![](media/image1.png){width="5.96875in" height="0.41944444444444445in"}

Top of Form

## Complete Summary

#### GUIDELINE TITLE

Depression.

#### BIBLIOGRAPHIC SOURCE(S)

University of Michigan Health System. Depression. Ann Arbor (MI):
University of Michigan Health System; 2005 Oct. 20 p. \[3 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: University of Michigan Health
System. Depression. Ann Arbor (MI): University of Michigan Health
System; 2004 May. 21 p.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [May 2, 2007, Antidepressant
    drugs](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Antidepressant):
    Update to the existing black box warning on the prescribing
    information on all antidepressant medications to include warnings
    about the increased risks of suicidal thinking and behavior in young
    adults ages 18 to 24 years old during the first one to two months of
    treatment.

-   [October 25, 2006, Effexor (venlafaxine
    HCl)](http://www.fda.gov/medwatch/safety/2006/safety06.htm#Effexor):
    Published retrospective studies report that venlafaxine overdosage
    may be associated with an increased risk of fatal outcome.

-   [May 12, 2006, Paxil (paroxetine) and Paxil
    CR](http://www.fda.gov/medwatch/safety/2006/safety06.htm#paxil):
    Changes to the Clinical Worsening and Suicide Risk subsection of the
    WARNINGS section in the prescribing Information related to adult
    patients, particularly those who are younger adults.

-   [December 8, 2005, Paxil
    (paroxetine)](http://www.fda.gov/medwatch/safety/2005/safety05.htm#Paxil3):
    Pregnancy category changed from C to D and new data and
    recommendations added to the WARNINGS section of prescribing
    information.

-   [October 17, 2005, Cymbalta (duloxetine
    hydrochloride)](http://www.fda.gov/medwatch/safety/2005/safety05.htm#Cymbalta):
    Healthcare professionals notified of revision to the
    PRECAUTIONS/Hepatotoxicity section of the prescribing information to
    include precaution against using in patients with chronic liver
    disease.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Depression including:

-   Major depressive disorder

-   Minor depression

-   Dysthymia

-   Seasonal affective disorder

-   Mood disorders associated with a general medical condition

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Screening\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Internal Medicine\
Obstetrics and Gynecology\
Psychiatry\
Psychology

#### INTENDED USERS

Physicians\
Psychologists/Non-physician Behavioral Health Clinicians\
Social Workers

#### GUIDELINE OBJECTIVE(S)

-   To improve the early recognition and treatment of depression in the
    primary care setting

-   To familiarize clinicians with appropriate treatment options, drug
    side effects, and interactions

-   To improve patient\'s understanding of depression as a treatable
    illness

-   To identify when referral is indicated

#### TARGET POPULATION

Adults with depressive disorders

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Screening and Diagnosis**

1.  Patient Health Questionnaire (PHQ-9)

2.  History

3.  Evaluation

4.  Physical examination

5.  Laboratory testing

**Treatment**

1.  Supportive care:

    -   Patient education

    -   Exercise

2.  Pharmacotherapy:

    -   Selective Serotonin Reuptake Inhibitors (SSRIs)

        -   citalopram (Celexa)

        -   escitalopram (Lexapro)

        -   fluoxetine (Prozac, Sarafem, Prozac Weekly)

        -   paroxetine (Paxil, Paxil CR)

        -   sertraline (Zoloft)

    -   Serotonin-2 Antagonist/Reuptake Inhibitor

        -   nefazodone (Serzone)

    -   Serotonin/Norepinephrine Reuptake Inhibitor (SNRIs)

        -   venlafaxine (Effexor XR)

        -   duloxetine (Cymbalta)

    -   Serotonin & alpha-2 Receptor Blocker

        -   mirtazapine (Remeron)

    -   Norepinephrine/Dopamine Reuptake Inhibitor

        -   bupropion (Wellbutrin SR, Wellbutrin XL, Wellbutrin IR)

```{=html}
<!-- -->
```
3.  Psychotherapy:

    -   Any psychotherapy

    -   Interpersonal psychotherapy (IPT)

    -   Cognitive behavioral psychotherapy (CBT)

    -   Marital therapy

4.  Treatments for severe or refractory depression:

    -   Electroconvulsive therapy, monoamine oxidase inhibitors (MAOIs),
        lithium, thyroid hormone supplementation, valproic acid,
        antidepressant augmentation, stimulant medication, referral

