ANNALS Depression

7/29/2019 ANNALS Depression

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clinic

in the clinic

Screening page ITC5-2

Diagnosis page ITC5-3

Treatment page ITC5-6

Practice Improvement page ITC5-12

CME Questions page ITC5-16

Section EditorBarbara Turner, MD, MSEDSankey Williams, MDDarren Taichman,MD, PhD

Physician WriterTonya L. Fancher, MD

Richard L. Kravitz, MD

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mksap/15/?pr31, and other resources referenced in each issue of In the Clinic.

CME Objective: To review current evidence for the screening, diagnosis, and

treatment of depression

The information contained herein should never be used as a substitute for

clinical judgment.

2010 American College of Physicians

Depression

wnloaded From: http://annals.org/ by Jose Roel on 10/04/2012


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Which patients are at especiallyhigh risk for depression?Risk factors for depression includeolder age (9) and associated neuro-logic conditions, female sex, alcoholdependence, comorbid medical andpsychiatric conditions (10, 11), per-sonal or family history of depression,recent childbirth (12), and stressfullife events (13) (Box). Although spe-cific biological factors predisposing

to depression may emerge, no clini-cally useful biological markers of de-pression have been identified.

A meta-analysis of the interaction betweenthe serotonin transporter gene (5-HTTLPR)and stressful life events yielded no associa-tion with risk for depression (14).

Should clinicians screen fordepression?Depression screening instrumentsdo not diagnose depression but canaccurately identify patients at risk.A 2009 U.S. Preventive ServicesTask Force guideline recommendsscreening adults for depressionwhen staff-assisted depression caresupports are in place to assure accu-rate diagnosis, effective treatment,and follow-up (15). Such supportsinclude outreach personnel and de-pression educators. Follow-up bythe clinician after diagnosis and be-ginning of treatment is critical.

Clinicians should consider screen-ing patients with identified riskfactors or who present with unex-plained somatic symptoms, comor-bid psychological conditions (forexample, panic disorder), substanceabuse, chronic pain, or nonreponseto effective treatments for medicalconditions (16).

A meta-analysis of screening studies sug-gested that screening is associated with a

9% absolute reduction in the proportion ofpatients with persistent depression at 6months. Assuming a prevalence of 10%,110 primary care patients would need tobe screened for depression to produce1 additional remission (1).

However, the absolute reduction,and therefore the utility of screen-ing for depression, is highlydependent on the prevalence ofthe illness in the population beingassessed. The optimum interval for

rescreening is unknown.

What methods should cliniciansuse to screen for depression?A positive response to a 2-iteminstrument (Box) had a sensitivityof 96% and a specificity of 57%,similar to longer instruments (17).

A meta-analysis of 9 case-finding instru-ments in 18 studies and a head-to-headstudy of screening instruments showedthat the 2-question instrument performed

as well as many of the longer ones (18).

2010 American College of Physicians ITC5-2 In the Clinic Annals of Internal Medicine 4 May 2010

1. Pignone MP, GaynesBN, Rushton JL, et al.Screening for depres-sion in adults: a sum-mary of the evidencefor the U.S. PreventiveServices Task Force.Ann Intern Med.2002;136:765-76.[PMID: 12020146]

2. Lustman PJ, AndersonRJ, Freedland KE, et al.Depression and poorglycemic control: ameta-analytic reviewof the literature. Dia-betes Care.2000;23:934-42.[PMID: 10895843]

3. Miranda J, Chung JY,Green BL, et al. Treat-ing depression inpredominantly low-income young mi-nority women: a ran-domized controlledtrial. JAMA.2003;290:57-65.[PMID: 12837712]

4. Gonzlez HM, VegaWA, Williams DR, et al.Depression care inthe United States: toolittle for too few. ArchGen Psychiatry.2010;67:37-46.[PMID: 20048221]

5. Katon WJ, Schoen-baum M, Fan MY, etal. Cost-effectivenessof improving primarycare treatment oflate-life depression.Arch Gen Psychiatry.2005;62:1313-20.[PMID: 16330719]

6. Hays RD, Wells KB,Sherbourne CD, et al.Functioning and

well-being outcomesof patients with de-pression comparedwith chronic generalmedical illnesses.Arch Gen Psychiatry.1995;52:11-9.[PMID: 7811158]

7. Remick RA. Diagnosisand management ofdepression in primarycare: a clinical updateand review. CMAJ.2002;167:1253-60.[PMID: 12451082]

Depression affects 5% to 10% of primary care patients (1) on average;however, this varies widely among clinical populations (2, 3). Only abouthalf of depressed patients receive treatment (4). Untreated depression

may prevent effective treatment of common co-occurring illnesses, such as dia-betes (5). Depression causes disability similar to that of other chronic medicalconditions (6, 7). Effective treatment reduces symptoms and improves quality oflife (8). Asking about depression is sometimes viewed as opening Pandoras box,but primary care clinicians can efficiently identify and manage most cases.

Screening

Risk Factors for Depression

Age

Alcohol dependence

Comorbid conditions

Female sex

Personal or family history of depression

Recent childbirth

Recent stressful events

Screening Questions for Depression

Over the past 2 weeks have you feltdown, depressed, hopeless?

Over the past 2 weeks have you feltlittle interest or pleasure in doingthings?



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2010 American College of PhysiciansITC5-3In the ClinicAnnals of Internal Medicine4 May 2010

Patients with a positive response to 1or both questions should have amore complete assessment to deter-mine whether they meet the criteriafor depression disorders according tothe Diagnostic and Statistical Man-ual of Mental Disorders, fourth edi-tion (DSM-IV) (19).

Other screening tools, such as the

Beck Depression Inventory ScalesII, the Center for EpidemiologicStudies Depression Scale-Revised,and the Zung Self-Rating Depres-sion Scale are also used. The Ed-inburgh Postnatal DepressionScale was developed to assesspostpartum depression (18, 20,21). In elderly persons, the Geri-atric Depression Rating Scale (22)

can be used, but clinicians shouldalso assess with the Mini-MentalState Examination, because cogni-tive impairment requires a specificinstrument (such as the interviewer-administered Cornell Scale forDepression in Dementia [23]).The Hopkins Symptom Checklist-25 has been validated in refugee

populations and is available inmany languages. These instru-ments are designed to assess theseverity of depressed mood, notthe diagnostic criteria for MajorDepressive Disorder as defined inDSM-IV Text Revision. ThePatient Health Questionnaire(PHQ-9) is both a diagnostic andseverity rating instrument (24).

