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'''Depression'''<br>
{{subpages}}
Diagnosis and classification of Depressive disorder<br>
{{TOC|right}}
 
'''Major depressive disorder''', along with [[anxiety]], is one of the most frequently occurring general psychiatric disorders.  It is characterized by symptoms of [[depression]], generalized melancholy, retreat from social contact, disrupted sleep patterns, [[akathisia]], or a feeling of restlessness and increased movement, and [[anhedonia]], or a diminished ability to experience pleasure.
 
==Cause/etiology==
The development of depression is influenced by a organic, environmental, and genetic factors, with genetics contributing about one third<ref name="pmid11007705">{{cite journal |author=Sullivan PF, Neale MC, Kendler KS |title=Genetic epidemiology of major depression: review and meta-analysis |journal=Am J Psychiatry |volume=157 |issue=10 |pages=1552–62 |year=2000 |pmid=11007705 |doi=}}</ref> or more<ref>Major Depressive Disorder. ({{OMIM|608516}})</ref>. The organic factors contributing to depression include a general systemic dysregulation that involves a disruption of neurotransmitters.  This condition can be acute, or on-going, and is generally corrected, in both cases, through medication.  Environmental factors can contribute to depression by either triggering a recurrent episode of chronic depression, or advancing a situational depression.
 
===Epidemiology===
Community studies generally show a varying prevalence of depression, with estimates of occurrence between 5 and 7.5%.  The one-year prevalence of major depressive disorder in the [[United States of America]] varies from 3% in the Epidemiological Catchment Area Study <ref name="pmid8427558">{{cite journal |author=Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK |title=The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services |journal=Arch. Gen. Psychiatry |volume=50 |issue=2 |pages=85–94 |year=1993 |pmid=8427558 |doi=}}</ref> to 10% in the National Co-morbity Study. <ref name="pmid8279933">{{cite journal |author=Kessler RC, McGonagle KA, Zhao S, ''et al'' |title=Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey |journal=Arch. Gen. Psychiatry |volume=51 |issue=1 |pages=8–19 |year=1994 |pmid=8279933 |doi=}}</ref>
 
==Monoamine-Deficiency Hypothesis==
Depression may be due to "deficiency in [[serotonin]] or [[norepinephrine]] neurotransmission in the brain."<ref name="pmid18172175">{{cite journal |author=Belmaker RH, Agam G |title=Major depressive disorder |journal=N. Engl. J. Med. |volume=358 |issue=1 |pages=55–68 |year=2008 |pmid=18172175 |doi=10.1056/NEJMra073096|url=http://content.nejm.org/cgi/content/full/358/1/55}}</ref>
 
==Diagnosis==
The core symptoms of depression are depressed mood and a lack of interest or pleasure from daily activities (anhedonia). Several additional features may be present, like lack of concentration, inappropriate guilt feelings, suicidal thoughts, psychomotor retardation or agitation and loss of libido. A diurnal variation, e.g. the symptoms are worse in the morning, may be present.
The core symptoms of depression are depressed mood and a lack of interest or pleasure from daily activities (anhedonia). Several additional features may be present, like lack of concentration, inappropriate guilt feelings, suicidal thoughts, psychomotor retardation or agitation and loss of libido. A diurnal variation, e.g. the symptoms are worse in the morning, may be present.
In Psychiatry a diagnosis is made with the use of a classification system. The newest version of this classifiaction system is the Diagnostic and Statistical Manual of Mental Disorders (fourth version, DSM-IV).
Criteria for a Major Depressive Episode according to DSM IV are:
A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.


(1) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).  
[[Primary care physician]]s and other non-psychiatrists physicians have difficulty diagnosing depression.  Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.<ref name="pmid17968628">{{cite journal |author=Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A |title=Recognition of depression by non-psychiatric physicians--a systematic literature review and meta-analysis |journal=J Gen Intern Med |volume=23 |issue=1 |pages=25–36 |year=2008 |pmid=17968628 |doi=10.1007/s11606-007-0428-5 |issn=}}</ref><ref name"pmid19640579">Mitchell A et al. (22 August 2009) Clinical diagnosis of depression in primary care: a meta-analysis.  Lancet 2009;374(9690):609-619
{{doi|10.1016/S0140-6736(09)60879-5}} PMID 19640579</ref>.
 
