Treatment for depression

Depression, for the purposes of this article, refers to the mental disorder known as major depressive disorder. This kind of depression is a recognised clinical condition and is becoming a common condition in developed countries, where up to 20% of the population is affected by this disorder at some stage of their lives. [cite web|url=http://www.beyondblue.org.au|title=Beyond Blue|accessdate=2007-04-30] Patients are usually assessed and managed as outpatients, and only admitted to an inpatient mental health unit if they are considered to pose a risk to themselves or others.

The three most commonly indicated treatments for depression are psychotherapy, medication, and electroconvulsive therapy. Psychotherapy is the treatment of choice in those under the age of 18, with medication offered only in conjunction with the former and generally not as a first line agent. Furthermore, pathology in the parents may need to be looked for and addressed in parallel.cite book |author=NICE |title=NICE Guidelines:depression in children and adolsecents |publisher=NICE |location=London |year=2005 |pages=p. 5 |isbn=1-84629-074-0 |url=http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English |accessdate=2008-08-16]

Psychotherapy

There are a number of different psychotherapies for depression, which may be provided to individuals or groups. Psychotherapy can be delivered by a variety of mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical social workers, counselors, and psychiatric nurses. With more complex and chronic forms of depression the most effective treatment is often considered to be a combination of medication and psychotherapy. [cite journal|last=Thase|first=ME|title=When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder?|journal= Psychiatric Quarterly |volume=70|issue=4|pages= 333–46|year=1999|pmid = 10587988 | doi = 10.1023/A:1022042316895] Psychotherapy is the treatment of choice in people under 18; medication is offered only in conjunction with the former and generally not as a first line agent. cite book |author=NICE |title=NICE guidelines: Depression in children and adolescents |publisher=NICE |location=London |year=2005 |pages=p. 5 |isbn=1-84629-074-0 |url=http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English |accessdate=2008-08-16]

The most studied form of psychotherapy for depression is "cognitive behavioral therapy" (CBT), thought to work by teaching clients to learn a set of cognitive and behavioral skills, which they can employ on their own. Earlier research suggested that cognitive-behavioral therapy was not as effective as antidepressant medication in the treatment of depression; however, more recent research suggests that it can perform as well as antidepressants in treating patients with moderate to severe depression.cite book |title=What Works for Whom? Second Edition: A Critical Review of Psychotherapy Research|last=Roth |first=Anthony |coauthors=Fonagy, Peter |year=2005|origyear=1996 |publisher=Guilford Press |location= |isbn=159385272X |pages=p. 78]

Two randomized, controlled trials of mindfulness-based cognitive therapy (MBCT), which includes elements of meditation, have been reviewed. MBCT was significantly more effective than "usual care" for the prevention of recurrent depression in patients who had had three or more depressive episodes. According to the review, the "usual care" did not include antidepressant treatment or any psychotherapy, and the improvement observed may have reflected the non-specific or placebo effects.cite journal |author=Coelho HF, Canter PH, Ernst E |title=Mindfulness-based cognitive therapy: evaluating current evidence and informing future research |journal=Journal of Consulting and Clinical Psychology |volume=75 |issue=6 |pages=1000–05 |year=2007 |month=December |pmid=18085916 |doi=10.1037/0022-006X.75.6.1000]

"Interpersonal psychotherapy" focuses on the social and interpersonal triggers that may cause depression. There is evidence that it is an effective treatment for depression. Here, the therapy takes a structured course with a set number of weekly sessions (often 12) as in the case of CBT, however the focus is on relationships with others. Therapy can be used to help a person develop or improve interpersonal skills in order to allow him or her to communicate more effectively and reduce stress.cite book |author=Weissman MM, Markowitz JC, Klerman GL |title=Comprehensive Guide to Interpersonal Psychotherapy |publisher=Basic Books |location=New York |year=2000 |pages= |isbn=0-465-09566-6 ]

"Psychoanalysis", a school of thought founded by Sigmund Freud that emphasizes the resolution of unconscious mental conflicts,cite book |author=Dworetzky J |title=Psychology |publisher=Brooks/Cole Pub. Co |location=Pacific Grove, CA, USA |year=1997 |pages=602 |isbn=0-314-20412-1] is used by its practitioners to treat clients presenting with major depression.cite journal |author=Doidge N, Simon B, Lancee WJ, "et al." |title=Psychoanalytic patients in the US, Canada, and Australia: II. A DSM-III-R validation study |journal=Journal of the American Psychoanalytic Association |volume=50 |issue=2 |pages=615–27 |year=2002 |pmid=12206545 |doi= |url=] A more widely practiced, eclectic technique, called "psychodynamic psychotherapy", is loosely based on psychoanalysis and has an additional social and interpersonal focus.cite book |author=Durand VM, Barlow D |title=Abnormal psychology: An integrative approach |publisher=Brooks/Cole Pub. Co |location=Pacific Grove, CA, USA |year=1999 |pages= |isbn=0-534-34742-8 ] In a meta-analysis of three controlled trials, psychodynamic psychotherapy was found to be as effective as medication for mild to moderate depression.cite journal |author=de Maat S, Dekker J, Schoevers R, "et al." |title=Short Psychodynamic Supportive Psychotherapy, antidepressants, and their combination in the treatment of major depression: A mega-analysis based on three Randomized Clinical Trials |journal=Depression and Anxiety |volume= 25|pages= 565|year=2007 |month=June |pmid=17557313 |doi=10.1002/da.20305]

