Major depressive disorder: Difference between revisions

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imported>Robert Badgett
imported>Robert Badgett
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* "most of the second-generation antidepressants had similar adverse effects...paroxetine was associated with an increased risk for sexual dysfunction."
* "most of the second-generation antidepressants had similar adverse effects...paroxetine was associated with an increased risk for sexual dysfunction."


The effectiveness is antidepressants depends on the severity of a patient's depression. This relationship may be due to thedeclining effect of placebo among more severely depressed patients.<ref name="pmid20042812">{{cite journal| author=Lo B| title=Commentary: Conflict of interest policies: an opportunity for the medical profession to take the lead. | journal=Acad Med | year= 2010 | volume= 85 | issue= 1 | pages= 9-11 | pmid=20042812  
The effectiveness is antidepressants depends on the severity of a patient's depression. This relationship may be due to thedeclining effect of placebo among more severely depressed patients.<ref name="pmid20042812">{{cite journal| author=Lo B| title=Commentary: Conflict of interest policies: an opportunity for the medical profession to take the lead. | journal=Acad Med | year= 2010 | volume= 85 | issue= 1 | pages= 9-11 | pmid=20042812
| 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=20042812 | doi=10.1097/ACM.0b013e3181c46e96 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
| 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=20042812 | doi=10.1097/ACM.0b013e3181c46e96 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>


{| class="wikitable" align="right"
{| class="wikitable" align="right"
|+ The effectiveness of antidepressants depending on severity of depression<ref name="pmid20042812">{{cite journal| author=Lo B| title=Commentary: Conflict of interest policies: an opportunity for the medical profession to take the lead. | journal=Acad Med | year= 2010 | volume= 85 | issue= 1 | pages= 9-11 | pmid=20042812  
|+ The effectiveness of antidepressants depending on severity of depression<ref name="pmid20042812">{{cite journal| author=Lo B| title=Commentary: Conflict of interest policies: an opportunity for the medical profession to take the lead. | journal=Acad Med | year= 2010 | volume= 85 | issue= 1 | pages= 9-11 | pmid=20042812
| 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=20042812 | doi=10.1097/ACM.0b013e3181c46e96 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
| 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=20042812 | doi=10.1097/ACM.0b013e3181c46e96 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
!American Psychiatric Association 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] (HDRS)!![[Number needed to treat]]!!Clinical significance (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; 2004.</ref>
!American Psychiatric Association 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] (HDRS)!![[Number needed to treat]]!!Clinical significance (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; 2004.</ref>
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| Very severe|| > 22|| 4|| Yes
| Very severe|| > 22|| 4|| Yes
|}
|}
{| class="wikitable"
|+ [[Randomized controlled trial]]s
! rowspan="2"|Trial!!rowspan="2"| Patients!!rowspan="2"| Intervention!!rowspan="2"|Comparison !!rowspan="2"|Outcome!!colspan="2"|Results
|-<br/>
! Intervention!!Control
|-
| Ford et al.<ref name="pmid18557664"/><br/>2008|| 299 men aged 75 years and older ''free'' of clinically significant depression|| 400 microg B(12) + 2 mg folic acid + 25 mg
B(6) per day||Placebo||[[Beck Depression Inventory]] score < 18 at 2 years||84.3% || 79.1%
|-
| cell || cell|| cell||Placebo|| cell|| cell|| cell
|-
| cell || cell|| cell||Placebo|| cell|| cell|| cell
|-
| cell || cell|| cell||Placebo|| cell|| cell|| cell
|-
| cell || cell|| cell||Placebo|| cell|| cell|| cell
|-
| cell || cell|| cell||Placebo|| cell|| cell|| cell
|}
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.


====Treatment failure====
====Treatment failure====

Revision as of 08:05, 8 April 2010

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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 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 PHQ2 is positive if either of the following are positive:

"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[10]. 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[11] and follow response to treatment.[12] A clinically relevant change is a PHQ-9 change of 5 or greater.[12] The PHQ-9 is available online in English and Spanish from the MacArthur Initiative.[13]

Treatment

Complementary alternative medicine

St. John's wort

Hypericum perforatum (St. John's wort) has conflicting evidence regarding its effectiveness.[14][15] For unclear reasons, the positive studies all were performed in Germany.[16][14] Publication bias has been especially noted in German studies of complementary alternative medicine.

A meta-analysis by the Cochrane Collaboration concluded:[17]

"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.[18]

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%.[19]

Exercise may help geriatric patients.[20]

Medications

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

Regarding the use of second-generation antidepressants, clinical practice guidelines by the American College of Physicians recommend:[21] [22]

  • "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."