8. Heiligenstein JH, WareJE Jr, Beusterien KM,et al. Acute effects offluoxetine versusplacebo on function-al health and well-be-ing in late-life depres-sion. IntPsychogeriatr. 1995;7Suppl:125-37.[PMID: 8580388]

9. McDonald WM,Richard IH, DeLong

MR. Prevalence, etiol-ogy, and treatment ofdepression in Parkin-sons disease. BiolPsychiatry.2003;54:363-75.[PMID: 12893111]

10. Kendler KS, GardnerCO, Prescott CA.Clinical characteris-tics of major depres-sion that predict riskof depression in rela-tives. Arch Gen Psy-chiatry. 1999;56:322-7. [PMID: 10197826]

11. Runeson B, AsbergM. Family history ofsuicide among sui-cide victims. Am J

Psychiatry.2003;160:1525-6.[PMID: 12900320]

12. Beck CT. Predictorsof postpartum de-pression: an update.Nurs Res.2001;50:275-85.[PMID: 11570712]

13. Person C, Tracy M,Galea S. Risk factorsfor depression after adisaster. J Nerv MentDis. 2006;194:659-66.[PMID: 16971817]

14. Risch N, Herrell R,Lehner T, et al. Inter-action between theserotonin trans-porter gene (5-HT-

TLPR), stressful lifeevents, and risk ofdepression: a meta-analysis. JAMA.2009;301:2462-71.[PMID: 19531786]

15. OConnor EA, Whit-lock EP, Beil TL, et al.Screening for de-pression in adult pa-tients in primarycare settings: a sys-tematic evidence re-view. Ann InternMed. 2009;151:793-803.[PMID: 19949145]

16. Terre L, Poston WS,Foreyt J, et al. Do so-matic complaints

predict subsequentsymptoms of de-pression? PsychotherPsychosom.2003;72:261-7.[PMID: 12920330]

17. Whooley MA, AvinsAL, Miranda J, et al.Case-finding instru-ments for depres-sion. Two questionsare as good as many.J Gen Intern Med.1997;12: 439-45.[PMID: 9229283]

Diagnosis

depression responds equally well tomedication or psychotherapy (26).Patients with severe major depres-sive disorder benefit more frommedication alone or combined withpsychotherapy than from psycho-therapy alone.

The PHQ-9 is easily scored toquantify the severity of depression(Table 2) (24). Like suicidality, se-vere functional impairment, such asinability to bathe or eat, may sug-gest the need for psychiatric con-sultation or hospitalization (27).

How can clinicians and patients

distinguish between normal

reactions to life events and

depression?

Subsyndromal depression is charac-terized by 2 to 4 DSM-IV

What are the diagnostic criteriafor depression?

Depression is diagnosed when 5 ormore DSM-IV symptoms occur inthe same 2 weeks with a changefrom previous functioning (Table 1)(19). One symptom must be eitherdepressed mood or anhedonia. Thecore symptoms of DSM-IV majordepression describe a specific depres-sion syndrome and do not necessari-ly represent a severity index. Only a

clinical interview or use of 1 of thepreviously described instruments canassess severity.

How can clinicians determine theseverity of depression?

Assessment of depressive symptomseverity helps guide treatment.Mild depression may not requiremedication (25). Mild-to-moderate

Screening... Clinicians should screen for depression as the first step in a system-atic evaluation of mood disorders in all adults. Adults who are older, are postpar-tum, have personal or family history of depression, or have comorbid medicalillness are at increased risk. Little evidence recommends one screening methodover another, so physicians can choose the method that best suits their patientpopulation and practice setting. The 2-question instrument is more efficient andperforms as well as longer instruments.

CLINICAL BOTTOM LINE



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18. Mulrow CD, WilliamsJW Jr, Gerety MB, etal. Case-finding in-struments for de-pression in primarycare settings. AnnIntern Med.1995;122:913-21.[PMID: 7755226]

19. Diagnosis and Sta-tisitical Manual ofMental Disorders 4thEdition. Washington,DC: AmericanPyschiatric Associa-tion; 1994.

20. Beck AT, Steer RA,Brown GK. BDI-II,Beck Depression In-ventory: Manual.2nd ed. Boston: Har-court-Brace; 1996.

21. Georgiopoulos AM,Bryan TL, Yawn BP, etal. Population-basedscreening for post-partum depression.Obstet Gynecol.1999;93:653-7.

[PMID: 10912961]22. Yesavage JA. Geri-

atric DepressionScale. Psychophar-macol Bull.1988;24:709-11.[PMID: 3249773]

23. Alexopoulos GS,Abrams RC, YoungRC, et al. CornellScale for Depressionin Dementia. BiolPsychiatry.1988;23:271-84.[PMID: 3337862]

24. Lwe B, Untzer J,Callahan CM, et al.Monitoring depres-sion treatment out-comes with the pa-

tient healthquestionnaire-9.Med Care.2004;42:1194-201.[PMID: 15550799]

25. Fournier JC,DeRubeis RJ, HollonSD, et al. Antidepres-sant drug effectsand depressionseverity: a patient-level meta-analysis.JAMA. 2010;303:47-53. [PMID: 20051569]

26. Thase ME, Green-house JB, Frank E, etal. Treatment of ma-

jor depression withpsychotherapy orpsychotherapy-phar-

macotherapy com-binations. Arch GenPsychiatry.1997;54:1009-15.[PMID: 9366657]

27. Depression in pri-mary care: detection,diagnosis, and treat-ment. Agency forHealthcare Policyand Research. ClinPract Guidel QuickRef Guide Clin.1993;5:1-20.


depressive symptoms, including de-pressed mood or anhedonia, formore than 2 weeks (Table 1). Situa-tional adjustment reaction withdepressed mood (adjustment disor-der) is subsyndromal depressionwith a clear precipitant. Adjustmentdisorder must abate within 6 monthsof the resolution of the stressor, andcareful observation and supportive

counseling are indicated. If the pa-tient meets criteria for major depres-sion, having a stressor does not alterthe diagnosis; however, the clinicianmay chose careful watchful waitingif the major depressive syndromeoccurred only after a defined event.

Differentiating normal grieving andpathologic grief from depression can

Table 1. Criteria for Major Depressive Episode, Based on the Diagnostic and Statistical Manual of

Mental Disorders*

Five or more of the following symptoms (one of which is depressed mood or loss of interest or pleasure) have oc-curred together for a 2-wk period and represent a change from previous functioning:

Depressed mood most of the day, nearly every day as self-reported or observed by others

Diminished interest or pleasure in all or almost all activities most of the day, nearly every day

Significant weight loss when not dieting, or weight gain; or decrease or increase in appetite nearly every day

Insomnia or hypersomnia nearly every day

Psychomotor agitation or retardation nearly every day

Fatigue or loss of energy nearly every day

Feelings of worthlessness or excessive or inappropriate guilt nearly every day

Diminished ability to think or concentrate nearly every day

Recurrent thoughts of death, recurrent suicidal ideation without a specific plan.

The symptoms do not meet criteria for a mixed episode.

The symptoms cause clinically significant distress or impairment in social, occupational, or other areas of functioning.

The symptoms are not due to the direct physiologic effects of a substance (drug or medication) or a general medicalcondition (hypothyroidism).

The symptoms are not better accounted for by bereavement, or the symptoms persist for more than 2 mo or arecharacterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psy-chotic symptoms, or psychomotor retardation.

* From American Psychiatric Association. Guidelines for the Treatment of Patients with Major Depressive Disorder. Wash-ington, DC: American Psychiatric Publishing; 1994.

Table 2. Patient Health Questionnaire-9*

Over the last 2 wk, how often have you been bothered by any of the following problems? (0 = not at all;1 = several days; 2 = more than one half the days; 3 = nearly every day)

1. Little interest or pleasure in doing things

2. Feeling down, depressed, or hopeless

3. Trouble falling or staying asleep or sleeping too much

4. Feeling tired or having little energy

5. Poor appetite or overeating

6. Feeling bad about yourself or that you are a failure or have let yourself or your family down

7. Trouble concentrating on things, such as reading the newspaper or watching television

8. Moving or speaking so slowly that other people have noticed or the opposite (i.e., being so fidgety or restless that

you have been moving around a lot more than usual)9. Thoughts that you would be better off dead or hurting yourself in some way

10. If you have checked off any problems, how difficult have these problems made it for you to do your work, takecare of things at home, or get along with other people?

* The 9 items reflect the 9 DSM-IV criteria. Item 10 assesses functional impairment. Like symptom severity, severe func-tional impairment may suggest the need for hospitalization and psychiatric consultation. 1999 Pfizer Inc. All rights re-served. Reproduced with permission.`

Items 1 through 9 are summed to yield a scale score ranging from 0 to 27. On this scale, 0 to 4 is considered nondepressed,5 to 9 is considered minor depression, 10 to 14 is considered mild depression, 15 to 19 is considered moderately severe de-pression, and 20 to 27 is considered severe depression.