5.  Controversial Areas (No specific recommendations made)

    -   St. John\'s Wort (hypericum perforatum)

    -   Withdrawal syndrome

#### MAJOR OUTCOMES CONSIDERED

-   Mortality rates by suicide

-   Depressive symptoms

-   Time to respond to pharmacotherapy

-   Frequency and severity of relapses

-   Outpatient visits and inpatient hospitalization

-   Mortality from myocardial infarction

-   Direct and indirect costs (including direct patient care, time lost
    from work, and potential income loss due to suicide) associated with
    major depressive disorder

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The literature search for this update began with results of the
literature search performed in 1997 to develop the initial guideline.
The literature search conducted in 2002 for this project was conducted
prospectively on Medline using the major keywords of depression,
depressive disorders; consensus development conferences, practice
guidelines, guidelines, outcomes and process assessment (health care);
clinical trials, controlled clinical trials, multicenter studies,
randomized controlled trials, cohort studies; adults; English language;
and published between 1/1/97 and 9/30/02.

Terms used for specific topic searches within the major key words
included epidemiology; national cost of treatment (economics); screening
(for depression, bipolar disorder; alcohol abuse); diagnosis; suicide
risk assessment; patient education; exercise; serotonin selective
reuptake inhibition (citalopram, escitalopram, fluoxetine, paroxetine,
sertraline), serotonin/norepinephrine reuptake inhibition (duloxetine,
mirtazapine, tricyclic antidepressants, venlafaxine),
norepinephrine/dopamine reuptake inhibition (bupropion), serotonin-2
antagonist/reuptake inhibition (nefazodone, trazodone), St. John´s Wort
(Hypericum Perforatum), maintenance on pharmacotherapy, continuation
duration, withdrawal syndrome (paroxetine/Paxil), medication adherence,
managing sexual side effects of pharmacologic agents, pregnancy and
pharmacologic agents, breast feeding and pharmacologic agents,
pharmacotherapy not included above; interpersonal psychotherapy,
cognitive behavioral therapy, short-term or focal psychodynamic
psychotherapy, marital therapy, psychotherapy, not included above; other
treatment not included above; ongoing clinical assessment; medical
comorbidity, alcohol abuse, panic (including generalized anxiety
disorder or phobia), obsessive compulsive disorder, eating disorders and
anorexia nervosa, partner violence, sexual assault, pregnancy (not
included above), postpartum (not included above); and depression not
included above.

The search was conducted in components each keyed to a specific causal
link in a formal problem structure (available upon request). The search
was supplemented with very recent clinical trials known to expert
members of the panel. Negative trials were specifically sought. The
search was a single cycle.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

A.  Randomized controlled trials

B.  Controlled trials, no randomization

C.  Observational trials

D.  Opinion of expert panel

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Conclusions were based on prospective randomized clinical trials if
available, to the exclusion of other data; if randomized controlled
trials were not available, observational studies were admitted to
consideration. If no such data were available for a given link in the
problem formulation, expert opinion was used to estimate effect size.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Consideration of benefits, harms, costs, and patient preferences

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

Pharmaceutical cost data were reviewed (see Table 5 in the original
guideline document).

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

University of Michigan Health System (UMHS) guidelines are reviewed by
leadership and in clinical conferences of departments to which the
content is most relevant. This guideline concerning depression was
reviewed by members of the following departments: Family Medicine;
General Medicine; Obstetrics and Gynecology; and Psychiatry.

Guidelines are approved by the Executive Committee of Clinical Affairs
(ECCA).

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

*Note from the National Guideline Clearinghouse (NGC)*: The following
key points summarize the content of the guideline. Refer to the original
guideline document for additional information. The levels of evidence
\[A-D\] are defined at the end of the \"Major Recommendations\" field.

**Diagnosis**

Depressed patients frequently present with somatic complaints to their
primary care doctor rather than complaining of depressed mood \[*C*\].

**Treatment**

Mild depression can be effectively treated with either medication or
psychotherapy. Moderate to severe depression may require an approach
combining medication and psychotherapy \[*A*\].

