Clinical depression medical therapy: Difference between revisions

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**Benefits: May have a lower risk of sexual impairment than other serotonergic antidepressants. A long half-life may reduce the risk of withdrawal symptoms upon tapering.  
**Benefits: May have a lower risk of sexual impairment than other serotonergic antidepressants. A long half-life may reduce the risk of withdrawal symptoms upon tapering.  
**Adverse effects: Despite 5-HT3 receptor antagonism, it has high rates of nausea.
**Adverse effects: Despite 5-HT3 receptor antagonism, it has high rates of nausea.
===Treatment failure===
{| class="wikitable" align="right"
|+ Treatment after SSRI ([[citalopram]]) failure<br/>([http://www.nimh.nih.gov/trials/practical/stard/ STAR*D] Studies)
! colspan="2"|Intervention!!colspan="2"|Outcome
|-
! Medication!! Mean final dose!!Remision %!! Quit 2˚ [[Drug toxicity|ADR]]s (%)
|-
| colspan="4"| Switch meds (NEJM 2006; PMID: 16554525<ref name="pmid16554525">{{cite journal| author=Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME et al.| title=Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 12 | pages= 1231-42 | pmid=16554525 | doi=10.1056/NEJMoa052963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16554525  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065297 Review in: Evid Based Ment Health. 2006 Nov;9(4):100] </ref>)
|-
| [[Bupropion]] SR||align="right"|283 mg||align="center"|21%||align="center"|27%
|-
| [[Sertraline]] (SSR)||align="right"|136 mg||align="center"| 18%||align="center"|21%
|-
| [[Venlafaxine]] ER (SNRI)||align="right"|194 mg||align="center"| 25%||align="center"|21%
|-
| colspan="4"| Augment meds (NEJM 2006; PMID: 16554526<ref name="pmid16554526">{{cite journal| author=Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D et al.| title=Medication augmentation after the failure of SSRIs for depression. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 12 | pages= 1243-52 | pmid=16554526 | doi=10.1056/NEJMoa052964 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16554526  }} </ref>)
|-
| [[Bupropion]] SR||align="right"|268 mg||style="background-color:lightgreen;text-align:center"|30%||align="center"|13%
|-
| [[Buspirone]]||align="right"|41 mg|| style="text-align:center"|30% || style="background-color:coral;text-align:center"|21%
|}
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> For patients with inadequate response, 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">{{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>, 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"/>
The STAR*D trial has reported the frequency of re-emrgence of suicidality for different second levels of treatment.<ref>http://dx.doi.org/10.4088/JCP.12m07777</ref>
In level 3 of the STAR*D trials, patients who had failed two trials of a [[second-generation antidepressant]], tended to better with [[nortriptyline]] than [[mirtazapine]].<ref name="pmid16816220">{{cite journal| author=Fava M, Rush AJ, Wisniewski SR, Nierenberg AA, Alpert JE, McGrath PJ et al.| title=A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 7 | pages= 1161-72 | pmid=16816220 | doi=10.1176/appi.ajp.163.7.1161 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16816220  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17255385 Review in: Evid Based Ment Health. 2007 Feb;10(1):16] </ref>
[[Aripiprazole]], originally introduced as an atypical antipsychotic agent, is approved as an adjunct to other antidepressants.<ref>{{citation
| title = Beneficial acute antidepressant effects of aripiprazole as an adjunctive treatment or monotherapy in bipolar patients unresponsive to mood stabilizers: results from a 16-week open-label trial
| date = December 2008 | volume = 9 | issue = 18 | pages = 3145-3149 | doi =10.1517/14656560802504490
| journal = Expert Opinion on Pharmacotherapy
| author = Marianna Mazza, Maria Rosaria Squillacioti1, Riccardo Daniele Pecora, Luigi Janiri1 & Pietro Bria
| url = http://informahealthcare.com/doi/abs/10.1517/14656560802504490}}</ref>


===Stopping medications===
===Stopping medications===

Revision as of 17:23, 19 May 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The treatment of depression is highly individualized to the patient, based on the patient's unique combination of biological, psychological and social health factors and the severity of their condition.[1] The three most conventional treatments for depression include medication, psychotherapy, and Electroconvulsive therapy, however new treatments and less conventional options are also available, including self help, life style changes, and vagus nerve stimulation.[1] If there is an imminent threat of suicide or the patient is a danger to others, hospitalization is employed as an intervention method to keep at-risk individuals safe until they cease to be a danger to themselves or others. At-risk individuals may also be placed in a partial hospitalization therapy, in which the patient sleeps at home but spends most of the day in a psychiatric hospital setting. This intensive treatment usually involves group therapy, individual therapy, medication management, and is used often in the case of children and adolescents.