Medication

To find the most effective pharmaceutical treatment, the dosages of medications must often be adjusted, different combinations of antidepressants tried, or antidepressant changed. Response rates to the first agent administered may be as low as 50%. [Depression Guideline Panel. Depression in primary care. Vol. 2. Treatment of major depression. Clinical practice guideline. No. 5. Rockville, MD: Agency for Health Care Policy and Research, 1999.] It may take anywhere from three to eight weeks after the start of medication before its therapeutic effects can be fully discovered. Patients are generally advised not to stop taking an antidepressant suddenly and to continue its use for at least four months to prevent the chance of recurrence. People with chronic depression need to take the medication for the rest of their lives.cite web
last = Mayo Clinic Staff
title = Depression
publisher = National Institute of Mental Health (NIMH)
date=2006-03-06
url = http://www.nimh.nih.gov/health/publications/depression/nimhdepression.pdf
accessdate = 2007-10-20 ]

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine, and citalopram are the primary medications considered, due to their relatively mild side effects and broad effect on the symptoms of depression and anxiety. Those who do not respond to the first SSRI tried can be switched to another; such a switch results in improvement in almost 50% of cases.cite journal |author=Sutherland JE, Sutherland SJ, Hoehns JD |title=Achieving the best outcome in treatment of depression |journal=Journal of Family Practice |volume=52 |issue=3 |pages=201–09 |year=2003 |month=March |pmid=12620174 |url=http://www.jfponline.com/Pages.asp?AID=1406] Another popular option is to switch to the atypical antidepressant bupropion (Wellbutrin) or to add bupropion to the existing therapy; [cite journal |author=Zisook S, Rush AJ, Haight BR, Clines DC, Rockett CB |title=Use of bupropion in combination with serotonin reuptake inhibitors |journal=Biological Psychiatry |volume=59 |issue=3 |pages=203–10 |year=2006 |pmid=16165100 |doi=10.1016/j.biopsych.2005.06.027] this strategy is possibly more effective.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=New England Journal of Medicine |volume=354 |issue=12 |pages=1231–42 |year=2006 |pmid=16554525 |doi=10.1056/NEJMoa052963] cite journal |author=Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ |title=Medication augmentation after the failure of SSRIs for depression |journal=New England Journal of Medicine |volume=354 |issue=12 |pages=1243–52 |year=2006 |pmid=16554526 |doi=10.1056/NEJMoa052964] It is not uncommon for SSRIs to cause or worsen insomnia; the sedating antidepressant mirtazapine (Zispin, Remeron) can be used in such cases.cite journal |author=Mayers AG, Baldwin DS |title=Antidepressants and their effect on sleep |journal=Human Psychopharmacology |volume=20 |issue=8 |pages=533–59 |year=2005 |month=December |pmid=16229049 |doi=10.1002/hup.726 |url=] cite journal |author=Winokur A, DeMartinis NA, McNally DP, Gary EM, Cormier JL, Gary KA |title=Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia |journal=Journal of Clinical Psychiatry |volume=64 |issue=10 |pages=1224–29 |year=2003 |month=October |pmid=14658972] cite journal |author=Lawrence RW |title=Effect of mirtazapine versus fluoxetine on "sleep quality" |journal=Journal of Clinical Psychiatry |volume=65 |issue=8 |pages=1149–50 |year=2004 |month=August |pmid=15323610 |doi= |url=http://article.psychiatrist.com/?ContentType=START&ID=10001013] Venlafaxine (Effexor) may be moderately more effective than SSRIs;cite journal |author=Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC |title=Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents |journal=Biological Psychiatry |volume=62 |issue=11 |pages=1217–27 |year=2007 |month=December |pmid=17588546 |doi=10.1016/j.biopsych.2007.03.027] however, it is not recommended as a first-line treatment because of the higher rate of side effects,cite journal|year=2007 |author=Cipriani A, Geddes JR, Barbui C |url=http://www.bmj.com/cgi/content/full/334/7587/215?grp=1 |title=Venlafaxine for major depression |journal=British Medical Journal|volume=334|pages=p. 215 (editorial)|doi=10.1136/bmj.39098.457720.BE |accessdate=2008-09-13] and its use is specifically discouraged in children and adolescents. [cite web|url=http://www.nice.org.uk/Guidance/CG28|title=Depression in children and young people: identification and management in primary, community and secondary care|month=September | year=2005|publisher=NHS National Institute for Health and Clinical Excellence |accessdate=2008-08-17] Fluoxetine is the only antidepressant recommended for people under the age of 18. [cite web|url=http://www.nice.org.uk/Guidance/CG28|title=Depression in children and young people: identification and management in primary, community and secondary care|month=September | year=2005|publisher=NHS National Institute for Health and Clinical Excellence |accessdate=2008-08-17]