===DSM-IV diagnostic criteria===
{{DSMCR}}
The [[Diagnostic and Statistical Manual of Mental Disorders|DSM-IV]] has created nine diagnostic criteria based on symptoms of depression. At least five of these should be present for two weeks in the absence of other explanations for the symptoms.
 
===Alternative diagnostic strategies===
====Patient Health Questionnaire 2====
The Patient Health Questionnaire (PHQ2) is a shorter questionnaire that may be as [[sensitivity and specificity|sensitive]] as the [[Diagnostic and Statistical Manual of Mental Disorders|DSM-IV]].<ref name="pmid10568646">{{cite journal |author=Spitzer RL, Kroenke K, Williams JB |title=Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire |journal=JAMA |volume=282 |issue=18 |pages=1737–44 |year=1999 |pmid=10568646 |doi=}}</ref> It has also been validated in elderly patients.<ref name="pmid17397440">{{cite journal |author=Li C, Friedman B, Conwell Y, Fiscella K |title=Validity of the Patient Health Questionnaire 2 (PHQ-2) in identifying major depression in older people |journal=J Am Geriatr Soc |volume=55 |issue=4 |pages=596–602 |year=2007 |pmid=17397440 |doi=10.1111/j.1532-5415.2007.01103.x}}</ref>  The accuracy of the PHQ2 with a score of 3 or more is:<ref name="pmid14583691">{{cite journal| author=Kroenke K, Spitzer RL, Williams JB| title=The Patient Health Questionnaire-2: validity of a two-item depression screener. | journal=Med Care | year= 2003 | volume= 41 | issue= 11 | pages= 1284-92 | pmid=14583691 | doi=10.1097/01.MLR.0000093487.78664.3C | pmc= | url= }} </ref>.
* Sensitivity 83%
* Specificity 92%
 
 
{| class="wikitable"
|+ PHQ2
! Question !! Not at all!! Several days!! More than half the days!! Nearly every day
|-
| Little interest or pleasure in doing things || 0 || 1 || 2 || 3
|-
| Feeling down, depressed, or hopeless || 0 || 1 || 2 || 3
|}
 
"During the past month, have you often been bothered by:"
#"little interest or pleasure in doing things?"
#"feeling down, depressed, or hopeless?"
 
If the PHQ2 is positive, then the SALSA questionnaire may be used to increase [[sensitivity and specificity|specificity]]<ref name="pmid9855385">{{cite journal |author=Brody DS, Hahn SR, Spitzer RL, ''et al'' |title=Identifying patients with depression in the primary care setting: a more efficient method |journal=Arch. Intern. Med. |volume=158 |issue=22 |pages=2469–75 |year=1998 |pmid=9855385 |doi=}}</ref>. A positive test is one of the above answers positive and two of the answers below positive:
 
#<b>S</b>leep disturbance nearly every day for the last 2 weeks?
#Have you experienced little interest or pleasure in doing things nearly every day for the last 2 weeks (<b>A</b>nhedonia)?
#Have you experienced <b>L</b>ow <b>S</b>elf esteem nearly every day for the last 2 weeks?
#Have you experienced decreased <b>A</b>ppetite nearly every day for the last 2 weeks?"
 
