Recognizing the Physical Symptoms of Depression

Recognizing+the+Physical+Symptoms+of+Depression%0d%0aVolume+2+%e2%80%a2+Number+2+%e2%80%a2+August+2004%0d%0a%0d%0a%0cIntroduction%0d%0aAlan+F.+Schatzberg%2c+M.D.%0d%0a%0d%0a%0cPhysical+Symptoms+Common+In+Psychiatric+Patients%0d%0aSymptom+Psychiatric+Patients+(%25)+Healthy+Subjects+(%25)%0d%0a%0d%0aTiredness%2c+lack+of+energy+Headache%2c+head+pains+Dizziness+or+faintness+Feeling+of+weakness+in+parts+of+body+Muscle+pains%2c+aches%2c+rheumatism+Stomach+pains+Chest+pains%0d%0a%0d%0a85+64+60+57+53+51+46%0d%0a%0d%0a40+48+14+23+27+20+14%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0aData+from+Kellner+R%2c+Sheffield+BF.+The+one-week+prevalence+of+symptoms+in+neurotic+patients+and+normals.+Am+J+Psychiatry+1973%3b130%3a102%e2%80%93105%0d%0a%0d%0a%0cWhy+Focus+on+Physical+Symptoms%3f%0d%0aA+growing+literature+explores+the+mind-body+connection+in+mental+illness+Depression+may+have+physical+causes+and+consequences+(like+appetite+and+sleep+disturbance%2c+fatigue%2c+and+chronic+pain)+The+presence+of+physical+symptoms+in+depression+may+affect+response+to+treatment%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cHow+Chronic+Pain+Affects+the+Symptoms+of+Depression%0d%0aMaurice+M.+Ohayon%2c+M.D.%2c+D.Sc.%2c+Ph.D.%0d%0a%0d%0a%0cPatients+With+Major+Depressive+Disorder%0d%0aReport+only+physical+symptoms+in+up+to+69%25+of+primary+care+cases1%0d%0aE.g.%2cinsomnia+or+hypersomnia%2c+psychomotor+agitation+or+retardation%2c+changes+in+appetite%2c+fatigue%0d%0a%0d%0aAre+at+4x+greater+risk+than+nondepressed+patients+for+having+a+chronic+painful+physical+condition+(CPPC)2+Are+more+likely+than+nondepressed+patients+to+have+long-term+medical+conditions3%0d%0aGE%2c+VonKorff+M%2c+Piccinelli+M%2c+et+al.+An+international+study+of+the+relation+between+somatic+symptoms+and+depression.+N+Engl+J+Med+1999%3b341%3a1329%e2%80%931335+2Ohayon+MM%2c+Schatzberg+AF.+Using+chronic+pain+to+predict+depressive+morbidity+in+the+general+population.+Arch+Gen+Psychiatry+2003%3b60%3a39%e2%80%9347+3Patten+SB.+Long-term+medical+conditions+and+major+depression+in+a+Canadian+population+study+at+waves+1+and+2.+J+Affect+Disord+2001%3b63%3a35%e2%80%9341%0d%0a1Simon%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cInfluence+of+CPPCs+on+Depressive+Symptoms%0d%0aMethod+General+population+respondents+%e2%89%a5+15+years+of+age+Total+N+%3d+18%2c980+in+5+European+countries+Interviewed+by+telephone+using+several+instruments%0d%0aSleep-EVAL%2c+DSM-IV%2c+and+International+Classification+of+Sleep+Disorders+criteria%2c+questions+about+painful+physical+conditions%2c+and+questions+about+psychological+and+physical+symptoms+of+depression%0d%0aOhayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cInfluence+of+CPPCs+on+Depressive+Symptoms%0d%0aResults%0d%0a%0d%0a17.1%25+of+respondents+with+at+least+1+CPPC%0d%0a4.0%25+of+respondents+with+major+depressive+disorder+(MDD)+Likelihood+of+either+condition+was+higher+among+patients+25+and+older+and+was+higher+among+women%0d%0a%0d%0aOhayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cPrevalence+of+MDD+by+Presence+of+CPPC+and+Age+Groupa%0d%0a%0d%0atotal+of+the+2+CPPC+categories+equals+the+total+prevalence+of+MDD+for+each+age+group.