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Digoxin

Shown below is an image that summarizes the steps in the chronic management of patients with heart failure.
ACE-I Starting dose Target dose
Captopril 6.25 mg t.i.d. 50 mg t.i.d.
Enalapril 2.5 mg b.i.d. 10-20 mg b.i.d.
Lisinopril > 2.5-5 mg daily 20-35 mg daily
Ramipril > 2.5 mg b.i.d. 5 mg b.i.d.
Trandolapril > 0.5 mg daily 4 mg daily



Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF


Treatment of underlying causes | Associated conditions



Biventricular Pacing or Cardiac Resynchronization Therapy (CRT) | Implantation of Intracardiac Defibrillator | Ultrafiltration | Left Ventricular Assist Devices (LVADs) | Cardiac Transplantation | Cardiac Surgery
Chronic Pharmacotherapy in HFrEF:
Drugs to Avoid | Drug Interactions
 | |  |  | Ca Channel Blockers | Nitrates | Hydralazine | Positive Inotropics | Anticoagulants |  | Antiarrhythmic Drugs | Nutritional Supplements | Hormonal Therapies | Lifestyle modification
Device therapy for heart failure with reduced ejection fraction: Implantable cardioverter-defibrillator | Cardiac resynchronization therapy | Devices under evaluation


  • Efficacy: Low
    • Sinus rhythm is maintained in <20% of patients
    • Symtoms are reduced in >=20%.
Adverse effects
  • Bradycardia
  • Hypotension
  • Edema
Contraindications
  • Bradycardia
  • Hypotension
  • Heart failure with depressed ejection fraction


Contraindications
Precautions during treatment


[1]

[2]

Books by Psychologists and Psychiatrists

  • Beck, A. T., Rush, A. J., Shaw, B. F., Emery, G. (1987). Cognitive therapy of depression. New York: Guilford.
  • Burns, David D. (1999). Feeling Good : The New Mood Therapy. Avon.
  • Griffin, J., Tyrrell, I. (2004) How to lift Depression – Fast. HG Publishing. ISBN 1-899398-41-4
  • Jacobson, Edith: "Depression; Comparative Studies of Normal, Neurotic, and Psychotic Conditions", International Universities Press, 1976, ISBN 0-8236-1195-7
  • Klein, D. F., & Wender, P. H. (1993). Understanding depression: A complete guide to its diagnosis and treatment. New York: Oxford University Press.
  • Kramer, Peter D. (2005). Against Depression. New York: Viking Adult.
  • Plesman, J. (1986). Getting off the Hook, Sydney Australia. A self-help book available on the internet.
  • Rowe, Dorothy (2003). Depression: The way out of your prison. London: Brunner-Routledge.
  • 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.
  • Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). Comprehensive guide to interpersonal psychotherapy. New York: Basic Books.
  • Bieling, Peter J. & Anthony, Martin M. (2003) Ending The Depression Cycle. New Harbinger Publications. ISBN 1572243333
  • For books on male depression, see Terrence Real

Historical Account

  • Healy, David. (1999). The Antidepressant Era, Paperback Edition, Harvard University Press. ISBN 0-674-03958-0

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Medical Therapy

Antidepressant drugs include selective serotonin reuptake inhibitors, 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 inhibitors (MAOIs).

The effect size is very small for moderate depression but increased with severity reaching the NICE criteria for 'clinical significance' for very severe depression.[3] 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.[4][5][6] According to the STAR*D randomized controlled trial, about 50% of patients with major depression have a response and about 30% of have remission of symptoms with usage of citalopram.[7]

Bupropion (Wellbutrin, Zyban), an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor, is also considered to be effective in the treatment of depression,[8] without sexual dysfunction or sexual side effects[9] and without weight gain. Bupropion has also been shown to be more effective than SSRIs at improving symptoms such as hypersomnia and fatigue in depressed patients.[10]

Measurement-based care, which guides mediation based on serial measurement of psychometric testing, improves outcomes according to randomized controlled trials[7][11].

Predictors of a response to treatment

Severity of depression

The effectiveness is antidepressants may[12] or may not[13][14] 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.

The effectiveness of antidepressants depending on severity of depression[12]
American Psychiatric Association
classification of severity[15]		 Hamilton Depression Rating Scale
(HDRS)		 Number needed to treat[12] Clinical significance
(NICE)[16]
Mild to moderate < 19 16 No
Severe 19 - 22 11 No
Very severe > 22  4 Yes
Genetic variations

Variations in the GRIK4 (glutamate receptor, ionotropic, kainate 4 protein) and HTR2A (5-hydroxytryptamine receptor) genes predict response to citalopram.[17]

Treatment failure

Treatment after monotherapy failure
(VAST-D Study)[18]
Intervention Outcome
Medication Mode final dose Remission % Quit 2˚ ADRs (%)
Switch medications
Bupropion SR 200 mg twice daily 22.3% 10%
Augment medications
Aripiprazole 10 mg 29% 5%
Bupropion SR 300 mg daily 27% 7%