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28. Moscicki EK. Identifi-cation of suicide riskfactors using epi-demiologic studies.Psychiatr Clin NorthAm. 1997;20:499-517. [PMID: 9323310]

29. Brody DS, Thomp-son TL 2nd, LarsonDB, et al. Recogniz-ing and managingdepression in pri-mary care. Gen HospPsychiatry.1995;17:93-107.[PMID: 7789790]

30. Mann JJ, Apter A,Bertolote J, et al. Sui-

cide preventionstrategies: a system-atic review. JAMA.2005;294:2064-74.[PMID: 16249421]

31. Vaiva G, Vaiva G,Ducrocq F, et al. Ef-fect of telephonecontact on furthersuicide attempts inpatients dischargedfrom an emergencydepartment: ran-domised controlledstudy. BMJ.2006;332:1241-5.[PMID: 16735333]

32. Stanford EJ, GoetzRR, Bloom JD. TheNo Harm Contract in

the emergency as-sessment of suicidalrisk. J Clin Psychiatry.1994;55:344-8.[PMID: 8071303]

33. Garvey KA, Penn JV,Campbell AL, et al.Contracting for safe-ty with patients: clin-ical practice andforensic implications.J Am Acad Psychia-try Law. 2009;37:363-70. [PMID: 19767501]

34. Karch DL, Barker L,Strine TW. Race/eth-nicity, substanceabuse, and mentalillness among sui-cide victims in 13 US

states: 2004 datafrom the National Vi-olent Death Report-ing System. Inj Prev.2006;12 Suppl 2:ii22-ii27. [PMID:17170166]

35. Hirschfeld RM, Cal-abrese JR, WeissmanMM, et al. Screeningfor bipolar disorderin the community. JClin Psychiatry.2003;64:53-9. [PMID:12590624]


be difficult. Major depression maybe transiently present in normalgrief; however, sadness without thecomplete syndrome is more com-mon. In some cultures, transient andlimited hallucinations (hearing orseeing the deceased person) or pas-sive suicidal thoughts (feeling thatone would be better off dead orshould have died with the deceasedperson) may be part of normal grief.The boundaries of normal grief areshaped by sociocultural factors.Symptoms of clinical depression be-yond normal grief include inappro-priate guilt, persistent thoughts ofdeath, morbid preoccupation withworthlessness, marked psychomotorretardation, prolonged functionalimpairment, and hallucinations ordelusions. Symptoms persisting be-yond 2 months should raise concern

about major depression.

How should clinicians assess adepressed patients risk for self-harm, including suicide?Each year, more than 30 000 U.S. cit-izens die by suicide. Mental healthconditions and addictive disorders,such as alcohol use disorders, are themost powerful risk factors for suicidein all age groups, present in morethan 90% of all suicides (28). In a pa-

tient with major depression, previoussuicide attempts are the best predictorof completed suicide (29). Most pa-tients who die by suicide have seen aphysician in the preceding months.Clinicians should assess for suicidalintent at each visit for depression.

Asking about and reducing access tolethal means (especially firearms) canreduce this risk (30). Close telephonefollow-up by an experienced psychia-trist can reduce the risk for suicide af-ter a previous attempt (31). Accurateassessment of suicidal risk and theneed for hospitalization is critical. Apsychiatrist should be consulted forany uncertainty regarding suicidalrisk. Previously, physicians used theNo Harm Contract (32), which is averbal or written agreement in whichsuicidal patients agree not to harm or

kill themselves for a particular time-frame and to seek immediate care ifsuicide is seriously considered orplanned.

A recent meta-analysis showed that there is

no evidence for the utility of these safetycontracts and that they afford the physicianlittle, if any, medicolegal protection (33).

In the absence of exacerbating fac-tors, when the patient has adequatesocial support and is able to give rea-sons for living, proceed with outpa-tient treatment and close follow-up.For poor social support, no clear in-dication of alliance for safety, or al-cohol or drug disorders, chooseemergency referral for hospitaliza-tion and psychiatric assessment.

When should clinicians consult amental health professional for

help diagnosing depression or arelated mood disorder?Although many mood disorderscan be successfully managed by theprimary care clinician, psychiatricconsultation should be consideredfor diagnostic uncertainty, psychi-atric comorbid conditions, signifi-cant suicidal ideation, or inadequateresponse to treatment. Psychiatricevaluation is warranted if the clini-cian finds psychotic symptoms

(delusions, hallucinations, disorgan-ized speech, or episodes of catato-nia) or substance abuse. Patientswith psychotic symptoms orcomorbid substance abuse are atgreater risk for suicide and warrantpsychiatric evaluation (34).

Also, screen patients for history ofmanic episodes (days to weeksmarked by unusually high energy,euphoria, hyperactivity, or impairedjudgment). The Mood DisordersQuestionnaire (MDQ) is a usefultool to identify a history of bipolarillness (35). Patients with a depressedmood and an undiagnosed bipolaraffective disorder may convert tofrank mania if prescribed an anti-depressant without a concurrentmood-stabilizing medication. Con-sult a psychiatrist for manic or



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36. Goldberg JF, ErnstCL. Features associ-ated with the de-layed initiation ofmood stabilizers atillness onset in bipo-lar disorder. J ClinPsychiatry.2002;63:985-91.[PMID: 12444811]

37. Paykel ES, Scott J,Teasdale JD, et al.Prevention of re-lapse in residual de-pression by cogni-

tive therapy: acontrolled trial. ArchGen Psychiatry.1999;56:829-35.[PMID: 12884889]

38. Fava GA, Rafanelli C,Grandi S, et al. Six-year outcome forcognitive behavioraltreatment of residualsymptoms in majordepression. Am JPsychiatry.1998;155:1443-5.[PMID: 9766780]

39. Kessler D, Lewis G,Kaur S, et al. Thera-pist-delivered Inter-net psychotherapyfor depression in pri-

mary care: a ran-domised controlledtrial. Lancet.2009;374:628-34.[PMID: 19700005]

40. Warmerdam L, vanStraten A, Twisk J, etal. Internet-basedtreatment for adultswith depressivesymptoms: random-ized controlled trial.J Med Internet Res.2008;10:e44.[PMID: 19033149]


hypomanic symptoms after startingan antidepressant. Mania may alsopresent as a mixed state of depres-sion with significant psychomotoragitation or racing thoughts. Thus,agitation after starting antidepressanttreatment is a source of concern.Delays in starting mood-stabilizingdrug therapy for bipolar disorder,even when mild, increases the risk

for suicidal behavior, poor social ad-justment, and more hospitalization(36). Adherence to antidepressantsshould be assessed, because it affectsresponse. The physician might ob-tain data, as needed, for related con-ditions (for example, thyroid disor-ders, HIV testing, urine toxicology),but extensive testing without a clearindication is not recommended.

What types of behavioralinterventions and psychotherapy

are most likely to be effective fordepression?