+Abbreviations%3a+CPPC+%3d+Chronic+Painful+Physical+Condition%2c+MDD+%3d+Major+Depressive+Disorder.+Reprinted+with+permission+from+Ohayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0a%0d%0aaThe%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cSubjects+With+MDD+Plus+At+Least+1+CPPC%0d%0aRepresented+43.4%25+of+subjects+with+MDD+Had+a+longer+duration+of+current+depressive+episode+than+depressed+subjects+without+a+CPPC%0d%0a31.4+months+vs.+24.3+months%0d%0a%0d%0aWere+more+likely+to+have+had+a+past+depressive+episode+than+depressed+subjects+without+a+CPPC%0d%0a24.4%25+vs.+17.4%25%0d%0a%0d%0aOhayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cFrequency+and+Severity+of+Depressive+Symptoms+in+Subjects+With+MDD+and+With+or+Without+CPPC%0d%0aSymptom+Feeling+sad%2c+depressed+nearly+every+day+Moderately+A+lot%2fextremely+Loss+of+interest+in+activities+nearly+every+day+Moderately+A+lot%2fextremely+Psychomotor+agitation+nearly+every+day+Moderately+A+lot%2fextremely+Psychomotor+retardation+nearly+every+day+Moderately+A+lot%2fextremely+Weight+loss+Weight+gain+With+CPPC+(N+%3d+330)%2c+%25+41.2***+28.0***+28.3+26.5+13.8*+7.9+5.9+14.1+7.7***+28.9+21.3**+Without+CPPC+(N+%3d+429)%2c+%25+30.7+17.9+24.8+21.5+9.2+5.4+3.8+10.2+2.5+23.6+10.4+OR+(95%25+CI)+1.6+(1.2+to+2.1)+1.8+(1.3+to+2.5)+1.2+(0.9+to+1.7)+1.3+(0.9+to+1.8)+1.6+(1.0+to+2.5)+1.5+(0.8+to+2.7)+1.6+(0.8+to+3.1)+1.5+(0.9+to+2.2)+3.3+(1.6+to+6.7)+1.3+(0.9+to+1.8)+2.3+(1.1+to+5.2)+(cont.)+*p+%3c+.05%2c+**p+%3c+.01%2c+***p+%3c+.001+vs.+patients+without+CPPC.+Abbreviations%3a+CPPC+%3d+Chronic+Painful+Physical+Condition%2c+MDD+%3d+Major+Depressive+Disorder.+Ohayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cFrequency+and+Severity+of+Depressive+Symptoms+in+Subjects+With+MDD+and+With+or+Without+CPPC+(cont.)%0d%0aSymptom+Insomnia+3%e2%80%934+nights%2fweek+5%e2%80%937+nights%2fweek+Hypersomnia+3%e2%80%934+nights%2fweek+5%e2%80%937+nights%2fweek+Fatigue+nearly+every+day+Moderately+A+lot%2fextremely+Feeling+of+worthlessness+or+guilt+nearly+every+day+Moderately+A+lot%2fextremely+Impaired+concentration+Moderately+A+lot%2fextremely+Suicidal+ideation+With+CPPC+(N+%3d+330)%2c+%25+43.1+31.1***+8.2+12.8+17.2+13.0***+12.3+7.4+16.5+13.4**+44.1+Without+CPPC+(N+%3d+429)%2c+%25+44.4+12.2+10.5+8.3+15.5+2.7+7.9+6.7+11.9+8.4+37.3+OR+(95%25+CI)+1.0+(0.7+to+1.3)+3.3+(2.2+to+4.7)+0.8+(0.5+to+1.3)+1.6+(1.0+to+2.6)+1.1+(0.8+to+1.7)+5.4+(2.8+to+10.5)+1.6+(1.0+to+2.6)+1.1+(0.6+to+1.9)+1.5+(1.0+to+2.2)+1.7+(1.1+to+2.7)+1.3+(1.0+to+1.8)%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a*p+%3c+.05%2c+**p+%3c+.01%2c+***p+%3c+.001+vs.+patients+without+CPPC.+Abbreviations%3a+CPPC+%3d+Chronic+Painful+Physical+Condition%2c+MDD+%3d+Major+Depressive+Disorder.+Ohayon+MM.+Specific+characteristics+of+the+pain%2fdepression+association+in+the+general+population.