Medical Therapy

Pharmacologic medical therapies for Major Depressive Disorder include:

Serotonin reuptake inhibitors

  • SSRIs are effective, well-tolerated medications used as a first-line treatment for MDD.
  • Possible adverse effects with SSRIs include serotonergic syndrome, impaired sexual dysfunction, withdrawal symptoms, and SIADH.
  • Co-administration with monoamine oxidase inhibitors is contraindicated.
  • Fluoxetine (Effective dose range: 20-80mg)
    • Benefits: It is associated with a low risk of withdrawal symptoms upon tapering due to its long-half-life
    • Adverse effects: See SSRIs side effects
  • Sertraline (Effective dose range: 50-200mg): has a dual mechanism of action, i.e., SSRI and dopamine reuptake inhibitor
    • Benefits: Low transplacental transmission during pregnancy; relatively low concentrations in breast milk
    • Adverse effects: Transient diarrhea during first few weeks of initiation of therapy
  • Paroxetine (Effective dose range: 20-50mg)
    • Benefits: Low transplacental transmission during pregnancy; relatively low concentrations in breast milk
    • Adverse effects: higher risk of withdrawal symptoms than other SSRIs, weight gain, potential higher risk of teratogenic effects (FDA pregnancy category D)
  • Citalopram (Effective dose range: 20-40mg)
    • Benefits: Few drug-drug interactions
    • Adverse effects: May prolong QTc interval, in particular at higher doses. It is not recommended in patients with congenital long QT syndrome of acute cardiac conditions (e.g. acute decompensated heart failure). It should be discontinued in patients with QTc interval >500ms. Doses of >20 mg are not recommended in the elderly or in patients with hepatic dysfunction.
  • Escitalopram (Effective dose range: 10-20mg)
    • Benefits: Few drug-drug interactions
    • Adverse effects: Modest effects on QTc interval

Serotonin-norepinephrine reuptake inhibitors

  • SNRIs have a dual mechanism of action. May be effective in treating concomitant pain conditions.
  • Adverse effects: Neuradrenergic symptoms (hypertension, dry mouth, constipation, insomnia, decreased appetite), serotonergic side effects (nausea, diarrhea, nervousness, insomnia, sexual dysfunction, withdrawal symptoms, SIADH, and hyponatremia).
  • Duloxetine (Effective dose range 60-120 mg)
    • May be effective in treating neuropathic pain and other pain condition. Smoking decreases the plasma levels of duloxetine.
  • Venlafaxine (Effective dose range 75-350 mg)
    • Adverse effects: Compared to other serotonergic antidepressants, is associated with a slightly increased incidence of nausea and vomiting, higher risk of withdrawal symptoms, and hypertesnion.
  • Desvenlafaxine (Effective dose range 50-100 mg)
    • Benefit: may reduce neuropathic pain
  • Levomilnacipran (Effective dose range 40-120 mg)

Tricyclic antidepressants

  • TCAs are considered second-line medications in the treatment of MDD due to greater side effects compared to SSRIs and SNRIs, in particular in the elderly.
  • Amitriptyline
  • Nortriptyline
  • Imipramine
  • Desipramine
  • Clomiprramine
  • Doxepine
  • Amoxepine

Monoamine oxidase inhibitors

  • Phenelzine
  • Tranylcipromine


Other antidepressants

  • Bupropion XR (Effective dose range 300--450 mg)
    • Atypical antidepressant
    • Approved for smoking cessation
    • Benefits: Weight neutral, minimal to no risk of sexual impairment, minimal withdrawal symptoms.
    • Adverse effects: Lower seizure threshold, particularly at higher doses.
  • Mirtazapine (Effective dose range 15-45 mg)
    • Atypical antidepressant
    • Benefits: faster onset of action than SSRIs, minimal sexual impairment, minimal withdrawal symptoms.
    • Adverse effects: increased appetite and sleep (may be beneficial in patients with reduced appetite and insomnia as symptoms of MDD), higher risk of weight gain
  • Trazodone
  • Vilazodone (Effective dose range 10-40 mg):
    • Serotonin partial agonist and reuptake inhibitor.
    • Benefits: May have a lower risk of sexual impairment than other serotonergic antidepressants
    • No generic formulation is currently available.
  • Vortioxetine (Effective dose range 10-20 mg):
    • Serotonin reuptake inhibitor and serotonin modulator
    • Benefits: May have a lower risk of sexual impairment than other serotonergic antidepressants. A long half-life may reduce the risk of withdrawal symptoms upon tapering.
    • Adverse effects: Despite 5-HT3 receptor antagonism, it has high rates of nausea.

Stopping medications

Patients are generally advised not to stop taking an antidepressant suddenly and to continue its use for at least four to months to prevent the chance of recurrence.[2] For patients that have chronic depression, medication may need to be continued for the remainder of their life.


Patients should be treated indefinitely if they have "three or more prior major depressive episodes or who have chronic major depressive disorder should proceed to the maintenance phase of treatment after completing the continuation phase."[2]

Antidepressant discontinuation syndrome

References

  1. 1.0 1.1 Mayo Clinic Staff (2006-03-06). "Depression Treatment Guide". Mayo Clinic. Retrieved 2007-10-20.
  2. 2.0 2.1 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]

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