1. Understanding Depression presented by
Vanessa Thompson, APRN, GNP-PMHNP-BC
Director Inpatient Behavioral Health Services
Spartanburg Regional Medical Center

2. No Conflict of Interest

3. Clinical Presentation
43 year old female with feelings of helplessness and hopelessness. Stating “I’m not myself; all I want to do is crawl in the bed and sleep so I don’t have to face my problems”.
I know I can’t, I need to keep moving. I want my life back, but I don’t see any light at the end of the tunnel.
My life seems like it has fallen apart and I can’t seem to get control of it.
I have so much to do with little help to do it
Life stressors:
Husband was in a MVA several months ago (out of work)
Mother diagnosed with CA (now moved in with her)
Mother of a 13 and 14 year old; both with busy schedules
What would you do for this patient……

4. What Do We Know About Depression
Very common
Associated with significant dysfunction
Under diagnosed
Often chronic or recurrent
Commonly present with other general medical conditions
Highly treatable
Multiple safe and effective treatments are available

5. Comorbidity Depression and pain often co-occur
MDD frequently co-occur with other psychiatric illness (PTSD, Anxiety, Schizophrenia)
The National Comorbidity Survey (US) reports that 51% of patients dx with MDD also suffer from a lifetime of anxiety
Increase rates of alcohol and drug abuse/misuse and dependence
About 1/3 of patients diagnosed with ADHD develop a comorbid depression
Depression and pain often co-occur
One or more pain symptoms are present in 65% of depressed patients (emotional vs physical pain)
5-85% of patient with pain may suffer from depression
1.5-2 fold increase risk of cardiovascular disease in patient diagnosis with depression

6. CVD and Depression
Patients with cardiovascular disease (CVD) more likely to experience depression1
Patients with depression 1.6 times more likely to develop coronary artery disease (CAD); even more likely with MDD1
Also 4 times more likely to experience a myocardial infarction (MI)1
Post-MI patients with depression less likely to follow lifestyle changes2
Pratt LA et al. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation. 1996;94(12):
Ziegelstein RC et al. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med. 2000;160(12):

7. Depression and Obesity
65% of the US population is overweight or obese
More obese women than men (54% vs. 46%)1
BMI ≥30 in women associated with nearly 50% increase in lifetime prevalence of depressive disorders2
Ogden CL et al. Prevalence of overweight and obesity in the United States, JAMA. 2006;295(13):
Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14.

8. Depression and Diabetes
Depression twice as prevalent in those with diabetes
More prevalent in women with diabetes than in men with diabetes
Anderson RJ et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):

9. Comorbid Medical Conditions
Asthma1
Pain2
Arthritis1
Cardiovascular disease1
Stroke3
Diabetes1
Obesity1
Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14.
Gureje O et al. A cross-national study of the course of persistent pain in primary care. Pain. 2001;92(1-2):
Gillen R et al. Depressive symptoms and history of depression predict rehabilitation efficiency in stroke patients. Arch Phys Med Rehabil. 2001;82(12):

10. In the United States about:
About 3.4% of people with MDD commit suicide
60% of people who commit suicide had depression or another mood disorder
The most common time of onset of MDD is between the ages of 20 and 30 years
Later peak between 30 and 40 years
Depressed individuals have a shorter life expectancies than those without depression (susceptibility to medical illnesses and suicide)

11. Drug and Alcohol Use
Benzodiazepines are central nervous system depressants increase risk of MDD
Toxic effects of sedative-hypnotic drugs including alcohol on neurochemistry decrease the levels of serotonin and norepinephrine or activation of immune mediated inflammatory pathway in the brain.
¼ of patients recovering from alcoholism experience anxiety and depression which can persist for up to 2 years
Methamphetamine abuse is also commonly associated with depression

12. Drug and Alcohol Use
Very high level of substance abuse occur in behavioral health patient
Especially alcohol, sedatives, and cannabis (where does the patient get them)
DSM-5 a diagnosis of mood disorder cannot be made if the cause is believed to be due to “the direct physiological effects of a substance”
When a syndrome is resembling MDD is believed to be caused immediately by substance abuse or by and adverse drug reaction it is referred to as “ “Substance-induced mood disturbance”
Excessive Alcohol consumption increases the risk of developing MDD