===Patient Health Questionnaire 9===
If the patient is diagnosed with depression, the Patient Health Questionnaire 9 (PHQ9) may measure severity<ref name="pmid11556941">{{cite journal |author=Kroenke K, Spitzer RL, Williams JB |title=The PHQ-9: validity of a brief depression severity measure |journal=J Gen Intern Med |volume=16 |issue=9 |pages=606–13 |year=2001 |pmid=11556941 |doi=}} {{PubMedCentral|1924626}}</ref> and follow response to treatment.<ref name="pmid15550799">{{cite journal |author=Löwe B, Unützer J, Callahan CM, Perkins AJ, Kroenke K |title=Monitoring depression treatment outcomes with the patient health questionnaire-9 |journal=Med Care |volume=42 |issue=12 |pages=1194–201 |year=2004 |pmid=15550799 |doi=}}</ref> A  clinically relevant change is a PHQ-9 change of 5 or greater.<ref name="pmid15550799"/> The PHQ-9 is available online in English and Spanish from the MacArthur Initiative.<ref name="PHQ9">{{cite web |url=http://www.depression-primarycare.org/clinicians/toolkits/materials/forms/phq9/ |title= Patient Health Questionnaire, Item 9 |accessdate=2008-01-14}}</ref> A [[meta-analysis]] of accuracy is available.<ref name="pmid22184363">{{cite journal| author=Manea L, Gilbody S, McMillan D| title=Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis. | journal=CMAJ | year= 2012 | volume= 184 | issue= 3 | pages= E191-6 | pmid=22184363 | doi=10.1503/cmaj.110829 | pmc=PMC3281183 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22184363  }} </ref>
 
==Treatment==
[[Clinical practice guideline]]s are available from the American Psychiatric Association.<ref>[http://www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx American Psychiatric Association] 2010. </ref>
===Complementary alternative medicine===
====L-Methylfolate====
L-Methylfolate may not be helpful.<ref>Anonymous (2010). [[http://www.medicalletter.org/restricted/articles/w1336d.html L-Methylfolate (Deplin) for Depression and Schizophrenia]]. The Medical Letter</ref>
 
====S-adenosyl methionine (SAMe)====
S-Adenosylmethionine may be beneficial according to a [[randomized controlled trial]].<ref name="pmid20595412">{{cite journal| author=Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M| title=S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. | journal=Am J Psychiatry | year= 2010 | volume= 167 | issue= 8 | pages= 942-8 | pmid=20595412 | doi=10.1176/appi.ajp.2009.09081198 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20595412  }} </ref>
 
====St. John's wort====
[[Hypericum perforatum]] (St. John's wort) has conflicting evidence regarding its effectiveness.<ref name="pmid16796730">{{cite journal |author=Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M |title=Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298] |journal=BMC Med |volume=4 |issue= |pages=14 |year=2006 |pmid=16796730 |doi=10.1186/1741-7015-4-14}}</ref><ref name="pmid11939866">{{cite journal |author= |title=Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial |journal=JAMA |volume=287 |issue=14 |pages=1807–14 |year=2002 |pmid=11939866 |doi=|url=http://jama.ama-assn.org/cgi/content/full/287/14/1807}}</ref> For unclear reasons, the positive studies all were performed in Germany.<ref name="pmid12132965">{{cite journal |author=Linde K, Melchart D, Mulrow CD, Berner M |title=St John's wort and depression |journal=JAMA |volume=288 |issue=4 |pages=447–8; author reply 448–9 |year=2002 |pmid=12132965 |doi=|url=http://jama.ama-assn.org/cgi/content/full/288/4/446}}</ref><ref name="pmid16796730">{{cite journal |author=Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M |title=Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298] |journal=BMC Med |volume=4 |issue= |pages=14 |year=2006 |pmid=16796730 |doi=10.1186/1741-7015-4-14}}</ref> [[Publication bias]] has been especially noted in German studies of complementary alternative medicine.
 
A [[meta-analysis]] by the [[Cochrane Collaboration]] concluded:<ref name="pmid18843608">{{cite journal |author=Linde K, Berner MM, Kriston L |title=St John's wort for major depression |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD000448 |year=2008 |pmid=18843608 |doi=10.1002/14651858.CD000448.pub3 |url=http://dx.doi.org/10.1002/14651858.CD000448.pub3 |issn=}}</ref>
:"the available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation"
 
===Nonmedical therapy===
Music therapy may help.<ref name="pmid18254052">{{cite journal |author=Maratos A, Gold C, Wang X, Crawford M |title=Music therapy for depression |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004517 |year=2008 |pmid=18254052 |doi=10.1002/14651858.CD004517.pub2}}</ref>
 
