, 95% CI -1.29 to -0.29). Bilateral ECT was more effective than unipolar ECT (22 trials, 1408 participants, SES -0.32, 95% CI -0.46 to -0.19).
INTERPRETATION: ECT is an effective short-term treatment for depression, and is probably more effective than drug therapy. Bilateral ECT is moderately more effective than unilateral ECT, and high dose ECT is more effective than low dose.

PMID 12642045  Lancet. 2003 Mar 8;361(9360):799-808. doi: 10.1016/S014・・・
著者: Linda van Diermen, Seline van den Ameele, Astrid M Kamperman, Bernard C G Sabbe, Tom Vermeulen, Didier Schrijvers, Tom K Birkenhäger
雑誌名: Br J Psychiatry. 2018 Feb;212(2):71-80. doi: 10.1192/bjp.2017.28.
Abstract/Text BACKGROUND: Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression.
METHOD: A meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors.
RESULTS: Of the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47, P = 0.001) and response (OR = 1.69, P < 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P < 0.001)). The severity of depression predicts response (SMD = 0.19, P = 0.001), but not remission. Data on melancholic symptoms were inconclusive.
CONCLUSIONS: ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression. Declaration of interest None.

PMID 29436330  Br J Psychiatry. 2018 Feb;212(2):71-80. doi: 10.1192/bj・・・
著者: Diana Rose, Pete Fleischmann, Til Wykes, Morven Leese, Jonathan Bindman
雑誌名: BMJ. 2003 Jun 21;326(7403):1363. doi: 10.1136/bmj.326.7403.1363.
Abstract/Text OBJECTIVE: To ascertain patients' views on the benefits of and possible memory loss from electroconvulsive therapy.
DESIGN: Descriptive systematic review.
DATA SOURCES: Psychinfo, Medline, Web of Science, and Social Science Citation Index databases, and bibliographies.
STUDY SELECTION: Articles with patients' views after treatment with electroconvulsive therapy.
DATA EXTRACTION: 26 studies carried out by clinicians and nine reports of work undertaken by patients or with the collaboration of patients were identified; 16 studies investigated the perceived benefit of electroconvulsive therapy and seven met criteria for investigating memory loss.
DATA SYNTHESIS: The studies showed heterogeneity. The methods used were associated with levels of perceived benefit. At least one third of patients reported persistent memory loss.
CONCLUSIONS: The current statement for patients from the Royal College of Psychiatrists that over 80% of patients are satisfied with electroconvulsive therapy and that memory loss is not clinically important is unfounded.

PMID 12816822  BMJ. 2003 Jun 21;326(7403):1363. doi: 10.1136/bmj.326.7・・・
著者: Sanjeev Kumar, Benoit H Mulsant, Angela Y Liu, Daniel M Blumberger, Zafiris J Daskalakis, Tarek K Rajji
雑誌名: Am J Geriatr Psychiatry. 2016 Jul;24(7):547-65. doi: 10.1016/j.jagp.2016.02.053. Epub 2016 Mar 8.
Abstract/Text OBJECTIVE: Late-life depression (LLD) is known to negatively impact cognition even after remission of mood symptoms. Electroconvulsive therapy (ECT) and newer nonconvulsive electrical and magnetic brain stimulation interventions have been shown to have cognitive effects in patients with neuropsychiatric disorders.
METHODS: This review systematically assessed the effects of ECT on cognition in LLD. EMBASE, Ovid Medline, and PsycINFO were systematically searched through June 2015. The search was limited to publications from peer-reviewed journals in the English language.
RESULTS: A total of 5,154 publications was identified; 318 were reviewed in full text, of which 39 publications related to ECT were included. We focused this review only on ECT because evidence on newer interventions was deemed insufficient for a systematic review. This literature suggests increased rates of interictal and postictal cognitive decline with ECT but no long-term (i.e., 6 months or longer) deleterious effects on cognition. Instead, long-term cognitive outcomes with ECT have been reported as either not changed or improved. This literature favors nondominant unilateral ECT over bilateral ECT for cognition.
CONCLUSION: Published literature on brain stimulation interventions in LLD is mainly limited to ECT. This literature suggests that deleterious effects of ECT in LLD are limited and transient, with better cognitive outcomes with unilateral ECT. There is not enough evidence to fully characterize long-term deleterious effects of ECT or effects of newer brain stimulation techniques on cognition in LLD.

Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
PMID 27067067  Am J Geriatr Psychiatry. 2016 Jul;24(7):547-65. doi: 10・・・
著者: Renan Boeira Rocha, Eduardo Ronconi Dondossola, Antônio José Grande, Tamy Colonetti, Luciane Bisognin Ceretta, Ives C Passos, Joao Quevedo, Maria Inês da Rosa
雑誌名: J Psychiatr Res. 2016 Dec;83:47-53. doi: 10.1016/j.jpsychires.2016.08.004. Epub 2016 Aug 5.
Abstract/Text OBJECTIVE: We performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT).
METHOD: A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain-derived neurotrophic factor", and "electroconvulsive therapy".
RESULTS: A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I(2) = 73%).
CONCLUSION: Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 27552533  J Psychiatr Res. 2016 Dec;83:47-53. doi: 10.1016/j.jpsy・・・
著者: Roumen V Milev, Peter Giacobbe, Sidney H Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Jonathan Downar, Mandana Modirrousta, Simon Patry, Fidel Vila-Rodriguez, Raymond W Lam, Glenda M MacQueen, Sagar V Parikh, Arun V Ravindran, CANMAT Depression Work Group
雑誌名: Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033. Epub 2016 Aug 2.
Abstract/Text BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.
METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Neurostimulation Treatments" is the fourth of six sections of the 2016 guidelines.
RESULTS: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance.
CONCLUSIONS: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments.

© The Author(s) 2016.
PMID 27486154  Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0・・・
著者: Tyler S Kaster, Zafiris J Daskalakis, Yoshihiro Noda, Yuliya Knyahnytska, Jonathan Downar, Tarek K Rajji, Yechiel Levkovitz, Abraham Zangen, Meryl A Butters, Benoit H Mulsant, Daniel M Blumberger
雑誌名: Neuropsychopharmacology. 2018 Oct;43(11):2231-2238. doi: 10.1038/s41386-018-0121-x. Epub 2018 Jun 18.
Abstract/Text Late-life depression (LLD) is a growing worldwide problem due to demographic changes, with limited treatment options due to high rates of pharmacotherapy adverse effects, accessibility of psychotherapy, and tolerability of electroconvulsive therapy. Novel neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), may overcome these limitations. The objective of this study is to determine the efficacy, tolerability, and cognitive effects of high-dose deep rTMS in LLD. In this study we randomized older adults between 60 and 85 years old with major depressive disorder (MDD) to sham or active deep rTMS (H1 coil, 6012 pulses, 18 Hz, 120% of resting motor threshold) delivered over the dorsolateral and ventrolateral prefrontal cortex 5 days per week over 4 weeks. Our primary outcome was remission of depression in an intention-to-treat analysis. We also assessed change in cognitive functioning with rTMS treatment and tolerability based on adverse effects. Fifty-two participants were randomized to active (n = 25) or sham H1 coil (n = 27). Remission rate was significantly higher with active than sham rTMS (40.0% vs 14.8%) with a number needed to treat of 4.0 (95% CI: 2.1-56.5). There was no change on any measure of executive function and no serious adverse events. Adverse effect profiles were similar between active and sham rTMS, except for reports of pain being significantly more common in the active condition (16.0% vs 0%). High-dose deep rTMS appears to be safe, well tolerated, and efficacious in the treatment of LLD.

PMID 29946106  Neuropsychopharmacology. 2018 Oct;43(11):2231-2238. doi・・・
著者: Ayse Akincigil, John R Bowblis, Carrie Levin, James T Walkup, Saira Jan, Stephen Crystal
雑誌名: Med Care. 2007 Apr;45(4):363-9. doi: 10.1097/01.mlr.0000254574.23418.f6.
Abstract/Text BACKGROUND: Antidepressants are effective in treatment of depression, but poor adherence to medication is a major obstacle to effective care.
OBJECTIVE: We sought to describe patient and provider level factors associated with treatment adherence.
METHODS: This was a retrospective, observational study using medical and pharmacy claims from a large health plan, for services provided between January 2003 and January 2005. We studied a total of 4312 subjects ages 18 or older who were continuously enrolled in the health plan with a new episode of major depression and who initiated antidepressant treatment. Treatment adherence was measured by using pharmacy refill records during the first 16 weeks (acute phase) and the 17-33 weeks after initiation of antidepressant therapy (continuation phase). Measures were based on Health Plan Employer Data and Information Set (HEDIS) quality measures for outpatient depression care.
RESULTS: Fifty-one percent of patients were adherent through the acute phase; of those, 42% remained adherent in the continuation phase. Receipt of follow-up care from a psychiatrist and higher general pharmacy utilization (excluding psychotropics) were associated with better adherence in both phases. Younger age, comorbid alcohol or other substance abuse, comorbid cardiovascular/metabolic conditions, use of older generation antidepressants, and residence in lower-income neighborhoods were associated with lower acute-phase adherence. Continuation-phase adherence was lower for HMO participants than for others.
CONCLUSION: In an insured population, many patients fall short of adherence to guideline recommended therapy for depression. Information from existing administrative data can be used to predict patients at highest risk of nonadherence, such as those with substance abuse, and to target interventions.