13. Practice Recommendation
Screen patients with any chronic health condition for depression, especially patients with diabetes, cardiovascular disease, or chronic pain.
So here is your first practice recommendation. Quite simply: Screen any patients with chronic health conditions for depression, especially those with diabetes, cardiovascular disease, or chronic pain.
Source: US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):
US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):
AAFP Approved source: Institute for Clinical Systems Improvement
Website:
Strength of Evidence: Grade A (randomized, controlled trials)

14. Two Questions Over the last two weeks:
Have you felt down, depressed, or hopeless? (Mood)
Have you felt little interest or pleasure in doing things? (Interest)

15. Two-Steps for Depression Screening
Step One: Two-Question Depression Screen
Step Two: If Screen is Positive…
Over the past 2 weeks have you felt down, depressed, or hopeless?
Over the past 2 weeks have you felt little interest or pleasure in doing things?
Probe deeper, be proactive, engage in conversation about mood and changes in behavior
24% - 40% of patients with positive screen receive MDD diagnosis
Others may have dysthymia, subsyndromal depressive disorders, anxiety, PTSD, substance abuse, panic disorder, or grief disorder
A “yes” to either question is a positive initial screen for depression…
US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):

16. Rating scales
The score on a rating scale alone is insufficient to diagnosis depression to the satisfaction of DSM or ICD
But provides an indication of the severity of symptoms for a time period
A person who scores above a given cut off point can be more thoroughly evaluated

17. Recommended Instruments
QIDS: Quick Inventory of Depressive Symptomatology (
PHQ-9: Patient Health Questionnaire-9 (
Both instruments are…
Validated
Quickly and easily administered and scored
Available to download
Available in English and Spanish
Helpful for initial screening AND evaluation of treatment response

18. What is Depression….
MDD is mental disorder characterized by a pervasive and persistent:
Low mood
Low self-esteem
Loss of interest of pleasure (in normally enjoyable activities)

19. What is depression
Major Depressive disorder is classified as a mood disorder in DSM-5
The diagnosis can be made on the presence of a single or recurrent major depressive episode.
A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks
Episodes may be isolated or recurrent and are categorized as mild (few symptoms minimum criteria)
Moderate or severe (mark impact on social or occupation functioning)
Episode with psychotic features-commonly referred to as psychotic depression is automatically rated as severe
If the patient has had an episode of mania or markedly elevated mood a diagnosis of bipolar disorder is made

20. MDD is a disabling condition that adversely affects a person’s
Family
Work
School life
Sleeping
Eating habits

21. Signs and Symptoms S I G E C A P
- Changes in sleep pattern - Changes in interests or activity - Feelings of guilt or increased worry - Changes in energy - Changes in concentration - Changes in appetite - Psychomotor disturbances - Suicidal ideation

22. Major Depressive Disorder (DSM-5)
Core symptoms: SIGECAPS
Depressed mood (sad, down, blue) AND/OR
Reduced interest or pleasure (I)
Somatic symptoms:
Change in appetite- significant weight loss (not dieting or weight gain) 5% of body weight in a month)(A)
Change in sleep pattern (insomnia or hypersomnia nearly every day)(S)
Reduced energy level (E)
Psychomotor agitation/retardation (nearly every day) observed by others(P)
Cognitive symptoms:
Poor concentration/easy distraction (C)
Inappropriate guilt/self reproach (G)
Thoughts of death, dying, suicide (not just the fear of dying)(S)
5 out of 9 for at least two weeks

23. Grief MDD Feelings of emptiness and loss
Dysphoria in grief likely decrease in intensity over days to weeks occurs like waves
Emotions triggered by thoughts or reminders of the deceased
Self esteem is generally preserved
Persistent depressed mood and inability to anticipate happiness or pleasure
Persistent and not tied to specific thoughts or preoccupations
Feelings of worthlessness and self- loathing

24. Signs and Symptoms
A depressed person may report multiple physical symptoms such as:
Fatigue
Insomnia
Headache
Digestive problems
Decrease appetite (resulting in weight loss)
Increase appetite (weight gain) stress eating
Body aches
Severe Cases the patient may have symptoms of psychosis
delusions
hallucinations (less common)
Assess for suicidality… plan, document, and refer

