Major depressive disorder: Difference between revisions

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{| class="wikitable" align="right"
{| class="wikitable" align="right"
|+ Treatment after SSRI ([[citalopram]]) failure ([www.nimh.nih.gov/trials/practical/stard/ STAR*D] Studies)
|+ Treatment after SSRI ([[citalopram]]) failure<br/>([http://www.nimh.nih.gov/trials/practical/stard/ STAR*D] Studies)
! &nbsp;!! Remision (%)!! Quit 2˚ [[Drug toxicity|ADR]]s (%)
! &nbsp;!! Remision (%)!! Mean final dose!!Quit 2˚ [[Drug toxicity|ADR]]s (%)
|-
|-
| colspan="3"| 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>)
| 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|| 21%|| &nbsp;
| [[Bupropion]] SR||align="center"|21%||align="right"|283 mg||align="center"|27%
|-
|-
| Sertraline|| 18%|| &nbsp;
| [[Sertraline]] (SSR)||align="center"| 18%||align="right"|136 mg||align="center"|21%
|-
|-
| Venlafaxine ER|| 25%|| &nbsp;
| [[Venlafaxine]] ER (SNRI)||align="center"| 25%||align="right"|194 mg||align="center"|21%
|-
|-
| colspan="3"| 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>)
| 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||style="background-color:lightgreen;"| 30%|| 13%
| [[Bupropion]] SR||style="background-color:lightgreen;text-align:center"|30%||align="right"|268 mg||align="center"|13%
|-
|-
| Buspirone|| style="background-color:lightgreen;"|30% || style="background-color:coral"|21%
| [[Buspirone]]|| style="background-color:lightgreen;text-align:center"|30% ||align="right"|41 mg|| style="background-color:coral;text-align:center"|21%
|}
|}


Approximately 30% of patients have remission of depression with medications.<ref name="pmid16390886">{{cite journal |author=Trivedi MH, Rush AJ, Wisniewski SR, ''et al'' |title=Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice |journal=The American journal of psychiatry |volume=163 |issue=1 |pages=28–40 |year=2006 |pmid=16390886 |doi=10.1176/appi.ajp.163.1.28}}</ref> For patients with inadequate response, either adding sustained-release [[bupropion]] (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]])<ref name="pmid16554526">{{cite journal |author=Trivedi MH, Fava M, Wisniewski SR, ''et al'' |title=Medication augmentation after the failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1243–52 |year=2006 |pmid=16554526 |doi=10.1056/NEJMoa052964}}</ref>, while switching medications can achieve remission in about 25% of patients<ref name="pmid16554525">{{cite journal |author=Rush AJ, Trivedi MH, Wisniewski SR, ''et al'' |title=Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1231–42 |year=2006 |pmid=16554525 |doi=10.1056/NEJMoa052963}}</ref>.
Approximately 30% of patients have remission of depression with medications.<ref name="pmid16390886">{{cite journal |author=Trivedi MH, Rush AJ, Wisniewski SR, ''et al'' |title=Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice |journal=The American journal of psychiatry |volume=163 |issue=1 |pages=28–40 |year=2006 |pmid=16390886 |doi=10.1176/appi.ajp.163.1.28}}</ref> For patients with inadequate response, either adding sustained-release [[bupropion]] (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]])<ref name="pmid16554526">{{cite journal |author=Trivedi MH, Fava M, Wisniewski SR, ''et al'' |title=Medication augmentation after the failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1243–52 |year=2006 |pmid=16554526 |doi=10.1056/NEJMoa052964}}</ref>, while switching medications can achieve remission in about 25% of patients<ref name="pmid16554525">{{cite journal |author=Rush AJ, Trivedi MH, Wisniewski SR, ''et al'' |title=Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1231–42 |year=2006 |pmid=16554525 |doi=10.1056/NEJMoa052963}}</ref>.

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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 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]

Treatment

Clinical practice guidelines are available from the American Psychiatric Association.[15]

Complementary alternative medicine

L-Methylfolate

L-Methylfolate may not be helpful.[16]

St. John's wort

Hypericum perforatum (St. John's wort) has conflicting evidence regarding its effectiveness.[17][18] For unclear reasons, the positive studies all were performed in Germany.[19][17] Publication bias has been especially noted in German studies of complementary alternative medicine.

