Download Major Depressive Disorder presented by

UNDERSTANDING
DEPRESSION
PRESENTED BY
Vanessa Thompson, APRN, GNP-PMHNP-BC
Director Inpatient Behavioral Health Services
Spartanburg Regional Medical Center
No Conflict of Interest
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……
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
COMORBIDITY

MDD frequently co-occur with other psychiatric
illness (PTSD, Anxiety, Schizophrenia)
•
Depression and pain often co-occur
•
One or more pain symptoms are present in
65% of depressed patients (emotional vs
physical pain)

The 1990-92 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
•
5-85% of patient with pain may suffer from
depression

About 1/3 of patients diagnosed with ADHD
develop a comorbid depression
•
1.5-2 fold increase risk of cardiovascular
disease in patient diagnosis with depression
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
1. Pratt LA et al. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation. 1996;94(12):3123-3129.
2. 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):1818-1823.
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
1. Ogden CL et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-1555.
2. Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14.
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):1069-1078.
COMORBID MEDICAL CONDITIONS
Asthma1
Pain2
Arthritis1
Cardiovascular
disease1
Stroke3
Diabetes1
Obesity1
1. Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14.
2. Gureje O et al. A cross-national study of the course of persistent pain in primary care. Pain. 2001;92(1-2):195-200.
3. Gillen R et al. Depressive symptoms and history of depression predict rehabilitation efficiency in stroke patients. Arch Phys Med Rehabil. 2001;82(12):1645-1649.
 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)
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
with depression
abuse is also commonly associated
DRUG AND ALCOHOL USE
 Very
high level of substance abuse occur in behavioral health
patient
 Especially
get them)
alcohol, sedatives, and cannabis (where does the patient
 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
PRACTICE RECOMMENDATION
Screen patients with any chronic
health condition for depression,
especially patients with diabetes,
cardiovascular disease, or chronic
pain.
US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):760-764
AAFP Approved source: Institute for Clinical Systems Improvement
Website: http://www.icsi.org/depression_5/depression__major__in_adults_in_primary_care_3.html
Strength of Evidence: Grade A (randomized, controlled trials)
TWO QUESTIONS
Over the last two weeks:
1.
Have you felt down, depressed, or
hopeless? (Mood)
2.
Have you felt little interest or pleasure
in doing things? (Interest)
TWO-STEPS FOR DEPRESSION SCREENING
Step One:
Two-Question Depression
Screen
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?

A “yes” to either question
is a positive initial screen
for depression…
Step Two: If Screen is
Positive…
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

US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):760-764
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
RECOMMENDED INSTRUMENTS
 QIDS:
Quick Inventory of
Depressive
Symptomatology
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
(http://www.ids-qids.org)
 PHQ-9:
Patient Health
Questionnaire-9
(www.phqscreeners.com)
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)
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
MDD is a disabling condition that
adversely affects a person’s
Family
Work
School life
Sleeping
Eating habits
SIGNS AND SYMPTOMS
S
I
G
E
C
A
P
S
- 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
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
GRIEF
MDD

Feelings of emptiness and loss


Dysphoria in grief likely decrease in
intensity over days to weeks occurs
like waves
Persistent depressed mood and
inability to anticipate happiness or
pleasure

Emotions triggered by thoughts or
reminders of the deceased
Persistent and not tied to specific
thoughts or preoccupations

Feelings of worthlessness and selfloathing


Self esteem is generally preserved
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
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
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)
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
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
B12
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 )
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
COMMON TYPES OF DEPRESSION
Major
Depression
Dysthymia
Bipolar
Disorder
Seasonal
Affective Disorder (SAD)
Major Depression
Dysthymia
 This
 People
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
with this illness are
mildly depressed for
years. They function fairly
well on a daily basis but
their relationships suffer
over time.
Season Affective
Disorder
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