PMID 17496721  Med Care. 2007 Apr;45(4):363-9. doi: 10.1097/01.mlr.000・・・
著者: Tarja K Melartin, Heikki J Rytsälä, Ulla S Leskelä, Paula S Lestelä-Mielonen, T Petteri Sokero, Erkki T Isometsä
雑誌名: J Clin Psychiatry. 2005 Feb;66(2):220-7.
Abstract/Text OBJECTIVE: Several evidence-based treatment guidelines for major depressive disorder (MDD) have been published. However, little is known about how recommendations for treatment are adhered to by patients in current usual psychiatric practice.
METHOD: The Vantaa Depression Study is a prospective, naturalistic cohort study of 269 psychiatric patients with a new episode of DSM-IV MDD who were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and Structured Clinical Interview for DSM-III-R Personality Disorders between February 1, 1997, and May 31, 1998, and again at 6 and 18 months. Treatments provided, as well as adherence to and attitudes toward both antidepressants and psychotherapeutic support/psychotherapy, were investigated among the 198 unipolar patients followed for 18 months.
RESULTS: Most depression patients (88%) received antidepressants in the early acute phase, but about half (49%) terminated treatment prematurely. This premature termination was associated with worse outcome of major depressive episodes, and with negative attitudes, mainly explained by fear of dependence on or side effects of antidepressants. Nearly all patients (98%) received some psychosocial treatment in the acute phase; about one fifth (16%) had weekly psychotherapy during the follow-up. About a quarter of patients admitted nonadherence to ongoing treatments.
CONCLUSION: Problems of psychiatric care seem most related to continuity of treatment. While adequate treatments are provided in the early acute phase, antidepressants are terminated too soon in about half of patients, often following their autonomous decisions. From a secondary and tertiary preventive point of view, improving continuity of treatment would appear a crucial task for improving the outcome of psychiatric patients with MDD.

PMID 15705008  J Clin Psychiatry. 2005 Feb;66(2):220-7.
著者: Vivien M Hunot, Rob Horne, Morven N Leese, Rachel C Churchill
雑誌名: Prim Care Companion J Clin Psychiatry. 2007;9(2):91-9.
Abstract/Text OBJECTIVE: Clinical guidelines recommend that antidepressant treatment should be continued for a minimum of 6 months following response in depression and anxiety disorders. However, adherence to antidepressants is low. This prospective cohort study investigated the influence of patients' antidepressant concerns, treatment preferences, and illness perceptions on adherence to antidepressants over a 6-month period.
METHOD: A cohort of 178 patients aged 18 to 74 years and newly issued with a prescription for antidepressants to treat any condition was followed up prospectively at 5 primary care practices in Southeast England. Adherence was measured through self-report and prescription refill data. Patient perceptions were quantified using validated outcome measures, the Beliefs about Medicine Questionnaire and the Illness Perception Questionnaire, at 4 timepoints. Patient treatment preferences were recorded using a specially designed questionnaire. Data collection took place between September 2000 and May 2002.
RESULTS: Of 147 participants (83%) who completed the study, 19% persisted with antidepressants in accordance with guideline recommendations throughout the 6-month period. Specific concern about antidepressant side effects (OR = 3.30, 95% CI = 2.20 to 4.97) and general worry about taking antidepressants (OR = 1.65, 95% CI = 1.13 to 2.40) were independent predictors of antidepressant nonuse. Preference for different treatment/uncertainty about preferred treatment was also a strong predictor (OR = 3.82, 95% CI = 1.35 to 10.77). However, illness perceptions were not associated with adherence.
CONCLUSIONS: Concerns about antidepressants and a mismatch between patients' preferred and prescribed treatment act as significant barriers to sustained adherence. This study highlights the central role of the patient-physician partnership in exploring antidepressant concerns, working with treatment preferences, and providing supportive continued management. The findings may inform the development of interventions within primary care programs to enhance commitment to treatment for common mental disorders.

PMID 17607330  Prim Care Companion J Clin Psychiatry. 2007;9(2):91-9.
著者: M R DiMatteo, H S Lepper, T W Croghan
雑誌名: Arch Intern Med. 2000 Jul 24;160(14):2101-7.
Abstract/Text BACKGROUND: Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression.
METHODS: Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it).
RESULTS: Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89).
CONCLUSIONS: Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.