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a5%e2%80%939%0d%0a%0d%0a%0cConclusions%0d%0aCPPCs+were+extremely+common+in+subjects+with+MDD+The+presence+of+a+CPPC+statistically+significantly+increased+the+frequency+and+severity+of+7+depressive+symptoms%0d%0aFeeling+sad+or+depressed%2c+psychomotor+agitation%2c+psychomotor+retardation%2c+weight+gain%2c+insomnia%2c+fatigue%2c+and+impaired+concentration%0d%0a%0d%0aSome+physical+symptoms+of+depression+may+be+attributable+to+chronic+pain+rather+than+depressive+illness%2c+but%2c+conversely%2c+physical+symptoms+may+be+due+to+MDD+rather+than+chronic+pain%0d%0a%0d%0aClinician+vigilance+and+discernment+is+necessary+to+determine+whether+physical+symptoms+indicate+depression%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cChildhood+Maltreatment+and+Adult+Health+and+Psychiatric+Outcomes%0d%0aBruce+A.+Arnow%2c+Ph.D.%0d%0a%0d%0a%0cPrevalence+Estimates+of+Childhood+Maltreatment+Vary+According+to+Study+Methodology%0d%0aDefinition+of+terms%0d%0aE.g.%2c+childhood+and+abuse%0d%0a%0d%0aSurvey+tactics+employed%0d%0aE.g.%2c+mailed+questionnaire%2c+face-to-face+interview%0d%0a%0d%0aRespondent+population%0d%0aE.g.%2c+general+public%2c+primary+care+patients%2c+psychiatric+patients%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cEstimated+Prevalence+in+the+General+Population%0d%0aChildhood+sexual+abuse1%0d%0a8%25+to+32%25+in+women+1%25+to+16%25+in+men%0d%0a%0d%0aChildhood+physical+abuse2%0d%0aApproximately+20%25+in+women+and+men%0d%0a%0d%0a1Finkelhor+2Briere%0d%0a%0d%0aD.+Current+information+on+the+scope+and+nature+of+child+sexual+abuse.+Future+Child+1994%3b4%3a31%e2%80%9353+J%2c+Elliot+DM.+Prevalence+and+psychological+sequelae+of+self-reported+childhood+physical+and+sexual+abuse+in+a+general+population+sample+of+men+and+women.+Child+Abuse+Negl+2003%3b27%3a1205%e2%80%931222%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cHigher+Prevalence+of+Childhood+Abuse+in+Specialized+Settings%0d%0a44%25+of+primary+care+patients+reported+sexual%2c+physical%2c+or+emotional+abuse+as+children1+53%25+of+women+in+emergency+psychiatric+care+reported+childhood+sexual+abuse%3b+42%25+reported+childhood+physical+abuse2+55%25+of+female+psychiatric+inpatients+reported+multiple+types+of+childhood+abuse3%0d%0a1Gould%0d%0a%0d%0aDA%2c+Stevens+NG%2c+Ward+A%2c+et+al.+Self-reported+childhood+abuse+in+an+adult+population+in+a+primary+care+setting%3a+prevalence%2c+correlates%2c+and+associated+suicide+attempts.+Arch+Fam+Med+1994%3b3%3a252%e2%80%93256+2Briere+J%2c+Woo+R%2c+McRae+B%2c+et+al.+Lifetime+victimization+history%2c+demographics%2c+and+clinical+status+in+female+psychiatric+emergency+room+patients.+J+Nerv+Ment+Dis+1997%3b185%3a95%e2%80%93101+3Swett+C%2c+Alpert+M.+Reported+history+of+physical+and+sexual+abuse+in+relation+to+dissociation+and+other+symptomatology+in+women+psychiatric+inpatients.+J+Interpersonal+Violence+1993%3b8%3a545%e2%80%93555%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cAdult+Psychiatric+Outcomes%0d%0aChildhood+maltreatment+is+associated+with+adult+psychiatric+sequelae%0d%0aMDD%2c+anxiety%2c+substance+abuse%2fdependence+are+especially+common+Greater+severity%2c+frequency%2c+and+number+of+types+of+maltreatment+exacerbate+risk%0d%0a%0d%0aIn+a+community+sample%2c+childhood+sexual+abuse+raised+the+rate+of+having+at+least+1+lifetime+psychiatric+disorder+from+49%25+in+women+and+51%25+in+men+to+78%25+in+women+and+82%25+in+men1%0d%0a1Molnar%0d%0a%0d%0aBE%2c+Buka+SL%2c+Kessler+RC.