The effectiveness is antidepressants depends on the severity of a patient's depression. This relationship may be due to thedeclining effect of placebo among more severely depressed patients.[23]

The effectiveness of antidepressants depending on severity of depression[23]
American Psychiatric Association classification of severity[24] Hamilton Depression Rating Scale (HDRS) Number needed to treat Clinical significance (NICE)[25]
Mild to moderate < 19 16 No
Severe 19 - 22 11 No
Very severe > 22 4 Yes
Randomized controlled trials
Trial Patients Intervention Comparison Outcome Results
Intervention Control
Ford et al.[26]
2008		 299 men aged 75 years and older free of clinically significant depression 400 microg B(12) + 2 mg folic acid + 25 mg

B(6) per day||Placebo||Beck Depression Inventory score < 18 at 2 years||84.3% || 79.1%

cell cell cell Placebo cell cell cell
cell cell cell Placebo cell cell cell
cell cell cell Placebo cell cell cell
cell cell cell Placebo cell cell cell
cell cell cell Placebo cell cell cell

Low folate levels may be associated with treatment resistance[27] and increased risk of relapse after treatment of depression[28]. Folic acid supplementation may[29] 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.."[30] New trials are ongoing.[31] Folic acid may not[26] prevent depression.

Treatment failure

Approximately 30% of patients have remission of depression with medications.[32] For patients with inadequate response, either adding sustained-release bupropion (initially 200 mg per day then increase by 100 mg up to total of 400 mg per day) 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)[33], while switching medications can achieve remission in about 25% of patients[34].

Screening

Screening asymptomatic patients appears to have no impact on the care of patients with depression.[35]