PMID 10904452  Arch Intern Med. 2000 Jul 24;160(14):2101-7.
著者: Scott A Bull, X Henry Hu, Enid M Hunkeler, Janelle Y Lee, Eileen E Ming, Leona E Markson, Bruce Fireman
雑誌名: JAMA. 2002 Sep 18;288(11):1403-9.
Abstract/Text CONTEXT: Although current depression treatment guidelines recommend continuing antidepressant therapy for at least 4 to 9 months, many patients discontinue treatment prematurely, within 3 months.
OBJECTIVES: To investigate the relationship between patient-physician communication and the continuation of treatment with antidepressants and to explore the demographics, adverse effects, therapeutic response, and frequency of follow-up visits.
DESIGN, SETTING, AND PATIENTS: A total of 401 telephone interviews of depressed patients being treated with selective serotonin reuptake inhibitor (SSRI) therapy between December 15, 1999, and May 31, 2000, were conducted and 137 prescribing physicians completed written surveys from Northern California Kaiser Permanente health maintenance organization outpatient clinics.
MAIN OUTCOME MEASURES: Patient-physician communication about therapy duration and about adverse effects; therapy discontinuation or medication switching within 3 months after start of SSRI therapy.
RESULTS: Ninety-nine physicians (72%) reported that they usually ask patients to continue using antidepressants for at least 6 months, but 137 patients (34%) reported that their physicians asked them to continue using antidepressants for this duration and 228 (56%) reported receiving no instructions. Patients who said they were told to take their medication for less than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said they were told to continue therapy longer. Patients who discussed adverse effects with their physicians were less likely to discontinue therapy than patients who did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported discussing adverse effects with their physicians were more likely to switch medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for depression, adverse effects, and lack of therapeutic response to medication were also associated with patients' discontinuing therapy.
CONCLUSIONS: Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy.

PMID 12234237  JAMA. 2002 Sep 18;288(11):1403-9.
著者: Irina A K Holma, K Mikael Holma, Tarja K Melartin, Erkki T Isometsä
雑誌名: Br J Psychiatry. 2008 Aug;193(2):163-4. doi: 10.1192/bjp.bp.107.045708.
Abstract/Text Practice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment. The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period.

PMID 18670005  Br J Psychiatry. 2008 Aug;193(2):163-4. doi: 10.1192/bj・・・
著者: R F Prien, D J Kupfer
雑誌名: Am J Psychiatry. 1986 Jan;143(1):18-23.
Abstract/Text A major problem for the practitioner is the lack of satisfactory guidelines as to how long continuation drug treatment of depressive episodes must be maintained to ensure that the episode is over. This often leads to either premature withdrawal of the drug and subsequent relapse or unnecessarily prolonged treatment. Results from a collaborative project of the National Institute of Mental Health provide the first study-derived guidelines on the length of continuation therapy. Findings indicate that withdrawal of such therapy is safe only after the patient has been free of significant symptoms for 16 to 20 weeks and that focusing on mild as well as severe symptoms is critical in this decision.

PMID 3510571  Am J Psychiatry. 1986 Jan;143(1):18-23.
著者: F W Reimherr, J D Amsterdam, F M Quitkin, J F Rosenbaum, M Fava, J Zajecka, C M Beasley, D Michelson, P Roback, K Sundell
雑誌名: Am J Psychiatry. 1998 Sep;155(9):1247-53.
Abstract/Text OBJECTIVE: The purpose of this study was to determine prospectively the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression (defined by DSM-III-R).
METHOD: The study was conducted at five outpatient psychiatric clinics in the United States. Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy, 20 mg/day (N=395 of 839 patients), were randomly assigned to one of four arms of a double-blind treatment study (50 weeks of placebo, 14 weeks of fluoxetine and then 36 weeks of placebo, 38 weeks of fluoxetine and then 12 weeks of placebo, or 50 weeks of fluoxetine). Relapse rate was the primary outcome measure. Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment.
RESULTS: Relapse rates (Kaplan-Meier estimates) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval, after 24 total weeks of treatment (fluoxetine, 26.4%; placebo, 48.6%), and the second interval, after 38 total weeks of treatment (fluoxetine, 9.0%; placebo, 23.2%). In the third interval, after 62 total weeks of treatment, rates were not significantly different between the groups (fluoxetine, 10.7%; placebo, 16.2%).
CONCLUSIONS: Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse.

PMID 9734550  Am J Psychiatry. 1998 Sep;155(9):1247-53.
著者: Masaki Kato, Hikaru Hori, Takeshi Inoue, Junichi Iga, Masaaki Iwata, Takahiko Inagaki, Kiyomi Shinohara, Hissei Imai, Atsunobu Murata, Kazuo Mishima, Aran Tajika
雑誌名: Mol Psychiatry. 2021 Jan;26(1):118-133. doi: 10.1038/s41380-020-0843-0. Epub 2020 Jul 23.
Abstract/Text A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (n = 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33-0.43, p < 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17-0.50, p < 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28-0.38, p < 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36-0.54, p < 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23-0.48, p < 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36-0.48, p < 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29-0.55, p < 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35-0.48, p < 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29-0.41, p < 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40-0.55, p < 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18-0.64, p = 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.