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.
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.
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 1015% 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.
Major Depressive disorder also know as:
Clinical
Major
depression
depression
Unipolar
disorder
Recurrent
depression
CAUSES OF MDD
Psychological
Psycho-social
Hereditary
Evolutionary
Biological
Long-term
factors
substance abuse/misuse
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
MAJOR NEUROTRANSMITTERS
Serotoni
n
Norepinephrine
Energy
Interest
Motivation
Anxiety
Irritability
Mood,
Emotion,
Cognitive
function
Drive
Dopamine
Impulsivity
Sex
Appetite
Aggression
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. 1998.
Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. 1996.
ROLE OF SEROTONIN IN THE CNS
 Serotonin
functions
influences a wide variety of brain
 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. 1998.
Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. 1996.
Nemeroff C. Scientific American. June 1998;42-49.
ROLE OF NOREPINEPHRINE IN THE CNS
 Norepinephrine
brain affecting
plays an important role in the
 Mood
 Learning
and memory
 Regulation
of sleep-wake cycle
 Regulation
of hypothalamic-pituitary axis
 Regulation
of sympathetic nervous system
Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed. 1998.
Nemeroff C. Scientific American. June 1998;42-49.Frazer A. J Clin Psychiatry. 2000;61(suppl 10)25-30.
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
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
SHOWN HERE ARE PET SCANS OF THE BRAIN SHOWING DIFFERENT ACTIVITY LEVELS IN A PERSON
WITH DEPRESSION, COMPARED TO A PERSON WITHOUT DEPRESSION
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 ...
ABNORMAL PROTEIN DEPOSITS (GREEN) IN MDD BRAIN. DEPRESSION
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.
TREATMENT
Three
common treatments for depression
Psychotherapy
Medication
Electroconvulsive
Psychotherapy
Therapy (ECT)
is the treatment of choice
(over medications) for people under 18 years
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
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”.
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, noninvasive treatment modality
that is FDA-approved for
treatment resistant patients

or the ones who cannot
tolerate medications due to
side effects
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
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
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
ALGORITHM
TREATMENT FOR DEPRESSION
Medication
Antidepressants can help ease the
symptoms of depression and return a
person to normal functioning.
Antidepressants are not habit forming.
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.
LENGTH OF ANTIDEPRESSANT TREATMENT
 Can
take 2-6 week to work (sometimes up to 12 weeks)
 Always
 Non
 All
titrate up for best tolerability to side effects
additive
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
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.
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.
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 http://www.fda.gov/cder/drug/antidepressants/default.htm
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
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?
1
Means
Do you have access to the tools or situation to
take your life according to your plan?
1
Intent
Do you intend to commit suicide? When?
1
History
Have you ever tried to take your own life?
1
Total
Depression in Women Series, PACE, 2007
U.S. SUICIDES
 11th
 8th
leading cause of death
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
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.
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- http://www.dshs.state.tx.us/mhprograms/tmapover.shtm
Kaiser Permanente Care Management Institute. Depression clinical practice guidelines.
http://www.guideline.gov/summary/summary.aspx?doc_id=9632&nbr=5152&ss=6&xl=999.
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 Manualhttp://www.dshs.state.tx.us/mhprograms/tmapover.shtm
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.
AAFP Approved source: National Guideline Clearinghouse. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9632&nbr=5152
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.
http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9632&nbr=5152
Strength of evidence: Consensus-based. A practice is recommended based on the consensus or expert opinion of the Guideline
Development Team.
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 Manualhttp://www.dshs.state.tx.us/mhprograms/tmapover.shtml
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
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
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
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
Selective Serotonin Inhibitors (SSRI’s)

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 10-80 mg/d usually given in AM (to reduce
insomnia)
Fluvoxamine (Luvox/Luvox CR)
Sertraline (Zoloft)

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

>95% protein bound

Minor inhibitor of P450-2D6 (not very significant)

Dosing 25-200/d usually given in AM (to reduce insomnia)

Metobalized by P450-3A4 and P450-2C19

Slightly more GI upset than Prozac

80% protein bound

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

Paroxetine (Paxil/Paxil CR/Pexeva)

>95% protein bound

P450-2D6 enzyme inhibitor >Prozac

Dosing 10-60 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
Citalopram (Celexa)


www.fda.gov/Drugs/DrugSafety/com269086.htm
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)
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP
OTHER ANTIDEPRESSANTS




Bupropion (Zyban/Wellbutrin, SR XL/Aplenzin, HBr Salt/Forfivo, XL/Budeprion
Desyenlafaxine (Pristiq)

Major metabolite of venlafaxine in and extended release table

Dosing 50 mg qd max 100 mg qd

½ life 11 hours

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

Less potent SSRI

May be as effective as Ritalin for ADD/ADHD in adults

Dosing 25-400 mg given at HS (used for sleep) or divided

Lesser risk of inducing mania in bipolar patient compared to SSRIs

Up to 600 mg/d can be used in hospitalized patient

Good choice for depressed smokers

92% protein binding

Adverse reaction priapism (very rare) drowsiness, orthostasis, anticholinergic effect