[[Cognitive behavioral therapy]] can reduce symptoms of [[major depression]] in [[geriatrics|geriatric]] patients although only a minority of patients have a reduction in symptoms of 50%.<ref name="pmid19996038">{{cite journal| author=Serfaty MA, Haworth D, Blanchard M, Buszewicz M, Murad S, King M| title=Clinical effectiveness of individual cognitive behavioral therapy for depressed older people in primary care: a randomized controlled trial. | journal=Arch Gen Psychiatry | year= 2009 | volume= 66 | issue= 12 | pages= 1332-40 | pmid=19996038
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19996038 | doi=10.1001/archgenpsychiatry.2009.165 }}</ref>
 
[[Exercise]] may help [[geriatrics|geriatric]] patients.<ref name="pmid19675114">{{cite journal| author=Blake H, Mo P, Malik S, Thomas S| title=How effective are physical activity interventions for alleviating depressive symptoms in older people? A systematic review. | journal=Clin Rehabil | year= 2009 | volume= 23 | issue= 10 | pages= 873-87 | pmid=19675114
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19675114 | doi=10.1177/0269215509337449 }}</ref>
 
[[Hypericum]] extracts (St John's wort) may help according to the [[Cochrane Collaboration]]. <ref name="pmid18843608"/>
 
Direct contact person-to-person prayer may be useful according to [[randomized controlled trial]]s. <ref name="pmid20391859">{{cite journal| author=Boelens PA, Reeves RR, Replogle WH, Koenig HG| title=A randomized trial of the effect of prayer on depression and anxiety. | journal=Int J Psychiatry Med | year= 2009 | volume= 39 | issue= 4 | pages= 377-92 | pmid=20391859 | doi= | pmc= | url= }} </ref><ref name="pmid19105001">{{cite journal| author=Bay PS, Beckman D, Trippi J, Gunderman R, Terry C| title=The effect of pastoral care services on anxiety, depression, hope, religious coping, and religious problem solving styles: a randomized controlled study. | journal=J Relig Health | year= 2008 | volume= 47 | issue= 1 | pages= 57-69 | pmid=19105001 | doi=10.1007/s10943-007-9131-4 | pmc= | url= }} </ref>
 
===Medications===
{{main|Second-generation antidepressant|Antidepressant}}
 
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>
 
Regarding the use of second-generation antidepressants, [[clinical practice guideline]]s by the [[American College of Physicians]]<ref name="pmid19017591">{{cite journal| author=Qaseem A, Snow V, Denberg TD, Forciea MA, Owens DK, Clinical Efficacy Assessment Subcommittee of American College of Physicians| title=Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. | journal=Ann Intern Med | year= 2008 | volume= 149 | issue= 10 | pages= 725-33 | pmid=19017591 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19017591  }} </ref> with accompanying [[systematic review]]<ref name="pmid19017592">{{cite journal| author=Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE et al.| title=Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. | journal=Ann Intern Med | year= 2008 | volume= 149 | issue= 10 | pages= 734-50 | pmid=19017592 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19017592  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19483031 Review in: Evid Based Med. 2009 Jun;14(3):82] </ref> and updated [[systematic review]]<ref name="pmid22147715">{{cite journal| author=Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux L, Van Noord M et al.| title=Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis. | journal=Ann Intern Med | year= 2011 | volume= 155 | issue= 11 | pages= 772-85 | pmid=22147715 | doi=10.1059/0003-4819-155-11-201112060-00009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22147715  }} </ref> recommend:
* "when clinicians choose pharmacologic therapy to treat patients with acute major depression, they select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences"
* "second-generation antidepressants did not significantly differ in efficacy, effectiveness, or quality of life. [[Mirtazapine]] had a significantly faster onset of action"
* "when treating symptom clusters in patients with accompanying depression, second-generation antidepressants did not differ in efficacy in treating accompanying [[anxiety]], [[pain]], and [[Somatoform disorder|somatization]]. Limited evidence suggests that some agents may be more effective in treating [[insomnia]]"
* "most of the second-generation antidepressants had similar adverse effects...paroxetine was associated with an increased risk for sexual dysfunction."
 