PMID 32704061  Mol Psychiatry. 2021 Jan;26(1):118-133. doi: 10.1038/s4・・・
著者: L Franchini, R Zanardi, M Gasperini, E Smeraldi
雑誌名: J Clin Psychiatry. 1999 Dec;60(12):861-5.
Abstract/Text BACKGROUND: The efficacy of citalopram, 20 to 60 mg/day, in relapse prevention in major depression was demonstrated in 6-month placebo-controlled studies. The authors tested the efficacy of citalopram, 40 mg/day, in relapse prevention over a 4-month period and citalopram, 20 mg/day, in recurrence prevention over a 24-month period.
METHOD: Fifty inpatients with recurrent major depressive disorder (DSM-IV criteria) who had had at least one depressive episode during the 18 months preceding the index episode were openly treated with citalopram, 40 mg/day. Thirty-six subjects had a stable response to citalopram and remained in the continuation treatment with citalopram, 40 mg/day, for 4 months as outpatients. At the time of recovery, 32 patients gave their written informed consent before entering the 24-month maintenance period with citalopram, 20 mg/day. They were evaluated monthly by trained psychiatrists on the basis of the 21-item Hamilton Rating Scale for Depression. Every 3 months, patients were given the Sheehan Disability Scale, a self-rating instrument, to assess their psychosocial adjustment.
RESULTS: No relapse was observed in the 4-month continuation period. Sixteen (50%) of 32 patients who entered the 24-month maintenance period had a new recurrence. Patients with recurrence showed a persistent moderate disability on Sheehan Disability Scale score, while no further differences were highlighted in clinical and demographic characteristics between patients with and without recurrence.
CONCLUSION: In agreement with previous findings, these data suggest that a full dose of antidepressant is strongly recommended in prophylactic therapy of patients with recurrent major depression. Moreover, it appears that psychosocial impairment may increase the risk of recurrence, thus conditioning a poor outcome.

PMID 10665634  J Clin Psychiatry. 1999 Dec;60(12):861-5.
著者: S A Montgomery, J G Rasmussen, P Tanghøj
雑誌名: Int Clin Psychopharmacol. 1993 Fall;8(3):181-8.
Abstract/Text A total of 147 patients who had responded in a placebo-controlled study to 6 weeks treatment of an episode of DSM-III-R major depression with either 20 mg or 40 mg citalopram were randomized double-blind to continue on the same dose of citalopram or to receive placebo during a 24-week study of the efficacy of citalopram in the prevention of relapse. The citalopram 20 and 40 mg groups showed a significant advantage compared with placebo both in relapses (p < 0.05) and in the survival analysis of time to relapse (p = 0.01 and p = 0.02, respectively). Both 20 and 40 mg citalopram appeared similarly safe and well tolerated with little difference in side effects from placebo. The results demonstrate that citalopram, at a dose of both 20 and 40 mg is effective and well tolerated in continuation treatment to consolidate response. The relapse rate in patients who had responded to placebo during the 6-week acute treatment study, who were continued double-blind with placebo but not included in the efficacy analysis, was similar to the rate in the formal placebo control group, suggesting that patients who respond to placebo in a short treatment course may nonetheless require long-term active treatment to prevent relapse.

PMID 8263316  Int Clin Psychopharmacol. 1993 Fall;8(3):181-8.
著者: Jean-Pierre Lépine, Vincent Caillard, Jean-Claude Bisserbe, Sylvie Troy, Jean-Michel Hotton, Patrice Boyer
雑誌名: Am J Psychiatry. 2004 May;161(5):836-42.
Abstract/Text OBJECTIVE: Previous antidepressant maintenance trials have used the same medication from acute through maintenance phases, confounding the interpretation of prophylactic effects. The purpose of this study was to determine whether sertraline prevents the recurrence of major depressive disorder among patients with recurrent depression who had been treated to remission with medications other than sertraline.
METHOD: Patients who had experienced at least three documented episodes of major depressive disorder within the last 4 years and who were currently in full remission were eligible. The last episode must have been treated for at least 4 months with any antidepressant except sertraline. For the initial single-blind placebo lead-in phase, 371 patients were included; 288 were included in the analyses for the 18-month double-blind phase in which patients were randomly assigned to sertraline (50 or 100 mg) or placebo (two capsules per day). Recurrence was defined as a depressive episode that fulfilled DSM-IV criteria or the appearance of symptoms that required the administration of another antidepressant treatment.
RESULTS: Sixty-one patients discontinued before the double-blind phase, including 33 who experienced a relapse. Out of the 288 who entered the double-blind prophylactic phase, 123 discontinued, including 65 for recurrences. Recurrences were significantly lower in the sertraline groups compared with placebo (sertraline, 50 mg: 16 [16.8%] of 95; sertraline, 100 mg: 16 [17.0%] of 94; placebo: 33 [33.3%] of 99). Patients treated with sertraline also had a significantly longer time until recurrence compared with placebo-treated patients.
CONCLUSIONS: Among remitted patients with a history of multiple depressive episodes, sertraline at a dose of either 50 or 100 mg/day prevented recurrences significantly more than did placebo.