-   **Drug treatment**. Fifty to sixty-five percent (50-65%) of patients
    respond to the first antidepressant \[*A*\]. No particular
    antidepressant agent is superior to another in efficacy or time to
    response. Choice can be guided by matching patients\' symptoms to
    side effect profile, presence of medical and psychiatric
    comorbidity, and prior response \[*A*\]. Relative costs can also be
    considered (e.g., generics). University of Michigan Health System
    (UMHS) preferred agents are Fluoxetine (generic) and citalopram
    (Celexa®). Patients treated with antidepressants should be closely
    observed for possible worsening of depression or suicidality,
    especially at the beginning of therapy or when the dose increases or
    decreases \[*C*\].

-   **Frequent initial visits**. Patients require frequent visits early
    in treatment to assess response to intervention, suicidal ideation,
    side effects, and psychosocial support systems \[*D*\].

-   **Continuation therapy**. Continuation therapy (9-12 months after
    acute symptoms resolve) decreases the incidence of relapse of major
    depression \[*A*\]. Long term maintenance or life-time drug therapy
    should be considered for selected patients based on their history of
    relapse and other clinical features \[*B*\].

-   **Education/support**. Patient education and support are essential.
    Social stigma and patient resistance to the diagnosis of depression
    continue to be a problem \[*D*\].

**Definitions**:

**Levels of Evidence**

A.  Randomized controlled trials

B.  Controlled trials, no randomization

C.  Observational trials

D.  Opinion of expert panel

#### CLINICAL ALGORITHM(S)

An algorithm is provided in the original guideline document for an
overview of treatment for depression.

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\").

Conclusions were based on prospective randomized clinical trials (RCTs)
if available, to the exclusion of other data; if RCTs were not
available, observational studies were admitted to consideration. If no
such data were available for a given link in the problem formulation,
expert opinion was used to estimate effect size.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Timely recognition and accurate diagnosis of depression

-   Appropriate treatment of depression, with accompanying improvement
    in patient mood and functioning

-   Appropriate continuation and maintenance therapy to decrease the
    incidence of relapse of major depression

-   Cost-effective prescription of antidepressant medications

**Subgroups Most Likely to Benefit**

Table 5 in the original guideline document includes patient profiles
most likely to benefit from specific drugs.

#### POTENTIAL HARMS

**Side effects associated with pharmacotherapy**: insomnia, akathisia (a
syndrome characterized by muscle restlessness), weight gain and sexual
dysfunction.

-   *Citalopram*: may be initially sedating or initially increase
    alertness; mild initial sedation is dose-dependent; sexual
    dysfunction common

-   *Escitalopram*: sexual dysfunction common

-   *Fluoxetine*: tends to produce more initial nervousness and arousal
    than other selective serotonin reuptake inhibitors (SSRIs); sexual
    dysfunction common

-   *Paroxetine*: tends to cause fewer arousal and insomnia effects
    common with SSRIs; possesses some anticholinergic effects; sexual
    dysfunction common

-   *Sertraline*: tends to increase alertness; sexual dysfunction common

-   *Nefazodone*: BLACK BOX WARNING: Liver damage and/or liver failure
    in 1/250,000 patients; fatigue and dizziness; sexual dysfunction
    unlikely.

-   *Venlafaxine*: side effects common to all SSRIs with more nausea;
    sustained hypertension risk; blood pressure increases are
    dose-dependent; constipation; sexual dysfunction less common.

-   *Duloxetine*: similar to SSRIs and venlafaxine; nausea and
    constipation most troublesome, but, unlike venlafaxine, does not
    appear to produce sustained hypertension; sexual dysfunction less
    common.

-   *Mirtazapine*: produces sleep; *lower* doses produce more sleep than
    do higher doses; weight gain; sexual dysfunction unlikely.

-   *Bupropion*: most activating antidepressant available; sexual
    dysfunction rare.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Do not combine any of the listed antidepressants with monoamine
    oxidase inhibitors (MAOIs).

-   Duloxetine is not to be prescribed ordinarily if concurrent heavy
    alcohol use and/or evidence of chronic liver disease.

-   Do not use bupropion (Wellbutrin) if history of seizure, head
    trauma, substance abuse, bulimia, anorexia or electrolyte
    disturbance.

-   Marital therapy should only be considered if violence is screened
    for and absent in the relationship.

