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==Medical Therapy==
==Medical Therapy==
Sufferers of severe depression may benefit from the use of [[antidepressant]] drugs. A widely-reported meta-analysis combined 35 clinical trials submitted to the [[FDA]] before licensing of four newer antidepressants. The authors found that although the antidepressants were statistically superior to [[placebo]] they often did not exceed the [[NICE]] criteria for a 'clinically significant' effect. In particular they found that the effect size was very small for moderate depression but increased with severity reaching '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>
Pharmacologic medical therapies for [[Major Depressive Disorder]] 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).
===[[Serotonin reuptake inhibitors]]===
*[[SSRI]]s are effective, well-tolerated medications used as a first-line treatment for MDD.
*Possible adverse effects with SSRIs: [[serotonergic]] symptoms including [[nausea]], [[diarrhea]], [[anxiety]] or [[nervousness]], [[insomnia]], [[sexual dysfunction]], [[withdrawal syndrome]], and [[hyponatremia]] in [[elderly]]. Most side effects are transient and self-limited; however, [[sexual dysfunction]] is usually persistent and may respond to a change in drug (for example to [[mirtazapine]] or [[bupropion]]) or dosage.
*During the early few weeks of initiation of [[SSRI]] therapy, anxiogenic effects of SSRI may aggravate [[suicidal ideation]] in patients with [[MDD]]. This can be managed by reducing the dose or adjunctive therapy with an [[anxiolytic]], for example, a [[benzodiazepine]].
*Co-administration with [[monoamine oxidase inhibitors]] is [[contraindicated]] due to the risk of [[serotonine syndrome]].
*'''[[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 [[SSRI]]s side effects
*'''[[Sertraline]]''' (Effective dose range: 50-200mg): has a dual mechanism of action, i.e., [[serotonine]] 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]] or 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]]


MAOIs may be the best medication for a small number of patients, however those patients will have to avoid a variety of foods and [[decongestant]] medications to reduce the chances of a [[hypertensive crisis]].
===[[Serotonin-norepinephrine reuptake inhibitors]]===
*[[Serotonin-norepinephrine reuptake inhibitors]] ([[SNRI]]s) are also considered first-line medications for the treatment of [[MDD]]. [[SNRI]]s have a dual mechanism of action. They 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, 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)


[[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>
===Other [[antidepressants]]===
*'''[[Bupropion]] XR''' (Effective dose range 300--450 mg)
**[[Atypical antidepressant]]  
**A [[noradrenergic]], [[dopaminergic]] drug with stimulat-like  effects
**Approved for smoking cessation
**Benefits: Weight neutral, minimal to no risk of [[sexual dysfunction]], minimal [[withdrawal symptoms]]. 
**Adverse effects: Lowers [[seizure]] threshold, particularly at higher doses.  
*'''[[Mirtazapine]]''' (Effective dose range 15-45 mg)
**[[Atypical antidepressant ]]
**Benefits: faster onset of action than [[SSRIs]], minimal [[sexual dysfunction]], 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 dysfunction[]] 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 dysfunction]] 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.


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>
===[[Tricyclic antidepressants]]===
*[[Tricyclic antidepressants]] ([[TCAs]]) are considered second-line or third-line medications in the treatment of [[MDD]] due to greater side effects compared to [[SSRI]]s and [[SNRI]]s, in particular in the elderly.
* they work by inhibiting serotonin and norepinephrine reuptake.
*Common side effects of [[TCA]]s include [[sedation]], [[orthostatic hypotension]], [[anticholinergic effects]], [[GI distress]], [[weight gain]], [[cardiac arrhythmias]], and QTc prolongation.
*[[TCA]]s include:
*[[Amitriptyline]]
*[[Nortriptyline]]
*[[Imipramine]]
*[[Desipramine]]
*[[Clomipramine]]
*[[Doxepin]]
*[[Amoxapine]]