Duloxetine (Cymbalta)
Trazodone (Desyrel)

Approved for chronic musculoskeletal pain, GAD, Fibromyalgia and
diabetic nerve pain

A serotonin and norephinephrine reuptake inhibitor

SSRI + 5HT1 a receptor partial agonist (like buspirone)

90% plasma protein binding

Available in 10mg, 20mg and 40mg tablets

Elimination ½ life of 12 hours


Dosing start with 20 mg qd max dose 120 mg qd or divided bid
Dosing 10mg/d x 7 days, then 20 mg/d x 7 days, the 40 mg/d thereafter (Give with
FOOD)

Contraindicated in Narrow-angle glaucoma

SE diarrhea, nausea, vomiting, insomnia and sexual dysfunction

SE decrease appetite, sweating, sexual dysfunction, nausea and drowsiness

½ life 25 hours

96-99% protein bound

Pregnancy category C

Venlafaxine (Effexor)

Approved for GAD, Panic disorder (with/without agoraphobia) and phobia

27% protein binding

Cautions with hypertensive patients

Dosing 75-375 mg/d

Vilazodone (Vilbryd)
Mirtazapine (Remeron)

85% protein binding

Dosing 15-45 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
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
COMMON ANTIDEPRESSANT SIDE EFFECTS
Tricyclic Antidepressants
Monoamine Oxidase Inhibitors:
Anticholinergic Side Effects

Blurred vision
Tachycardia
Delirium

Postural hypotension

Constipation
Urinary Retention
Dry Mouth

Hepatic complications hydrazine >non hydrazine

Decrease Memory
Cholinergic rebound upon abrupt d/c

Arrhythmias-prolong Q-T interval

Sexual dysfunction
CNS Effects
stimulation (most with tranylcypromine)
Anticholinergic (less than TCAs)

Drowsiness (very common)

Stimulation (more with 2*amines)

Sedation (most with pheneizine)

Toxic Psychosis (anticholinergic effect)

hypertensive crisis-tyamine-containing foods
Selective Serotonin Reuptake Inhibitors: (SSRIs)
Autonomic Side Effect

Nasal Congestion

Sexual dysfunction
weight loss

Parkinsonism, Other movement problems

Hyponatremia
anxiety
sweating

Sexual dysfunction (less than with SSRIs)

Nausea
rare abnormal bleeding
insomnia

Highest with Amoxapine and Maprotilline

Headache
diarrhea

All antidepressant lower seizure threshold
Seizures
weight gain (long term)
Serotonin Norephinephrine Reuptake Inhibitors (SRNIs)
Cardiac Side Effects

Similar to SSRIs
Dry mouth
hypertension

Somnolence (drowsiness)
Dizziness
orthostatic hypotension

Heart Block-1st or 2nd is contraindicated

Arrhythmias-prolong Q-T interval
Mirtazapine (Remeron)

Hypotension/orthostasis


Tachycardia (Direct, anticholinergic, and reflex)

Weight gain

Allergic Reactions: Rash, urticarial, photo sensitivity, and fever

Hepatic obstruction jaundice (very rare)

Endocrinologic (SIADH)

Caution in pregnancy and breastfeeding
Somnolence
Increase appetite with weight gain
dizziness
Bupropion (Wellbutrin)
Other
Agranulocytosis (rare)

Anxiety
Seizure

Weight loss
Insomnia
hypertension
Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa,
PharmD, BCPP and James Wiola, PharmD, BCPP
OTHER INTERVENTIONS

Obtain an adequate amount of
sleep


Seek emotional support from family
and friends
Don’t make long-term
commitments or important
decisions unless necessary

Don’t assume things are hopeless

Focus on positive aspects of your life


Pace yourself, modify your
schedule, and set realistic goals
Don’t engage in “emotional
reasoning” (i.e.: because I feel
awful, my life is terrible)

Reduce or eliminate the use of
alcohol or drugs


Exercise or engage in some form of
physical activity
Don’t assume responsibility for
events which are outside of your
control


Eat a proper, well-balanced diet
Don’t avoid treatment as a way of
coping
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……
THANK YOU
A SPECIAL THANKS TO DR. GRAVELY AND DR. MEMON MY SUPERVISING PHYSICIANS