depression

1. Depression for the Internist
By
Chevelle Brudey

2. Objectives
• Identify a clinically-significant depression
• Take an excellent, concise history
• Describe common mimics of depression
• Know which medications are first-line for
depression
• Manage a patient who is not improving
adequately on initial pharmacotherapy
• Use non-pharmacological strategies for
management of depression

3. Depression is Important
• Common
• Costly
• A leading cause of disability worldwide
• Associated with a wide range of adverse
outcomes including death
• Under-recognized

5. What is a clinically-significant
depression?
• Avoid pathologizing normal emotion
• Avoid dismissing symptoms in patients with
significant stressors

6. Clinical Depression
• Sadness, loss of pleasure or decreased pleasure
AND
• Distress or Functional impairment
AND
• Symptoms are not better explained by
something else

8. The Depressed Mindset*
• Negative self-image, sometimes worthlessness
• Negative perception of the world, heightened
perception of unfairness
• Pessimism, sometimes hopelessness, about the
future
*Beck’s Cognitive Triad

9. DSM 5 Depressive Disorders
• Major depressive disorder
• Other specified depressive disorder
• Unspecified depressive disorder
• Persistent depressive disorder (formerly
dysthymia or chronic MDD)

10. DSM 5 Major Depressive Disorder*
A) Five or more of the following symptoms have been present during the same 2-week period and represent
a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of
interest or pleasure.
Note: Do not include symptoms that are clearly due to a general medical condition or mood-incongruent
delusions or hallucinations.
1) Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg
feels sad or empty) or observation made by others (eg appears tearful)
2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly
every day (as indicated by either subjective account or observation made by others)
3) Significant weight loss when not dieting or weight gain (e.g. a change of more than 5% of body
weight in a month) or a decrease or increase in appetite nearly every day
4) Insomnia or hypersomnia nearly every day
5) Psychomotor agitation or retardation nearly every day (observable by others, not merely
subjective feelings of restlessness or being slowed down)
6) Fatigue or loss of energy nearly every day
7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional)
nearly every day (not merely self-reproach or guilt about being sick)
8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by
subjective account or observable by others)
9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific
plan, or a suicide attempt or a specific plan for committing suicide.
B) The symptoms cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning .
C) The episode is not attributable to the direct physiological effects of a substance or to another
medical condition.
D) The occurrence of the major depressive episode is not better explained by schizoaffective disorder… and
other psychotic disorders
E) There has never been a manic episode or a hypomanic episode
*DSM 5

12. Etiology of depression
• Stressors
• Neurotransmitter deficit
• HPA axis dysfunction
• Altered neural networks
• Inflammation
• Genetics

13. Approach to the Patient
• Take an adequate clinical history
• Distinguish depression from common mimics
• Engage with the patient

15. The Clinical History
• Safety
• Substance use disorder?
• Bipolarity?
• Psychosis

16. Safety
• When you go to sleep at night, do you ever wish
that you would just not wake up in the morning?
• Do you ever think about taking your life?

17. Safety
• Suicidality
▫ Passive suicidal ideation
▫ Active suicidal ideation
▫ Access to lethal means (eg guns)
▫ A plan to commit suicide
▫ Suicidal intent
▫ History of suicide attempts
• Protective factors

18. Risk Factors for Suicide Include*:
• Adolescence or late life
• White race
• Male gender
• Previous potentially lethal attempt
• Family history of suicide
• Living alone
• Divorced, separated or single marital status
• Physical Illness
• Hopelessness
• Low self-esteem
• Insomnia
*Kaplan and Sadock Synopsis of Psychiatry, 10th Ed, 2001.

19. Safety
• Getting a complete history assists with safety
assessment
• More important than asking all
SIGECAPS questions

20. The Clinical History
• Safety
• Substance use disorder?
• Bipolarity?
• Psychosis

21. Substance Use
• Clinically important
• Affects patient outcomes
• Requires additional specialized treatment
• Treatment of comorbid depression improves
outcomes

22. The Clinical History
• Safety
• Substance use disorder?
• Bipolarity?
• Psychosis

23. How to Screen for Bipolarity
• Have you ever felt like you were hyper, on top of
the world or full of yourself for several days?
• Have you ever been persistently irritable, for
several days, so that you had arguments or fights
with people outside your family?*
*Adapted from MINI 5