+Child+sexual+abuse+and+subsequent+psychopathology%3a+results+from+the+National+Comorbidity+Survey.+Am+J+Pub+Health+2001%3b91%3a753%e2%80%93760%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cAssociation+Between+Childhood+Sexual+and%2for+Physical+Abuse+and+Adult+Mental+Health+Symptoms+in+Primary+Care%0d%0a%0d%0a*p+%3c+.001+vs.+patients+with+no+abuse.+aHigh+%3d+upper+1%2f3+of+score+range+on+Symptom+Checklist-22+Data+from+McCauley+J%2c+Kern+DE%2c+Kolodner+K%2c+et+al.+Clinical+characteristics+of+women+with+a+history+of+childhood+abuse%3a+unhealed+wounds.+JAMA+1997%3a277%3a1362%e2%80%931368%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cRelative+Risk+of+MDD+Among+Adults+Who+Report+Childhood+Abuse+Compared+With+Adults+Who+Do+Not%0d%0aPhysical+abuse%3a+2.4x+greater+Sexual+abuse%3a+1.8x+greater%0d%0a%0d%0aBoth+physical+and+sexual+abuse%3a+3.3x+greater%0d%0a%0d%0aWise+L%2c+Zierler+S%2c+Krieger+N%2c+et+al.+Adult+onset+of+major+depressive+disorder+in+relation+to+childhood+and+adolescent+violence+victimization%3a+a+case-control+study.+Lancet+2001%3b358%3a881%e2%80%93887%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cSignificant+Associations+of+the+Relationship+Between+Childhood+Maltreatment+and+Adult+MDD%0d%0aEarlier+onset+of+MDD1+High+comorbidity+and+chronicity+of+MDD1%2c2%0d%0a%0d%0aSuicide+attempts+in+adulthood3%0d%0a%0d%0a1Bernet%0d%0a%0d%0aCZ%2c+Stein+MB.+Relationship+of+childhood+maltreatment+to+the+onset+and+course+of+major+depression+in+adulthood.+Depress+Anxiety+1999%3b9%3a169%e2%80%93174+2Brown+GW%2c+Moran+P.+Clinical+and+psychosocial+origins+of+chronic+depressive+episodes%2c+pt.1%3a+a+community+survey.+Br+J+Psychiatry+1994%3b165%3a447%e2%80%93452+3Bifulco+A%2c+Moran+P%2c+Baines+R%2c+et+al.+Exploring+psychological+abuse+in+childhood%2c+pt.+2%3a+association+with+other+abuse+and+adult+clinical+depression.+Bull+Menninger+Clin+2002%3b66%3a241%e2%80%93258%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cPhysical+Symptoms+Linked+to+Childhood+Victimization%0d%0aChronic+pelvic+pain1%0d%0a%0d%0aFibromyalgia2%0d%0aIrritable+bowel+syndrome3+Headache4%0d%0aE%2c+Katon+W%2c+Harrop-Griffiths+J%2c+et+al.+Relationships+of+chronic+pelvic+pain+to+psychiatric+diagnoses+and+childhood+sexual+abuse.+Am+J+Psychiatry+1988%3b145%3a75%e2%80%9380+2Walker+EA%2c+Keegan+D%2c+Gardner+G%2c+et+al.+Psychosocial+factors+in+fibromyalgia+compared+with+rheumatoid+arthritis%2c+pt.+2%3a+sexual%2c+physical%2c+and+emotional+abuse+and+neglect.+Psychosom+Med+1997%3b59%3a572%e2%80%93577+3Talley+NJ%2c+Fett+SL%2c+Zinsmeister+AR%2c+et+al.+Gastrointestinal+tract+symptoms+and+self-reported+abuse%3a+a+populationbased+study.+Gastroenterology+1994%3b107%3a1040%e2%80%931049+4Golding+JM.+Sexual+assault+history+and+headache%3a+5+general+population+studies.