Starting treatment with combination therapy may increase effectiveness.<ref name="pmid20008946">{{cite journal| author=Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R| title=Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. | journal=Am J Psychiatry | year= 2010 | volume= 167 | issue= 3 | pages= 281-8 | pmid=20008946
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20008946 | doi=10.1176/appi.ajp.2009.09020186 }} </ref>
 
Low [[folic acid|folate]] levels may be associated with treatment resistance<ref name="pmid15323594">{{cite journal| author=Papakostas GI, Petersen T, Mischoulon D, Ryan JL, Nierenberg AA, Bottiglieri T et al.| title=Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. | journal=J Clin Psychiatry | year= 2004 | volume= 65 | issue= 8 | pages= 1090-5 | pmid=15323594
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=15323594 }} </ref> and increased risk of relapse after treatment of depression<ref name="pmid15323595">{{cite journal| author=Papakostas GI,  Petersen T, Mischoulon D, Green CH, Nierenberg AA, Bottiglieri T et al.|  title=Serum folate, vitamin B12, and homocysteine in major depressive  disorder, Part 2: predictors of relapse during the continuation phase of  pharmacotherapy. | journal=J Clin Psychiatry | year= 2004 | volume= 65 |  issue= 8 | pages= 1096-8 | pmid=15323595
|  url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=15323595  }} </ref>. Folic acid supplementation may<ref name="pmid1974941">{{cite journal| author=Godfrey PS, Toone BK, Carney MW, Flynn TG, Bottiglieri T, Laundy M et al.| title=Enhancement of recovery from psychiatric illness by methylfolate. | journal=Lancet | year= 1990 | volume= 336 | issue= 8712 | pages= 392-5 | pmid=1974941
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=1974941 }}</ref> or may not help. A systematic review of trials though 2004 concluded "limited available evidence suggests folate may have a  potential role as a supplement to other treatment for depression.  It is currently unclear if this is the case both for people with normal  folate  levels, and for those with folate deficiency.."<ref name="pmid15260915">{{cite journal| author=Taylor MJ, Carney SM, Goodwin GM, Geddes JR| title=Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. | journal=J Psychopharmacol | year= 2004 | volume= 18 | issue= 2 | pages= 251-6 | pmid=15260915
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=15260915 | doi=10.1177/0269881104042630 }} </ref> New trials are ongoing.<ref name="pmid18005429">{{cite journal| author=Roberts SH, Bedson E, Hughes D, Lloyd K, Menkes DB, Moat S et al.| title=Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial. | journal=BMC Psychiatry | year= 2007 | volume= 7 | issue=  | pages= 65 | pmid=18005429
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=18005429 | doi=10.1186/1471-244X-7-65 | pmc=PMC2238748 }} </ref> [[Folic acid]] may not<ref name="pmid18557664">{{cite journal| author=Ford AH, Flicker L, Thomas J, Norman P, Jamrozik K, Almeida OP| title=Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. | journal=J Clin Psychiatry | year= 2008 | volume= 69 | issue= 8 | pages= 1203-9 | pmid=18557664
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=18557664 }} </ref> prevent depression.
 
====Predictors of a response to treatment====
=====Severity of depression=====
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="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.
 
{| class="wikitable" align="right"
|+ The effectiveness of antidepressants depending on severity of depression<ref name="pmid20051569"/>!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>
|-
| Mild to moderate||align="center"|< 19||align="center"|16||align="center"|No
|-
| Severe||align="center"|19 - 22||align="center"|11||align="center"|No
|-
| Very severe||align="center"|> 22||align="center"| &nbsp;4||align="center"|Yes
|}
 
 


(2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)


(3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.  
=====Genetic variations=====
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>


(4) insomnia or hypersomnia nearly every day
====Treatment failure====


(5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
{| 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%
|}


(6) fatigue or loss of energy nearly every day
When treated with monotherapy for depression, approximately 30% of patients have remission of symptoms while 50% have a response to medications.<ref name="pmid16390886"/> 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"/>, while switching medications can achieve remission in about 25% of patients<ref name="pmid16554525"/>. 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"/>


(7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
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>


(8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
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>


(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
[[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>


