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| [[Congestive heart failure digoxin|Digoxin]]
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| ;Shown below is an image that summarizes the steps in the chronic management of patients with heart failure.
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| {| class="wikitable
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| !ACE-I !! Starting dose!! Target dose
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| | Captopril||align="center"|6.25 mg t.i.d.||align="center"|50 mg t.i.d.
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| | Enalapril||align="center"|2.5 mg b.i.d.||align="center"|10-20 mg b.i.d.
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| | Lisinopril||align="center"|> 2.5-5 mg daily||align="center"| 20-35 mg daily
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| | Ramipril||align="center"|> 2.5 mg b.i.d.||align="center"| 5 mg b.i.d.
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| | Trandolapril||align="center"|> 0.5 mg daily||align="center"| 4 mg daily
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| |}
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| : '''[[Congestive heart failure acute pharmacotherapy|Acute Pharmacotherapy]]'''
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| : '''[[Congestive heart failure with preserved EF pharmacotherapy|Chronic Pharmacotherapy in HFpEF]]
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| :'''[[Congestive heart failure treatment of underlying causes|Treatment of underlying causes]] | [[Congestive heart failure treatment of associated conditions|Associated conditions]]'''
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| : [[Congestive heart failure biventricular pacing or cardiac resynchronization therapy|Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)]] | [[Congestive heart failure implantation of intracardiac defibrillator|Implantation of Intracardiac Defibrillator]] | [[Congestive heart failure ultrafiltration|Ultrafiltration]] | [[Congestive heart failure left ventricular assist devices|Left Ventricular Assist Devices (LVADs)]] | [[Congestive heart failure cardiac transplantation|Cardiac Transplantation]] | [[Congestive heart failure cardiac surgery|Cardiac Surgery]]
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| : '''[[Chronic Pharmacotherapy|Chronic Pharmacotherapy in HFrEF]]:'''
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| :'''[[Congestive heart failure drugs to avoid|Drugs to Avoid]] | [[Congestive heart failure drug interactions|Drug Interactions]]'''
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| | | | | [[Congestive heart failure calcium channel blockers|Ca Channel Blockers]] | [[Congestive heart failure vasodilators|Nitrates]] | [[Congestive heart failure vasodilators|Hydralazine]] | [[Congestive heart failure positive inotropics|Positive Inotropics]] | [[Congestive heart failure anticoagulants|Anticoagulants]] | | [[Congestive heart failure antiarrhythmic Drugs|Antiarrhythmic Drugs]] | [[Congestive heart failure other pharmacotherapies#Nutritional Supplements|Nutritional Supplements]] | [[Congestive heart failure other pharmacotherapies#Hormonal Therapies|Hormonal Therapies]] | [[Congestive heart failure lifestyle modification|Lifestyle modification]]
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| : '''[[Device therapy for heart failure with reduced ejection fraction]]''': [[Implantable cardioverter-defibrillator]] | [[Cardiac resynchronization therapy]] | [[ Devices under evaluation]]
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| *Efficacy: Low
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| **Sinus rhythm is maintained in <20% of patients
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| **Symtoms are reduced in >=20%.
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| =====Adverse effects=====
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| *Bradycardia
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| *Hypotension
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| *Edema
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| =====Contraindications=====
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| *Bradycardia
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| *Hypotension
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| *Heart failure with depressed ejection fraction
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| =====Contraindications=====
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| *[[Bradycardia]]
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| *[[Hypotension]]
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| =====Precautions during treatment=====
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| *Monitor for [[bradycardia]]
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| <ref>{{cite book | last = LastName | first = FirstName | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association,American Psychiatric Association | location = Arlington, VA Washington, D.C | year = 2013 | isbn = 978-0-89042-554-1 }}</ref>
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| <ref> ....</ref>
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| ==Books by Psychologists and Psychiatrists==
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| * Beck, A. T., Rush, A. J., Shaw, B. F., Emery, G. (1987). ''Cognitive therapy of depression''. New York: Guilford.
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| * Burns, David D. (1999). ''Feeling Good : The New Mood Therapy''. Avon.