Tricyclic antidepressants have more side effects than SSRIs and are usually reserved for the treatment of inpatients, for whom the tricyclic antidepressant amitriptyline, in particular, appears to be more effective.cite journal |author=Anderson IM |title=SSRIS versus tricyclic antidepressants in depressed inpatients: A meta-analysis of efficacy and tolerability |journal=Depression and Anxiety |volume=7 Suppl 1 |issue= |pages=11–17 |year=1998 |pmid=9597346|doi=] cite journal |author=Anderson IM |title=Selective serotonin reuptake inhibitors versus tricyclic antidepressants: A meta-analysis of efficacy and tolerability |journal=Journal of Affective Disorders |volume=58 |issue=1 |pages=19–36 |year=2000 |month=April |pmid=10760555 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0165-0327(99)00092-0] A different class of antidepressants, the monoamine oxidase inhibitors, have historically been plagued by questionable efficacy and life-threatening adverse effects. They are still used only rarely, although newer agents of this class, with a better side effect profile, have been developed.cite journal |author=Krishnan KR |title=Revisiting monoamine oxidase inhibitors |journal=Journal of Clinical Psychiatry |volume=68 Suppl 8 |issue= |pages=35–41 |year=2007 |pmid=17640156 |doi= |url=http://article.psychiatrist.com/?ContentType=START&ID=10003141]

Augmentation

Physicians often add a medication with a different mode of action to bolster the effect of an antidepressant in cases of treatment resistance; a 2002 large community study of 244,859 depressed Veterans Administration patients found that 22% had received a second agent, most commonly a second antidepressant. [cite journal |author=Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC|year=2006|title=What happened to lithium? Antidepressant augmentation in clinical settings |journal=American Journal of Psychiatry |volume=163 |issue=7 |pages=1219–25 |pmid=16816227 |doi=10.1176/appi.ajp.163.7.1219] Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. [cite journal |author=Bauer M, Dopfmer S |year=1999|title=Lithium augmentation in treatment-resistant depression: Meta-analysis of placebo-controlled studies |journal=Journal of Clinical Psychopharmacology |volume=19 |issue=5 |pages=427–34 |pmid=10505584 |doi=10.1097/00004714-199910000-00006 ] Furthermore, lithium dramatically decreases the suicide risk in recurrent depression.cite journal |author=Guzzetta F, Tondo L, Centorrino F, Baldessarini RJ |title=Lithium treatment reduces suicide risk in recurrent major depressive disorder |journal=J Clin Psychiatry |volume=68 |issue=3 |pages=380–83 |year=2007 |month=March |pmid=17388706 |doi= |url=http://article.psychiatrist.com/?ContentType=START&ID=10002980] Addition of atypical antipsychotics when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit at the cost of more frequent side effects.cite web |url=http://www.psychiatrictimes.com/display/article/10168/1147436 |title=Evidence Grows for Value of Antipsychotics as Antidepressant Adjuncts - Psychiatric Times |author=Bender KJ |date=2008-02-01 |format=htm |publisher=Psychiatric Times|accessdate=2008-08-06] There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function. [cite journal |author=Nierenberg AA, Fava M, Trivedi MH, Wisniewski SR, Thase ME, McGrath PJ, Alpert JE, Warden D, Luther JF, Niederehe G, Lebowitz B, Shores-Wilson K, Rush AJ |year=2006|title=A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: A STAR*D report |journal=American Journal of Psychiatry |volume=163 |issue=9 |pages=1519–30 |pmid=16946176 |doi=10.1176/appi.ajp.163.9.1519]

Efficacy of medication and psychotherapy

Two recent meta-analyses of clinical trial results submitted to the FDA concluded that antidepressants are statistically superior to placebo but their overall effect is low-to-moderate. In that respect they often did not exceed the National Institute for Health and Clinical Excellence criteria for a "clinically significant" effect. In particular, the effect size was very small for moderate depression but increased with severity reaching "clinical significance" for very severe depression.cite journal |author=Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT |title=Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration |journal=PLoS Med. |volume=5 |issue=2 |pages=e45 |year=2008 |month=February |pmid=18303940 |pmc=2253608 |doi=10.1371/journal.pmed.0050045 |url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045&ct=1] cite journal |author=Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R |title=Selective publication of antidepressant trials and its influence on apparent efficacy |journal=N. Engl. J. Med. |volume=358 |issue=3 |pages=252–60 |year=2008 |month=January |pmid=18199864 |doi=10.1056/NEJMsa065779 |url=] These result were consistent with the earlier clinical studies in which only patients with severe depression benefited from either psychotherapy or treatment with an antidepressant, imipramine, more than from the placebo treatment.cite journal |author=Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF, Glass DR, Pilkonis PA, Leber WR, Docherty JP |title=National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments |journal=Archives of General Psychiatry |volume=46 |issue=11 |pages=971–82; discussion 983 |year=1989 |pmid=2684085] cite journal |author=Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA, Hedeker D |title=Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program |journal=Journal of Consulting and Clinical Psychology |volume=63 |issue=5 |pages=841–47 |year=1995 |pmid=7593878 |doi=] cite journal |author=Sotsky SM, Glass DR, Shea MT, Pilkonis PA, Collins JF, Elkin I, Watkins JT, Imber SD, Leber WR, Moyer J |title=Patient predictors of response to psychotherapy and pharmacotherapy: Findings in the NIMH Treatment of Depression Collaborative Research Program |journal=American Journal of Psychiatry |volume=148 |issue=8 |pages=997–1008 |year=1991 |pmid=1853989 |doi=] Despite obtaining similar results, the authors argued about their interpretation. One author concluded that there "seems little evidence to support the prescription of antidepressant medication to any but the most severelydepressed patients, unless alternative treatments have failed to provide benefit." The other author agreed that "antidepressant 'glass' is far from full" but disagreed "that it is completely empty". He pointed out that the first-line alternative to medication is psychotherapy, which does not have superior efficacy.cite journal |author=Turner EH, Rosenthal R |title=Efficacy of antidepressants |journal=BMJ |volume=336 |issue=7643 |pages=516–7 |year=2008 |month=March |pmid=18319297 |pmc=2265347 |doi=10.1136/bmj.39510.531597.80 |url=]