PMID 15121648  Am J Psychiatry. 2004 May;161(5):836-42.
著者: Ewgeni Jakubovski, Anjali L Varigonda, Nicholas Freemantle, Matthew J Taylor, Michael H Bloch
雑誌名: Am J Psychiatry. 2016 Feb 1;173(2):174-83. doi: 10.1176/appi.ajp.2015.15030331. Epub 2015 Nov 10.
Abstract/Text OBJECTIVE: Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder.
METHOD: The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder.
RESULTS: Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54).
CONCLUSIONS: Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.

PMID 26552940  Am J Psychiatry. 2016 Feb 1;173(2):174-83. doi: 10.1176・・・
著者: Toshi A Furukawa, Andrea Cipriani, Philip J Cowen, Stefan Leucht, Matthias Egger, Georgia Salanti
雑誌名: Lancet Psychiatry. 2019 Jul;6(7):601-609. doi: 10.1016/S2215-0366(19)30217-2. Epub 2019 Jun 6.
Abstract/Text BACKGROUND: Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
METHODS: We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.
FINDINGS: 28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.
INTERPRETATION: For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.
FUNDING: Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 31178367  Lancet Psychiatry. 2019 Jul;6(7):601-609. doi: 10.1016/・・・
著者: Matthijs Oud, Lars de Winter, Evelien Vermeulen-Smit, Denise Bodden, Maaike Nauta, Lisanne Stone, Marieke van den Heuvel, Reham Al Taher, Ireen de Graaf, Tim Kendall, Rutger Engels, Yvonne Stikkelbroek
雑誌名: Eur Psychiatry. 2019 Apr;57:33-45. doi: 10.1016/j.eurpsy.2018.12.008. Epub 2019 Jan 16.
Abstract/Text BACKGROUND: Cognitive-behavioral therapy (CBT) is first choice of treatment for depressive symptoms and disorders in adolescents, however improvements are necessary because overall efficacy is low. Insights on CBT components and contextual and structural characteristics might increase the efficacy. The aim of our approach is to evaluate the efficacy of CBT for youth with depression and investigate the influence of specific components, contextual and structural factors that could improve effects.
METHODS: A systematic review of randomized controlled trials was conducted, searches were undertaken in CINAHL, CENTRAL, EMBASE, MEDLINE/PubMed and PsycINFO. Outcomes were meta-analyzed and confidence in results was assessed using the GRADE-method. Meta-regression was used to pinpoint components or other factors that were associated with an in- or decrease of effects of CBT.
RESULTS: We included 31 trials with 4335 participants. Moderate-quality evidence was found for CBT reducing depressive symptoms at the end of treatment and at follow-up, and CBT as indicated prevention resulted in 63% less risk of being depressed at follow-up. CBT containing a combination of behavioral activation and challenging thoughts component (as part of cognitive restructuring) or the involvement of caregiver(s) in intervention were associated with better outcomes for youth on the long term.
CONCLUSIONS: There is evidence that CBT is effective for youth with a (subclinical) depression. Our analyses show that effects might improve when CBT contains the components behavioral activation and challenging thoughts and also when the caregiver(s) are involved. However, the influential effects of these three moderators should be further tested in RCTs.

Copyright © 2018 Elsevier Masson SAS. All rights reserved.
PMID 30658278  Eur Psychiatry. 2019 Apr;57:33-45. doi: 10.1016/j.eurps・・・
著者: Felipe B Schuch, Davy Vancampfort, Justin Richards, Simon Rosenbaum, Philip B Ward, Brendon Stubbs
雑誌名: J Psychiatr Res. 2016 Jun;77:42-51. doi: 10.1016/j.jpsychires.2016.02.023. Epub 2016 Mar 4.
Abstract/Text The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79-1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26978184  J Psychiatr Res. 2016 Jun;77:42-51. doi: 10.1016/j.jpsy・・・
著者: Siri Kvam, Catrine Lykkedrang Kleppe, Inger Hilde Nordhus, Anders Hovland
雑誌名: J Affect Disord. 2016 Sep 15;202:67-86. doi: 10.1016/j.jad.2016.03.063. Epub 2016 May 20.
Abstract/Text BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) examines the efficacy of physical exercise as treatment for unipolar depression, both as an independent intervention and as an adjunct intervention to antidepressant medication.
METHODS: We searched PsycINFO, EMBASE, MEDLINE, CENTRAL, and Sports Discus for articles published until November 2014. Effect sizes were computed with random effects models. The main outcome was reduction in depressive symptoms or remission.
RESULTS: A total of 23 RCTs and 977 participants were included. Physical exercise had a moderate to large significant effect on depression compared to control conditions (g=-0.68), but the effect was small and not significant at follow-up (g=-0.22). Exercise compared to no intervention yielded a large and significant effect size (g=-1.24), and exercise had a moderate and significant effect compared to usual care (g=-0.48). The effects of exercise when compared to psychological treatments or antidepressant medication were small and not significant (g=-0.22 and g=-0.08, respectively). Exercise as an adjunct to antidepressant medication yielded a moderate effect (g=-0.50) that trended toward significance.
LIMITATIONS: Use of the arms with the largest clinical effect instead of largest dose may have overestimated the effect of exercise.
CONCLUSIONS: Physical exercise is an effective intervention for depression. It also could be a viable adjunct treatment in combination with antidepressants.