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| * Griffin, J., Tyrrell, I. (2004) ''How to lift Depression – Fast''. HG Publishing. ISBN 1-899398-41-4
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| * [[Edith Jacobson|Jacobson, Edith]]: "Depression; Comparative Studies of Normal, Neurotic, and Psychotic Conditions", International Universities Press, 1976, ISBN 0-8236-1195-7
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| * Klein, D. F., & Wender, P. H. (1993). ''Understanding depression: A complete guide to its diagnosis and treatment''. New York: Oxford University Press.
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| * Kramer, Peter D. (2005). ''Against Depression''. New York: Viking Adult.
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| * Plesman, J. (1986). [http://books.google.com/books?lr=&ie=ISO-8859-1&q=foreword+Jurriaan+Plesman&btnG=Search Getting off the Hook], Sydney Australia. A self-help book available on the internet.
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| * Rowe, Dorothy (2003). ''Depression: The way out of your prison''. London: Brunner-Routledge.
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| * Sarbadhikari, S. N. (ed.) (2005) ''Depression and Dementia: Progress in Brain Research, Clinical Applications and Future Trends''. Hauppauge, [[Nova Science Publishers]]. ISBN 1-59454-114-0.
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| * Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). ''Comprehensive guide to interpersonal psychotherapy''. New York: Basic Books.
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| * Bieling, Peter J. & Anthony, Martin M. (2003) ''Ending The Depression Cycle.'' New Harbinger Publications. ISBN 1572243333
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| * For books on male depression, see [[Terrence Real]]
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|
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| ===Historical Account===
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| *[[David Healy (psychiatrist)|Healy, David]]. (1999). ''The Antidepressant Era'', Paperback Edition, Harvard University Press. ISBN 0-674-03958-0
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| [[af:Kliniese depressie]]
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| [[ar:الاكتئاب عند الإنسان]]
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| [[bs:Klinička depresija]]
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| [[ca:Depressió]]
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| [[cs:Deprese (psychologie)]]
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| [[da:Depression]]
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| [[de:Depression]]
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| [[et:Depressioon]]
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| [[el:Κλινική κατάθλιψη]]
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| [[es:Depresión]]
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| [[eo:Deprimo]]
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| [[fr:Dépression (médecine)]]
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| [[ko:우울증]]
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| [[hr:Klinička depresija]]
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| [[id:Depresi]]
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| [[it:Depressione (malattia)]]
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| [[he:דיכאון]]
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| [[ku:Klînîk depresyon]]
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| [[la:Depressio (psychiatria)]]
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| [[lt:Depresija]]
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| [[hu:Depresszió]]
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| [[ms:Kemurungan]]
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| [[nl:Klinische depressie]]
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| [[nds-nl:Depressie (psychologie)]]
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| [[ja:うつ病]]
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| [[no:Depresjon (sykdom)]]
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| [[nn:Depresjon]]
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| [[oc:Depression]]
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| [[uz:Klinik depressiya]]
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| [[pl:Depresja (choroba)]]
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| [[pt:Depressão nervosa]]
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| [[ro:Depresie (boală)]]
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| [[ru:Большая депрессия (психиатрия)]]
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| [[simple:Depression (illness)]]
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| [[sk:Depresia (psychológia)]]
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| [[sr:Klinička depresija]]
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| [[fi:Masennus]]
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| [[sv:Depression]]
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| [[vi:Trầm cảm]]
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| [[tr:Klinik depresyon]]
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| [[uk:Депресія (медицина)]]
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| [[yi:קלינישע דעפרעסיע]]
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| [[zh:憂鬱症]]
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| {{WH}}
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| {{WS}}
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| [[Category:Disease]]
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| [[Category:Psychiatry]]
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| [[Category:Medical emergencies]]
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| ==Medical Therapy==
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| [[Antidepressant]] drugs include [[selective serotonin reuptake inhibitor]]s, such as [[escitalopram oxalate]] (Lexapro), [[citalopram]] (Celexa), [[fluoxetine]] (Prozac), [[paroxetine]] (Paxil), and [[sertraline]] (Zoloft), are the primary medications considered for patients, having fewer side effects than the older [[monoamine oxidase inhibitor]]s (MAOIs).