25. Diagnosis Of MDD Is based on the patient’s self-reported experience
Behavior reported by family and friends (if patient gives you permission always follow up with family and friends; a different perspective)
Mental status examination

26. Clinical Assessment
Done by a trained LPC, LSIW, LMSW, NP, psychiatrist, or psychologist
Record current state
Biographical history
Current symptoms
Family history
Social factors
Relevant information that may be impacting the patient’s mood
Current ways to regulate mood (legal/illegal)
Mental State Exam
Assess current mood
Thought content (helpless or hopelessness)
Self harm or suicide and an absence of positive thoughts or plan
Rating scales (Hamilton Rating Scale for depression or Beck Depression Inventory)

27. Differential Diagnoses
Dysthymia disorder--(a chronic, milder mood disturbance in which a person reports a low mood almost daily over a 2 year span)
Adjustment disorder with depressed mood-- (a mood disturbance appearing as a psychological response to an identifiable event or stressor)
Bipolar disorder—also know as manic-depressive disorder is a condition in which depressive phases alternates with mania
Substance abuse mood disorders

28. Diagnosis Of MDD
There is no laboratory test to diagnosis a Major Depressive Disorder; however: R/O medical conditions that may mimic MDD
TSH and thyroid panel RPR
B U/A C & S
CMP Chest x-ray
CBC CT-Scans/MRIs
UDS ETHO level
Vitamin D HIV
Hep C (for those at high risk or have concurrent depression)
UCG (r/o pregnancy; medications start)
ESR (r/o systemic infection or chronic disease)
Testosterone levels (dx hypogonadism as a cause of depression in males)
Cortisol level (screen for hypothalamic-pituitary adrenal axis deficiency )
Consider in your lab work-up to add vitamin D level (given risk for MDD, cognitive decline, etc) if deficient as well as possible HIV and HEP C for those who are at risk who have concurrent depression, as sometimes these are risks and causative agents of depression.   Also consider in your lab work to add cortisol to screen for hypothalamic-pituitary-adrenal axis deficiency which could cause concurrent depression.

29. Explore the Differentials
Depressive Disorders
Psychiatric
Major Psychoses
Adjustment D/O w/ depression
Bereavement (up to 2 months)
General Medical
Hypothyroidism = classic rule-out
Post-CVA, Post-MI
Ca of head of pancreas
Substance-Related
Alcohol abuse, cocaine/amphetamine withdrawal
Rx meds: steroids, b-blockers, a-methyldopa

30. Common Types of Depression
Major Depression
Dysthymia
Bipolar Disorder
Seasonal Affective Disorder (SAD)

31. Major Depression Dysthymia
This type causes symptoms that may:
Begin suddenly, possibly triggered by a loss, crisis or change
Interfere with normal functioning
Continue for months or years
It is possible for a person to have only one episode of major depression. It is more common for episodes to be long lasting or to occur several times during a person’s life
People with this illness are mildly depressed for years. They function fairly well on a daily basis but their relationships suffer over time.

32. Season Affective Disorder Bipolar Disorder
This is a depression that results from changes in the season. Most cases begin in the fall or winter, or when there is a decrease in sunlight.
Bipolar Disorder
People with this type of illness change back and forth between periods of depression and periods of mania (an extreme high).
Symptoms of mania may include:
Less need for sleep
Overconfidence
Racing thoughts
Reckless behavior
Increased energy
Mood changes are usually gradual, but can be sudden

33. Subtypes of MDD
Melancholic depression-characterized by a loss of pleasure in most or all activities, failure to react to pleasurable stimuli, a depressed mood more pronounce than that of grief or loss, worsening symptoms in the morning hours, early-morning waking, excessive weight loss (not anorexia)
Atypical depression-characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness(hypersomnia), a sensation of heaviness in limbs, significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection
Catatonic depression is a rare and sever form of MDD involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movement. Catatonic symptoms also occurs in schizophrenia ore manic episodes, or seen in neuroleptic malignant syndrome.

34. Subtypes of MDD
Postpartum depression associates with puerperium not elsewhere classified, refer to the intense sustained and sometimes disabling depression experience by women after giving birth. Postpartum depression occurs within one month of delivery. It can last up to 3 months post delivery. Has an incidence rate of % among new mothers.
Seasonal affective disorder (SAD) is a form of depression episodes comes on in the fall or winter and resolves in the spring. The diagnosis is made if at least 2 episodes have occurred in colder months with non at the time over a 2 year period.

