Transcript Slide 1

Managing Depression in Primary Care:
A Pragmatic Review of the Evidence
Bradley N. Gaynes, MD, MPH
Professor of Psychiatry
University of North Carolina School of Medicine
November 29, 2011
1
Objectives
• Identify key concepts of evidence-based
depression care.
• Review screening with a depression
instrument.
• Clarify key points in diagnosing depression.
• Examine a Measurement-Based Care
approach to managing primary care
depression.
• Provide prescription tips.
I. Key Concepts of
Evidence-based Depression Care
• The USPSTF (2009) recommends screening adults for
depression when staff-assisted depression care
supports are in place to assure accurate diagnosis,
effective treatment, and follow-up. (Grade B)
• The choice of screener is less important than finding
one that works in your setting, and systematically
applying it
• Major depression presenting for treatment in
primary care settings is nearly identical to that
presenting in psychiatric settings (Gaynes, 2007a)
Distribution of HAMD17 by Setting
Percent
Primary
Specialty
20
18
16
14
12
10
8
6
4
2
0
<12
12-14 15-17 18-20 21-23 24-26 27-29 30-32 33-35 36-52
HAMD17 Score
Kolmogorov-Smirnov Two-Sample Test Statistic 0.81
p-value 0.52
Figure 1
(Gaynes, 2007a)
Key Concepts of
Evidence-based Care
• Remission of a depression rather than
merely response is the treatment goal.
(Rush, 2007)
• Physicians should ensure maximal but
tolerable doses for 6-8 weeks before
deciding that an intervention has failed
• Identical remission rates can be achieved
in primary and specialty settings when
similar evidence-based care is provided
(Gaynes, 2008)
Key Concepts of
Evidence-based Care
• Should the first treatment fail, either switching
treatment or augmenting the current treatment is
reasonable.
• The likelihood of remission after two welldelivered medication trials substantially
decreases.
Treatment Phases of Major Depression
Remission
Increased
severity
Relapse
Euthymia
Symptoms
Recurrence
Relapse
Response
Syndrome
Treatment phases
Acute
(6 to 12 wk)
Adapted from: Kupfer DJ. J Clin Psychiatry.
1991;52(suppl 5):28-34.
Time
Continuation Maintenance
(4 to 9 mo)
(1 y)
II. Screening with a
Depression Instrument
• Objective: to identify and clarify cases of
depressive illness
• Note that it can be used to monitor
response to illness also
• Scoring is simple, and total score has
clinical relevance
Screening Can Improve Depression
Outcome in Primary Care, But Only
With Adequate Support
• Data Synthesis: Nine trials indicate that
primary care depression screening and
care management programs with staff
assistance, such as case management or
mental health specialist involvement, can
increase depression response and
remission.
• Benefit was not evident in screening
programs without staff assistance in
depression care.
O’Connor et al, 2009
9
How Do You Measure
Depressive Severity?
10
Over the last 2 weeks how often have you been bothered by any of the following problems?
Several
days
2
More
than
half the
days
Nearly every
day
o
o
o
o
2. Feeling down, depressed, or hopeless
o
o
o
o
3. Trouble falling/staying asleep, sleeping too much
o
o
o
o
4. Feeling tired or having little energy
o
o
o
o
5. Poor appetite or overeating
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
O
0
1
Not at
all
1. Little interest or pleasure in doing things
Complete Questions 1 - 9 Initially then at all Critical Decision
Points (CDPs)
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
could have noticed. Or the opposite-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. (if positive, complete
the Suicide Risk Assessment)
___ X
0
=
Per Category
______
+
___ X
1
=
___ X
2 =
______
______
+
_+
PHQ-9 Total
Score:
3
___ X 3 =
_______ =
______
PHQ-9 Scores, Severity and Proposed Treatment Actions
PHQ-9 Score
Depression
Severity
1–4
None
None
5–9
Mild
Watchful waiting; repeat PHQ-9 at follow-up
10 – 14
Moderate
Treatment plan, considering counseling, followup and/or pharmacotherapy
15 – 19
Moderately
Severe
Immediate initiation of pharmacotherapy and/or
psychotherapy
20 – 27
Severe
Immediate initiation of pharmacotherapy and, if severe
impairment or poor response to therapy, expedited
referral to a mental health specialist for psychotherapy
and/or collaborative management
Proposed Treatment Actions
Kroenke, 2002
12
III. Clinical Review of Mania and
Psychosis
• Mania:
– “Has there ever been a period of 4 days or more when you
were feeling so good, “high”, excited, or hyper that you got
into trouble, or your family or friends worried about you, or a
doctor said you were manic?”