Antidepressants in general are as effective as psychotherapy for major depression, and this conclusion holds true for both severe and mild forms of MDD.cite journal |author=Cuijpers P, van Straten A, van Oppen P, Andersson G |title=Are Psychological and Pharmacologic Interventions Equally Effective in the Treatment of Adult Depressive Disorders? A Meta-Analysis of Comparative Studies|journal=Journal of Clinical Psychiatry |volume= |issue= |pages=e1–e11 |year=2008 |month=August |pmid= |doi= |url=http://www.psychiatrist.com/abstracts/abstracts.asp?abstract=oap/ej08r04112.htm] cite journal |author=Imel ZE, Malterer MB, McKay KM, Wampold BE |title=A meta-analysis of psychotherapy and medication in unipolar depression and dysthymia |journal=J Affect Disord |volume=110 |issue=3 |pages=197–206 |year=2008 |month=October |pmid=18456340 |doi=10.1016/j.jad.2008.03.018] In contrast, medication gives better results for dysthymia. The subgroup of SSRIs may be slightly more efficacious than psychotherapy. On the other hand, significantly more patients drop off from the antidepressant treatment than from psychotherapy, likely because of the side effects of antidepressants. Successful psychotherapy appears to prevent the recurrence of depression even after it has been terminated or replaced by occasional "booster" sessions. The same degree of prevention can be achieved by continuing antidepressant treatment.

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is a treatment where seizures are electrically induced in anesthetized patients for therapeutic effect. ECT is most often used as a "last resort" (from the perspective of hospital psychiatrists) for severe major depression which has not responded to trials of antidepressant or, less often, psychotherapy or supportive interventions.cite journal |author=American Psychiatric Association |authorlink=American Psychiatric Association|year=2000 |month=April |title=Practice guideline for the treatment of patients with major depressive disorder|journal=American Journal of Psychiatry |volume=157 |issue=Supp 4 |pages=1–45 |pmid=10767867 |url=http://www.guideline.gov/summary/summary.aspx?doc_id=2605#s23] It has a quicker effect than antidepressant therapy, and thus may be the treatment of choice in emergencies such as catatonic depression where the patient has ceased oral intake of fluid or nutrients, or where there is severe suicidality. Some evidence suggests it is the most effective treatment for depression in the short-term [cite journal |author=The UK ECT Review Group |year=2003|title=Efficacy and safety of electroconvulsive therapy in depressive disorders: A systematic review and meta-analysis |journal=The Lancet |volume=361 |issue=9360 |pages=799–808 |id= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673603127055] and one study, without a comparison group or assessment of additional treatments given, suggested that in the minority who remit it may be related to improved self-rated quality of life in both the short-term (which was correlated with the degree of amnesia) and after six months. [cite journal |author=McCall WV, Prudic J, Olfson M, Sackeim H |year=2006 |month=February |title=Health-related quality of life following ECT in a large community sample |journal= Journal of Affective Disorders |volume=90 |issue=2–3 |pages=69–74 |pmid=16412519] However, the first systematic documentation of the effectiveness of ECT in community practice in the 65 years of its use found much lower remission rates than in prior research, and most of those relapsed. [cite journal |author=Prudic J, Olfson M, Marcus SC, Fuller RB, Sackeim HA |title=Effectiveness of electroconvulsive therapy in community settings |journal=Biol. Psychiatry |volume=55 |issue=3 |pages=301–12 |year=2004 |pmid=14744473| doi = 10.1016/j.biopsych.2003.09.015 ] ECT on its own does not usually have a sustained benefit, as virtually all those who remit end up relapsing within 6 months following a course, even when given a placebo. [Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, Greenberg RM, Crowe RR, Cooper TB, Prudic J.(2001) [http://jama.ama-assn.org/cgi/content/abstract/285/10/1299?ijkey=26825a5fbea146e584cd6459ea113828f4f202fa&keytype2=tf_ipsecsha Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial.] JAMA. 2001 Mar 14;285(10):1299-307.] The relapse rate in the first six months may be reduced by the use of psychatric medications or further ECT (though the latter is not recommended by some authorities, such as NICE), but remains high. [Tew JD Jr, Mulsant BH, Haskett RF, Joan P, Begley AE, Sackeim HA. (2007) Relapse during continuation pharmacotherapy after acute response to ECT: a comparison of usual care versus protocolized treatment] Ann Clin Psychiatry. 2007 Jan-Mar;19(1):1-4 PMID 17453654] [Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain MM, Rasmussen K, et al. (2006) Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006 Dec;63(12):1337-44. PMID 17146008] Short-term memory loss, disorientation, headache and other adverse effects are common, as are long-term memoryHarvnb|Barlow|2005| p=239] and other neurocognitive deficits, which may persist. The American Psychiatric Association and the National Institute for Health and Clinical Excellence have concluded that the evidence they had suggested that the procedure, when administered according to their standards and without complications, does not cause brain damage in adults.cite web | url = http://www.psych.org/research/apire/training_fund/clin_res/index.cfm | author = American Psychiatric Association | title=Electroconvulsive Therapy (ECT) | accessdate=2007-12-29] cite book | author= National Institute for Clinical Excellence|authorlink = National Institute for Health and Clinical Excellence| title = Guidance on the use of electroconvulsive therapy | publisher =National Institute for Health and Clinical Excellence | date = 2003 | location = London | pages = | url = http://www.nice.org.uk/nicemedia/pdf/59ectfullguidance.pdf|isbn = 1-84257-282-2|format=PDF]