+J+Nerv+Ment+Dis+1999%3b187%3a+624%e2%80%93629%0d%0a1Walker%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cOther+Adult+Health+Outcomes+Associated+With+Childhood+Maltreatment+or+Household+Dysfunctiona%0d%0aCorrelated+disease+states1%0d%0aHeart+disease%2c+cancer%2c+chronic+lung+disease%2c+and+liver+disease+Alcoholism%2fdrug+abuse%2c2+driving+while+intoxicated%2c2+irregular+seatbelt+use%2c2+risky+sexual+behaviors%2c1%2c2+sedentary+lifestyle%2c1%2c2+obesity%2c1%2c2+and+cigarette+smoking2%0d%0a%0d%0aIncreased+health-risk+behaviors%0d%0a%0d%0aillness%2c+imprisonment%2fcriminality%2c+substance+abuse%2c+and%2for+violence.+VJ%2c+Anda+RF%2c+Nordenberg+D%2c+et+al.+Relationship+of+childhood+abuse+and+household+dysfunction+to+many+of+the+leading+causes+of+death+in+adults.+Am+J+Prev+Med+1998%3b14%3a245%e2%80%93258+2Walker+EA%2c+Gelfand+A%2c+Katon+WJ%2c+et+al.+Adult+health+status+of+women+with+histories+of+childhood+abuse+and+neglect.+Am+J+Med+1999%3b107%3a332%e2%80%93339%0d%0a1Felitti%0d%0a%0d%0aaE.g.%2cmental%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cMedical+Utilization%0d%0aElevated+among+adults+with+depression1+Elevated+among+adults+with+a+history+of+childhood+abuse2+Higher+among+adults+with+psychological+distress+%2b+childhood+sexual+abuse+than+among+adults+with+either+condition+alone3+Higher+still+among+adults+with+psychological+distress+%2b+sexual+abuse+%2b+physical+abuse3%0d%0a%0d%0aGE%2c+VonKorff+M%2c+Barlow+W.+Health+care+costs+of+primary+care+patients+with+recognized+depression.+Arch+Gen+Psychiatry+1995%3b52%3a850%e2%80%93856+2Walker+EA%2c+Unutzer+J%2c+Rutter+C%2c+et+al.+Costs+of+health+care+use+by+women+HMO+members+with+a+history+of+childhood+abuse+and+neglect.+Arch+Gen+Psychiatry+1999%3b56%3a609%e2%80%93613+3Arnow+BA%2c+Hart+S%2c+Hayward+C%2c+et+al.+Severity+of+child+maltreatment%2c+pain+complaints%2c+and+medical+utilization+among+women.+J+Psychiatr+Res+2000%3b34%3a413%e2%80%93421%0d%0a%0d%0a1Simon%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cConclusions%0d%0aReported+rates+of+childhood+abuse+are+highest+in+psychiatric+settings+Childhood+maltreatment+is+associated+with%0d%0aAdult+psychiatric+sequelae%2c+especially+depression+Both+medically+explained+and+unexplained+physical+symptoms%2c+especially+chronic+pain+Health-risk+behaviors+in+adulthood+A+graded+relationship+between+severity+of+maltreatment+and+adult+outcomes+including+poor+psychological+outcomes%2c+pain+complaints%2c+and+medical+utilization%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cThe+Nature+of+Depression+and+Its+Treatment+With+Dual-Acting+Antidepressants%0d%0aPedro+L.+Delgado%2c+M.D.%0d%0a%0d%0a%0cRecurrence+of+MDD%0d%0a75%25+to+90%25+of+people+with+depression+will+have+multiple+episodes1%2c2%0d%0aEach+episode+is+more+easily+provoked+than+the+last3+Residual+symptoms+following+recovery+increase+risk+of+recurrence4%0d%0a%0d%0a1Angst%0d%0a%0d%0aJ.+How+recurrent+and+predictable+is+depressive+illness%3f+In%3a+Montgomery+SA%2c+Rouillon+F%2c+eds.+Long-Term+Treatment+of+Depressive+Perspectives+in+Psychiatry%2c+vol+3.+Chichester%2c+England%3a+Wiley%3b1992%3a1%e2%80%9313+2Kupfer+DJ.+Long-term+treatment+of+depression.+J+Clin+Psychiatry+1991%3b52(suppl+5)%3a28%e2%80%9334+3Kendler+KS%2c+Thornton+LM%2c+Gardner+CO.+Stressful+life+events+and+previous+episodes+in+the+etiology+of+major+depression+in+women%3a+an+evaluation+of+the+%e2%80%9ckindling%e2%80%9d+hypothesis.