35. Major Depressive disorder also know as:
Clinical depression
Major depression
Unipolar disorder
Recurrent depression

36. Causes of MDD
Psychological
Psycho-social
Hereditary
Evolutionary
Biological factors
Long-term substance abuse/misuse

37. Causes of Depression
Psychological are based on theories of personalities, interpersonal communication and learning
Biological theories focus on monoamine chemicals,
Serotonin
Norepinephrine
Dopamine
Which are naturally present in the brain and assist communication between nerve cells. Serotonin is hypothesized to regulate other neurotransmitter system; decrease in serotonin activity may allow theses systems to act in unusual and erratic ways.
Monoamine hypothesis of depression postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression

38. Major Neurotransmitters
Serotonin
Norepinephrine
Anxiety
Irritability
Energy
Interest
Impulsivity
Mood, Emotion, Cognitive function
Sex
Appetite
Aggression
Motivation
Drive
Dopamine

39. Role of Dopamine in the CNS
Dopamine modulates various brain functions
Mood
Cognition
Motor function
Drive
Aggression
Motivation
Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed
Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed

40. Role of Serotonin in the CNS
Serotonin influences a wide variety of brain functions
Mood
Sleep
Cognition
Sensory perception
Temperature regulation
Nociception (e.g., migraine headache)
Appetite
Sexual behavior
Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed
Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed
Nemeroff C. Scientific American. June 1998;42-49.

41. Role of Norepinephrine in the CNS
Norepinephrine plays an important role in the brain affecting
Mood
Learning and memory
Regulation of sleep-wake cycle
Regulation of hypothalamic-pituitary axis
Regulation of sympathetic nervous system
Slide 9
Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed
Nemeroff C. Scientific American. June 1998;42-49.Frazer A. J Clin Psychiatry. 2000;61(suppl 10)25-30.

42. Causes of Depression Biological
Biopsychosocial model propose that biological psychological and social factors all play a role in depression
The diathesis-stress model specifies that depression results when a preexisting vulnerability is activated by stressful life event(s)
Depression may be directly caused by a damage to the cerebellum
Researcher in New Zealand concluded that variation among the serotonin transporter (5-HTT) gene affects the chances a person who experience a very stressful life event will experience depression
Swedish study estimated that heritability of depression the degree in which individual difference in occurrence are associated with genetic differences
Around 40% of women and 30% of men

43. Other Hypotheses MRI scans of patients with depression have revealed:
A number of difference in the brain structure compared to those who are not depressed
Recent meta-analyses of neuroimaging studies in major depression reported that compared to controls depressed patients had increased volume of the lateral ventricles and adrenal gland and smaller volumes of basal ganglia, thalamus, hippocampus and frontal lobe (including the orbitofrontal cortex and gyrus rectus)
Hyperintensities have been associates with patients with a late onset, and have led to the development of the theory of vascular depression
There may be a link between depression and neurogenesis of the hippocampus a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood

44. Shown here are PET scans of the brain showing different activity levels in a person with depression, compared to a person without depression

45. this MRI image depicts where a person at high risk for depression has lost a significant portion of brain tissue in the right lateral cortex of ...

46. Abnormal protein deposits (green) in MDD brain. Depression

47. Other Hypotheses
The hormone estrogen has been implicated in depressive disorder after puberty and reduce rate after menopause
Personality and its development appears to be integral to the occurrence of persistence of depression with negative emotions as a common precursor
Poverty and social isolation are associated with increased risk of mental illness
Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorder later in life.

48. Treatment Three common treatments for depression Psychotherapy
Medication
Electroconvulsive Therapy (ECT)
Psychotherapy is the treatment of choice (over medications) for people under 18 years
Will start with ECT

49. Psychotherapy
This can help many depressed people understand themselves and cope with their problems. For example:
Interpersonal therapy works to change relationships that affect depression
Cognitive-behavioral therapy helps people change negative thinking and behavior patterns

50. In-Office Therapeutic Approaches to Management of Depression
Supportive Treatment - Identify and reinforce positive behaviors and coping mechanisms that patient has used in the past or is using now
“Even though you’ve felt lousy, you have gone to work everyday and done what you need to do. That shows a lot of resilience”.
“Let’s think about ways you’ve handled situations like that in the past and see how you can apply those skills you already have”.