Copyright © 2016 Elsevier B.V. All rights reserved.
PMID 27253219  J Affect Disord. 2016 Sep 15;202:67-86. doi: 10.1016/j.・・・
著者: Long Tao, Rui Jiang, Kuo Zhang, Zhikan Qian, Peng Chen, Yili Lv, Yuyou Yao
雑誌名: Psychiatry Res. 2020 Sep;291:113247. doi: 10.1016/j.psychres.2020.113247. Epub 2020 Jun 22.
Abstract/Text The effect of light therapy in treating seasonal affective disorder has been demonstrated amongst previous studies. However, the effect of light therapy in treating non-seasonal depression remains unclear. This meta-analysis aimed to determine the efficacy of light therapy in non-seasonal depression. We searched for randomized controlled trials (RCTs) in the PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Database up to February 2020. The pooled post-trial standardized mean difference in depression scores with corresponding 95% confidence intervals was calculated to evaluate the efficacy of light therapy in non-seasonal depression. A total of 23 RCTs with 1120 participants were included. The meta-analysis demonstrated the light therapy was significantly more effective than comparative treatments. Subgroup analyses revealed that none of the factors explained the significantly heterogeneity. Light therapy has a statistically significant mild to moderate treatment effect in reducing depressive symptoms, can be used as a clinical therapy in treating non-seasonal depression. But the quality of evidence is still low, more well-designed studies with larger sample size and high quality are needed to confirm the efficiency of light therapy in treating non-seasonal depression.

Copyright © 2020 Elsevier B.V. All rights reserved.
PMID 32622169  Psychiatry Res. 2020 Sep;291:113247. doi: 10.1016/j.psy・・・
著者: W Stephen Waring, Ann Graham, Julie Gray, Allen D Wilson, Catherine Howell, D Nicholas Bateman
雑誌名: Br J Clin Pharmacol. 2010 Dec;70(6):881-5. doi: 10.1111/j.1365-2125.2010.03728.x.
Abstract/Text AIMS: A QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia.
METHODS: A retrospective case control study of patients presenting to hospital after overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary outcome variable was QT higher than the nomogram, and was compared with occurrence of QT(c) (QT corrected by Bazett's formula) greater than ≥440 ms and QT(c) ≥500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals.
RESULTS: There were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QT(c) was ≥440 ms in 23.1% (95% CI 19.8, 26.8%), and QT(c) was ≥500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be associated with QT higher than the nomogram compared with the other agents (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated with QT(c) ≥440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013).
CONCLUSIONS: The QT nomogram was associated with a lower false positive rate than widely accepted QT(c) criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QT(c) criteria and merits further investigation in a clinical setting.

© 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.
PMID 21175443  Br J Clin Pharmacol. 2010 Dec;70(6):881-5. doi: 10.1111・・・
著者: M Bauer, S Dopfmer
雑誌名: J Clin Psychopharmacol. 1999 Oct;19(5):427-34.
Abstract/Text The addition of lithium to the treatment regimens of previously nonresponding depressed patients has been repeatedly investigated in controlled studies. The authors undertook this meta-analysis to investigate the efficacy of lithium augmentation of conventional antidepressants. An attempt was made to identify all placebo-controlled trials of lithium augmentation in refractory depression. Only double-blind studies that involved participants who had been treated with lithium or placebo addition after not responding to conventional antidepressants were to be included in the meta-analysis. Further inclusion criteria were the use of accepted diagnostic criteria for depression and the use of response criteria based on the acceptable measurement of depression as an outcome variable. Studies were located by a search of the MEDLINE database, a search in the Cochrane Library, and an intensive search by hand of reviews on lithium augmentation. Nine of 11 placebo-controlled, double-blind studies were included in this meta-analysis. Aggregating three studies with a total of 110 patients that used a minimum lithium dose of 800 mg/day, or a dose sufficient to reach lithium serum levels of > or = 0.5 mEq/L, and a minimum treatment duration of 2 weeks, the authors found that the pooled odds ratio of response during lithium augmentation compared with the response during placebo treatment was 3.31 (95% confidence interval, 1.46-7.53). The corresponding relative response rate was 2.14 (95% confidence interval, 1.23-3.70), the absolute improvement in response rate was 27% (95% confidence interval, 9.8%-44.2%), and the number of patients needed to be treated to obtain one more responder was 3.7. Inclusion of six more studies that fulfilled inclusion criteria but which treated subjects with additional lithium for less than 2 weeks or with a lower lithium dose (total, 234 patients) resulted in even higher estimates. Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients who fail to respond to antidepressant monotherapy.