+Am+J+Psychiatry+2000%3b157%3a1243%e2%80%931251+4Judd+LL%2c+Akiskal+HS%2c+Maser+JD%2c+et+al.+Major+depressive+disorder%3a+a+prospective+study+of+residual+subthreshold+depressive+symptoms+as+predictor+of+rapid+relapse.+J+Affect+Disord+1998%3b50%3a97%e2%80%93108%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cWhy+Aim+to+Prevent+Recurrence+of+Depressive+Episodes%3f%0d%0aMuch+of+the+burden+of+MDD+is+linked+to+its+chronic+nature1%2c2+Episodes+tend+to+become+more+frequent%2c+severe%2c+and+treatment+resistant+over+time3%0d%0a%0d%0aNumber+(and+duration)+of+previous+episodes+may+predict+relapse3%0d%0aProlonged+depression+and+multiple+episodes+may+cause+brain+damage+(loss+of+hippocampal+volume)4%2c5%0d%0aJ.+How+recurrent+and+predictable+is+depressive+illness%3f+In%3a+Montgomery+SA%2c+Rouillon+F%2c+eds.+Long-Term+Treatment+of+Depressive+Perspectives+in+Psychiatry%2c+vol+3.+Chichester%2c+England%3a+Wiley%3b1992%3a1%e2%80%9313+2Kupfer+DJ.+Long-term+treatment+of+depression.+J+Clin+Psychiatry+1991%3b52(suppl+5)%3a28%e2%80%9334+3Keller+MB%2c+Boland+RJ.+Implications+of+failing+to+achieve+successful+long-term+maintenance+treatment+of+recurrent+unipolar+major+depression.+Biol+Psychiatry+1998%3b44%3a348%e2%80%93360+4Sheline+YI%2c+Sanghavi+M%2c+Mintun+MA%2c+et+al.+Depression+duration+but+not+age+predicts+hippocampal+volume+loss+in+medically+healthy+women+with+recurrent+major+depression.+J+Neurosci+1999%3b19%3a5034%e2%80%935043+5Bremner+JD%2c+Narayan+M%2c+Anderson+ER%2c+et+al.+Hippocampal+volume+reduction+in+major+depression.+Am+J+Psychiatry+2003%3b160%3a1516%e2%80%931518%0d%0a1Angst%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cNeurobiology+of+Depression%3a+Serotonin+and+Norepinephrine%0d%0aAre+part+of+the+body%e2%80%99s+endogenous+analgesic+system+Play+overlapping+but+divergent+roles+in+depression+Are+involved+in+the+etiology+of+some+physical+and+emotional+symptoms+of+depression+Affect+how+medications+work+to+treat+depression%0d%0aSome+beneficial+effects+of+antidepressant+treatment+may+be+due+to+neurogenesis+(cell+growth)+in+affected+areas+of+the+depressed+brain%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cDual-Acting+Antidepressants%0d%0aOverall%2c+dual-acting+agents+appear+to+be+more+effective+than+single-acting+agents+in+improving+mood%2c+reducing+pain%2c+and+increasing+the+chance+of+remission+Tricyclic+antidepressant+(TCA)+imipramine+induces+neurogenesis+even+in+mice+genetically+modified+to+have+no+5-HT1A+receptors1+Serotonin-norepinephrine+reuptake+inhibitors+(SNRIs)+venlafaxine2+and+duloxetine3+have+reduced+pain+sensitivity+in+a+dosedependent+manner+in+patients+with+diabetic+neuropathy%0d%0a1Santarelli%0d%0a%0d%0aL%2c+Saxe+MD%2c+Gross+C%2c+et+al.+Requirement+of+hippocampal+neurogenesis+for+the+behavioral+effects+of+antidepressants.+Science+2003%3b301%3a805%e2%80%93809+2Kunz+NR%2c+Goli+V%2c+Entsuah+R%2c+et+al.+Diabetic+neuropathic+pain+management+with+venlafaxine+extended+release.+Eur+Neuropsychopharmacol+2000%3b10(suppl+3)%3aS389+J+Clin+Psychiatry+3Goldstein+DJ%2c+Lu+Y%2c+Iyengar+S%2c+et+al.+Duloxetine+in+the+treatment+of+the+pain+associated+with+diabetic+neuropathy.