Three types of psychotherapeuticoptions have proven to be effective:cognitive behavioral therapy (CBT),interpersonal therapy (IPT), andproblem-solving therapy (PST). Theaim of CBT is to modify thoughtsand behaviors to yield positive emo-tions. It is also used to treat residualsymptoms after drug therapy andmay help prevent relapse in patientswith a history of recurrent depression(38). IPT targets conflicts and roletransitions contributing to the depres-sive episode. It is only useful whenthe patient has the capacity for psy-chological insight and is committedto longer-term therapy. In PST, pa-tients learn to cope better with specif-ic everyday problems. Sophisticatedbehavioral interventions and psy-chotherapy require specialized train-

ing, but primary care clinicians canoften employ basic tenets of thesetherapies, such as asking a patient tokeep a journal about situations inwhich they feel more depressed to re-view at monitoring visits. Therapistsoften combine all 3 techniques. Web-based CBT and PST lessons are ef-fective and may provide another

How should clinicians decidewhether to recommend

psychotherapy, drug therapy, or

both?

A recent meta-analysis questionsthe benefits of antidepressant med-ication compared with placebo inpatients with mild or moderatesymptoms (25).

Fournier and colleagues examined individ-

ual patient-level data from 6 randomized,

controlled trials and found that the mag-

nitude of benefit from antidepressantsincreased with the severity of depression

symptoms and may be minimal (or nonex-

istent) in patients with mild or moderate

symptoms (25).

Patients with mild-to-moderatemajor depression may benefitequally from psychotherapy ormedication (26). Combined thera-py shows no short-term benefit, al-though psychotherapy may protectbetter against relapse (37). Patient

preference remains the primary fac-tor in choosing initial therapy.Therapist availability and insurancepolicies can also be barriers to care.Severely depressed patients benefitmore from antidepressant medica-tion, alone or in combination withpsychotherapy, than from psycho-therapy alone (26).

Diagnosis... The DSM-IV criteria are the standard for diagnosing major depres-sion. The risk for suicide and comorbid mental and physical illness should be as-sessed in each patient. If clinicians are uncertain about the diagnosis, risk forsuicide, or need for hospitalization, psychiatric consultation should be considered.

CLINICAL BOTTOM LINE

Treatment



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Table 3. Drug Treatment for Depression

Agent, Daily Dose* Benefits Side Effects and Notes

Second-generation As a class: Effective, As a class: Nausea, diarrhea, decreased appetite, nervousness, insomnia,antidepressants well tolerated somnolence, sweating, impaired sexual function; hyponatremia in the

elderly. Contraindicated with MAOIs. Potential for drug interactionswith drugs metabolized in liver. Delicate risk/benefit calculus inpregnancy.

Bupropion, 300450 mg Less weight gain than other Lowers seizure threshold. Relatively contraindicated in patients with(75225 mg) second-generation agents, fewer history of seizures, family history of seizures, or head trauma. Missed

sexual side effects. Approved for doses should not be taken with next dose. Use with caution with othersmoking cessation drugs that may lower seizure threshold and in patients with impaired

hepatic function or anorexia/bulimia.Citalopram, 2060 mg Few drug interactions See class effects. Relatively selective 5-HT reuptake inhibitor, but clinical

(1040 mg) implications unclear.

Duloxetine, 3060 mg May be effective in comorbid Agitation, urinary retention. Withdrawal symptoms may occur.pain and depression

Escitalopram, 520 mg (510 mg) Few drug interactions See class effects. Similar to citalopram.

Fluoxetine, 2060 mg (540 mg) Longest clinical experience. See class effects. Among the first newer antidepressants on the market.Long half-life mitigates effects ofmissed doses. Withdrawalsymptoms rare

Mirtazapine, 1545 mg Faster onset of action than Increased appetite, somnolence. Both may be an advantage in(7.530 mg) citalopram, fluoxetine, hospitalized patients. Use caution with renal impairment. Avoid

paroxetine or sertraline concomitant benzodiazepines and alcohol.

Paroxetine, 2050 mg (540 mg) Long clinical experience More weight gain and sexual adverse events. Withdrawal syndrome not

uncommon. Long-acting formulations may be less prone to withdrawalsyndrome.

Sertraline, 50200 mg Long clinical experience Higher incidence of diarrhea. Generally well-tolerated.(25150 mg)

Trazodone, 50400 mg Less effective in doses


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41. Clinical Efficacy As-sessment Subcom-mittee of AmericanCollege of Physi-cians. Using second-generation antide-pressants to treatdepressive disorders:a clinical practiceguideline from theAmerican College ofPhysicians. Ann In-

tern Med.2008;149:725-33.[PMID: 19017591]

42. Cipriani A, La Ferla T,Furukawa TA, et al.Sertraline versusother antidepressiveagents for depres-sion. Cochrane Data-base Syst Rev.2010:CD006117.[PMID: 20091586]

43. Williams JW Jr, Mul-row CD, Chiquette E,et al. A systematicreview of newerpharmacotherapiesfor depression inadults: evidence re-port summary. Ann

Intern Med.2000;132:743-56.[PMID: 10787370]

44. STAR*D Study Team.Medication aug-mentation after thefailure of SSRIs fordepression. N Engl JMed. 2006;354:1243-52. [PMID: 16554526]

45. Lin EH, Von Korff M,Katon W, et al. Therole of the primarycare physician in pa-tients adherence toantidepressant ther-apy. Med Care.1995;33:67-74.[PMID: 7823648]

46. Wells KB, Sher-

bourne C, Schoen-baum M, et al. Im-pact ofdisseminating quali-ty improvement pro-grams for depres-sion in managedprimary care: a ran-domized controlledtrial. JAMA.2000;283:212-20.[PMID: 10634337]

47. Dubicka B, Hadley S,Roberts C. Suicidalbehaviour in youthswith depressiontreated with new-generation antide-pressants: meta-analysis. Br J

Psychiatry.2006;189:393-8.[PMID: 17077427]

48. Stone M, LaughrenT, Jones ML, et al.Risk of suicidality inclinical trials of anti-depressants inadults: analysis ofproprietary datasubmitted to USFood and Drug Ad-ministration. BMJ.2009;339:b2880.[PMID: 19671933]


approach for patients to access psy-chotherapeutic interventions (39, 40).

How should clinicians select fromthe many antidepressant drugtherapies?Clinicians face a wide array of anti-depressant drug options (Table 3).The most commonly prescribeddrugs are the second-generation

antidepressants: selective serotoninreuptake inhibitors [SSRIs], sero-tonin norepinephrine reuptake in-hibitors [SNRIs], and bupropion.First-generation antidepressants(tricyclic antidepressants [TCAs]and monoamine oxidase inhibitors[MAOIs]) may offer similar effec-tiveness, but with more toxicity(41). Generally, TCAs are avoidedbecause of considerable dry mouth,constipation, and dizziness. TCAs

are relatively contraindicated inpatients with coronary artery dis-ease, congestive heart failure, andarrhythmias. They are also poten-tially fatal in overdose. MAOIs arealso used infrequently, even by psy-chiatric specialists, because of themany dietary restrictions and thepotential for hypertensive crisis (ex-cept for the newer selegeline patch).Primary care clinicians should con-sult with a psychiatrist before con-sidering MAOI therapy.

Drug selection is based on tolera-bility, safety, evidence of effective-ness in the patient or a first-degreerelative, and cost.

A recent review of 59 mostly low-quality

studies found a trend in favor of sertraline

over other antidepressants in terms of effi-

cacy and acceptability (42).

Regardless of the drug, most pa-tients treated with antidepressantsexperience improvement by 6weeks (43). However, relatively fewachieve baseline levels of mood and

functioning at this point (44), andmany require dose adjustment,switching to another drug, aug-mentation with a second agent, orthe addition of psychotherapy.

How should clinicians monitor

response to drug therapy?

Treatment for depression requires atleast 6 to 9 months with close fol-low-up (Table 4). The first 2 weeksof drug therapy are often the most

challenging. The pessimism andhopelessness intrinsic to depressionand the relatively rapid onset of sideeffects can lead to nonadherence:28% of depressed primary carepatients stop taking their medica-tion in the first month, and 44%stop within 3 months (45).