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| The effect size is very small for moderate depression but increased with severity reaching the [[NICE]] criteria for 'clinical significance' for very severe depression.<ref>{{cite web |url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045 |title=Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration |accessdate=2008-02-26 |author=Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT |authorlink= |coauthors= |date=February 2008 |format=htm |work= |publisher=PLoS Medicine |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> This result is consistent with the earlier clinical studies where only patients with severe depression benefited from the treatment with a tricyclic antidepressant [[imipramine]] or from psychotherapy more than from the placebo treatment.<ref name="pmid2684085">{{cite journal |author=Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF, Glass DR, Pilkonis PA, Leber WR, Docherty JP |title=National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments |journal=Arch. Gen. Psychiatry |volume=46 |issue=11 |pages=971–82; discussion 983 |year=1989 |pmid=2684085 |doi=}}</ref><ref name="pmid7593878">{{cite journal |author=Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA, Hedeker D |title=Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program |journal=J Consult Clin Psychol |volume=63 |issue=5 |pages=841–7 |year=1995 |pmid=7593878 |doi=}}</ref><ref name="pmid1853989">{{cite journal |author=Sotsky SM, Glass DR, Shea MT, Pilkonis PA, Collins JF, Elkin I, Watkins JT, Imber SD, Leber WR, Moyer J |title=Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program |journal=Am J Psychiatry |volume=148 |issue=8 |pages=997–1008 |year=1991 |pmid=1853989 |doi=}}</ref> According to the STAR*D [[randomized controlled tria]]l, about 50% of patients with major depression have a response and about 30% of have remission of symptoms with usage of [[citalopram]].<ref name="pmid16390886">{{cite journal| author=Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L et al.| title=Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 1 | pages= 28-40 | pmid=16390886 | doi=10.1176/appi.ajp.163.1.28 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16390886 }} </ref>
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| [[Bupropion]] (Wellbutrin, Zyban), an atypical [[antidepressant]] that acts as a [[norepinephrine reuptake inhibitor|norepinephrine]] and [[dopamine reuptake inhibitor]], is also considered to be effective in the treatment of depression,<ref>{{cite journal | author = Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, Pradko JF, Johnston JA. | title = 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL | journal = Prim Care Companion J Clin Psychiatry| volume = 7|issue = 3|pages = 106–113| year = 2005 |pmid=16027765 }}</ref> without sexual dysfunction or sexual side effects<ref> For the review, see: {{cite journal | author = Clayton AH| title = Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge | journal = Primary Psychiatry| volume = 10| issue=1 |pages = 55–61 | year = 2003}}</ref> and without weight gain. Bupropion has also been shown to be more effective than [[SSRI]]s at improving symptoms such as [[hypersomnia]] and [[fatigue (medical)|fatigue]] in depressed patients.<ref>{{cite journal | author = Baldwin DS, Papakostas GI| title = Symptoms of Fatigue and Sleepiness in Major Depressive Disorder | journal = J Clin Psychiatry| volume = 67 (suppl 6)| pages = 9–15 | year = 2006 |pmid=16848671}}</ref>
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| Measurement-based care, which guides mediation based on serial measurement of psychometric testing, improves outcomes according to randomized controlled trials<ref name="pmid16390886">{{cite journal| author=Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L et al.| title=Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 1 | pages= 28-40 | pmid=16390886 | doi=10.1176/appi.ajp.163.1.28 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16390886 }} </ref><ref name="pmid22807244">{{cite journal| author=Yeung AS, Jing Y, Brenneman SK, Chang TE, Baer L, Hebden T et al.| title=Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians. | journal=Depress Anxiety | year= 2012 | volume= 29 | issue= 10 | pages= 865-73 | pmid=22807244 | doi=10.1002/da.21983 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22807244 }} </ref>.