Other conventional methods of treatment

t John's wort

St John's wort extract is used extensively in Europe to treat mild and moderate depression. It is a prescription antidepressant in several European countries but is classified as an herbal supplement and sold over the counter in the U.S. Opinions on its efficacy for major depression differ. A systematic meta-analysis of 37 trials conducted by Cochrane Collaboration indicated statistically significant weak-to-moderate effect as compared to placebo. The same meta-analysis found that St John's wort efficacy for major depression is not different from prescription antidepressants.cite journal |author=Linde K, Mulrow CD, Berner M, Egger M |title=St John's wort for depression |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD000448 |year=2005 |pmid=15846605 |doi=10.1002/14651858.CD000448.pub2] NCCAM and other NIH-affiliated organizations hold that St John's wort has minimal or no effects beyond placebo in the treatment of major depression, based primarily on one study with negative outcome conducted by NCCAM. [ [http://nccam.nih.gov/health/stjohnswort/sjwataglance.htm St. John's Wort and Depression] NCCAM on St John's wort and depression] ] [ [http://www.nimh.nih.gov/health/publications/depression/treatment.shtml How is depression detected and treated?] NIMH on depression, including a section on St John's wort]

AM-e

S-Adenosyl methionine (SAM-e) is available as a prescription antidepressant in Europe and an over-the-counter dietary supplement in the United States. Fairly strong evidence from 16 clinical trials suggests it to be more effective than placebo and as effective as standard antidepressant medication for the treatment of major depression.cite journal |author=Mischoulon D, Fava M |title=Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence |journal=Am. J. Clin. Nutr. |volume=76 |issue=5 |pages=1158S–61S |year=2002 |month=November |pmid=12420702 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=12420702] cite journal |author=Bressa GM |title=S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies |journal=Acta Neurol. Scand., Suppl. |volume=154 |issue= |pages=7–14 |year=1994 |pmid=7941964 |doi= |url=] cite web
title = Investigating SAM-e
publisher = Geriatric Times
date=2001
url = http://www.geriatrictimes.com/g010923.html
accessdate = 2006-12-08 ]

Repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) use in treatment-resistant depression is supported by multiple controlled studies, and it has been approved for this indication in Europe, Canada and Australia, but not in the U.S. A 2008 meta-analysis based on 32 trials found a robust effect of this method on depression, and it appeared similarly effective for both uncomplicated depression and depression resistant to medication.cite journal |author=Schutter DJ |title=Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis |journal=Psychol Med |volume= |issue= |pages=1–11 |year=2008 |month=April |pmid=18447962 |doi=10.1017/S0033291708003462 |url=] However, it was inferior to ECT in a side-by-side randomized trial.cite journal |author=Eranti S, Mogg A, Pluck G, "et al" |title=A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression |journal=Am J Psychiatry |volume=164 |issue=1 |pages=73–81 |year=2007 |month=January |pmid=17202547 |doi=10.1176/appi.ajp.164.1.73 |url=]

Vagus nerve stimulation

Vagus nerve stimulation (VNS) uses an implanted electrode and generator to deliver electrical pulses to the vagus nerve, one of the primary nerves emanating from the brain. It is an approved therapy for treatment-resistant depression and is sometimes used as an adjunct to existing antidepressant treatment. The support for this method comes mainly from open-label trials, which indicate that several months may be required to see a benefit. The only large double-blind trial conducted lasted only 10 weeks and yielded inconclusive results; VNS failed to show superiority over a sham treatment on the primary efficacy outcome, but the results were more favorable for the secondary outcome.cite journal |author=Rush AJ, Marangell LB, Sackeim HA, "et al." |title=Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial |journal=Biological Psychiatry |volume=58 |issue=5 |pages=347–54 |year=2005 |month=September |pmid=16139580 |doi=10.1016/j.biopsych.2005.05.025]

Alternative treatment methods

Bright light therapy

A meta-analysis of bright light therapy commissioned by the American Psychiatric Association found it to be more effective than placebo—usually, dim light—for both seasonal affective disorder and for nonseasonal depression, with effect sizes similar to those for conventional antidepressants. For non-seasonal depression, adding light therapy to the standard antidepressant treatment was not effective.cite journal |author=Golden RN, Gaynes BN, Ekstrom RD, "et al" |title=The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence |journal=American Journal of Psychiatry |volume=162 |issue=4 |pages=656–62 |year=2005 |month=April |pmid=15800134 |doi=10.1176/appi.ajp.162.4.656 |url=] A meta-analysis of light therapy for non-seasonal depression conducted by Cochrane Collaboration, studied a different set of trials, where light was used mostly as an addition to medication or sleep deprivation. A moderate statistically significant effect of light therapy was found; however, it disappeared if a different statistical technique was used.cite journal |author=Tuunainen A, Kripke DF, Endo T |title=Light therapy for non-seasonal depression |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD004050 |year=2004 |pmid=15106233 |doi=10.1002/14651858.CD004050.pub2 |url=] Both analyses noted poor quality of most studies and their small size, and urged caution in the interpretation of their results. The short 1-2 weeks duration of most trials makes it unclear whether the effect of light therapy could be sustained in the longer term.

