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ALTERNATIVETHERAPIESjulaug2011VOL.17NO.429AnEvidence-basedIntegrativeCAMModelforDepressioncanbereplacedwherewarrantedlifestyleadjustmentssuchasdietaryimprovementandreductionofalcoholandcaffeineade-quaterelaxationandregularexerciseappropriatepsychologicalinterventionsandimprovedsocialdynamics.Individualx0Interventionsx0Overviewx0ofx0EvidenceAliteraturereviewwasrequiredtodeterminewhichnon-pharmaceuticaloptionshavesufCcientevidenceofefCcacyinthetreatmentofdepressedmood.Theseevidence-basedtreatmentswerethenappliedascomponentstoformaworkingclinicalmodel.AsdetailedinTable1superiorefCcacyovercontrolswasfoundforseveralinterventions.SpeciCcallyevidentiarysupportinvaryingdegreeswasfoundforherbalmedicinesHypericumx0perforatumRhodiolax0roseaCrocusx0sativusnutrientsL-tryptophanand5-hydroxytryptamine5-HTPomega-3fattyacidsS-adenosylmethionineSAMedehydroepiandrosteroneDHEAwasomittedasitisahormoneandapharmacologicaldrugpsychologicaltechniquesegcognitivebehavioralthera-pyinterpersonaltherapymindfulnessphysicalexerciseaero-bicanaerobicyogaandsocialinterventionseggrouptherapysocialskilldevelopment.Evidence-basedx0Interventionsx0tox0Treatx0DepressionAntidepressants.Inadditiontosyntheticantidepressantsseveralnaturalproductshaveevidenceasthymoleptics.AmongthemHypericumx0perforatumStJohnx19swortSJWatraditionalphytomedicineusedtotreatnervoussystemdisordershaslevel-AevidenceTable1.Enoughhumanclinicaltrialshavebeenconduct-edforseveralmeta-analysestobeconducted.34Allmeta-analyseshaverevealedthatSJWprovidesasigniCcantantidepressanteffectcomparedtoplaceboandanequivalentefCcacycomparedtosyn-theticantidepressants.Invivoandinvitrostudieshaverevealedantidepressantactivityviamodulationofserotonindopaminenorepinephrinepathwaysinvolvingneurotransmittertransportsystemsincreasedbindingtovariousreceptorsanddecreasedneurotransmitterdegradation.35AsidefromSJWtheherbalmedicinesRhodiolax0roseax0rosenrootandCrocusx0sativussaffroncurrentlypossessthemostevidenceasmonoamineandneuroen-docrinemodulatorsandhavepreliminaryhumanclinicalevi-denceofefficacyintreatingMDD.3637Rhodiolax0roseaisastimulatingadaptogenwhichpossessesantidepressantantifa-tigueandtonicactivity.3638InanimalmodelsRhodiolax0roseahasbeendocumentedtoincreasenoradrenalinedopamineandserotonininthebrainstemandhypothalamusandtoincreasethebloodbrainpermeabilitytoneurotransmitterprecursors.39AsdetailedinTable1onerandomizedcontrolledtrialRCThasdocumentedefCcacyagainstplacebointhetreatmentofdepres-sionhoweverfurtherstudiesneedtobeconductedtoconCrmefCcacy.SaffronisdevelopingclinicalevidenceasaneffectiveantidepressantwithseveralstudiesdisplayingpositiveresultsvsplaceboandcomparableefCcacyvsapositivepharmaceuticalcontrol.37Themechanismsresponsiblefortheantidepressantactionsarepositedtobemediatedviareuptakeinhibitionofdopaminenorepinephrineserotoninandn-methyl-D-aspartateNMDAreceptorantagonism.37Safranalaconstituentfromsaf-fronispositedtoexertselectiveGABA-aagonismandpossibleopioidreceptormodulationasdemonstratedviaintracere-broventricularadministrationinananimalmodel.3740SAMeisanendogenouscompoundproducedfrommethio-nineandvariousmethylatorsegB6B12folateinthebody.4142SAMeservesasanecessarymethyldonorofmethylgroupsinvolvedwiththemetabolismandsynthesisofneurotransmit-ters.42InvivostudieshaveconsistentlyshownthatSAMepos-sessesantidepressantpropertiesandmanyhumanclinicaltrialsusingSAMeinMDDhaverevealedbeneficialantidepressanteffectscomparabletosyntheticantidepressants.L-tryptophanisanessentialmonoamineprecursorrequiredforthesynthesisofserotoninandhasbeenstudiedextensivelyinthelatterhalfofthe20thcenturyasanantidepressant.43AlthoughmanypositivestudiesexistonlyoneRCTofsufCcientmethodologicalrigorusingthenutrientasamonotherapyinthetreatmentofMDDwasfoundtoexist.EightcontrolledadjuvancystudiesusingL-tryptophanwithantidepressantshoweverprovideencourag-ingevidencewithL-tryptophanaugmentationbeingeffectiveinincreasingtheantidepressantresponsewithphenezinesulphateclomipraminetranylcypromineandDuoxetine.44Otherclinicalstudiesusingtricyclicsdiscoverednoadditionalbenefitcom-paredplacebohowever.Omega-3fattyacidsmayalsohavearoleinreducingdepres-sionespeciallyifaninDammatorycausationispresentalinkbetweeninDammationanddepressionhasbeendocumented.8Epidemiologicalstudieshavedemonstratedthatincreasedriskofdepressivesymptomsmaybecorrelatedwithlowerdietaryome-ga-3CshoileicosapentaenoicacidEPAanddocosahexaenoicacidDHA.45Studiesalsohavedemonstratedthatpeoplewithdepressedmoodhaveatendencytowardsahigherratioofserumarachidonicacidtoessentialfattyacidsandanoveralllowerserumlevelofomega-3comparedtohealthycontrols.46SeveralhumanclinicaltrialshavebeenconductedassessingtheefCcacyofEPADHAoracombinationofboth.47Clinicalevidenceregardingtheuseofessentialfattyacidsasamonotherapyforunipolarorbipolardepressionisequivocalwithamixtureofpositiveandnegativetrials.Thismaybedueinparttomanystudiesusingoliveoilasanx1cinertx1dcontrolandsomestudiesusinghigherDHAtoEPAratioorDHAalone.Preparationshigh-erinEPAvsDHAinthetreatmentofdepressionmaybeadvisedasistheuseofahigherinitialdosagetocorrectanyrelativeimbalancetogreaterratioofarachidonicacidtoessentialfattyacids.444849Clinicaltrialsusingessentialfattyacidsadjuvantlywithantidepressantshaveprovidedevidenceofagreaterreduc-tionofdepressionlevel.44AdjuvantprescriptionofessentialfattyacidswithantidepressantscanbeadvisedincasesofdeCciencyorifcomorbidcardiovascularorinflammatorydisordersarepresent.Evidencecurrentlysuggeststhatomega-3fattyacidsexertantidepressantactivityviabeneCcialeffectsonneurotrans-mission.Thismayoccurviamodulationofneurotransmitternorepinephrinedopamineandserotoninreuptakedegrada-tionsynthesisandreceptorbindingantiinDammatoryeffect