B. The symptoms do not meet criteria for a Mixed Episode.
==Screening==
Screening asymptomatic patients appears to have no impact on the care of patients with depression.<ref name="pmid18390942">{{cite journal |author=Gilbody S, Sheldon T, House A |title=Screening and case-finding instruments for depression: a meta-analysis |journal=CMAJ |volume=178 |issue=8 |pages=997-1003 |year=2008 |pmid=18390942 |doi=10.1503/cmaj.070281 |url=http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=18390942}}</ref>


C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
==References==
<small>
<references>


D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
</references>
</small>


E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
[[Category: Psychology Catalogs]]
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Major depressive disorder, along with anxiety, is one of the most frequently occurring general psychiatric disorders. It is characterized by symptoms of depression, generalized melancholy, retreat from social contact, disrupted sleep patterns, akathisia, or a feeling of restlessness and increased movement, and anhedonia, or a diminished ability to experience pleasure.

Cause/etiology

The development of depression is influenced by a organic, environmental, and genetic factors, with genetics contributing about one third[1] or more[2]. The organic factors contributing to depression include a general systemic dysregulation that involves a disruption of neurotransmitters. This condition can be acute, or on-going, and is generally corrected, in both cases, through medication. Environmental factors can contribute to depression by either triggering a recurrent episode of chronic depression, or advancing a situational depression.

Epidemiology

Community studies generally show a varying prevalence of depression, with estimates of occurrence between 5 and 7.5%. The one-year prevalence of major depressive disorder in the United States of America varies from 3% in the Epidemiological Catchment Area Study [3] to 10% in the National Co-morbity Study. [4]

Monoamine-Deficiency Hypothesis

Depression may be due to "deficiency in serotonin or norepinephrine neurotransmission in the brain."[5]

Diagnosis

The core symptoms of depression are depressed mood and a lack of interest or pleasure from daily activities (anhedonia). Several additional features may be present, like lack of concentration, inappropriate guilt feelings, suicidal thoughts, psychomotor retardation or agitation and loss of libido. A diurnal variation, e.g. the symptoms are worse in the morning, may be present.

Primary care physicians and other non-psychiatrists physicians have difficulty diagnosing depression. Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.[6][7].

DSM-IV diagnostic criteria

Note: The American Psychiatric Association, which publishes the Diagnostic and Statistical Manual of Mental Disorders, forbids the unauthorized reproduction of their diagnostic criteria. A narrative of the DSM-IV-TR criteria follows. The DSM-IV has created nine diagnostic criteria based on symptoms of depression. At least five of these should be present for two weeks in the absence of other explanations for the symptoms.

Alternative diagnostic strategies

Patient Health Questionnaire 2

The Patient Health Questionnaire (PHQ2) is a shorter questionnaire that may be as sensitive as the DSM-IV.[8] It has also been validated in elderly patients.[9] The accuracy of the PHQ2 with a score of 3 or more is:[10].

  • Sensitivity 83%
  • Specificity 92%


PHQ2
Question Not at all Several days More than half the days Nearly every day
Little interest or pleasure in doing things 0 1 2 3
Feeling down, depressed, or hopeless 0 1 2 3

"During the past month, have you often been bothered by:"

  1. "little interest or pleasure in doing things?"
  2. "feeling down, depressed, or hopeless?"

If the PHQ2 is positive, then the SALSA questionnaire may be used to increase specificity[11]. A positive test is one of the above answers positive and two of the answers below positive:

  1. Sleep disturbance nearly every day for the last 2 weeks?
  2. Have you experienced little interest or pleasure in doing things nearly every day for the last 2 weeks (Anhedonia)?
  3. Have you experienced Low Self esteem nearly every day for the last 2 weeks?
  4. Have you experienced decreased Appetite nearly every day for the last 2 weeks?"

Patient Health Questionnaire 9

If the patient is diagnosed with depression, the Patient Health Questionnaire 9 (PHQ9) may measure severity[12] and follow response to treatment.[13] A clinically relevant change is a PHQ-9 change of 5 or greater.[13] The PHQ-9 is available online in English and Spanish from the MacArthur Initiative.[14] A meta-analysis of accuracy is available.[15]

Treatment

Clinical practice guidelines are available from the American Psychiatric Association.[16]

Complementary alternative medicine

L-Methylfolate

L-Methylfolate may not be helpful.[17]

S-adenosyl methionine (SAMe)

S-Adenosylmethionine may be beneficial according to a randomized controlled trial.[18]

St. John's wort

Hypericum perforatum (St. John's wort) has conflicting evidence regarding its effectiveness.[19][20] For unclear reasons, the positive studies all were performed in Germany.[21][19] Publication bias has been especially noted in German studies of complementary alternative medicine.