24. Why Screen for Bipolarity?
• Different diagnosis
• Different treatment – mood stabilizers

25. Approach to the Patient
• Take an adequate clinical history
• Distinguish depression from common
mimics
• Engage with the patient

26. Differential Diagnosis
• Hypoactive delirium
• Substance-induced depression
• Depression due to a general medical condition
• Bipolar disorder

27. Depression Mimics
You are seeing a 45 year old male who is
hospitalized for chemotherapy. He was recently
diagnosed with AML, and his family feels that he
is struggling with the diagnosis. He is withdrawn,
sleeps most of the day, and eats very little. When
you evaluate him, you are surprised that he thinks
he is hospitalized for an arm fracture. He is
disoriented to date, but is able to state his name.

28. Hypoactive Delirium
You are seeing a 45 year old male who is
hospitalized for chemotherapy. He was recently
diagnosed with AML, and his family feels that he
is struggling with the diagnosis. He is withdrawn,
sleeps most of the day, and eats very little. When
you evaluate him, you are surprised that he thinks
he is hospitalized for an arm fracture. He is
disoriented to date, but is able to state his name.

29. Depression Mimics
A 29 year old male is admitted for chest pain in
the setting of recent cocaine use. You notice that
he is very sleepy, has an excellent appetite, and
complains of low mood.

30. Cocaine Withdrawal
A 29 year old male is admitted for chest pain in
the setting of recent cocaine use. You notice that
he is very sleepy, has an excellent appetite, and
complains of low mood.
Caveat: Comorbid substance use and
depressive disorders are common.

31. Depression Mimics
A 55 year old male with no prior history of
depression is seeing you in clinic after a recent
COPD exacerbation. He feels he was started on
“an antidepressant or something” that has caused
him to become depressed. He reports sadness,
poor sleep, rumination on negative thoughts and
lack of pleasure. You review his discharge
summary and note that he was treated with
bronchodilators and steroids.

32. Steroid-induced Depression
A 55 year old male with no prior history of
depression is seeing you in clinic after a recent
COPD exacerbation. He feels he was started on
“an antidepressant or something” that has caused
him to become depression. He reports sadness,
poor sleep, rumination on negative thoughts and
lack of pleasure. You review his discharge
summary and note that he was treated with
bronchodilators and steroids.

33. Depression Due to GMC
• Direct physiological effect – eg Cushing’s,
adrenal insufficiency, hypothyroidism,
hyperthyroidism, stroke
• Not a psychological response to a medical
stressor

34. Approach to the Patient
• Take an adequate clinical history
• Distinguish depression from common mimics
• Engage with the patient

35. Treatment Options
• Medications
• Behavioral therapy
• Psychotherapy
• Advanced therapies – ECT, TMS, ketamine
infusions

37. First-Line Medications
• SSRIs, SNRIs, bupropion and mirtazapine are
first-line medications for depression.
• TCAs and MAOIs have similar efficacy, but use is
more complex.
• About 1/3 to ½ of patients achieve remission
with an SSRI; 2/3 of patients have a clinically
significant response.

38. SSRI Equivalent Doses
• Fluoxetine 20 mg
• Paroxetine 20 mg
• Citalopram 20 mg
• Escitalopram 10 mg
• Sertraline 50
• Fluvoxamine 50 to 100 mg
• Lower starting dose in patients with high anxiety

39. SSRI Basics
• Onset of action in weeks
• Most have half life of about one day
• Need to be taken daily
• Some are available as liquid formulations

40. SSRI Side Effects
• GI
▫ Try taking with food
• Insomnia or drowsiness
▫ Change timing of dose
• Decreased libido, Anorgasmia, Erectile
dysfunction, Delayed ejaculation
▫ Wait, decrease dose, switch, add medications
• Increased initial anxiety
▫ Decrease dose

41. SSRI Tips
• Fluoxetine
▫ Longer half life
▫ Many drug interactions - Don’t use with tamoxifen
• Paroxetine
▫ Half life less than a day
▫ Sedating – often dosed at night
▫ Among SSRIs - Most likely to cause weight gain
▫ Anticholinergic – avoid in elderly
▫ May have higher incidence of sexual side effects
▫ Many drug interactions - Don’t use with tamoxifen
• Citalopram
▫ Very mild QT prolongation. Caution with other QT-prolonging medications
▫ Fewer drug interactions
• Escitalopram
▫ Fewer drug interactions
• Sertraline
▫ Increased absorption with food
▫ More likely to cause GI side effects
▫ Fewer drug interactions
• Fluvoxamine
▫ Shorter half-life

