Major Depressive Disorder

characterized by a combination of symptoms

that interfere with a person's ability to work,
sleep, study, eat, and enjoy once-pleasurable
activities
Major depression is disabling and prevents a
person from functioning normally
National Institute of Mental Health
Signs and Symptoms
Persistent sad, anxious, or "empty" feelings
Feelings of hopelessness or pessimism
Feelings of guilt, worthlessness, or helplessness
Irritability, restlessness
Loss of interest in activities or hobbies once pleasurable, including sex
Fatigue and decreased energy
Difficulty concentrating, remembering details, and making decisions
Insomnia, early-morning wakefulness, or excessive sleeping
Overeating, or appetite loss
Thoughts of suicide, suicide attempts
Aches or pains, headaches, cramps, or digestive problems that do not
ease even with treatment
National Institute of Mental Health
DSM 5 Criteria for Major Depressive
Disorder
At least five 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.
Depressed mood most of the day, nearly every day (feels sad or empty) or
observation made by others (appears tearful)
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)
Significant weight loss when not dieting or weight gain (e.g., a change of more
than 5% of body weight in a month), or decrease or increase in appetite nearly
every day
Insomnia or hypersomnia nearly every day
Psychomotor agitation or retardation nearly every day (observable by others, not
merely subjective feelings of restlessness or being slowed down)
Fatigue or loss of energy nearly every day
Feelings of worthlessness or excessive or inappropriate guilt (which may be
delusional) nearly every day (not merely self-reproach or guilt about being sick)
Diminished ability to think or concentrate, or indecisiveness, nearly
every day (either by subjective account or as observed by others)
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
The symptoms do not meet criteria for a mixed episode.
The symptoms cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
The symptoms are not due to the direct physiological effects of a
substance (e.g., a drug of abuse, a medication) or a general medical
condition (e.g., hypothyroidism).

MAO Inhibitors


Tricyclic Antidepressants (TCAs)

The Tricyclic
Antidepressants has five
actions:
1. Block the reuptake of
serotonin (SRI)
2. Blocks the reuptake of
norepinephrine (NRI)
3. Blocks alpha 1 adrenergic
receptors (alpha)
4. Blocks H1 histamine
receptors (H1)
5. Blocks muscarinc
cholinergic receptors (M1)
Therapeutic
Effects
Side
Effects
Side
Effects
Selective Serotonin Reuptake
Inhibitors
Fluoxetine
Sertraline
Paroxetine
Fluvoxamine
Citalopram
Adverse Effects
Acute stimulation of 2A and 2C receptors in
the projection from raphe to limbic cortex
Mental agitation
Anxiety
Panic attacks
Adverse Effects
Acute stimulation of 2A receptors in basal
ganglia
Restlessness (akathisia)
Psychomotor retardation
Mild Parkinsonism
Dsytonic movements

Adverse Effects
Stimulation of 2A receptors in brainstem sleep
centers
Myoclonus at night
Nocturnal awakenings
Adverse Effects
Stimulation of 2A receptors in spinal cord
Inhibit spinal reflexes of orgasm and ejaculation
causing sexual dysfunction
Adverse Effects
Stimulation of 2A receptors in mesocortical
pleasure centers
Apathy
Decreased libido
Adverse Effects
Stimulation of serotonin 3 receptors in
hypothalamus/brainstem
Nausea/vomiting

Adverse Effects
Stimulation of Serotonin 3 and 4 receptors GIT
Increased bowel motility
GI cramps
Diarrhea
Selective Noradrenergic Reuptake
Inhibitor
SNRI
Dual Reuptake Blockade
- Norepinephrine and serotonin blockade and lesser extent of
dopamine reuptake only
- Maybe confused with TCA
- Properties of SNRI and NRI
Venlafaxine
Desvenlafaxine
Duloxetine

SNRI
Depending on the dose, it has different degrees of
inhibition
- 5-HT (most potent) present at low doses
- norepinephrine (moderate potency) present at high
doses
- dopamine (least potent) present at very high doses
SNRI
Advantages
- Dual action (5-HT and NE)
- Higher reported remission rate than SSRI

Disadvantages
- Titration may be necessart
- May also cause serotonin syndrome
Norepinephrine and Dopamine
Reuptake Blockers (NDRIs)
Definition
Mechanism of Action
NDRI
Bupropion
Prodrug metabolized and gives rise to a
hydroxylated active metabolite that mediates
antidepressant efficacy via norepinephrine and
dopamine reuptake blockade.
Available as Bupropion SR and Immediate Release
Bupropion
Indications
Useful in patients who cannot tolerate
serotonergic side effects of SSRIs
For patients whose depression does not
respond to boosting the serotonin
Useful in decreasing the craving associated
with smoking cessation