• Psychotic symptoms:
– “Has there even been a time when your mind seemed to be
playing tricks on you, so that you heard voices or sounds
others didn’t hear? Or saw things others didn’t see? Or
were afraid there was someone out to harm you when
others didn’t think so?”
Reprint permission granted by the
Cartoon Bank.
IV. Overview of MeasurementBased Care of Depression
• Goals
– Monitor depressive severity closely with PHQ-9
– Consider medication side effects
– Make decisions at Critical Decision Points
(CDPs)
– Evidence-based treatment algorithm
– Manage aggressively and treat to remission
How Does It Work?
• At each visit, measures taken on
– Depressive severity, to assess RESPONSE
– Side effects, to assess TOLERABILITY
• At CRITICAL DECISION POINTS, decisions
about dose changes are made
• Algorithm is a guide; clinicians and patients
make ultimate decision
• Goal is REMISSION
How Do You Define Remission?
• No Response:
PHQ-9 ≥ 10
• Partial Response:
PHQ-9 = 5-9
• Remission:
PHQ-9 < 5
17
How Often Does
Patient Follow-up?
• Follow-up every 4 weeks within acute phase
of treatment
• Telephone contact in between to check on
tolerance, adherence (by physician extender)
• In person contact at Critical Decision Points,
at which time the clinician can change dosing
to general categories of Low, Medium, and
High
19
Antidepressant Dosing Range
Total Daily Dose Range (mg)
SSRI
Trade Name
Starting-Low
Middle
High
Fluoxetine*
Prozac
10 qAM X 1 wk, then 20 qAM
40 qAM
60 qAM
Sertaline*
Zoloft
50 qAM X 1 wk, then 100 qAM
150 qAM
200 qAM
Paroxetine*
Paxil
10 qAM X 1 wk, then 20 qAM
40 qAM
60 qAM
Citalopram*;
Escitalopram
Celexa;
Lexapro
10 qAM X 1 wk, then 20qAM;
10 q AM
40 qAM;
20 q AM
40 qAM;
20 q AM
Buproprion SR* (avoid
w/ seizure hx)
Wellbutrin SR
150 qAM X 1 wk, then 100
BID
150 BID
200 BID
Mirtazapine*
Remeron
15 qHS X 1k, then 30 qHS
45 qHS
60 qHS
Venlafaxine* XR
Effexor XR
37.5 qAM X 1 wk, then 75 qAM
X 1wk, then 150 qAM
225 qAM
300 qAM
Non-SSRI
* = generic available
Which Antidepressant Do
You Use First?
• It does not matter, assuming patient:
– has NOT already demonstrated failure to respond
to an adequate trial of that medication
– Has not demonstrated intolerance of the medicine
– Is not on medications with problematic drug
interactions
Do Medications Differ in Treating
Major Depressive Disorder?
• 72 head-to-head trials (including 3
effectiveness trials) on 16,780 patients
• 18 studies assessed quality of life
• We conducted 4 meta-analyses and
62 adjusted indirect comparisons
– Outcome of interest: response to
treatment
Gartlehner, 2007
Major Depressive Disorder:
Evidence Similar Efficacy
• Overall, no substantial differences
in efficacy
• Statistically significant results from
meta-analyses: modest and likely
not clinically important
• No differences in quality of life
Strength of evidence: moderate
Tolerability and Discontinuation
Rates Are Also Similar
• Overall discontinuation rates do not differ
significantly among drugs
• Venlafaxine has higher discontinuation
rates because of adverse events but lower
discontinuation rates because of lack of
efficacy than SSRIs.