A meta-analysis by the Cochrane Collaboration concluded:[22]

"the available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation"

Nonmedical therapy

Music therapy may help.[23]

Cognitive behavioral therapy can reduce symptoms of major depression in geriatric patients although only a minority of patients have a reduction in symptoms of 50%.[24]

Exercise may help geriatric patients.[25]

Hypericum extracts (St John's wort) may help according to the Cochrane Collaboration. [22]

Direct contact person-to-person prayer may be useful according to randomized controlled trials. [26][27]

Medications

For more information, see: Second-generation antidepressant and Antidepressant.


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.[28]

Regarding the use of second-generation antidepressants, clinical practice guidelines by the American College of Physicians[29] with accompanying systematic review[30] and updated systematic review[31] recommend:

  • "when clinicians choose pharmacologic therapy to treat patients with acute major depression, they select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences"
  • "second-generation antidepressants did not significantly differ in efficacy, effectiveness, or quality of life. Mirtazapine had a significantly faster onset of action"
  • "when treating symptom clusters in patients with accompanying depression, second-generation antidepressants did not differ in efficacy in treating accompanying anxiety, pain, and somatization. Limited evidence suggests that some agents may be more effective in treating insomnia"
  • "most of the second-generation antidepressants had similar adverse effects...paroxetine was associated with an increased risk for sexual dysfunction."

Starting treatment with combination therapy may increase effectiveness.[32]

Low folate levels may be associated with treatment resistance[33] and increased risk of relapse after treatment of depression[34]. Folic acid supplementation may[35] or may not help. A systematic review of trials though 2004 concluded "limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.."[36] New trials are ongoing.[37] Folic acid may not[38] prevent depression.

Predictors of a response to treatment

Severity of depression

The effectiveness is antidepressants may[39] or may not[40] 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[39]!American Psychiatric Association
classification of severity[41]!! Hamilton Depression Rating Scale
(HDRS)!!Number needed to treat[39]!!Clinical significance
(NICE)[42]
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.[43]

Treatment failure

Treatment after SSRI (citalopram) failure
(STAR*D Studies)
Intervention Outcome
Medication Mean final dose Remision % Quit 2˚ ADRs (%)
Switch meds (NEJM 2006; PMID: 16554525[44])
Bupropion SR 283 mg 21% 27%
Sertraline (SSR) 136 mg 18% 21%
Venlafaxine ER (SNRI) 194 mg 25% 21%
Augment meds (NEJM 2006; PMID: 16554526[45])
Bupropion SR 268 mg 30% 13%
Buspirone 41 mg 30% 21%

When treated with monotherapy for depression, approximately 30% of patients have remission of symptoms while 50% have a response to medications.[28] 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)[45], while switching medications can achieve remission in about 25% of patients[44]. 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."[44]

The STAR*D trial has reported the frequency of re-emrgence of suicidality for different second levels of treatment.[46]

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.[47]

Aripiprazole, originally introduced as an atypical antipsychotic agent, is approved as an adjunct to other antidepressants.[48]

Screening

Screening asymptomatic patients appears to have no impact on the care of patients with depression.[49]

References

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  2. Major Depressive Disorder. (Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 608516. World Wide Web URL: http://omim.org/.)
  3. Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK (1993). "The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services". Arch. Gen. Psychiatry 50 (2): 85–94. PMID 8427558[e]
  4. Kessler RC, McGonagle KA, Zhao S, et al (1994). "Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey". Arch. Gen. Psychiatry 51 (1): 8–19. PMID 8279933[e]
  5. Belmaker RH, Agam G (2008). "Major depressive disorder". N. Engl. J. Med. 358 (1): 55–68. DOI:10.1056/NEJMra073096. PMID 18172175. Research Blogging.
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