Clinicians should follow up pa-tients within 1 to 2 weeks of start-ing therapy to ask about acceptanceof medication, reinforce educational

messages, reassess suicidality, andaddress adverse events. Telephonefollow-up by a trained nurse is alsoeffective (46). Addressing specificadverse effects is critical to

Table 4. Follow-up for Depression*

Depression Severity Suggested Follow-up

Minor Watchful waiting, re-evaluate in 48 wk

Mild (PHQ-9 score of 1014) Contact by phone or in-person monthly(whether or not antidepressants are prescribed)

Moderate (PHQ-9 score of 1519) Contact by phone or in-person every 24 wk

Severe (PHQ-9 score of20) Contact by phone or in-person every 24 wkuntil PHQ-9 score improved by at least 5 points

If no active treatment, receiving on-going Contact by phone or in-person every 23 mostable antidepressants or counseling after remission

PHQ-9 = Patient Health Questionnaire.

* Adapted from The MacArthur Initiative in Depression and Primary Care (www.depression-primarycare.org).



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49. Grunebaum MF, EllisSP, Li S, et al. Antide-pressants and sui-cide risk in the Unit-ed States,1985-1999. J ClinPsychiatry.

2004;65:1456-62.[PMID: 15554756]

50. Reynolds CF 3rd,Dew MA, Pollock BG,et al. Maintenancetreatment of majordepression in oldage. N Engl J Med.2006;354:1130-8.[PMID: 16540613]

51. Spier SA. Use ofbupropion with SRIsand venlafaxine. De-press Anxiety.1998;7:73-5.[PMID: 9614595]

52. Carpenter LL, JocicZ, Hall JM, et al. Mir-tazapine augmenta-tion in the treatment

of refractory depres-sion. J Clin Psychia-try. 1999;60:45-9.[PMID: 10074878].

53. Shelton RC, Pa-pakostas GI. Aug-mentation of antide-pressants withatypical antipsy-chotics for treat-ment-resistant majordepressive disorder.Acta PsychiatrScand. 2008;117:253-9. [PMID: 18190674]

54. Candy M, Jones L,Williams R, et al. Psy-chostimulants fordepression.Cochrane Database

Syst Rev.2008:CD006722.[PMID: 18425966]

55. Hardy SE.Methylphenidate forthe treatment of de-pressive symptoms,including fatigueand apathy, in med-ically ill older adultsand terminally illadults. Am J GeriatrPharmacother.2009;7:34-59.[PMID: 19281939]

56. Obrocea G. Thyroidhormone augmen-tation in treatmentresistant depression.Clin Pyschopharma-

col Neurosci.2008;6:3-10

57. Cooper-Kazaz R,Lerer B. Efficacy andsafety of triiodothy-ronine supplemen-tation in patientswith major depres-sive disorder treatedwith specific sero-tonin reuptake in-hibitors. Int J Neu-ropsychopharmacol.2008;11:685-99.[PMID: 18047754]


maintaining adherence untilpatients respond. In addition, anti-depressants may be associated withan increased risk for suicide in chil-dren, adolescents, and young adults.

A meta-analysis of 2741 patients age 6 to

18 years showed an increased relative risk

for self-harm or suicide-related events in

patients treated with newer-generation

antidepressants compared with those giv-en placebo (4.8% vs. 3.0%; P = 0.01; num-

ber-needed-to-treat for harm, 55). Because

actual suicide is rare in such studies, the in-crease in risk for suicide, rather than for sui-

cidal behaviors, can only be inferred (47).

The U.S. Food and Drug Admin-istration (FDA) has issued aPublic Health Advisory recom-mending close monitoring of allpatients treated with antidepres-sants, particularly in the first 1 to

2 months of treatment. A warningstatement regarding a possible in-creased risk for suicide has beenadded to FDA Patient Informa-tion Sheets for citalopram, duloxe-tine, venlafaxine, escitalopram,fluvoxamine, paroxetine, fluoxe-tine, mirtazapine, bupropion, andsertraline. Clinicians should askabout agitation, irritability, orunusual changes in behavior.Compared with placebo, adults

younger than 25 years have anincreased risk for suicidal behavior(odds ratio, 2.3) (48). The FDArecommends weekly follow-up inthese patients for the first month,biweekly for the next month, andmonthly thereafter. Most evidencesuggests that, when properlyadministered, antidepressantsavert many more suicides thanthey cause (49).

If response to medication is inade-

quate after 6 to 8 weeks of therapy,treatment should be modified. Re-currence of depression after a firstepisode is common. Cliniciansshould educate patients and theirfamilies to self-assess for symptomsand risk for recurrent episodes.Surveillance for recurrence or re-lapse should continue indefinitely.

How long should clinicians treat

depressed patients with drugs, and

when should they consider long-term maintenance on drug

therapy?

The goal of treatment is completeremission of symptoms and return tonormal functioning. For the firstepisode, antidepressant treatment maytake 1 to several months until remis-sion is achieved and should be con-tinued for another 4 to 9 months.Although not strictly evidence-based,some clinicians advocate treatmentfor at least 1 year to maintain remis-sion for a full annual cycle of holidaysand anniversaries. For multipleepisodes of depression, an even longerduration of therapy may be beneficial(41). For older patients (>70 years)with major depression who respondto an SSRI, consider treating for 2years to prevent recurrence (50).

When should clinicians consider

switching drugs because of a

suboptimum response to initialdrug therapy?

Most patients starting antidepres-sant therapy do not achieve com-plete remission, so increasing thedose of the current medication orchanging drugs is often necessary.

STAR*D (Sequenced Treatment Alterna-

tives to Relieve Depression) randomly as-

signed patients to 1 of several treatment

sequences, all starting with 12 weeks of

citalopram. The study showed that 30% of

patients achieved complete remission af-

ter 12 weeks of citalopram. Of those who

did not improve with citalopram, about

25% responded to an alternative agent

(sertraline, venlafaxine, or bupropion) and

another one-third responded to augmen-

tation with bupropion (44)

For a partial response, the dose of

the initial agent should be maxi-mized as tolerated before switchingto another medication or addinga second drug. When a partialresponse continues, the clinician canrefer for psychotherapy, change anti-depressants, or augment treatmentwith bupropion, mirtazapine, or anontraditional agent.



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58. Carney RM, Freed-land KE, Rubin EH, etal. Omega-3 aug-mentation of sertra-line in treatment ofdepression in pa-tients with coronaryheart disease: a ran-domized controlledtrial. JAMA.

2009;302:1651-7.[PMID: 19843899]

59. Golden RN, GaynesBN, Ekstrom RD, etal. The efficacy oflight therapy in thetreatment of mooddisorders: a reviewand meta-analysis ofthe evidence. Am JPsychiatry.2005;162:656-62.[PMID: 15800134]

60. Mead GE, Morley W,Campbell P, et al. Ex-ercise for depression.Cochrane DatabaseSyst Rev.2009:CD004366.[PMID: 19588354]

61. Morgan AJ, Jorm AF.Self-help interven-tions for depressivedisorders and de-pressive symptoms:a systematic review.Ann Gen Psychiatry.2008;7:13.[PMID: 18710579]

62. Nurnberg HG, Hens-ley PL. Selectivephosphodiesterasetype-5 inhibitortreatment of sero-tonergic reuptake in-hibitor antidepres-sant-associatedsexual dysfunction: areview of diagnosis,treatment, and rele-

vance. CNS Spectr.2003;8:194-202.[PMID: 12595814]

63. Wright SK, SchroeterS. Hyponatremia as acomplication of se-lective serotonin re-uptake inhibitors. JAm Acad NursePract. 2008;20:47-51.[PMID: 18184165]

64. Osteoporotic Frac-tures in Men StudyGroup. Associationof low bone mineraldensity with selec-tive serotonin reup-take inhibitor use byolder men. Arch In-tern Med.

