Depression
Presenter: Robert R Edger MD
 Goals:
 How to identify it
 How to assess suicide potential
 What medications used to treat depression
 Course of the illness
 This talk should give some ideas about what
questions you should ask your doctor about
this illness.
What is Major Depression?
 A complex interaction between multiple
vulnerability genes and environmental factors
 It is a chronic and recurrent illness and may be
progressive, in that there may be structural
changes in the brain at a cellular level e.g.,
changes in cortical thickness and
neurodegeneration.
 Associated with changes in endocrine function,
immune function and autonomic function: e.g.
obesity, hypertension, increase cholesterol,
increased inflammation
Epidemiology
 National Comorbidity Survey-Replication
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showed life time prevalence of 16.2%; 12
month prevalence 6.6%
Delay in treatment is on average 3 years
It is the leading cause of disability in the
world according to WHO
Women: Men 2:1
Only about a quarter of people with it ever
get treated
Neurobiology
 Stress and trauma, early and late life adversity
for example child abuse, can result in the way
genes function in the brain
 Neurocircuitry controlling mood is effected:
disconnect between cortical regulation and
deeper structures in the brain
 This leads to emotional dysregulation, cognitive
impairment, behavioral symptoms, physical
impairment and systemic manifestations like
tiredness
Psychiatric Management of
Depression
 One of the best predictors of success in
treating depression is establishing a good
relationship with your doctor. If possible get
family to come with you to give history
 Tell the doctor if there were past treatment
response, hospitalizations, suicide attempts
 Was there any past abuse, trauma, substance
use, medical conditions, sexual dysfunction,
problems at work, and in relationships;
problems in the military
Assessment
 Family History: of mental illness, legal
problems, substance abuse, suicide
 Medical Conditions that may present as
depression: thyroid disease, stroke,
Parkinson’s disease, dementia, metabolic
conditions, e.g. hypercalcemia, diabetes;
malignancy, infections.
 Medications that induce depression: antirejection agents, chemotherapy agents,
interferon, steroids, antibiotics, accutane
Assessment
 Is there Psychosis, Bipolar mood swings,
mixed mania, switch to mania secondary to
antidepressants (20% risk)
 Psychosis is where there are hallucinations,
paranoia, judgment and insight are gone
 Bipolar Disorder is characterized by mood
swings: highs and lows
 Screening tools: Patient Health
Questionnaire-9 (PHQ-9)
Suicide Assessment
 We may hide suicidal/homicidal ideation as it is
such frightening territory
 Try to get collateral information: family, friends;
elicit their support in monitoring; assess
whether there is intent, not just thoughts of
suicide
 Are there lethal means available: guns
 Be aware of potential for aggression and
homicide, especially in patients with history of
violent behavior and in post partum depressions
Factors to Consider in
Assessing Suicide Risk
 Lifetime history, nature, seriousness, and
number of previous attempts and aborted
attempts
 Presence of hopelessness, psychic pain,
decreased self-esteem, narcissistic
vulnerability. Presence of severe anxiety,
panic attacks, agitation, impulsivity
Factors to Consider in
Assessing Suicide Risk
Nature of cognition, such as loss of executive
function, thought constriction (tunnel vision),
polarized thinking, closed-mindedness, poor
coping and problem-solving skills
 Presence of psychotic symptoms, such as
command hallucinations or poor reality
testing
 Presence of alcohol or other substance
 Recent psychiatric hospitalization
Factors to Consider in Assessing Suicide Risk
Older male adults highest risk; teens risk of copy cat
suicide
Presence of disabling medical illness
Presence of acute or chronic psychosocial stressors,
actual or perceived interpersonal losses, financial
difficulties or changes in socioeconomic status
(retirement), family discord, domestic partner
violence
Factors to Consider in
Assessing Suicide Risk
Absence of psychosocial support, such as poor relationships
with family, unemployment, living alone, unstable or poor
therapeutic relationship, recent loss of a relationship
History of childhood traumas, particularly sexual and physical
abuse
Family history of or recent exposure to suicide especially in
teenagers, copy cat attempts
Absence of protective factors, such as children in the home,
sense of responsibility to family, pregnancy, life satisfaction,
cultural beliefs, or religiosity
Enhance treatment Adherence
 Explain: when and how often to take medicine
 Reminder systems: pill boxes, alarms
 Take medications for several weeks to get
benefit
 Take medication even after feeling better
 Consult with doctor before d/c of medication
 Tell your doctor about concerns and fears,
understanding of meds, correct misconceptions
 Explain what to do if problems arise
 Concerns about cost need to be discussed: use
generics, patient assistance programs
Education of Patient and Family
Depression is not a moral defect but a
medical illness; the family may be convinced
there is nothing wrong
 Explain course of treatment: first side effects
may occur, neurovegetative symptoms may
remit, then mood improves
 Identify stressors that may trigger relapse