Acupuncture

Exercise

Exercise, when used in conjunction with medication by non-suicidal patients, can have beneficial effects in preventing the return of depression. Patients who completed 30 minutes of brisk exercise at least three times a week were found to have a significantly lower incidence of relapse.cite web
last = Merritt
first = Richard
title = Study: Exercise Has Long-Lasting Effect on Depression
publisher = Duke University News
date=2000-09-22
url = http://dukenews.duke.edu/2000/09/exercise922.html
accessdate = 2007-10-20]

Vigorous exercise has significant physiological effects which help to reduce stress and counter depression. Also, by improving fitness and self-esteem, exercise may enable the sufferer to cope better with demanding events and situations and so reduce the likelihood of depressing failure. [citation|url=http://books.google.co.uk/books?id=A6oIAAAACAAJ|title=Conquering Depression and Anxiety Through Exercise|author=Keith W. Johnsgard|year=2004|isbn=9781591021926]

Exercise in natural surroundings such as the countryside or parks is especially recommended because contact with nature and green spaces has a positive effect upon mental health. [citation|url=http://news.bbc.co.uk/1/hi/sci/tech/7417516.stm|title=Putting a spring in your step|author=Nick Higham|publisher=BBC|date=23 May 2008] Gardening is an ideal activity of this sort, providing mental, practical and social benefits. [citation|url=http://news.bbc.co.uk/1/hi/health/332459.stm|publisher=BBC|title=Gardening aids mentally ill|date=1 May, 1999]

Deep Brain Stimulation

Tryptophan

Tryptophan and 5-hydroxytryptophan may be more effective than placebo in alleviating depression according to the Cochrane Collaboration meta-analysis. However, only two out of 108 trials were of sufficient quality to be included in this analysis.cite journal |author=Shaw K, Turner J, Del Mar C |title=Tryptophan and 5-hydroxytryptophan for depression |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD003198 |year=2002 |pmid=11869656 |doi=10.1002/14651858.CD003198 |url=]

Tryptophan is the precursor of the neurotransmitter serotonin. It has shown some promise as an antidepressant alonecite journal | author = Thomson J, Rankin H, Ashcroft GW, Yates CM, McQueen JK, Cummings SW | title = The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo | journal = Psychological medicine | volume = 12 | issue = 4 | pages = 741–51 | year = 1982 | pmid = 7156248 | doi = | issn = ] and as an augmenter of antidepressant drugs.cite journal | author = Levitan RD, Shen JH, Jindal R, Driver HS, Kennedy SH, Shapiro CM | title = Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects | journal = Journal of psychiatry & neuroscience : JPN | volume = 25 | issue = 4 | pages = 337–46 | year = 2000 | pmid = 11022398 | doi = | issn = | url = http://www.cma.ca/index.cfm/ci_id/12652/la_id/1.htm] Foods rich in tryptophan include bananas, chickpeas, chocolate, cottage cheese, dates, eggs, fish, oats, mangoes, milk, peanuts, poultry, pumpkin seeds, red meat, sesame, spirulina, sunflower seeds and yogurt.

Omega-3 fatty acids

Omega-3 fatty acids have been studied in clinical trials for major depression primarily as an adjunctive to antidepressant therapy. A meta-analysis of eight such trials indicated a statistically significant superiority of combinations with omega-3 fatty acids over single antidepressants; however, the authors warned that, due to multiple problems with these trials, a reliable conclusion is difficult to achieve.cite journal |author=Appleton KM, Hayward RC, Gunnell D, "et al" |title=Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials |journal=Am. J. Clin. Nutr. |volume=84 |issue=6 |pages=1308–16 |year=2006 |month=December |pmid=17158410 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=17158410]

Omega-3 fatty acids have been shown to help many people with depression, the theory being that Omega-3 helps nourish brain cells that release serotonin into the brain. Omega-3 fatty acids are present, for example, in cold-water fish such as salmon, in flax seed, in fish oil capsules and in flax seed capsules.

"Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach." (American Journal of Psychiatry 163:969-978, June 2006) [http://ajp.psychiatryonline.org/cgi/content/abstract/163/6/969 Am J Psychiatry 163:969-978, June 2006doi: 10.1176/appi.ajp.163.6.969] ]

DHEA

Dehydroepiandrosterone (DHEA), a metabolic precursor for several hormones including estrogen and testosterone, has been promoted as a remedy for many ailments. Sold in the 1970s and 1980s as a weight-loss aid, it was subsequently banned for over-the-counter sale, but then unbanned, and is currently available as a supplement in the US. It has been shown to be more effective than placebo in two small double-blind trials: in one as an adjunct to antidepressant treatment,cite journal |author=Wolkowitz OM, Reus VI, Keebler A, "et al." |title=Double-blind treatment of major depression with dehydroepiandrosterone |journal=American Journal of Psychiatry |volume=156 |issue=4 |pages=646–49 |year=1999 |month=April |pmid=10200751 |doi= |url=http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=10200751] and as monotherapy in another.cite journal |author=Schmidt PJ, Daly RC, Bloch M, "et al." |title=Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression |journal=Archives of General Psychiatry |volume=62 |issue=2 |pages=154–62 |year=2005 |month=February |pmid=15699292 |doi=10.1001/archpsyc.62.2.154 |url=]