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|
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| ====Predictors of a response to treatment====
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| =====Severity of depression=====
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| The effectiveness is antidepressants may<ref name="pmid20051569">{{cite journal| author=Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC et al.| title=Antidepressant drug effects and depression severity: a patient-level meta-analysis. | journal=JAMA | year= 2010 | volume= 303 | issue= 1 | pages= 47-53 | pmid=20051569 | doi=10.1001/jama.2009.1943 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20051569 }} </ref> or may not<ref name="pmid31303567">{{cite journal| author=Hieronymus F, Lisinski A, Nilsson S, Eriksson E| title=Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis. | journal=Lancet Psychiatry | year= 2019 | volume= | issue= | pages= | pmid=31303567 | doi=10.1016/S2215-0366(19)30216-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31303567 }} </ref><ref name="pmid22393205">{{cite journal| author=Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ| title=Benefits From Antidepressants: Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine. | journal=Arch Gen Psychiatry | year= 2012 | volume= | issue= | pages= | pmid=22393205 | doi=10.1001/archgenpsychiatry.2011.2044 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22393205 }} </ref> depend on the severity of a patient's depression. This relationship may be due to the declining effect of placebo among more severely depressed patients.
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| {| class="wikitable
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| |+ The effectiveness of antidepressants depending on severity of depression<ref name="pmid20051569">{{cite journal| author=Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC et al.| title=Antidepressant drug effects and depression severity: a patient-level meta-analysis. | journal=JAMA | year= 2010 | volume= 303 | issue= 1 | pages= 47-53 | pmid=20051569 | doi=10.1001/jama.2009.1943 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20051569 }} </ref>
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| !American Psychiatric Association<br/>classification of severity<ref name="isbn1-58562-218-4">{{cite book |author=First, Michael B. |title=Handbook of Psychiatric Measures, Second Edition |publisher=American Psychiatric Publishing, Inc |location= |year=2007 |pages= |isbn=1-58562-218-4 |oclc= |doi= |accessdate=}}</ref>!! [http://healthnet.umassmed.edu/mhealth/HAMD.pdf Hamilton Depression Rating Scale]<br/>(HDRS)!![[Number needed to treat]]<ref name="pmid20051569"/>!!Clinical significance<br/>(NICE)<ref>National Institute for Clinical Excellence. [http://guidance.nice.org.uk/CG90 Depression: Management of Depression in Primary and Secondary Care]. London, England: National Institute for Clinical Excellence; 2009.</ref>
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| |-
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| | Mild to moderate||align="center"|< 19||align="center"|16||align="center"|No
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| |-
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| | Severe||align="center"|19 - 22||align="center"|11||align="center"|No
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| |-
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| | Very severe||align="center"|> 22||align="center"| 4||align="center"|Yes
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| |}
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| =====Genetic variations=====
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| Variations in the GRIK4 ([[glutamate]] receptor, ionotropic, kainate 4 protein) and HTR2A ([[serotonin|5-hydroxytryptamine]] receptor) genes predict response to citalopram.<ref name="pmid17671280">{{cite journal| author=Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ et al.| title=Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. | journal=Am J Psychiatry | year= 2007 | volume= 164 | issue= 8 | pages= 1181-8 | pmid=17671280 | doi=10.1176/appi.ajp.2007.06111790 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17671280 }} </ref>
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| ====Treatment failure====
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| {| class="wikitable" align="right"
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| |+ Treatment after monotherapy failure<br/>(VAST-D Study)<ref name="pmid28697253">{{cite journal| author=Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, Yoon J et al.| title=Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. | journal=JAMA | year= 2017 | volume= 318 | issue= 2 | pages= 132-145 | pmid=28697253 | doi=10.1001/jama.2017.8036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28697253 }} </ref>
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| ! colspan="2"|Intervention!!colspan="2"|Outcome
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| ! Medication!! Mode final dose!!Remission %!! Quit 2˚ [[Drug toxicity|ADR]]s (%)
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| | colspan="4"| Switch medications
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| | [[Bupropion]] SR||align="right"|200 mg twice daily||align="center"|22.3%||style="background-color:coral;text-align:center"|10%