A meta-analysis by the Cochrane Collaboration concluded:[20]

"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.[21]

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%.[22]

Exercise may help geriatric patients.[23]

Hypericum extracts (St John's wort) may help according to the Cochrane Collaboration. [20]

Direct contact person-to-person prayer may be useful according to randomized controlled trials. [24][25]

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:[26] [27]

  • "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.[28]

The effectiveness of antidepressants depending on severity of depression[28]
American Psychiatric Association classification of severity[29] Hamilton Depression Rating Scale (HDRS) Number needed to treat Clinical significance (NICE)[30]
Mild to moderate < 19 16 No
Severe 19 - 22 11 No
Very severe > 22 4 Yes

Starting treatment with combination therapy may increase effectiveness.[31]

Low folate levels may be associated with treatment resistance[32] and increased risk of relapse after treatment of depression[33]. Folic acid supplementation may[34] 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.."[35] New trials are ongoing.[36] Folic acid may not[37] prevent depression.

Treatment failure

Treatment after SSRI (citalopram) failure
(STAR*D Studies)
  Remision (%) Mean final dose Quit 2˚ ADRs (%)
Switch meds (NEJM 2006; PMID: 16554525[38])
Bupropion SR 21% 283 mg 27%
Sertraline (SSR) 18% 136 mg 21%
Venlafaxine ER (SNRI) 25% 194 mg 21%
Augment meds (NEJM 2006; PMID: 16554526[39])
Bupropion SR 30% 268 mg 13%
Buspirone 30% 41 mg 21%

Approximately 30% of patients have remission of depression with medications.[40] 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)[39], while switching medications can achieve remission in about 25% of patients[38].

Aripiprazole, originally introduced as an atypical antipsychotic agent, is approved as an adjunct to other antidepressants.[41]

Screening

Screening asymptomatic patients appears to have no impact on the care of patients with depression.[42]

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. ↑ Kroenke K, Spitzer RL, Williams JB (2003). "The Patient Health Questionnaire-2: validity of a two-item depression screener.". Med Care 41 (11): 1284-92. DOI:10.1097/01.MLR.0000093487.78664.3C. PMID 14583691. Research Blogging.
  11. ↑ 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]
  12. ↑ 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
  13. ↑ 13.0 13.1 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]
  14. ↑ Patient Health Questionnaire, Item 9. Retrieved on 2008-01-14.
  15. ↑ American Psychiatric Association 2010.
  16. ↑ Anonymous (2010). [L-Methylfolate (Deplin) for Depression and Schizophrenia]. The Medical Letter
  17. ↑ 17.0 17.1 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.
  18. ↑ (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]
  19. ↑ 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]
  20. ↑ 20.0 20.1 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. Cite error: Invalid <ref> tag; name "pmid18843608" defined multiple times with different content
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ Boelens PA, Reeves RR, Replogle WH, Koenig HG (2009). "A randomized trial of the effect of prayer on depression and anxiety.". Int J Psychiatry Med 39 (4): 377-92. PMID 20391859. [e]
  25. ↑ Bay PS, Beckman D, Trippi J, Gunderman R, Terry C (2008). "The effect of pastoral care services on anxiety, depression, hope, religious coping, and religious problem solving styles: a randomized controlled study.". J Relig Health 47 (1): 57-69. DOI:10.1007/s10943-007-9131-4. PMID 19105001. Research Blogging.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 28.0 28.1 Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC et al. (2010). "Antidepressant drug effects and depression severity: a patient-level meta-analysis.". JAMA 303 (1): 47-53. DOI:10.1001/jama.2009.1943. PMID 20051569. Research Blogging.
  29. ↑ First, Michael B. (2007). Handbook of Psychiatric Measures, Second Edition. American Psychiatric Publishing, Inc. ISBN 1-58562-218-4. 
  30. ↑ National Institute for Clinical Excellence. Depression: Management of Depression in Primary and Secondary Care. London, England: National Institute for Clinical Excellence; 2004.
  31. ↑ Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R (2010). "Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study.". Am J Psychiatry 167 (3): 281-8. DOI:10.1176/appi.ajp.2009.09020186. PMID 20008946. Research Blogging.
  32. ↑ 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.
  33. ↑ 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.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ 38.0 38.1 Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME 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. Review in: Evid Based Ment Health. 2006 Nov;9(4):100 Cite error: Invalid <ref> tag; name "pmid16554525" defined multiple times with different content
  39. ↑ 39.0 39.1 Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D 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. Cite error: Invalid <ref> tag; name "pmid16554526" defined multiple times with different content
  40. ↑ 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.
  41. ↑ Marianna Mazza, Maria Rosaria Squillacioti1, Riccardo Daniele Pecora, Luigi Janiri1 & Pietro Bria (December 2008), "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", Expert Opinion on Pharmacotherapy 9 (18): 3145-3149, DOI:10.1517/14656560802504490
  42. ↑ 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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