Chromium picolinate

Chromium picolinate was found to be equivalent to placebo for atypical depression overall but possibly efficacious in the sub-group of patients with severe carbohydrate craving.cite journal |author=Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR |title=A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving |journal=J Psychiatr Pract |volume=11 |issue=5 |pages=302–14 |year=2005 |month=September |pmid=16184071 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1527-4160&volume=11&issue=5&spage=302]

Zinc

Serum levels of zinc are found to be low in depressed patients and supplementation with zinc has been demonstrated to be of benefit. [citation|url=http://www.if-pan.krakow.pl/pjp/pdf/2005/6_713.pdf|title=Zinc and depression.|author=Gabriel Nowak, Bernadeta Szewczyk, Andrzej Pilc|journal=Pharmacological Reports|year=2005] Zinc is found in beans, meat, nuts, oysters, whole grains and seeds.

Cranial electrotherapy stimulation

Eleuthero

"Eleutherococcus senticosus" is used in Traditional Chinese Medicine and is now used in the West as Eleuthero or Siberian Ginseng. The plant is an adaptogen or tonic and has been shown to have significant antidepressant effects in rats. [citation|url=http://www.springerlink.com/content/t6512435001n1418/
title=Antidepressant activity of some phytopharmaceuticals and phenylpropanoids
journal=Pharmaceutical Chemistry Journal|volume=40|Number=11|date=November, 2006|doi=10.1007/s11094-006-0205-5|pages=614-619|author=V. A. Kurkin1, A. V. Dubishchev1, V. N. Ezhkov1, I. N. Titova1 and E. V. Avdeeva1] [cite journal |author=Deyama T, Nishibe S, Nakazawa Y |title=Constituents and pharmacological effects of Eucommia and Siberian ginseng |journal=Acta Pharmacol. Sin. |volume=22 |issue=12 |pages=1057–70 |year=2001 |month=Dec |pmid=11749801 |doi= |url=]

Inositol

Inositol has been shown through various studies to be an effective treatment for depression, bipolar disorder, obsessive-compulsive disorder [cite journal
author= Palatnik A, Frolov K, Fux M, Benjamin J
title= Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder
journal= Journal of Clinical Psychopharmacology
year= 2001
volume= 21
issue= 3
pages= 335–339
pmid=11386498
doi= 10.1097/00004714-200106000-00014 ] [cite journal
author= Fux M, Levine J, Aviv A, Belmaker RH
title= Inositol treatment of obsessive-compulsive disorder
journal= American Journal of Psychiatry
year= 1996
volume= 153
issue= 9
pages= 1219–21
pmid=8780431 ] [cite journal
author= Di Paolo G, De Camilli P
title= Phosphoinositides in cell regulation and membrane dynamics
journal= Nature
year= 2006
volume= 443
issue= 7112
pages= 651–7
pmid=17035995
doi= 10.1038/nature05185 ] and panic attacks.

affron

Saffron, the flowers of "Crocus sativus" have been shown to have antidepressant properties.cite web
url=http://www.actahort.org/books/650/650_54.htm
title=Antidepressant effect of "Crocus sativus" L. stigma extracts and their constituents, crocin and safranal, in mice.
accessdate=2008-08-17
last=
first=] Two of the active ingredients are crocin and safranal.

Minerals

In the late 1800s there was a vogue for consumption of lithia water which contained a significant quantity of lithium. Some claimed that this cured depression, but its effectiveness is not clear. [citation|url=http://books.google.co.uk/books?id=qq1DZjH0K6cC|pages=57|title=Bipolar Puzzle Solution|author=Bryan L. Court, Court, Gerald E. Nelson, L. Court Bryan|publisher=Taylor & Francis|year=1996|isbn=9781560324935]

Magnesium deficiency is common and may cause depression. Supplementation or changes in diet may therefore be helpful. [citation|url=http://linkinghub.elsevier.com/retrieve/pii/S0306987706001034|title=Rapid recovery from major depression using magnesium treatment.|journal=Medical Hypotheses|Volume=67|Issue=2|Pages=362-370|author=G. Eby, K. Eby] Foodstuffs rich in magnesium include include whole grains, beans and seeds, halibut and spinach.

Vitamin B₈

Inositol or vitamin B₈ is found in cereals with high bran content, nuts, beans, and fruit, especially cantaloupe melons and oranges. It has been shown to be an effective treatment for depression, bipolar disorder and obsessive-compulsive disorder [cite journal
author= Palatnik A, Frolov K, Fux M, Benjamin J
title= Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder
journal= Journal of Clinical Psychopharmacology
year= 2001
volume= 21
issue= 3
pages= 335–339
pmid=11386498
doi= 10.1097/00004714-200106000-00014 ] [cite journal
author= Fux M, Levine J, Aviv A, Belmaker RH
title= Inositol treatment of obsessive-compulsive disorder
journal= American Journal of Psychiatry
year= 1996
volume= 153
issue= 9
pages= 1219–21
pmid=8780431 ] [cite journal
author= Di Paolo G, De Camilli P
title= Phosphoinositides in cell regulation and membrane dynamics
journal= Nature
year= 2006
volume= 443
issue= 7112
pages= 651–7
pmid=17035995
doi= 10.1038/nature05185 ] and panic attacks. The therapeutic dosage of inositol seems to be between 6-20 g/day, with 12-18 g/day being more likely an effective dosage. [ [http://discovermagazine.com/2005/may/vitamin-cure/?page=1 discovermagazine.com (May 2005)] ]