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| | colspan="4"| Augment medications
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| |-
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| | [[Aripiprazole]]||align="right"|10 mg|| style="background-color:lightgreen;text-align:center"|29% || style="text-align:center"|5%
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| |-
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| | [[Bupropion]] SR||align="right"|300 mg daily ||style="text-align:center"|27%||align="center"|7%
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| |}
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|
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| After starting medications, treatment should be switched if there is no response within one month.<ref name="ngc24158 >American Psychiatric Association (APA). [http://www.guideline.gov/content.aspx?id=24158 Practice guideline for the treatment of patients with major depressive disorder]. 3rd ed. Arlington (VA): American Psychiatric Association (APA); 2010 Oct. 152 p. [1170 references]</ref>
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| When treated with monotherapy for depression, approximately 30% of patients have remission of symptoms while 50% have a response to medications.<ref name="pmid16390886">{{cite journal |author=Trivedi MH, Rush AJ, Wisniewski SR, ''et al'' |title=Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice |journal=The American journal of psychiatry |volume=163 |issue=1 |pages=28–40 |year=2006 |pmid=16390886 |doi=10.1176/appi.ajp.163.1.28}}</ref>
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| For patients with inadequate response, [[randomized controlled trial]]s provide guidance.<ref name="pmid28697253">{{cite journal| author=Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, Yoon J et al.| title=Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. | journal=JAMA | year= 2017 | volume= 318 | issue= 2 | pages= 132-145 | pmid=28697253 | doi=10.1001/jama.2017.8036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28697253 }} </ref><ref name="pmid16554526">{{cite journal |author=Trivedi MH, Fava M, Wisniewski SR, ''et al'' |title=Medication augmentation after the failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1243–52 |year=2006 |pmid=16554526 |doi=10.1056/NEJMoa052964}}</ref>
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| * The original VAST-D trial, that did not include [[aripiprazole]], confirms that augmenting with bupropion is the most effective of options other than augmentation with [[aripiprazole]]. In this trial, either adding sustained-release [[bupropion]] ("bupropion was 200 mg per day during weeks 1 and 2, increasing to 300 mg per day by week 4 and to 400 mg per day (the final dose) during week 6") or [[buspirone]] (up to 60 mg per day) for augmentation as a second drug can cause remission in approximately 30% of patients ([[bupropion]] may be more effective than [[buspirone]])<ref name="pmid16554526"/>, while switching medications can achieve remission in about 25% of patients<ref name="pmid16554525">{{cite journal |author=Rush AJ, Trivedi MH, Wisniewski SR, ''et al'' |title=Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1231–42 |year=2006 |pmid=16554525 |doi=10.1056/NEJMoa052963}}</ref>. Alternatively, "extended-release venlafaxine, the starting daily dose of 37.5 mg for 7 days was increased to 75 mg from day 8 to 14, to 150 mg from day 15 to 27, to 225 mg from day 28 to 41, to 300 mg from day 42 to 62, and to 375 mg from day 63 onward."<ref name="pmid16554525"/>
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| * The PReDICT trial found that among patients who initially were treated with either an SSRI or CBT, remission was increased when the opposite treatment (CBT or SSRI) was added to non-remitters<ref name="pmid30764648">{{cite journal| author=Dunlop BW, LoParo D, Kinkead B, Mletzko-Crowe T, Cole SP, Nemeroff CB et al.| title=Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression. | journal=Am J Psychiatry | year= 2019 | volume= | issue= | pages= appiajp201818091075 | pmid=30764648 | doi=10.1176/appi.ajp.2018.18091075 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30764648 }} </ref>.
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| * The newer VAST-D trial found that augmentation with [[aripiprazole]] is effective.<ref name="pmid28697253"/> The dose of aripiprazole was 2 mg of with titration to 5, 10, or 15 mg daily as guided by measurement-based care using the PHQ-9.<ref name="pmid28697253"/> ''However'', aripiprazole led to more [[adverse drug reaction]]s including somnolence, akathisia, and weight gain. The second most effective was augmentation with [[buproprion]] starting at 150 mg sustained release to 300 mg or 400 mg daily as guided by measurement-based care using the PHQ-9.
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|
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| * More recently, [[mirtazapine]], was found not to add to SSRIs<ref name="pmid30381374">{{cite journal| author=Kessler DS, MacNeill SJ, Tallon D, Lewis G, Peters TJ, Hollingworth W et al.| title=Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). | journal=BMJ | year= 2018 | volume= 363 | issue= | pages= k4218 | pmid=30381374 | doi=10.1136/bmj.k4218 | pmc=6207929 | url=https://www.ncbi.nlm.n
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