Strength of evidence: high
General Adverse
Events Similar
• However, incidence of specific adverse events
can differ significantly among drugs
– Nausea and vomiting: higher rates with venlafaxine than
with SSRIs
– Somnolence: higher rates with trazodone than with
other drugs
– Diarrhea: higher rates with sertraline than with other
drugs
– Weight gain: higher rates with mirtazapine than with
SSRIs
Severe Adverse Events:
Sexual Dysfunction Differs
• Fewer sexual side effects for
bupropion than for fluoxetine,
paroxetine, and sertraline
• Among SSRIs, highest rate for
paroxetine
Strength of evidence: moderate
Selection of Antidepressant is
Primarily Guided by Side Effects
• No difference among antidepressant
in terms of likelihood of remission or
response
• BUT, they do differ by side effect
What Do You Do If Patient
Endorses Suicidal Ideation?
28
First, clarify whether the ideation is
active or passive currently
• Current vs. not:
– Are you having these thoughts right now? When did
you last have them?
• Active vs. Passive:
– Do you have thoughts you’d be better off dead, or
are you having thoughts of harming or killing
yourself?
• IF active suicidal ideation currently, you need to
further assess plans and intent
29
Next, assess intent and plan
• Do you have any plans on how you would
harm yourself?
• IF yes, what have you thought about?
Have you actually done anything to hurt
yourself?
30
Key demographic risk factors for
completed suicides
• Age, noteworthy in two groups
– Individuals aged 65 and older, especially white
males over 85 years (59/100,000)
– Adolescents and young adults aged 15-24 years,
for whom it is the third leading cause of death
(10.3/100,000)
• Single or living alone
• Male sex
31
Other key variables to consider
•
•
•
•
•
•
•
•
•
Past psychiatric hospitalizations
Past suicide attempts
Family history of suicide attempts
History of substance use (impulsivity)
Any other history of impulsivity
Availability of social support
Access to means to harm self
Why now? Is there a crisis?
Hopelessness
32
Assessment of Suicide Risk
Risk
Description
Action
Low Risk
No current thoughts, no major risk
factors
Continue follow-up visits and
monitoring
Intermediate Risk
Current thoughts, but no plans,
with or without risk factors
Assess suicide risk carefully at each
visit and contract with patient to call
you if suicide thoughts become more
prominent;
Consider referral to mental health
professional
Acute/High Risk
Current thoughts with plans
Emergency management by qualified
expert; referral to Emergency room
or psychiatric hospital for continued
evaluation and management
•MacArthur Foundation Toolkit. http://www.depression-primarycare.org/clinicians/toolkits/
33
How Well Does It Work
in Primary Care?
Similar Outcomes in Primary Care and
Psychiatric Care Settings (N = 2876)
100
90
80
QIDS-SR-16 Response
HAM-D-17 Remission
QIDS-SR-16 Remission
70
60
Percent
50
(%)
40
30
47.6
45.7
33.1
32.5
26.6
28
Primary Care
Psychiatric Care
20
10
0
Gaynes et al, 2008
What else have
STAR*D and MBC
Demonstrated?
Providing An
Adequate Trial is Key
•
From treatment initiation, physicians
should ensure maximal but tolerable
doses for 6-8 weeks before deciding
that an intervention has failed.
Psychotherapy Is
A Reasonable Option If Available
• For most presentations, an antidepressant
and an evidence-based psychotherapy
produce equivalent outcomes
• However, for a severe depression, a
medication produces quicker improvement.
39
Does Collaborative Care Improve
Comorbid Medical Illness?
• In DM, compared with controls, patients in
the intervention group had
– Greater overall 12-month improvement across
glycated hemoglobin levels (difference, 0.58%)
– LDL cholesterol levels (difference, 6.9 mg per
deciliter [0.2 mmol per liter])
– Systolic blood pressure (difference, 5.1 mm Hg)
– SCL-20 depression scores (difference, 0.40
points) (P<0.001).