51. Treatment
ECT still is the gold standard for treatment resistant major depression
with safety and efficacy in the elderly
even preferred in pregnancy for psychotic depression due to minimal fetal risks
TMS as a relatively newer, non- invasive treatment modality that is FDA-approved for treatment resistant patients
or the ones who cannot tolerate medications due to side effects
FYI:  the oncology department at SMC recently purchased a device for "brain wave optimization" that is not yet covered by insurance or FDA approved for depression; Hunter Mahon has more information on this should you desire

52. Treatment
Vagal Nerve Stimulation:  also used by neurologist for Parkinson's Disease but requires the surgical implantation of the stimulator (not used widely for depression)
Medical Foods (medications such as deplin (L-methylfolate) are used to "supplement" antidepressants 
Bright light therapy:  used for seasonal affective disorder (especially in Scandinavian countries who have less sunlight); 10,000 lux of energy 30 minutes a day which uses minimal ultraviolet  light during the fall and winter

53. TREATMENT The main aims of treatment: improve mood and quality of life
reduce the risk of medical complications
improve compliance with and outcome of physical treatment
facilitate the "appropriate" use of healthcare resources
Primary care staff should be familiar with properties and use of:
1) common antidepressant drugs & brief psychological treatments
2) assessment of suicidal thinking and risk
Patients with more enduring or severe symptoms will usually require specific treatment - usually drug therapy
For patients with suicidal ideation / whose depression has not responded to initial management, specialist referral is the next step

54. TREATMENT
Much depressive illness of all types is successfully treated in primary care
Four main reasons for referral to specialist psychiatric services:
1) Condition is severe
2) Failing to respond to treatment (e.g. Psychomotor retardation)
3) Complicated by other factors (e.g. Personality disorder)
4) Presents particular risks (e.g. Agitation and psychotic behaviour)
Principal decision is whether to treat with drugs or a talking therapy
Most patients in primary care settings would prefer a talking therapy
Effectiveness is limited to particular forms of psychotherapy
Mild-Mod. Depression: CBT and antidepressants are equally effective
Severe Depression: antidepressant drugs are more effective

55. Algorithm

56. Treatment for Depression
Medication
Antidepressants can help ease the symptoms of depression and return a person to normal functioning.
Antidepressants are not habit forming.

57. Treatment Goal
The goal of treatment with antidepressant medication in the acute phase is the remission of major depressive disorder symptoms
APA Practice Guidelines for the Treatment of Psychiatric Disorders.

58. Length of Antidepressant Treatment
Can take 2-6 week to work (sometimes up to 12 weeks)
Always titrate up for best tolerability to side effects
Non additive
All antidepressants lower the seizure threshold
Higher risk with bupropion, amoxapine, and maporotilline
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

59. Treatment of Depression
Most antidepressant medications increase the levels of one or more monoamines-the neurotransmitters serotonin, norepinephrine and dopamine in the synaptic cleft between neurons in the brain.

60. Antidepressants’ Mechanism of action
Once therapy is initiated an increase in neurotransmission occurs
The postsynaptic receptors begin to down-regulate
This correlates with antidepressant response
Down regulation of the postsynaptic receptor takes time after medication is initiated.

61. Antidepressant Warnings
All patients being treated with antidepressants for any indication should be monitored closely for:
Clinical worsening
Suicidality
Unusual changes in behavior
Monitor these patients especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Antidepressant Use in Children, Adolescents, and Adults

62. The Suicide Question
If an adult, child, or adolescent says, “I want to kill myself, or I'm going to commit suicide”
Always take this statement seriously and immediately seek assistance from a qualified mental health professional
People often feel uncomfortable talking about death. However, asking the adult, child, or adolescent whether he or she is depressed or thinking about suicide can be helpful.
Rather than putting thoughts in the person's head, such a question will provide assurance that somebody cares and will give the person the chance to talk about problems

63. Suicide Risk Screening
Measure
Suicide Risk Screening Questions
Score
Ideation
Have you had thoughts of taking your own life 1
Plans
Have made any plans to take your life?
Means
Do you have access to the tools or situation to take your life according to your plan?
Intent
Do you intend to commit suicide? When?
History
Have you ever tried to take your own life?
Total
Depression in Women Series, PACE, 2007