+Presented+at+the+156th+Annual+Meeting+of+the+American+Psychiatric+Association%3b+May+17%e2%80%9322%2c+2003%3b+San+Francisco%2c+Calif.+Abstract+NR185%3a68%e2%80%9369%0d%0a%0d%0a%0cConclusions%0d%0aEarly%2c+aggressive%2c+effective+intervention+in+depression+is+recommended%0d%0a%0d%0aDual-acting+antidepressants+that+inhibit+reuptake+of+both+serotonin+and+norepinephrine+treat+a+wider+array+of+depressive+symptoms+(psychological+and+physical)+than+antidepressants+that+target+either+neurotransmitter+alone%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cThe+Search+for+Better+Outcomes+in+the+Treatment+of+Depression%0d%0aVivien+K.+Burt%2c+M.D.%2c+Ph.D.%0d%0a%0d%0a%0cResponse+and+Remission%0d%0aResponse+to+antidepressant+treatment+frequently+falls+short+of+remission+Full+remission+is+achieved+more+readily+when+the+entire+spectrum+of+depressive+symptoms+is+targeted%0d%0aWith+medication+(single-acting+vs.+dual-acting+agents)+With+psychotherapy%0d%0a%0d%0aSome+special+populations+(such+as+women)+may+respond+preferentially+to+certain+antidepressant+classes%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cDual-+Versus+Single-Acting+Agents%0d%0aCombination+of+fluoxetine+(serotonergic+action)+and+desipramine+(noradrenergic+action)+was+more+effective+in+treating+depression+than+either+agent+alone1+Dual-acting+TCAs+were+more+effective+in+treating+depression+than+single-acting+TCAs+or+selective+serotonin+reuptake+inhibitors+(SSRIs)2%e2%80%934%0d%0aTCAs+have+a+considerable+side+effect+profile%2c+can+be+lethal+in+overdose%0d%0a1Nelson%0d%0a%0d%0aJ%2c+Mazure+C%2c+Jatlow+P%2c+et+al.+Combining+norepinephrine+and+serotonin+reuptake+inhibition+mechanisms+for+treatment+of+depression%3a+a+double-blind%2c+randomized+study.+Biol+Psychiatry+2004%3b55%3a296%e2%80%93300+2Anderson+IM.+SSRIs+versus+tricyclic+antidepressants+in+depressed+inpatients%3a+a+meta-analysis+of+efficacy+and+tolerability.+Depress+Anxiety+1998%3b7(suppl+1)%3a11%e2%80%9317+3Danish+University+Antidepressant+Group.+Paroxetine%3a+a+selective+serotonin+reuptake+inhibitor+showing+better+tolerance%2c+but+weaker+J+Clin+Psychiatry+antidepressant+effect+than+clomipramine+in+a+controlled+multicenter+study.+J+Affect+Disord+1990%3b18%3a289%e2%80%93299+4Danish+University+Antidepressant+Group.+Citalopram%3a+clinical+effect+profile+in+comparison+with+clomipramine%3a+a+controlled+multicenter+study.+Psychopharmacology+(Berl)+1986%3b90%3a131%e2%80%93138%0d%0a%0d%0a%0cDual-+Versus+Single-Acting+Agents%0d%0aVenlafaxine+(SNRI)+%3e+SSRIs1%0d%0a9%25+of+venlafaxine-treated+patients+discontinued+treatment+vs.+7%25+of+SSRI-treated+patients%0d%0a%0d%0a45%25+of+venlafaxine-treated+patients+achieved+remission+vs.+35%25+of+SSRI-treated+patients%0d%0a%0d%0aMirtazapine+(noradrenergic+and+specific+serotonergic+antidepressant)+%3e+SSRIs2%0d%0a13.4%25+of+fluoxetine-treated+patients+discontinued+treatment+vs.+10.6%25+of+mirtazapine-treated+patients+Reduction+in+Hamilton+Rating+Scale+for+Depression+(HAM-D)+scores+from+baseline+was+greater+with+mirtazapine+than+fluoxetine%0d%0a1Thase%0d%0a%0d%0aME%2c+Entsuah+AR%2c+Rudolph+RL.+Remission+rates+during+treatment+with+venlafaxine+or+selective+serotonin+reuptake+inhibitors.