After starting medications, treatment should be switched if there is no response within one month.[19]

When treated with monotherapy for depression, approximately 30% of patients have remission of symptoms while 50% have a response to medications.[7]

For patients with inadequate response, randomized controlled trials provide guidance.[18][20]

  • 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)[20], while switching medications can achieve remission in about 25% of patients[21]. 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."[21]
  • 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[22].
  • The newer VAST-D trial found that augmentation with aripiprazole is effective.[18] 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.[18] However, aripiprazole led to more adverse drug reactions 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.
  • 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
  1. ↑ LastName, FirstName (2013). Diagnostic and statistical manual of mental disorders : DSM-5. Arlington, VA Washington, D.C: American Psychiatric Association,American Psychiatric Association. ISBN 978-0-89042-554-1.
  2. ↑ ....
  3. ↑ Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (February 2008). "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration" (htm). PLoS Medicine. Retrieved 2008-02-26.
  4. ↑ Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF, Glass DR, Pilkonis PA, Leber WR, Docherty JP (1989). "National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments". Arch. Gen. Psychiatry. 46 (11): 971–82, discussion 983. PMID 2684085.
  5. ↑ Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA, Hedeker D (1995). "Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program". J Consult Clin Psychol. 63 (5): 841–7. PMID 7593878.
  6. ↑ Sotsky SM, Glass DR, Shea MT, Pilkonis PA, Collins JF, Elkin I, Watkins JT, Imber SD, Leber WR, Moyer J (1991). "Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program". Am J Psychiatry. 148 (8): 997–1008. PMID 1853989.
  7. ↑ 7.0 7.1 7.2 Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L; et al. (2006). "Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice". Am J Psychiatry. 163 (1): 28–40. doi:10.1176/appi.ajp.163.1.28. PMID 16390886.
  8. ↑ Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, Pradko JF, Johnston JA. (2005). "15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL". Prim Care Companion J Clin Psychiatry. 7 (3): 106–113. PMID 16027765.
  9. ↑ For the review, see: Clayton AH (2003). "Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge". Primary Psychiatry. 10 (1): 55–61.
  10. ↑ Baldwin DS, Papakostas GI (2006). "Symptoms of Fatigue and Sleepiness in Major Depressive Disorder". J Clin Psychiatry. 67 (suppl 6): 9–15. PMID 16848671.
  11. ↑ Yeung AS, Jing Y, Brenneman SK, Chang TE, Baer L, Hebden T; et al. (2012). "Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians". Depress Anxiety. 29 (10): 865–73. doi:10.1002/da.21983. PMID 22807244.
  12. ↑ 12.0 12.1 12.2 Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC; et al. (2010). "Antidepressant drug effects and depression severity: a patient-level meta-analysis". JAMA. 303 (1): 47–53. doi:10.1001/jama.2009.1943. PMID 20051569.
  13. ↑ Hieronymus F, Lisinski A, Nilsson S, Eriksson E (2019). "Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis". Lancet Psychiatry. doi:10.1016/S2215-0366(19)30216-0. PMID 31303567.
  14. ↑ Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ (2012). "Benefits From Antidepressants: Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine". Arch Gen Psychiatry. doi:10.1001/archgenpsychiatry.2011.2044. PMID 22393205.
  15. ↑ First, Michael B. (2007). Handbook of Psychiatric Measures, Second Edition. American Psychiatric Publishing, Inc. ISBN 1-58562-218-4.
  16. ↑ National Institute for Clinical Excellence. Depression: Management of Depression in Primary and Secondary Care. London, England: National Institute for Clinical Excellence; 2009.
  17. ↑ Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ; et al. (2007). "Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort". Am J Psychiatry. 164 (8): 1181–8. doi:10.1176/appi.ajp.2007.06111790. PMID 17671280.
  18. ↑ 18.0 18.1 18.2 18.3 Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, Yoon J; et al. (2017). "Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial". JAMA. 318 (2): 132–145. doi:10.1001/jama.2017.8036. PMID 28697253.
  19. ↑ American Psychiatric Association (APA). 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]
  20. ↑ 20.0 20.1 Trivedi MH, Fava M, Wisniewski SR; et al. (2006). "Medication augmentation after the failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1243–52. doi:10.1056/NEJMoa052964. PMID 16554526.
  21. ↑ 21.0 21.1 Rush AJ, Trivedi MH, Wisniewski SR; et al. (2006). "Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1231–42. doi:10.1056/NEJMoa052963. PMID 16554525.
  22. ↑ Dunlop BW, LoParo D, Kinkead B, Mletzko-Crowe T, Cole SP, Nemeroff CB; et al. (2019). "Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression". Am J Psychiatry: appiajp201818091075. doi:10.1176/appi.ajp.2018.18091075. PMID 30764648.
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