64. U.S. Suicides 11th leading cause of death
8th leading cause of death for males
19th leading cause of death for females
1.3% deaths suicide
29% heart diseases
23% malignant neoplasms
6.8% cerebrovascular disease

65. Steps for Choosing an Effective Antidepressant
Recognize that some antidepressants may be more effective in certain populations even though most are generally of equal effectiveness.
Ask about personal or family history of treatment with antidepressants, particularly about side effects.
Consider the burden of side effects, particularly weight gain and sexual side effects in midlife women.
Consider drug-drug interactions with other medications the patient is taking or may take.
Consider the potential lethality of the antidepressant in the case of an overdose.
Use antidepressant side effects for efficacy.
Moore DP, Jefferson JW. Mood Disorders. In: Moore & Jefferson: Handbook of Medical Psychiatry, 2nd ed. Philadelphia: Mosby; 2004.

66. If Initial Treatment Ineffective
Medication trial should last 8-12 weeks
If no side effects or tolerability issues, increase dosage every 2-3 weeks until
Remission achieved
Max dose achieved
Side effects limit titration
Combine antidepressants and psychotherapy
Combine antidepressants or consider augmentation trial
Considering tailoring your treatment for specific sub-populations (e.g., elderly, midlife women etc).
Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual-
Kaiser Permanente Care Management Institute. Depression clinical practice guidelines.

67. Follow Up after Initial Treatment
Individualize visit frequency for each patient
Patient’s starting or switching to a new RX should be seen every two weeks until stable
Patient’s at increased risk for suicidality or self-injury seen more frequently
Contact all patients in early phase of treatment to assess for suicidality or self-injury
Assess response with validated tool
Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual-

68. Practice Recommendation
Base a choice of antidepressant on the patient’s prior response, patient and clinician preference, potential side effects, and cost.
Choose any class of antidepressant as a first-line treatment for MDD.
Ask patients from different ethnic groups about their treatment preference for MDD.
Choosing an antidepressant is more of an art than an exact science. So there is no specific recommendation on the first antidepressant to choose.
AAFP Approved source: National Guideline Clearinghouse.

69. Practice Recommendation
Follow up with patients on antidepressants for MDD:
At least once within the first month
At least once more 4 to 8 weeks after the first contact
Assess for adherence, side effects, suicidal ideation, and response.
AAFP Approved Source: National Guideline Clearinghouse.
Strength of evidence: Consensus-based. A practice is recommended based on the consensus or expert opinion of the Guideline Development Team.

70. Continuation Continuation bridges remission to recovery
Patients who remit should continue Rx at least 6-9 months after remission at same dosage at which response was achieved
Visits every 3 months
Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual-

71. Major depression and antidepressants
Recurrence Rates of Major Depression
After 1 year
After 2 years
After 5 years
After 1st espisode
25%
42%
60%
After 2nd episode
41%
59%
74%
Length of Antidepressant Treatment
1st time depressed
6 month to 1 year
2nd time depressed
2 years (have a 70% chance of relapse)
3 or more times depressed
Lifetime therapy with a > 90% chance of relapse
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

72. Follow-Up Considerations In The First Three Months
Week
Treatment Actions 2
Check patient compliance to medication usage. Assess for adherence, side effects, suicidal ideation, and patient response. Adjust, as appropriate, medication and dosage. 4
Re-check patient compliance to medication usage. Assess for adherence, side effects, suicidal ideation, and patient response. 6
Adjust, as appropriate, medication and dosage.
7 - 12
Monthly communication with patient; Patients Appointments every 3rd or 4th week; Further Medication or Medication Dosage Adjustments; Goal: Remission

73. Drug Treatment Tricyclic Antidepressants (TCAs)
since the 1950s effective and cheap
limit compliance variable degrees of sedation
fatal in overdose (except Lofepramine)
dose-related anticholinergic side effects, postural hypotension
Monoamine Oxidise Inhibitors (MAOI’s)
rare fatalities tyramine-free diet
Selective Serotonin Re-uptake Inhibitors (SSRI’s)
fluoxetine lack sedation - no anticholinergic effects
improved compliance less immediate benefit for disturbed sleep
safe in overdose single or narrow range of doses works