===Stopping medications===
===[[Monoamine oxidase inhibitors]]===
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.<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> For patients that have chronic depression, medication may need to be continued for the remainder of their life.
*[[Monoamine oxidase inhibitors]] ([[MAOI]]s) are considered second-line or third-line medications in the treatment of [[MDD]] due to greater side effects compared to [[SSRI]]s and [[SNRI]]s, in particular in the elderly.
*Combination of [[MAOI]]s with other serotonergic drugs, i.e., [[TCA]]s, [[SSRI]]s, or [[SNRI]]s are contraindicated due to increased risk of [[serotonin syndrome]].  
*[[MAOI]]s include:
**[[Phenelzine]]
**[[Tranylcypromine]]


 
===Clinical Hints===
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."<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>
*Initiation of [[SSRI]]s may be associated with early transient [[anxiety]], aggravating [[suicidal ideation]]. Reducing the dose or adding a [[benzodiazepine]] may be helpful in these patients.
In [[MDD]] patients with [[insomnia]], [[benzodiazepines]], [[zolpidem]], [[trazodone]], or [[mirtazapine]] are helpful.
*In addition, when depressed patients begin to clinically improve, their physical energy also improves, enabling them to carry out suicidal acts that they did not have the power to perform before. This is known as [[paradoxical suicide]].
*Antidepressants may take as long as 6-8 weeks to take effect.
*The goal of treatment is achieving complete remission of symptoms and return to normal functioning.  
*In patients who fail to respond to an [[SSRI]], or experience intolerable side effects, another medication in this class may be tried. However, some physicians prefer to switch to another medication with a different mechanism of action.  
*[[Psychotherapy]] may be added in the treatment of patients with a partial response to pharmacotherapy alone.
*In patients with first episode of [[major depression]], maintenance treatment for at least months may be helpful in preventing [[relapse]]. In patients with recurrent major depressive episodes, long-term treatment may be beneficial.  
*In patients experiencing intolerable sexual side effects with [[SSRI]]s, [[bupropion]] or [[mirtazapine]] may be considered.  
*[[Bupropion]] may be beneficial in patients with [[anergy]] and [[psychomotor retardation]] due to its stimulant-like effects.  
*[[Hospitalization]] may be considered in patients with significant [[suicidal ideation]] or intent without adequate family support or safe-guards at home. Patients who express intent to hurt others or those who are not able to care for themselves may also be hospitalized.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 16:51, 20 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

Serotonin-norepinephrine reuptake inhibitors

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) are also considered first-line medications for the treatment of MDD. SNRIs have a dual mechanism of action. They 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, 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)

Other antidepressants

Tricyclic antidepressants

Monoamine oxidase inhibitors

Clinical Hints

In MDD patients with insomnia, benzodiazepines, zolpidem, trazodone, or mirtazapine are helpful.

  • In addition, when depressed patients begin to clinically improve, their physical energy also improves, enabling them to carry out suicidal acts that they did not have the power to perform before. This is known as paradoxical suicide.
  • Antidepressants may take as long as 6-8 weeks to take effect.
  • The goal of treatment is achieving complete remission of symptoms and return to normal functioning.
  • In patients who fail to respond to an SSRI, or experience intolerable side effects, another medication in this class may be tried. However, some physicians prefer to switch to another medication with a different mechanism of action.
  • Psychotherapy may be added in the treatment of patients with a partial response to pharmacotherapy alone.
  • In patients with first episode of major depression, maintenance treatment for at least months may be helpful in preventing relapse. In patients with recurrent major depressive episodes, long-term treatment may be beneficial.
  • In patients experiencing intolerable sexual side effects with SSRIs, bupropion or mirtazapine may be considered.
  • Bupropion may be beneficial in patients with anergy and psychomotor retardation due to its stimulant-like effects.
  • Hospitalization may be considered in patients with significant suicidal ideation or intent without adequate family support or safe-guards at home. Patients who express intent to hurt others or those who are not able to care for themselves may also be hospitalized.

References

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

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