Clinical depression medical therapy: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(26 intermediate revisions by 2 users not shown)
Line 13: Line 13:


==Medical Therapy==
==Medical Therapy==
[[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). 
Pharmacologic medical therapies for [[Major Depressive Disorder]] include:


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>
===[[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]]


[[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>
===[[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)


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>.
===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.


====Predictors of a response to treatment====
===[[Tricyclic antidepressants]]===
=====Severity of depression=====
*[[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.
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.
* 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]]


{| class="wikitable
===[[Monoamine oxidase inhibitors]]===
|+ 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>
*[[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.
!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>
*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:
| Mild to moderate||align="center"|< 19||align="center"|16||align="center"|No
**[[Phenelzine]]
|-
**[[Tranylcypromine]]
| Severe||align="center"|19 - 22||align="center"|11||align="center"|No
|-
| Very severe||align="center"|> 22||align="center"| &nbsp;4||align="center"|Yes
|}


=====Genetic variations=====
===Clinical Hints===
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>
*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.
====Treatment failure====
*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]].
{| class="wikitable" align="right"
*Antidepressants may take as long as 6-8 weeks to take effect.  
|+ 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>
*The goal of treatment is achieving complete remission of symptoms and return to normal functioning.  
! colspan="2"|Intervention!!colspan="2"|Outcome
*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.
! Medication!! Mode final dose!!Remission %!! Quit 2˚ [[Drug toxicity|ADR]]s (%)
*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.
| colspan="4"| Switch medications
*[[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.
| [[Bupropion]] SR||align="right"|200 mg twice daily||align="center"|22.3%||style="background-color:coral;text-align:center"|10%
|-
| colspan="4"| Augment medications
|-
| [[Aripiprazole]]||align="right"|10 mg|| style="background-color:lightgreen;text-align:center"|29% || style="text-align:center"|5%
|-
| [[Bupropion]] SR||align="right"|300 mg daily ||style="text-align:center"|27%||align="center"|7%
|}
 
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>
 
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, [[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>
 
* 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"/>
* 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>.
* 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.
 
* 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.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30381374  }} </ref>.
 
{| 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!!Remission %!! 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%
|}
 
The STAR*D trial has reported the frequency of re-emergence 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===
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.
 
 
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>


==References==
==References==

Latest revision as of 16:51, 20 May 2021

Clinical Depression Microchapters

Home

Patient Information

Major Depressive Disorder (Patient Information)

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Clinical Depression from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Substance/Medication-induced Depressive Disorder

Depressive Disorder due to a Medical Condition

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Psychotherapy

ECT

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Follow-up

Follow-Up

Case Studies

Case #1

Clinical depression medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Clinical depression medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Clinical depression medical therapy

CDC on Clinical depression medical therapy

Clinical depression medical therapy in the news

Blogs on Clinical depression medical therapy

Directions to Hospitals Treating Clinical depression

Risk calculators and risk factors for Clinical depression medical therapy

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.

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Clinical_depression_medical_therapy&oldid=1701321"