-   See Table 5 in the original guideline document for selected
    important drug-drug interactions.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

These guidelines should not be construed as including all proper methods
of care or excluding other acceptable methods of care reasonably
directed to obtaining the same results. The ultimate judgment regarding
any specific clinical procedure or treatment must be made by the
physician in light of the circumstances presented by the patient.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Chart Documentation/Checklists/Forms\
Clinical Algorithm

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

University of Michigan Health System. Depression. Ann Arbor (MI):
University of Michigan Health System; 2005 Oct. 20 p. \[3 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1998 Jun (revised 2005 Oct)

#### GUIDELINE DEVELOPER(S)

University of Michigan Health System - Academic Institution

#### SOURCE(S) OF FUNDING

Internal funding for University of Michigan Health System (UMHS)
guidelines is provided by the Office of Clinical Affairs. No external
funds are used.

#### GUIDELINE COMMITTEE

Depression Guideline Team

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Team Leaders*: Thomas L. Schwenk, MD, Family Medicine; Linda B.
Terrell, MD, General Medicine

*Team Members*: R. Van Harrison, PhD, Medical Education; Elizabeth M.
Shadigian, MD, Obstetrics & Gynecology; Marcia A. Valenstein, MD,
Psychiatry

*Guidelines Oversight Team*: Connie J. Standiford, MD; Lee A. Green, MD,
MPH; R. Van Harrison, PhD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

The University of Michigan Health System endorses the Guidelines of the
Association of American Medical Colleges and the Standards of the
Accreditation Council for Continuing Medical Education that the
individuals who present educational activities disclose significant
relationships with commercial companies whose products or services are
discussed. Disclosure of a relationship is not intended to suggest bias
in the information presented, but is made to provide readers with
information that might be of potential importance to their evaluation of
the information

**Team Member; Relationship; Company**

Thomas Schwenk, MD (none)\
Linda Terrell, MD (none)\
Van Harrison, PhD (none)\
Elizabeth Shadigian, MD (none)\
Marcia Valenstein, MD, Research Grant, Pfizer

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: University of Michigan Health
System. Depression. Ann Arbor (MI): University of Michigan Health
System; 2004 May. 21 p.

#### GUIDELINE AVAILABILITY

Electronic copies: Available for download in Portable Document Format
(PDF) from the [University of Michigan Health System Web
site](http://cme.med.umich.edu/pdf/guideline/depression04.pdf).

#### AVAILABILITY OF COMPANION DOCUMENTS

-   Continuing Medical Education (CME) information is available from the
    [University of Michigan Health System Web
    site](http://cme.med.umich.edu/iCME/depression04/default.asp).

-   Additionally, the [original guideline
    document](http://cme.med.umich.edu/pdf/guideline/depression04.pdf)
    includes a Quick Screen for Depression and the Patient Health
    Questionnaire (PHQ-9)

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on May 20, 1999. The information was
verified by the guideline developer on June 17, 1999. This NGC summary
was updated by ECRI on October 12, 2004. The updated information was
verified by the guideline developer on October 22, 2004. This summary
was updated by ECRI on August 15, 2005, following the U.S. Food and Drug
Administration advisory on antidepressant medications. This summary was
updated by ECRI on October 3, 2005, following the U.S. Food and Drug
Administration advisory on Paxil (paroxetine). This summary was updated
by ECRI on October 20, 2005, following the U.S. Food and Drug
Administration advisory on Cymbalta (duloxetine hydrochloride). This NGC
summary was updated by ECRI on December 16, 2005. This summary was
updated by ECRI on May 31, 2006 following the U.S. Food and Drug
Administration advisory on Paxil (paroxetine hydrochloride). This
summary was updated by ECRI on November 22, 2006, following the FDA
advisory on Effexor (venlafaxine HCl). This summary was updated by ECRI
Institute on November 9, 2007, following the U.S. Food and Drug
Administration advisory on Antidepressant drugs.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is
copyrighted by the University of Michigan Health System (UMHS).

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

NGC, AHRQ, and its contractor ECRI Institute make no warranties
concerning the content or clinical efficacy or effectiveness of the
clinical practice guidelines and related materials represented on this
site. Moreover, the views and opinions of developers or authors of
guidelines represented on this site do not necessarily state or reflect
those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or
hosting of guidelines in NGC may not be used for advertising or
commercial endorsement purposes.

Readers with questions regarding guideline content are directed to
contact the guideline developer.

Bottom of Form

© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008