42. Behavioral Interventions
• Increasing exercise
• Doing things for pleasure
• Being productive (work, school, household
chores)

44. Case
A 35 year old female with a history of type 2 diabetes
mellitus and migraine headaches presents to your PCIM
clinic complaining of depressed mood that has been
worsening over the past 6 months, since her mother’s
death in a car accident. She reports crying spells, insomnia
and decreased appetite. She has lost 10 lbs since her last
appointment with you 8 months ago.
You complete your evaluation and determine that your
patient has a clinically significant depression that can be
safely managed in the outpatient setting.
You recommend increased exercise, and she agrees to
spend time with her girlfriends at least once a week. You
also decide to start fluoxetine 20 mg daily.

45. In general, which of the following is a
first-line medication for depression?
A) sertraline
B) mirtazapine
C) fluoxetine
D) bupropion
E) venlafaxine

46. In general, which of the following is a
first-line medication for depression?
A) sertraline
B) mirtazapine
C) fluoxetine
D) bupropion
E) venlafaxine

47. Follow-up Visit
Your patient starts taking fluoxetine 20 mg. She
returns to see you 10 weeks later and reports no
improvement. What would you do next?

49. Next Step
• Switch
• Augment

50. Follow-up Visit
Your patient starts taking fluoxetine 20 mg. She
returns to see you 10 weeks later and reports no
improvement. What would you do next?
A) Increase fluoxetine to 40 mg daily
B) Switch to sertraline
C) Switch to venlafaxine XR

51. STAR-D: Switching Antidepressants*
• Patients who do not tolerate citalopram or for
whom adequate treatment does not result in
remission
• Switch from citalopram to:
▫ Bupropion SR
▫ Sertraline
▫ Venlafaxine XR
NEJM 2006, 354 (12): 1231-42.

52. The Next Step
• Evidence for increasing SSRI doses is mostly
anecdotal.
• If a patient does not respond to one SSRI,
evidence supports switching to another
medication:
▫ In the same class OR
▫ In another class

53. Follow-up Visit
Your patient starts taking fluoxetine 20 mg. She
returns to see you 10 weeks later and reports no
improvement. What would you do next?
A Increase fluoxetine to 40 mg daily
B Switch to sertraline
C Switch to venlafaxine XR
You start sertraline 50 mg daily, and instruct patient
to increase the dose to 100 mg daily in one week.

54. Another Follow-up Visit
On follow-up, your patient reports improved
appetite and sleep. Her mood is also somewhat
better, but she continues to have frequent crying
spells.
What medications could you add to augment the
effect of sertraline?

55. STAR-D: Augmentation*
• Patients who do not tolerate citalopram or for
whom adequate treatment does not result in
remission
• Citalopram plus:
▫ Bupropion SR OR
▫ Buspirone
*NEJM 2006, 354: 1243-52

56. Medication Augmentation
• Evidence based strategies include SSRI plus:
▫ Buspirone, or
▫ Bupropion, or
▫ Mirtazapine*
*J Clin Psychopharmacol, 2012, 32 (2): 278-81.

57. You decide to add bupropion XL 150 mg daily. At
follow-up, your patient reports that her
depression has lifted.
Since this is her first lifetime episode of
depression, you continue her medication for a
further 9 months after she has achieved
remission.

58. Duration of Treatment
• First episode
• Recurrent episodes or high-risk patients
• Longer in elderly patients

59. Approach to the Patient
• Take an adequate clinical history
▫ Assess safety. Screen for substance use disorder
and bipolar disorder.
• Distinguish depression from common mimics
▫ Hypoactive Delirium, Substance-induced
Depression, Depression due to GMC, Bipolar
Disorder
• Engage with the patient
▫ Establish patient preferences and develop a
treatment plan.

60. In Summary
• SSRIs, SNRIs, bupropion and mirtazapine are
first-line medications.
• Reserve dose increases for patients with
medication inadequate duration or dose.
• Switching is an evidence-based strategy.
• Augmenting with bupropion, buspirone or
mirtazapine is another evidence-based strategy.
• Encourage increased exercise and prosocial
behavior.
• Establishing rapport and displaying empathy
improve outcomes.

61. Questions?