2007;167:1246-51.[PMID: 17592097]

65. Smoller JW, AllisonM, Cochrane BB, etal. Antidepressantuse and risk of inci-dent cardiovascularmorbidity and mor-tality among post-menopausal womenin the WomensHealth Initiativestudy. Arch InternMed. 2009;169:2128-39. [PMID: 20008698]


Compared with withdrawing onedrug and starting another, combina-tion therapy offers faster effects, po-tential for synergistic or complemen-tary effects, and avoidance ofwithdrawal symptoms when stop-ping the first agent. But with a morecomplex regimen, drug interactionsand adverse effects can increase.

Adding bupropion to an SSRI orvenlafaxine therapy may enhanceresponse or treat side effects inmany patients (51). Similar re-sponse rates occur when addingmirtazapine to SSRI treatment(52). Combinations of MAOIs andeither SSRIs or TCAs are not rec-ommended, because of increasedrisk for the serotonin syndrome(with confusion, nausea, autonomicinstability, and hyperreflexia).

Adding atypical antipsychotics,psychostimulants, and thyroid hor-mone remains controversial. Anti-psychotics added to SSRIs fortreatment-resistant depression showsome benefit but also carry signifi-cant risks, so their use should belimited to psychiatrists (53).

A Cochrane review of psychostimulants(dexamphetamine, methylphenidate, me-

thylamphetamine, demoline, modafinil) for

moderate-to-severe depression found short-

term improvement in depression symptomsand fatigue (54). A second review of 19 con-

trolled trials on adults older than 65 years

supported this recommendation for methyl-

phenidate; however, dosing, when to initiatetherapy, and how to monitor side effects re-

mains unclear (55).

Studies are conflicting about the ef-fectiveness of adding thyroid hor-mone (triiodothyronine [T3] andlevothyroxine [T4]) to antidepres-sants. (56, 57). More research is need-

ed before these therapies can be rec-ommended for use in primary care.Augmentation with other nontradi-tional agents has also shown mixedresults: omega-3 fatty acids added tosertraline in patients with coronaryheart disease did not improve depres-sive outcomes (58), whereas lighttherapy (6000 to 10 000 lux for 30 to

90 minutes each morning) for winterdepression (59), yoga, self-help books,exercise (60), relaxation therapy (61),and acupuncture seem useful.

What are the common adverse

effects of antidepressant drugs

and how should clinicians manage

these effects?

Specific types of side effects aremore common with particulardrugs and should guide choice ofmedications (Table 3). Sexual sideeffects of SSRIs include decreasedlibido or interest (men andwomen), anorgasmia (women), anddelayed ejaculation (men). To ad-dress these side effects, considerpretreatment counseling, switchingto a drug with a different mecha-nism of action (for example, bupro-pion or mirtazapine), or usingsildenafil for SSRI-associated erec-tile dysfunction if no contraindica-tions (62). Switching to bupropioncan reduce undesired weight gain.Agitation or excessive activation,most commonly with fluoxetine,warrants switching to another SSRIand considering mixed mania.Adding a low-dose tricyclic agent,mirtazapine, trazodone, or a seda-tive-hypnotic may reduce insomnia

early in the course of treatment.During SSRI initiation, cliniciansmay also provide a short course ofbenzodiazepines to counter anxietywith major depression or earlySSRI treatment. SSRIs are associ-ated with hyponatremia in elderlypersons (63) and may promoteosteoporosis (64).

Analysis from the Womens Health Initia-

tive found that although antidepressant

use did not increase the risk for coronary

heart disease, SSRI use was associated withan increased risk for hemorrhagic and fa-

tal stroke and that both SSRI and TCA were

associated with increased mortality (65).

Conversely, OConnor and colleagues stud-

ied 1006 patients with clinical heart failure

and reported that depression, and not anti-

depressant use, was associated with in-

creased mortality (66).



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66. OConnor CM, JiangW, Kuchibhatla M, etal. Antidepressantuse, depression, andsurvival in patientswith heart failure.Arch Intern Med.2008;168:2232-7.[PMID: 19001200]

67. Linde K, Berner MM,Kriston L. St Johns

wort for major de-pression. CochraneDatabase Syst Rev.2008:CD000448.[PMID: 18843608]

68. Obach RS. Inhibitionof human cy-tochrome P450 en-zymes by con-stituents of St. JohnsWort, an herbalpreparation used inthe treatment of de-pression. J Pharma-col Exp Ther.2000;294:88-95.[PMID: 10871299]

69. de Maat MM,Hoetelmans RM,Math RA, et al. Drug

interaction betweenSt Johns wort andnevirapine. AIDS.2001;15:420-1.[PMID: 11273226]

70. Ondrizek RR, ChanPJ, Patton WC, et al.Inhibition of humansperm motility byspecific herbs usedin alternative medi-cine. J Assist ReprodGenet. 1999;16:87-91. [PMID: 10079411]

71. Pies R. Handbook ofEssential Psy-chopharmacology,second ed. Ameri-can Psychiatric Pub-lishing; 2005.

72. Chambers CD, Her-nandez-Diaz S, VanMarter LJ, et al. Se-lective serotonin-re-uptake inhibitorsand risk of persistentpulmonary hyper-tension of the new-born. N Engl J Med.2006;354:579-87.[PMID: 16467545]

73. U.S. Food and DrugAdministration. FDAPublic Health Advi-sory: TreatmentChallenges of De-pression in Pregnan-cy. 2006. Accessed atwww.fda.gov/Drugs/DrugSafety/Pub-

licHealthAdvi-sories/ucm124348.htm on 25 March2010.

74. Einarson A, Pistelli A,DeSantis M, et al.Evaluation of the riskof congenital cardio-vascular defects as-sociated with use ofparoxetine duringpregnancy. Am JPsychiatry.2008;165:749-52.[PMID: 18381907]


When should clinicians consult a

psychiatrist for help in managing

drug therapy?

Treatment-resistant depression iscommon and may require psychiatricconsultation. Referral may be neces-sary for patients who have not re-sponded to agents familiar to theprimary care provider, have repeatedfailures, or have side effects that aredifficult to manage. The thresholdfor referral should be lower for moreseverely impaired patients. TheAgency for Healthcare Research andPolicy recommends a psychiatricconsult for severe symptoms; height-ened suicide risk; comorbid, psychi-atric, or substance abuse problems;or lack of response to appropriatetreatment (27).

Electroconvulsive therapy can be

considered for depressed patientswho have psychotic features, suici-dal thoughts, no response to anti-depressants, or who cannot tolerateantidepressants. Electroconvulsivetherapy should be managed by apsychiatrist (7).

When should clinicians consider

hospitalizing depressed patients?

Hospitalization should be consideredfor significant suicidal ideation or in-

tent without safeguards in the familyenvironment, express intent to hurtothers, requirement for close obser-vation (to assess self-care and adher-ence), detoxification or substanceabuse treatment, electroconvulsivetherapy candidates, or dysfunctionalfamily systems worsening the de-pressive disorder or interfering withtreatment. When a patients life is injeopardy, hospitalization against theirwishes is necessary. The conditionsof such involuntary hospitalizationare governed by state-specific legalrequirements.

What should clinicians advisepatients about

complementaryalternative

treatments for depression?