74. Drug Treatment
Selective Serotonin Re-uptake Inhibitors (SSRI’s) - Newer
Sertraline lack sedation - no anticholinergic effects
improved compliance favourable on glucose metabolism
Platelet SSRI Decreased and favourable of CHD patients
Remission Prolonged remission with Sertraline
safe in overdose single or narrow range of doses works
Dual Norepinephrine and Serotonin Re-uptake Inhibitors (SSRI’s) – Newer
Similar in action and benefits as SSRIs but also inhibit the noradrenaline pathways
Problem in hypertensive patients

75. Selective Serotonin Inhibitors (SSRI’s)
Fluvoxamine (Luvox/Luvox CR)
Metabolized by P450-12A
80% protein bound
Give with food to decrease nausea
Usually given in the PM (AM if insomnia occurs)
Can give bid
Drug interactions MAOis, propranolol, metoprolol
Bradycardia/hypotension,
Increase digoxin and warfarin levels
Citalopram (Celexa)
Metobalized by P450-3A4 and P450-2C19
Drug interaction with QT-prolonging drugs (contraindicated)
Adult dosing (10-40mg/d (clinical trials showed 60 mg no more effective than 40 mg)
60 mg dose increase QT by about 18.5 msec
Escitalopram (Lexapro)
S-optical isomer (enantiomer) of citalopram
2-4 times as potent as citalopram
Little or no drug interactions
Dosing 5-20 mg/d (max dose in geriatric patients is 10 mg/day)
Fluoxetine (Prozac, Sarafem)
VERY LONG T1/2 (4-16 days)
May be good for non-compliant patients
95% protein bound
Potent inhibitor of P450-2D6
Dosing mg/d usually given in AM (to reduce insomnia)
Sertraline (Zoloft)
>95% protein bound
Minor inhibitor of P450-2D6 (not very significant)
Dosing /d usually given in AM (to reduce insomnia)
Slightly more GI upset than Prozac
Paroxetine (Paxil/Paxil CR/Pexeva)
P450-2D6 enzyme inhibitor >Prozac
Dosing mg/d usually given at HS
Most sedating
Anticholinergic
most likely to cause weight gain of all SSRIs
Pregnancy Category D/not good for breast milk
FDA as issued a warning in children due to increase emotional lability
Busy Slide
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

76. Other Antidepressants
Bupropion (Zyban/Wellbutrin, SR XL/Aplenzin, HBr Salt/Forfivo, XL/Budeprion
A derivative of the weight loss medication diethytpropion (Tenuate)
Usually dosed in the AM and mid-afternoon (not to late due to insomnia)
Not to exceed 450mg/d (150mg TID regular release) or XL and 400 mg/d SR due to seizure risk
Contraindicated in those with seizures or eating disorder, or abruptly discontinuing ETOH or BZDs
May be as effective as Ritalin for ADD/ADHD in adults
Lesser risk of inducing mania in bipolar patient compared to SSRIs
Good choice for depressed smokers
Duloxetine (Cymbalta)
Approved for chronic musculoskeletal pain, GAD, Fibromyalgia and diabetic nerve pain
A serotonin and norephinephrine reuptake inhibitor
90% plasma protein binding
Elimination ½ life of 12 hours
Dosing start with 20 mg qd max dose 120 mg qd or divided bid
Contraindicated in Narrow-angle glaucoma
SE decrease appetite, sweating, sexual dysfunction, nausea and drowsiness
Venlafaxine (Effexor)
Approved for GAD, Panic disorder (with/without agoraphobia) and phobia
27% protein binding
Cautions with hypertensive patients
Dosing mg/d
Desyenlafaxine (Pristiq)
Major metabolite of venlafaxine in and extended release table
Dosing 50 mg qd max 100 mg qd
½ life 11 hours
Trazodone (Desyrel)
Less potent SSRI
Dosing mg given at HS (used for sleep) or divided
Up to 600 mg/d can be used in hospitalized patient
92% protein binding
Adverse reaction priapism (very rare) drowsiness, orthostasis, anticholinergic effect
Vilazodone (Vilbryd)
SSRI + 5HT1 a receptor partial agonist (like buspirone)
Available in 10mg, 20mg and 40mg tablets
Dosing 10mg/d x 7 days, then 20 mg/d x 7 days, the 40 mg/d thereafter (Give with FOOD)
SE diarrhea, nausea, vomiting, insomnia and sexual dysfunction
½ life 25 hours
96-99% protein bound
Pregnancy category C
Mirtazapine (Remeron)
85% protein binding
Dosing mg/d usually given at HS
SE-somnolence, increase appetite, weight gain, dizziness
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