Kanna

Kanna ("Sceletium tortuosum") is a succulent herb commonly found in South Africa. In doses as low as 50 mg, users have reported improvements in mood, decreased anxiety, relaxation and a sense of well-being. It contains about 1-1.5% alkaloids and those which are believed to be psychoactive include mesembrine, mesembrenone, mesembrenol and tortuosamine. [http://erowid.org/plants/kanna/kanna_journal1.shtml Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review.] ]

There is about 0.3% mesembrine in the leaves and 0.86% in the stems of the plant. [http://www.plantzafrica.com/medmonographs/scelettort.pdf www.plantzafrica.com] ] This has been shown to be a potent serotonin reuptake inhibitor.Pharmaceutical compositions containing mesembrine and related compounds. [http://patft.uspto.gov/netacgi/nph-Parser?patentnumber=6,288,104 U.S. Patent 6,288,104] [http://www.pat2pdf.org/pat2pdf/foo.pl?number=6,288,104 (PDF)] ]

Flower remedies

Bach flower remedies and Australian bush flower essences are homeopathic remedies prepared from various flowers. Current clinical evidence does not support any hypothesized action or efficacy beyond placebo effects. [cite journal| author = E. Ernst| title = "Flower remedies": a systematic review of the clinical evidence| journal = Wiener Klinische Wochenschrift| volume = 114| issue = 23-24| pages = 963–966| date = December 30 2002| pmid = 12635462]

Four "Bach flower remedies" are described in connection with depression: gentian for very mild depression or pessimism; gorse for more serious depression; sweet chestnut for severe depression; and mustard for depression that comes from within and is not related to external circumstances. [cite book|title=Heal Thyself|first=Dr Edward|last=Bach|year=1931] [cite book|title=Flower Essences and Vibrational Healing|last=Gurudas|year=1983] [cite book|title=The Bach Remedies Workbook|first=Stefan|last=Ball|year=1998] Two "Australian bush flower essences" are described in connection with depression: waratah for depression; and Sunshine Wattle for pessimism and defeatism, especially after a long run of bad luck. [cite book|title=Australian Bush Flower Essences|first=Ian|last=White|year=1991]

Potassium phosphate

The homeopathic dilution of potassium phosphate) is claimed to bring some short-term relief to depressed patients. [The Homeopathy Bible, Ambika Wauters (Godsfield Publications) 2007 ISBN 184181 306 0]

Meditation

Meditation has been shown to be of benefit in a number of ways, including lowering blood pressure and stress levels. The most helpful and gentle form of meditation for a clinically depressed person may be the repetition—silently or aloud—of a mantra. [cite book|title=Timeless Healing|first=Dr Herbert|last=Benson|year=1996] cite book|title=Natural Healing|first=Mark|last=Bricklin|year=1983]

Neurofeedback

Neurofeedback is a form of biofeedback therapy in which brain activity is monitored using an EEG. The output is presented to the patient who is then able to see any variation in the brain waves associated with depression and may then develop some ability to reduce them, so improving their mood. The resulting direct control of mental state is thought to be similar to that achieved by the mental exercises of yoga.citation|url=http://books.google.co.uk/books?id=R60NAAAACAAJ|title=Natural Healing for Depression|author=James Strohecker, Nancy Shaw Strohecker, David E. Bresler|isbn=9780399525377|year=1999|chapter=2,4,10] [citation|url=http://books.google.co.uk/books?id=uqPqRIb9wCAC|isbn=9780813542874|title=Biofeedback for the Brain|author=Paul G. Swingle|year=2008]

Reiki

Reiki is a form of energy medicine originated in 1922 by Mikao Usui. A 2008 systematic review of the current scientific research concluded that any recommendation of Reiki for the management of depression is not evidence-based.Fact|date=August 2008

Religion

Numerous studies and clinical trials have looked at the relationship between religion and depression. These have looked at the matter from Buddhist, Christian and Muslim perspectives. These indicate that religious faith helps to prevent the onset of depression and assists recovery if depression should still occur. [citation|title=Faith And Mental Health|author=Harold George Koenig|isbn=9781932031911|year=2005|url=http://books.google.co.uk/books?id=B9bSdb7bLckC]

leep

Depression is commonly associated with poor sleep - difficulty going to sleep, early waking and general lassitude during the day. The two interact to worsen the condition of each other. Good sleep hygiene is therefore important to help break this vicious circle. [citation|url=http://www.nice.org.uk/nicemedia/pdf/CG023NICEguideline.pdf|title=Depression|publisher=NICE|date=December 2004] This would include measures such as regular bed times, avoidance of stimulants such as caffeine and management of disturbances such as sleep apnea.

Chi Kung

The traditional Chinese exercise of Chi Kung and related martial arts such as Tai Chi can help to prevent and relieve depression. [citation|title=Effects of mindful and non-mindful exercises on people with depression: A systematic review|Author= Tsang, Hector W. H.; Chan, Edward P.; Cheung, W. M.|journal=British Journal of Clinical Psychology|Volume=47|Number=3|date=September 2008|pages=303-322|Publisher=British Psychological Society|url=http://www.ingentaconnect.com/content/bpsoc/bjcp/2008/00000047/00000003/art00005]

References

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