St. Johns wort (Hypericum) may bebeneficial for subsyndromal

depression or for patients who areunwilling or cannot take conven-tional therapy for mild depression.

A Cochrane review suggests that Hyper-

icum extracts are as effective as standardantidepressants for mild depression andhave fewer side effects (67).

St. Johns wort should not be used

for moderate-to-severe majordepression, because of lack of benefit.Although St. Johns wort has mixedresults in randomized, placebo-controlled trials, serious adverseeffects are uncommon. Many trialswith positive findings have usedstandardized doses of 0.3% hyper-icin, 300 mg three times a day (67).

There are important caveats to theuse of St Johns wort. To avoidsymptoms of serotonin excess, do

not use with SSRIs. Through acti-vation of the cytochrome P450 sys-tem, St. Johns wort may reduceplasma concentration of digoxin,theophylline, simvastatin, and war-farin (68). Severe drug interactionshave also been reported with anti-retroviral therapy; St. Johns wortcan decrease concentrations of pro-tease inhibitors and nonnucleosidereverse transcriptase inhibitors (69).At high concentrations, St. Johns

wort may harm sperm cells and leadto decreased fertility (70). The Na-tional Institute of Healths NationalCenter for Complementary and Al-ternative Medicine is a good re-source for more information (http://nccam.nih.gov/health/stjohnswort).

If a patient relapses aftercessation of depression treatment,should clinicians resume previouslyeffective therapy or select a newtherapy?

Recurrence of major depressionrequires long-term maintenancetherapy with the same antidepres-sant that previously led to remis-sion. Lifetime therapy may berequired for patients with 3 ormore depressive episodes or withfirst recurrence and risk factors formore recurrences (family history of



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bipolar disorder, recurrence


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75. Cohen LS, AltshulerLL, Harlow BL, et al.Relapse of major de-pression duringpregnancy inwomen who main-tain or discontinueantidepressant treat-ment. JAMA.2006;295:499-507.[PMID: 16449615]

76. Miller LJ. Psychiatric

medication duringpregnancy: under-standing and miniz-ing risks. PsychiatrAnn. 1994;24:69-75.

77. Delgado PL. Ap-proaches to the en-hancement of pa-tient adherence toantidepressant med-ication treatment. JClin Psychiatry.2000;61 Suppl 2:6-9.[PMID: 10714617]

78. Ong MK, RubensteinLV. Wishing upon aSTAR*D: the promiseof ideal depressioncare by primary careproviders. Psychiatr

Serv. 2009;60:1460-2.[PMID: 19880461]

79. Gilbody S, Bower P,Fletcher J, et al. Col-laborative care fordepression: a cumu-lative meta-analysisand review oflonger-term out-comes. Arch InternMed. 2006;166:2314-21. [PMID: 17130383]

80. Weissman MM, Olf-son M. Translatingintergenerational re-search on depres-sion into clinicalpractice. JAMA.2009;302:2695-6.[PMID: 20040558]

81. Gilbody S, Sheldon T,House A. Screeningand case-finding in-struments for de-pression: a meta-analysis. CMAJ.2008;178:997-1003.[PMID: 18390942]

82. Unutzer J, Katon WJ,Fan MY, et al. Long-term cost effects ofcollaborative care forlate-life depression.Am J Manag Care.2008;14:95-100.[PMID: 18269305]

83. Bower P, Rowland N.Effectiveness andcost effectiveness ofcounselling in pri-

mary care. CochraneDatabase Syst Rev.2006;3:CD001025.[PMID: 16855955]

84. Sherbourne CD,Wells KB, Duan N, etal. Long-term effec-tiveness of dissemi-nating quality im-provement fordepression in pri-mary care. Arch GenPsychiatry.2001;58:696-703.[PMID: 11448378]


checking with the physician, and re-

solve questions regarding antidepres-

sants and potential side effects with the

physician (45).

Nonadherence often begins in thefirst weeks of therapy and is related tobeliefs about the illness, concerns overside effects, ineffectiveness of treat-ment, cost of medications, and diverse

cultural and attitudinal factors (77).Clinicians should routinely ask pa-tients and their families about theirbeliefs. Personalizing educationalmessages to address the patients be-liefs will enhance the benefit. When-ever possible, family involvement mayimprove acceptance of and supportfor the patients condition and mayenhance response. Patients and theirfamilies should receive appropriatewritten and electronic patient educa-

tion materials about depression andits management. Clinicians can im-prove the effect of printed material byintensive reinforcement of key educa-tional messages (45).

How can primary care practices

improve depression care?

Improving outcomes in depressioncare requires systems change (78).Elements shown to support im-provement include collaborativecare involving primary care clini-cians and mental health specialists,systematic tracking of outcomeswith decision support, and use ofnurses or office staff to coordinatefollow-up (79, 80). Recommenda-tions to adopt screening strategiesusing questionnaires without orga-nizational enhancements may notbe justified (81). Changing physi-cian behavior requires structuredinterventions that operate inde-pendently of physician initiation.

Most collaborative care models re-quire additional resources, but someare cost-saving (82), and overallcosts seem commensurate withdemonstrated benefit. Implementa-tion of these approaches requiresinitiative at the level of the healthcare delivery system rather than inthe doctor-patient relationship.

A meta-analysis of 37 RCTs showed that

collaborative care is more effective than

standard care in improving depression

outcomes (83).

What criteria are used to judge

the quality of depression care?

The Ambulatory Care Quality Al-liance has adopted 2 antidepressantmedication management measures

developed by the National Com-mittee for Quality Assurance: anti-depressant therapy for at least 12weeks after the initial diagnosis andtreatment and continuous antidepressant therapy for at least 6months after the initial diagnosisand treatment. For more informa-tion, see www.aqaalliance.org/performancewg.htm.

A study of 1299 patients in a primary care

HMO compared usual care with 2 quality-

improvement programs: one offered med-

ication-focused management, and the

other emphasized psychotherapy. Both

interventions showed benefit versus usual

care at 6 and 12 months, but only the psy-

chotherapy intervention showed a persist-

ent benefit at 24 months in both clinical

outcomes and mental healthrelated

quality of life (84).

What do professional

organizations recommend

regarding screening for and

managing depression?

In 2009, the U.S. Preventive Serv-ices Task Force issued guidelines onscreening for depression (www.ahrq.gov/clinic/uspstf/ix.htm). The TaskForce recommends screening adultsin clinical practices with staff-assisted depression care supports.The Task Force also issued a guide-line on screening for suicide risk in2004 (www.ahrq.gov/clinic/uspstf/uspssuic.htm).

The American Psychiatric Associa-tion published its Practice Guidelinefor the Treatment of Patients withMajor Depressive Disorder in 2002,and a third edition is under develop-ment (www.psych.org/psych_pract/treatg/pg/MDD2e_05-15-06.pdf). Updates to this guideline



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inthec

linic

Tool Kit

in the clinic

Depression

PIER Moduleshttp://pier.acponline.org/physicians/diseases/d954/d954.html

Access the PIER module on depression from the American College of

Physicians. PIER modules provide an evidence-based, electronic resourcefor clinical recommendations and links to patient information materials atthe point of care.