40
What If The Initial Attempt Doesn’t
Produce Remission?
• Might add Bupropion up to 400 mg/day
SR (or 450 mg/day XL)
– For SR, add 75 mg/day for first week, and if
tolerated increase to 150 mg/day (low dose)
– Increase per protocol to middle range (300
mg/day in BID dosing) or high range (400
mg/day in BID dosing) at Critical Decision Points.
No single dosage should exceed 200 mg.
• Might add Mirtazapine
– 15mg (low); 30 mg (medium); 45 mg (high)
41
With persistence and the provision
of MBC, there is hope
Cumulative Remission Rate by
Treatment Step
Cumulative % Remission
80
70
60
63%
67%
57%
50
40
30
33%
20
10
0
1
2
3
4
Treatment Step
Gaynes, 2007b
Prescription Tips
• All antidepressant medications have a similar
likelihood of being effective; selection is based
primarily on the wish to benefit from (or avoid)
particular side effects.
• If a patient has a substantial amount of coexisting
anxiety, start the dose a little lower but know that
the ultimate dose may need to be on the higher
end.
• The first 4-6 weeks of antidepressant treatment is
the time period when patients are at greatest risk to
stop medications prematurely; monitor closely
during this time.
Prescription Tips
• If a patient has a partial but less than
complete response, adding a 2nd
psychiatric medication to augment the
response is a reasonable strategy
• After two failures to remit with an
adequate trial, consider psychiatric
consultation
Summary
• The PHQ-9 is an easy to use, effective tool
to both identify patients with major
depression and to monitor their response to
treatment.
• After a positive screen, physicians should
clinically confirm a diagnosis of MDD.
• Physicians should ensure maximal but
tolerable doses for at least 8 weeks before
deciding that an intervention has failed.
• Remission is the goal of treatment.
Summary (cont)
• Should the first treatment fail, either
switching treatment or augmenting the
current treatment is reasonable.
• The likelihood of remission after two welldelivered medication trials substantially
decreases.
– Such patients likely require more complicated
regimens.
– Given the thin existing database, these
patients are best referred to psychiatrists for
more complex treatments.
References
•
•
•
•
•
•
•
•
•
Gartlehner G, Hansen R, Thieda P, et al. Comparative Effectiveness of Secondgeneration Antidepressants in the Pharmacologic Treatment of Depression. Agency
for Healthcare Research and Quality. Available at:
http://effectivehealthcare.ahrq.gov/reports/topic.cfm?topic=8&sid=39&rType=3.
Gaynes BN, Rush AJ, Trivedi MH, et al. (2007). Major Depression Symptoms in
Primary Care and Psychiatric Care Settings: A Cross-Sectional Analysis. Ann Fam
Med, 5(2):126-134.
Gaynes BN, Rush AJ, Trivedi MH, et al. (2008). Primary vs. Specialty Care
Outcomes for Depressed Outpatients Managed with Measurement-Based Care:
Results from STAR*D. Journal of General Internal Medicine, 23(5), 551-560.
Katon WJ, Lin EHB, Korff MV, et al. Collaborative Care for Patients with Depression
and Chronic Illnesses. N Engl J Med 2010; 363:2611-2620
Kupfer, DJ. (1991). Long-Term Treatment of Depression. Journal of Clinical
Psychiatry. 52 (5 suppl), 28-34.
Kroenke K, Spitzer R. (2002). The PHQ-9: A new depression diagnostic and severity
measure. Psychiatric Annals. 32(9). 508- 515.
O’Connor EA, Whitlock EP, Beil TL, and Gaynes BN. Screening for Depression in
Adult Patients in Primary Care Settings: A Systematic Evidence Review. Ann Intern
Med. 2009;151:793-803.
Rush AJ. STAR*D: what have we learned? Am J Psychiatry. Feb 2007;164(2):201204.
U.S. Preventive Services Task Force. Screening for depression in adults: U.S.
preventive services task force recommendation statement. Ann Intern Med. 2009
Dec 1;151(11):784-92.