 Encourage routines: sleep/wake cycle,
eating, exercise, decrease alcohol, caffeine,
tobacco products
Pharmacotherapy
The range of possible treatments:
psychotherapy, medications, Light Therapy,
ECT, complementary and alternative
medications
There are no replicable, robust findings to
suggest one agent is superior to another
No psychotherapy has been shown robustly
to be better than others; psychodynamic,
interpersonal therapies may have more
benefit
Antidepressant Medications
 They do differ in their potential to cause side
effects; if they are going to work it will be in
the first 1-2 weeks
 SSRI’s, SNRI’s Mirtazapine and Bupropion are
optimal agents to try first; Bupropion also has
an indication for smoking cessation
Selective Serotonin Reuptake
Inhibitors (SSRI)
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Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Paroxetine (Paxil)
Sertraline (Zoloft)
Vilazodone (Viibryd)
Dose depends on the individual; elderly need
lower doses; GI Side effects; sexual side effects
most common; seizures; fall risk; Osteopenia;
weight gain
NDRI Norepinephrine Dopamine
Reuptake Inhibitors
 Bupropion (Wellbutrin)
 Beware in using it if you have a seizure history
 Don’t use it with a history of bulimia
 Commonly used with other antidepressants
although no proof that it helps
Serotonin Norepinephrine
Reuptake Inhibitors SNRI
 Venlafaxine (Effexor)
 Desvenlafaxine (Pristiq)
 Duloxetine (Cymbalta)
 Side effects may include elevated blood
pressure, headaches, sexual dysfunction,
sleep disruption
Other Antidepressants
 Serotonin Modulators: Nefazodone,
Trazodone
 Nefazodone: can rarely cause liver damage
 Norepinephrine Serotonin Modulator:
Mirtazapine
 Mirtazapine (Remeron) can stimulate
appetite and be useful in cancer treatment; it
can raise cholesterol and be sedating; can be
a good add on medication; helps with sleep
Tricyclic Antidepressants
 Amitriptyline, Doxepin, Imipramine,
Desipramine, Nortriptyline
 Many side effects: cognitive impairment,
narrow angle glaucoma, delirium, fall risk,
urinary retention, cardiac arrhythmia,
orthostatic hypotension, constipation, dry
mouth, seizures, sedation, sexual
dysfunction, can be lethal in overdoses
Monoamine Oxidase Inhibitors
(MAOI),Folic Acid, Omega3
 Phenelzine, Tranylcypromine, Isocarboxazid
 Selegeline (Emsam) Patch
 Dietary restriction: no aged cheese or meats;
red wine, draft beer, fava or broad beans
 Risk of hypertension and stroke
 L-Methylfolate (Deplin)
 Omega 3 use between 1000-2000 mg daily
Response to Treatment
 Remission is the goal: at least 3 weeks
without sad mood or reduced interests and
no more than 3 symptoms of depression
remaining.
 This only occurs in about 40-45% of patients
in the best of hands
 Residual symptoms predict recurrence.
 If you don’t respond in 2 weeks to a
medication, consider adding medication, or
augmentation
Augmentation
 Lithium: most studied adjunct. Useful in
suicide prevention. Blood level of Lithium to
attain has not been confirmed. Use at night
as there is less risk to renal side effects.
 Thyroid supplementation: triiodothyronine
25-50 mcg/day.
Augmentation: Atypical
Antipsychotics
 May increase the rate of response or
remission to people who haven’t responded
to 2 or more antidepressant trials, even if
psychotic symptoms are not present
 Use lower doses:
 Olanzapine: (Zyprexa); Aripiprazole (Abilify);
Quetiapine (Seroquel); metabolic side effects
limit utility (weight gain, diabetes)
Augmentation
 Stimulants: methylphenidate (Ritalin)or
Dextroamphetamine (Adderall)
 Modafinil (Provigil) and Nuvigil: may help
with fatigue or hypersomnolence (caution
when using with Oral Contraceptives)
 Anticonvulsants: carbamazepine (Tegretol),
valproic acid (Depakote), Lamotrigine
(Lamictal).
Continuation Phase
 Treat at least 4-9 months to prevent relapse
assuming good control of depression
 The risk of relapse is highest in the first 6
months after remission
 Use same dosing as during the acute phase
 Monitor for contributors to relapse:
substance use, general medical conditions,
psychosocial stressors, decrease adherence
to medications
Maintenance Phase
 Within the first 6 months following recovery
from a major depression, 20% of patients will
experience a recurrence.
 Between 50-85% of patients will have a life
time recurrence usually within 2-3 years
 The risk of subsequent recurrences increases
by 16% with each successive episode.
 Patients with prior episodes of depression are
at risk for mania, hypomania, dysthymia or
chronic low grade depression
Maintenance Phase
 People who have had 3 episodes of Major
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Depression-need medication indefinitely
Patients with risk factors: residual symptoms,
ongoing psychosocial stressors, family history of
mood disorder, the severity of prior episodes
Presence of psychosis in prior episodes and
suicidal risk
In general the same medications and dose
should be used as in acute and continuation
phases
Relapse and recurrence of symptoms can still
recur in up to 25% of patients
Discontinuation
 Treatment can be discontinued if
maintenance is not indicated.
 The highest rate of relapse is 2 months after
discontinuation of medications. Close
monitoring should be done in this period.
 Always taper and be aware of discontinuation
symptoms, which may mimic depressive
symptoms: disturbance of mood, energy,
sleep and appetite