77. Antidepressant discontinuation Syndrome (ADS)
Antidepressant withdrawal associated with an antidepressant’s side effects
Occurs mostly with a short ½ life antidepressant
Tricyclics withdrawal may include cholinergic “rebound”
Abdominal cramping
Diarrhea
Parkinsonism
Other movement problems
Insomnia Nausea, sensory disturbance, anxiety, agitation and flu-like symptoms.
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

78. Common Antidepressant Side Effects
Tricyclic Antidepressants
Anticholinergic Side Effects
Blurred vision Tachycardia Delirium
Constipation Urinary Retention Dry Mouth
Decrease Memory Cholinergic rebound upon abrupt d/c
CNS Effects
Drowsiness (very common)
Stimulation (more with 2*amines)
Toxic Psychosis (anticholinergic effect)
Autonomic Side Effect
Nasal Congestion
Parkinsonism, Other movement problems
Sexual dysfunction (less than with SSRIs)
Seizures
Highest with Amoxapine and Maprotilline
All antidepressant lower seizure threshold
Cardiac Side Effects
Heart Block-1st or 2nd is contraindicated
Arrhythmias-prolong Q-T interval
Hypotension/orthostasis
Tachycardia (Direct, anticholinergic, and reflex)
Other
Weight gain Agranulocytosis (rare)
Allergic Reactions: Rash, urticarial, photo sensitivity, and fever
Hepatic obstruction jaundice (very rare)
Endocrinologic (SIADH)
Caution in pregnancy and breastfeeding
Monoamine Oxidase Inhibitors:
Postural hypotension stimulation (most with tranylcypromine)
Hepatic complications hydrazine >non hydrazine
Arrhythmias-prolong Q-T interval
Sexual dysfunction Anticholinergic (less than TCAs)
Sedation (most with pheneizine)
hypertensive crisis-tyamine-containing foods
Selective Serotonin Reuptake Inhibitors: (SSRIs)
Sexual dysfunction weight loss weight gain (long term)
Hyponatremia anxiety sweating
Nausea rare abnormal bleeding insomnia
Headache diarrhea
Serotonin Norephinephrine Reuptake Inhibitors (SRNIs)
Similar to SSRIs Dry mouth hypertension
Somnolence (drowsiness) Dizziness orthostatic hypotension
Mirtazapine (Remeron)
Somnolence Increase appetite with weight gain dizziness
Bupropion (Wellbutrin)
Anxiety Seizure hypertension
Weight loss Insomnia
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

79. Other Interventions Obtain an adequate amount of sleep
Seek emotional support from family and friends
Focus on positive aspects of your life
Pace yourself, modify your schedule, and set realistic goals
Reduce or eliminate the use of alcohol or drugs
Exercise or engage in some form of physical activity
Eat a proper, well-balanced diet
Don’t make long-term commitments or important decisions unless necessary
Don’t assume things are hopeless
Don’t engage in “emotional reasoning” (i.e.: because I feel awful, my life is terrible)
Don’t assume responsibility for events which are outside of your control
Don’t avoid treatment as a way of coping

80. Clinical Presentation
43 year old female with feelings of helplessness and hopelessness. Stating “I’m not myself; all I want to do is crawl in the bed and sleep so I don’t have to face my problems”.
I know I can’t, I need to keep moving. I want my life back, but I don’t see any light at the end of the tunnel.
My life seems like it has fallen apart and I can’t seem to get control of it.
I have so much to do with little help to do it
Life stressors:
Husband was in a MVA several months ago (out of work)
Mother diagnosed with CA (now moved in with her)
Mother of a 13 and 14 year old; both with busy schedules
What would you do for this patient……

81. Thank You A Special Thanks to Dr. Gravely and Dr
Thank You A Special Thanks to Dr. Gravely and Dr. Memon my supervising Physicians