Depression Scaleswww.chcr.brown.edu/pcoc/cesdscale.pdf

Center for Epidemiological Studies Depression Scale

http://healthnet.umassmed.edu/mhealth/ZungSelfRatedDepressionScale.pdf

Zung Self-Depression Scale

www.stanford.edu/~yesavage/GDS.html

Geriatric Depression Scale

www.nelmh.org/downloads/other_info/hopkins_symptom_checklist.pdf

Hopkins Symptom Checklist

www.aap.org/practicingsafety/Toolkit_Resources/Module2/EPDS.pdf

Edinburgh Postnatal Depression Scale

Patient Informationwww.doctorsforadults.com/images/healthpdfs/depression.pdf

Downloadable brochure on depression and how internists can help.

www.depression-primarycare.orgPatient education handouts on depression symptoms, management, med-ications, and psychological counseling.

www.annals.org/intheclinic/toolkit-depression.html

Download an electronic copy of the patient information sheet on the nextpage for duplication and use in your office

www.nlm.nih.gov/medlineplus/depression.html

Public-oriented information on depression, including educational informa-tion from the National Institutes of Mental Health and other organiza-tions, recent studies, and news. Many resources are available in Spanish.

4 May 2010Annals of Internal MedicineIn the ClinicITC5-14 2010 American College of Physicians

are available (www.psych.org/psych_pract/treatg/pgMDDWatch.pdf).

The MacArthur Initiative in De-pression and Primary Care, in col-laboration with Dartmouth Collegeand Duke University, has expandedthe work of the AHRQ by devel-oping a comprehensive Web sitethat offers provider guidelines and

patient education resources

covering all aspects of depressionmanagement. It can be accessed atwww.depression-primarycare.org.

Pharmacologic therapy of majordepression and dysthymia is cov-ered in clinical guidelines from theAmerican College of Physiciansthat were issued in 2008 (www.annals.org/cgi/content/149/

10/725.abstract).



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In the Clinic

Annals of Internal Medicine

PatientIn

formation

THINGS YOU SHOULDKNOW ABOUTDEPRESSION

Depression makes you feel sad and makes it hard to door enjoy anything. Talking to a therapist or takingthe right medicine can make you feel better.

What You Can Do Dont be afraid to ask for help.

If the doctor gives you medicine, take it every day.

Dont expect your medicine to work for 2 to 4 weeksafter you start it.

Keep taking your medicine even if you feel better.

Dont stop your medicine without checking withyour doctor.

Expect to take your medicine for at least 6 months.

See the doctor 1 to 2 weeks after you start medicineand then again in 6 weeks.

Ask your doctor about side effectsputting onweight, feeling nervous, or having trouble with sex.

Ask your doctor about the right people to talk toand how your family can help you.

If you feel bad or need help, call your doctor or 911or go to the emergency room right away.

Ask your doctor about seeing aspecialist if: Your medicines dont seem to be working

Your medicines have too many side effects

You are having strange thoughts or big mood swings

You feel you may hurt yourself or other people

You are drinking too much or taking street drugs

For More Informationwww.nlm.nih.gov/medlineplus/depression.htmlMedlinePLUS

www.nami.org/Template.cfm?Section=By_Illness/TaggedPage/TaggedPageDisplay.cfmNational Alliance on Mental Illness

www.nimh.nih.gov/publicat/depression.cfmNational Institutes of Mental Health

www.fda.govU.S. Food and Drug Administration (search for depression drugs)

www.cancer.gov/espanol/pdq/cuidados-medicos-apoyo/depresion/patient/National Cancer Institute (Spanish)



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5.

4.

3.

CME Questions

A 25-year-old woman is evaluated for a 2-month history of feeling down andhopeless after her fianc ended theirengagement. She believes that the brokenengagement was somehow her fault. The

patient also reports spending less time withfriends, restricting previously enjoyablesocial activities, and having difficultyconcentrating. During the past week, shehas been thinking increasingly aboutending her life and has been fingering aknife when at home alone whilecontemplating cutting her wrists. She livesat home with her mother and two sisters,who are concerned and have expressedfeelings of support and willingness to help.The patient is willing to make a no-harmcontract of calling or going to theemergency department if suicidal feelingsintensify. She has no history of suicideattempts. Medical history is unremarkable,and she takes no medications. Her fathercommitted suicide several years ago.Findings on physical examination areunremarkable.

Which is the most appropriate initialcare for this patient?

A. Corroborate her account by

contacting her former fiancB. Reassurance and careful follow-up

and observation

C. Start an antidepressant and followup in 2 weeks

D. Urgent mental health referral

A 70-year-old woman is evaluatedbecause of depressed mood, anhedonia,decreased appetite, impaired sleep, anddecreased energy. Although the patientfeels somewhat hopeless about thefuture, she adamantly states that shewould never take her own life. Her

judgment seems intact. Medical historyis unremarkable, and she has not hadprevious episodes of depression. She istaking no medications. Findings onphysical examination are unremarkable.

Sertraline, 50 mg/d, is begun. The patientreturns for a follow-up visit 5 weeks later

and reports that she is tolerating themedication well but has no significantchange in symptoms, which is validatedwith a standardized symptom assessmenttool. The sertraline is therefore increased to

100 mg/d. Six weeks later, she again reportsno side effects and no improvement.

Which is most appropriate at this time?

A. Add methylphenidate

B. Discontinue sertraline and begincitalopram

C. Reassess in 4 weeks

D. Refer for electroconvulsive therapy

A 72-year-old woman is evaluated for a4-month history of insomnia, withdifficulty falling asleep. The patient wasthe major caretaker for her husband,

who had advanced heart failure and diedsuddenly 4 months ago. She has lost 3.6kg (8 lb) and does not have much of anappetite. The patient used to volunteerat the hospital, but she does not enjoygoing there any more. She also does nothave much energy. The patient is tearfuland says that nearly everything remindsher of her husband. Medical history isotherwise unremarkable. The physicalexamination is unremarkable.

Which is the most appropriatemanagement option for this patient?

A. Begin dextroamphetamineB. Begin mirtazapine at bedtimeC. Begin zolpidem at bedtime

D. Reassure the patient and schedule afollow-up appointment in 3 months

A 37-year-old woman is evaluated in theoffice for major depression that wasdiagnosed 3 months ago and treatedwith sertraline. Five weeks afterinitiation of treatment, she had nosuicidal ideation, and her depressivesymptoms had improved, with a 5-point

decrease in her Patient HealthQuestionnaire (PHQ-9) score. Duringtodays visit, she reports that herdepressive symptoms have continued toimprove, although she has experienced

sexual dysfunction manifested bybothersome anorgasmia. She is alsooverweight and is worried about gainingmore weight.

Blood pressure is 140/80 mm Hg. Her body

mass index is 29 kg/m2. The remainder ofthe physical examination is normal.

Which is the most appropriatealternative treatment option for thispatients depression?

A. BupropionB. CitalopramC. Fluoxetine

D. Mirtazapine

A 29-year-old woman has an 8-monthhistory of insomnia, difficultyconcentrating, fatigue, and irritability. Shehas trouble falling asleep, awakens after 2or 3 hours, and has difficulty returning tosleep. The patient is concerned that herimpaired concentration is interfering withher work as an attorney and has tried tocompensate by spending long hours in theoffice. Her social activities have decreasedbecause of the extended work hours. Shebroke up with her boyfriend several monthsago and is concerned that she will soon be30 years old and that her biological clockis ticking. She frequently lies awake in bedwondering if she will make partner at her

law firm as well as whether she will everget married and have children. She hasoccasional episodes of crampy abdominalpain, but her appetite is unchanged and herweight has been stable.

Findings on physical examination areunremarkable. Body mass index is 24 kg/m2.Results of routine laboratory studies,including thyroid function tests, are normal.The patient refuses to see a psychotherapistbecause she finds talk therapy difficult.

Which is the most appropriatepharmacologic agent at this time?

A. Alprazolam

B. ImipramineC. QuetiapineD. Sertraline

1.

2.

Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP, accessed at

http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/

to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.

ANNALS Depression

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