PMID 10505584  J Clin Psychopharmacol. 1999 Oct;19(5):427-34.
著者: Francesca Guzzetta, Leonardo Tondo, Franca Centorrino, Ross J Baldessarini
雑誌名: J Clin Psychiatry. 2007 Mar;68(3):380-3.
Abstract/Text OBJECTIVE: Evidence that clinical treatment reduces suicide risk in major depressive disorder (MDD) is limited and inconsistent. Since lithium shows major antisuicidal effects in bipolar disorders and in heterogeneous mood disorder samples, we evaluated evidence of antisuicidal effects of lithium in patients with recurrent MDD.
DATA SOURCES: We searched MEDLINE (January 1966 to April 2006; search terms: lithium, suicide, affective disorder, depression, major depression, and mood disorder) for studies reporting suicides or suicide attempts during treatment with and without lithium in recurrent MDD patients, and we added data for 78 new subjects, provided from the Lucio Bini Mood Disorders Research Center in Sardinia, Italy. Suicide rates were pooled and analyzed by use of incidence-rate ratios (IRRs) and meta-analytic methods.
DATA SYNTHESIS: Eight studies involved 329 MDD patients and exposure for 4.56 years (1149 person-years) with, and 6.27 years (1285 person-years) without, lithium. Overall risk of suicides and suicide attempts was 88.5% lower with vs. without lithium: 0.17%/y versus 1.48%/y (IRR = 8.71; 95% CI: 2.10 to 77.2, p = .0005); for completed suicides (85% risk reduction), IRR = 6.77 (95% CI: 1.29 to 66.8, p = .01). Meta-analysis by risk difference and risk ratio supported these findings, and sensitivity analysis yielded similar results with studies omitted serially.
CONCLUSIONS: This is the first meta-analysis suggesting antisuicidal effects of lithium in recurrent MDD, similar in magnitude to that found in bipolar disorders.

PMID 17388706  J Clin Psychiatry. 2007 Mar;68(3):380-3.
著者: J Craig Nelson, George I Papakostas
雑誌名: Am J Psychiatry. 2009 Sep;166(9):980-91. doi: 10.1176/appi.ajp.2009.09030312. Epub 2009 Aug 17.
Abstract/Text OBJECTIVE: The authors sought to determine by meta-analysis the efficacy and tolerability of adjunctive atypical antipsychotic agents in major depressive disorder.
METHOD: Searches were conducted of MEDLINE/PubMed (1966 to January 2009), the Cochrane database, abstracts of major psychiatric meetings since 2000, and online trial registries. Manufacturers of atypical antipsychotic agents without online registries were contacted. Trials selected were acute-phase, parallel-group, double-blind controlled trials with random assignment to adjunctive atypical antipsychotic or placebo. Patients had nonpsychotic unipolar major depressive disorder that was resistant to prior antidepressant treatment. Response, remission, and discontinuation rates were either reported or obtained. Data were extracted by one author and checked by the second. Data included study design, number of patients, patient characteristics, methods of establishing treatment resistance, drug doses, duration of the adjunctive trial, depression scale used, response and remission rates, and discontinuation rates for any reason or for adverse events.
RESULTS: Sixteen trials with 3,480 patients were pooled using a fixed-effects meta-analysis. Adjunctive atypical antipsychotics were significantly more effective than placebo (response: odds ratio=1.69, 95% CI=1.46-1.95, z=7.00, N=16, p<0.00001; remission: odds ratio=2.00, 95% CI=1.69-2.37, z=8.03, N=16, p<0.00001). Mean odds ratios did not differ among the atypical agents and were not affected by trial duration or method of establishing treatment resistance. Discontinuation rates for adverse events were higher for atypical agents than for placebo (odds ratio=3.91, 95% CI=2.68-5.72, z=7.05, N=15, p<0.00001).
CONCLUSIONS: Atypical antipsychotics are effective augmentation agents in major depressive disorder but are associated with an increased risk of discontinuation due to adverse events.

PMID 19687129  Am J Psychiatry. 2009 Sep;166(9):980-91. doi: 10.1176/a・・・

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