+Br+J+Psychiatry+2001%3b178%3a234%e2%80%93241+2Wheatley+D%2c+van+Moffaert+M%2c+Timmerman+L%2c+et+al.+Mirtazapine%3a+efficacy+and+tolerability+in+comparison+with+fluoxetine+in+patients+with+moderate+to+severe+major+depressive+disorder.+J+Clin+Psychiatry+1998%3b59%3a306%e2%80%93312%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cPain%2c+Anxiety%2c+and+SNRIs%0d%0aVenlafaxine+(at+higher+doses)+and+duloxetine+may+be+especially+efficacious+in+alleviating+physical%2c+anxious%2c+and+negative+mood+symptoms+of+depression%0d%0aDuloxetine+showed+a+higher+affinity+than+venlafaxine+for+serotonin+and+norepinephrine+receptors1%0d%0a%0d%0aCompared+with+placebo%2c+duloxetine+significantly+reduced+overall+HAM-D+scores+(p+%3c+.001)%2c2+somatic+symptoms+(p+%3d+.013)%2c2+pain+(p+%3c+.001)%2c2+and+anxiety+(p+%3c+.005)3%0d%0aFP%2c+Dreshfield-Ahmad+LJ%2c+Threlkeld+PG%2c+et+al.+Comparative+affinity+of+duloxetine+and+venlafaxine+for+serotonin+and+norepinephrine+transporters+in+vitro+and+in+vivo%2c+human+serotonin+receptor+subtypes%2c+and+other+neuronal+receptors.+Neuropsychopharmacology+2001%3b25%3a871%e2%80%93880+2Detke+MJ%2c+Lu+Y%2c+Goldstein+DJ%2c+et+al.+Duloxetine%2c+60+mg+once+daily%2c+for+major+depressive+disorder%3a+a+randomized+double-blind+placebo-controlled+trial.+J+Clin+Psychiatry+2002%3b63%3a308%e2%80%93315+3Dunner+D%2c+Goldstein+D%2c+Mallinckrodt+C%2c+et+al.+Duloxetine+in+the+treatment+of+anxiety+symptoms+associated+with+depression.+Depress+Anxiety+2003%3b18%3a53%e2%80%9361%0d%0a1Bymaster%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cDuloxetine+Versus+Placebo+in+MDD%0d%0a%0d%0a*p+%3c+.001+vs.+placebo.+Abbreviations%3a+HAM-D-17+%3d+17-item+Hamilton+Rating+Scale+for+Depression%2c+LS+%3d+least+squares%2c+MDD+%3d+Major+Depressive+Disorder%2c+SNRI+%3d+serotonin-norepinephrine+reuptake+inhibitor.+Reprinted+with+permission+from+Detke+MJ%2c+Lu+Y%2c+Goldstein+DJ%2c+et+al.+Duloxetine%2c+60+mg+once+daily%2c+for+major+depressive+disorder%3a+a+randomized+double-blind+placebo-controlled+trial.+J+Clin+Psychiatry+2002%3b63%3a308%e2%80%93315%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cSymptoms+of+Somatic+and+Pure+Depression+by+Sex%0d%0a%0d%0a*p+%3c+.05+vs.+patients+with+pure+depression.+Data+from+Silverstein+B.+Gender+differences+in+the+prevalence+of+clinical+depression%3a+the+role+played+by+depression+associated+with+somatic+symptoms.+Am+J+Psychiatry+1999%3b156%3a480%e2%80%93482%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cDuloxetine+Efficacy+for+Overall+Pain+in+Women+by+Age%0d%0a%0d%0a*p+%3d+.043%2c+**p+%3c+.001+vs.+placebo.+Reprinted+with+permission+from+Burt+VK.+Plotting+the+course+to+remission%3a+the+search+for+better+outcomes+in+the+treatment+of+depression.+J+Clin+Psychiatry+2004%3b65(suppl+12)%3a20%e2%80%9325%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0cConclusions%0d%0aDual-acting+agents+that+modulate+serotonin+and+norepinephrine+are+more+effective+than+single-acting+agents+in+treating+the+emotional+and+physical+symptoms+of+depression%0d%0aIncluding+pain%0d%0aEspecially+in+women+of+perimenopausal+age%0d%0a%0d%0aJ+Clin+Psychiatry%0d%0a%0d%0a%0c