References

  1. ↑ Sullivan PF, Neale MC, Kendler KS (2000). "Genetic epidemiology of major depression: review and meta-analysis". Am J Psychiatry 157 (10): 1552–62. PMID 11007705. [e]
  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.
  6. ↑ Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A (2008). "Recognition of depression by non-psychiatric physicians--a systematic literature review and meta-analysis". J Gen Intern Med 23 (1): 25–36. DOI:10.1007/s11606-007-0428-5. PMID 17968628. Research Blogging.
  7. ↑ 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
  8. ↑ Spitzer RL, Kroenke K, Williams JB (1999). "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". JAMA 282 (18): 1737–44. PMID 10568646. [e]
  9. ↑ Li C, Friedman B, Conwell Y, Fiscella K (2007). "Validity of the Patient Health Questionnaire 2 (PHQ-2) in identifying major depression in older people". J Am Geriatr Soc 55 (4): 596–602. DOI:10.1111/j.1532-5415.2007.01103.x. PMID 17397440. Research Blogging.
  10. ↑ Brody DS, Hahn SR, Spitzer RL, et al (1998). "Identifying patients with depression in the primary care setting: a more efficient method". Arch. Intern. Med. 158 (22): 2469–75. PMID 9855385. [e]
  11. ↑ Kroenke K, Spitzer RL, Williams JB (2001). "The PHQ-9: validity of a brief depression severity measure". J Gen Intern Med 16 (9): 606–13. PMID 11556941. [e] Full text at PubMed Central
  12. ↑ 12.0 12.1 Löwe B, Unützer J, Callahan CM, Perkins AJ, Kroenke K (2004). "Monitoring depression treatment outcomes with the patient health questionnaire-9". Med Care 42 (12): 1194–201. PMID 15550799. [e]
  13. ↑ Patient Health Questionnaire, Item 9. Retrieved on 2008-01-14.
  14. ↑ 14.0 14.1 Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M (2006). "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]". BMC Med 4: 14. DOI:10.1186/1741-7015-4-14. PMID 16796730. Research Blogging.
  15. ↑ (2002) "Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial". JAMA 287 (14): 1807–14. PMID 11939866. [e]
  16. ↑ Linde K, Melchart D, Mulrow CD, Berner M (2002). "St John's wort and depression". JAMA 288 (4): 447–8; author reply 448–9. PMID 12132965. [e]
  17. ↑ Linde K, Berner MM, Kriston L (2008). "St John's wort for major depression". Cochrane Database Syst Rev (4): CD000448. DOI:10.1002/14651858.CD000448.pub3. PMID 18843608. Research Blogging.
  18. ↑ Maratos A, Gold C, Wang X, Crawford M (2008). "Music therapy for depression". Cochrane Database Syst Rev (1): CD004517. DOI:10.1002/14651858.CD004517.pub2. PMID 18254052. Research Blogging.
  19. ↑ Serfaty MA, Haworth D, Blanchard M, Buszewicz M, Murad S, King M (2009). "Clinical effectiveness of individual cognitive behavioral therapy for depressed older people in primary care: a randomized controlled trial.". Arch Gen Psychiatry 66 (12): 1332-40. DOI:10.1001/archgenpsychiatry.2009.165. PMID 19996038. Research Blogging.
  20. ↑ Blake H, Mo P, Malik S, Thomas S (2009). "How effective are physical activity interventions for alleviating depressive symptoms in older people? A systematic review.". Clin Rehabil 23 (10): 873-87. DOI:10.1177/0269215509337449. PMID 19675114. Research Blogging.
  21. ↑ Gartlehner, Gerald; Bradley N. Gaynes, Richard A. Hansen, Patricia Thieda, Angela DeVeaugh-Geiss, Erin E. Krebs, Charity G. Moore, Laura Morgan, Kathleen N. Lohr (2008-11-18). "Comparative Benefits and Harms of Second-Generation Antidepressants: Background Paper for the American College of Physicians". Ann Intern Med 149 (10): 734-750. Retrieved on 2008-11-18.
  22. ↑ Qaseem, Amir; Vincenza Snow, Thomas D. Denberg, Mary Ann Forciea, Douglas K. Owens, for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (2008-11-18). "Using Second-Generation Antidepressants to Treat Depressive Disorders: A Clinical Practice Guideline from the American College of Physicians". Ann Intern Med 149 (10): 725-733. Retrieved on 2008-11-18.
  23. ↑ 23.0 23.1 Lo B (2010). "Commentary: Conflict of interest policies: an opportunity for the medical profession to take the lead.". Acad Med 85 (1): 9-11. DOI:10.1097/ACM.0b013e3181c46e96. PMID 20042812. Research Blogging.
  24. ↑ First, Michael B. (2007). Handbook of Psychiatric Measures, Second Edition. American Psychiatric Publishing, Inc. ISBN 1-58562-218-4. 
  25. ↑ National Institute for Clinical Excellence. Depression: Management of Depression in Primary and Secondary Care. London, England: National Institute for Clinical Excellence; 2004.
  26. ↑ 26.0 26.1 Ford AH, Flicker L, Thomas J, Norman P, Jamrozik K, Almeida OP (2008). "Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial.". J Clin Psychiatry 69 (8): 1203-9. PMID 18557664.
  27. ↑ Papakostas GI, Petersen T, Mischoulon D, Ryan JL, Nierenberg AA, Bottiglieri T et al. (2004). "Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression.". J Clin Psychiatry 65 (8): 1090-5. PMID 15323594.
  28. ↑ Papakostas GI, Petersen T, Mischoulon D, Green CH, Nierenberg AA, Bottiglieri T et al. (2004). "Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy.". J Clin Psychiatry 65 (8): 1096-8. PMID 15323595.
  29. ↑ Godfrey PS, Toone BK, Carney MW, Flynn TG, Bottiglieri T, Laundy M et al. (1990). "Enhancement of recovery from psychiatric illness by methylfolate.". Lancet 336 (8712): 392-5. PMID 1974941.
  30. ↑ Taylor MJ, Carney SM, Goodwin GM, Geddes JR (2004). "Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials.". J Psychopharmacol 18 (2): 251-6. DOI:10.1177/0269881104042630. PMID 15260915. Research Blogging.
  31. ↑ Roberts SH, Bedson E, Hughes D, Lloyd K, Menkes DB, Moat S et al. (2007). "Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.". BMC Psychiatry 7: 65. DOI:10.1186/1471-244X-7-65. PMID 18005429. PMC PMC2238748. Research Blogging.
  32. ↑ Trivedi MH, Rush AJ, Wisniewski SR, et al (2006). "Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice". The American journal of psychiatry 163 (1): 28–40. DOI:10.1176/appi.ajp.163.1.28. PMID 16390886. Research Blogging.
  33. ↑ Trivedi MH, Fava M, Wisniewski SR, et al (2006). "Medication augmentation after the failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1243–52. DOI:10.1056/NEJMoa052964. PMID 16554526. Research Blogging.
  34. ↑ Rush AJ, Trivedi MH, Wisniewski SR, et al (2006). "Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1231–42. DOI:10.1056/NEJMoa052963. PMID 16554525. Research Blogging.
  35. ↑ Gilbody S, Sheldon T, House A (2008). "Screening and case-finding instruments for depression: a meta-analysis". CMAJ 178 (8): 997-1003. DOI:10.1503/cmaj.070281. PMID 18390942. Research Blogging.
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