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3.4  Selective  Serotonin  Reuptake  Inhibitor  /  Ma.  Joyce  C.  Joyas,  MD  /  170927  
Selective Serotonin Reuptake Inhibitor Treatment:
Objectives: • Acute phase:
• Define: Response, Remission, Relapse and Recurrence o Primary aim is to induce remission of MDD and achieve full
return to baseline level of functioning.
• To know the mechanism of action of SSRI
o When considering treatment for the patient consider the
• To know the different SSRIs
• To know the indications for SSRI
! Severity of the symptoms
! Presence of co-occuring disorders or psychosocial
24F, single came in to the clinic due to insomnia for almost 2 weeks.
! BPS and environmental factors contributing to the current
(+) loss of interest playing badminton after losing a job a month ago
episode of depression
(+) blank stares, crying spells mostly during the day
! Patient preference
(+) guilt that she can no longer provide for her family
! Prior treatment experiences
(+) depressed mood
(+) negative thoughts that t
Selective Serotonin Reuptake Inhibitor (SSRI)
• Mode of action:
PMHX: patient has childhood asthma
o Part 1:
FHX: DM, HTN and Cancer, mother had post partum blues
" The Serotonin (5HT) neuron is conceptualized as having a
PE and Neuro: Unremarkable
relative deficiency the neurotransmitter 5HT. The number of
MSE: Slouch position, mood is depressed, affect is constricted, no
5HT receptors is upregulated, incuding presynaptic 5HT1A
paranoia, no AH, coherent, with pause in between sentence, fair judgment
autoreceptors as well as postsynaptic 5HT receptors.
and poor insight.

o Part 2:
" When SSRI is administered, it immediately blocks the
• Major depressive disorder
serotonin reuptake pump or sertonin transporter (SERT).
" This causes serotonin to increase only in the
DSM 5 Criteria of MDD:
somatodendriticc area of the serotonin neuron, nt nt very
• Criteria for Major Depressive Episode
much in the axon terminal
o Five (or more) of the following symptoms have been present
during the same 2-week period and represent a change from
o Part 3:
previous functioning; at least one of the symptoms is either (l)
" The conequence of serotonin increasing in the
depressed mood or (2) loss of interest or pleasure.
somatodendritic area of serotonin (5HT) neuron.
o Note: Do not include symptoms that are clearly due to a general
" The somatodendritic 5HT1A autoreceptors desensitized or
medical condition, or mood-incongruent delusions or
o Part 4:
Major Depressive Disorder
" Once the somatodendritic receptors downregulate, there is
1. Depressed mood most of the day, nearly every day, as indicated by
no longer inhibition of impulse flow in the serotonin (5HT)
either subjective report (e.g., feels sad or empty) or observation made
by others (e.g., appears tearful). Note: In children and adolescents,
" The neuronal impulse flow is turned on
can be irritable mood.
" The consequence of this is release of 5HT in axon terminal
2. Markedly diminished interest or pleasure in all, or almost all, activities
" The increase is delayed as compared with the increase of
most of the day, nearly every day (as indicated by either subjective
5Ht in the somatodendritic areas of 5HT neuron
account or observation made by others)
" This delay is the result of the time it takes somatodendritic
3. Significant weight loss when not dieting or weight gain (e.g., a change
5HT to downregulate the 5HT1A autoreceptors and turn on
of more than 5% of body weight in a month), or decrease or increase
neuronal impulse flow in the 5HT neuron.
in appetite nearly every day. Note: In children, consider failure to
" This delay may explain why antidepressants do not relieve
make expected weight gains
depression immediately.
4. Insomnia or hypersomnia nearly every day
" It is also the reason why the mechanism of action of
5. Psychomotor agitation or retardation nearly every day (observable by
antidepressants may be linked to increasing neuronal
others, not merely subjective feelings of restlessness or being slowed
impulse flow in 5HT neurons
" 5HT levels at axon terminals before an SSRI can exert its
6. Fatigue or loss of energy nearly every day
antidepressant effects.
7. Feelings of worthlessness or excessive or inappropriate guilt (which
may be delusional) nearly every day (nat merely self-reproach or guilt
o Part 5:
about being sick)
" Once the SSRIs have blocked the reuptake pump or
8. Diminished ability to think or concentrate, or indecisiveness, nearly
serotonin transporter (SERT), increased somatodendritic
every day (either by subjective account or as observed by others)
serotonin (5HT) desensitized somatodendritic 5HT1A
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal
autoreceptors turned on neuronal impulse flow and
ideation without a specific plan, or a suicide attempt or a specific plan
increased release of 5HT from axon terminals
for committing suicide
o Final step:
" The desensitization of post synaptic 5HT receptors
(desensitization may mediate the reduction of SSRI side
effects as tolerance develops).

Trans  Group:  Chachams  

Edited  By:  raqber  
Page  1  of  3  
Citalopram Fluoxetine
• Class: SSRI • Class: SSRI
• 20-60 mg • Prescribed for:
• Half life: 23-45 hours o Depression
• Weak inhibitor of CYP450 2D6 o Prementrual dysphoric disorder (PMDD)
• It has mild antagonist actions at histamine H1 receptors o Obsessive compulsive disoder (OCD)
• Inactive R enantiomer may interfere with the therapeutic actions of o Panic Disorder
the S enantiomer at serotonin reuptake o Bulimia Nervosa
• Some evidence suggests that Citalopram treatment during the luteal o Post traumatic disorder (PTSD)
phase may be more effective than continuous treatment for patients o Social anxiety disorder ( Social phobia)
with PMDD o Bipolar II Disorder (With Olanzapinem not available in the
• Prescribed for: • Mode of action:
o Depression o Boosts neurotransmitter serotonin
o Prementrual dysphoric disorder (PMDD) o Blocks serotonin reuptake pump
o Obsessive compulsive disoder (OCD) o Desentizes serotonin receptors, especially serotonin 1A
o Panic Disorder receptors
o Generalized anxiety disorder o Presumably increase serotogenic neurotransmission
o Post traumatic disorder (PTSD) o Fluoxetine also has antagonist properties at 5HT2C receptors,
o Social anxiety disorder ( Social phobia) which could increase NE and Dopamine neurotransmission
• Drug Interaction: • Some patients may experience increased energy or activation early
o Atomoxatine after initiation of treatment
! theoretically citalopram can increase the atomoxetine • Fluoxetine has been specifically studied in combination with
levels. Olanzapine which is excellent fo bipolar depression, treatment
o Tramadol resistant unipolar depression and psychotic depression.
! increases risk of seizure in patients taking anti- • It can cause insomnia and anorexia
depressants • 20 mg
o Can cause fatal “serotonin syndrome” when combined with MAO • 20-80 mg for depression and anxiety
inhibitor. Do not use MAOI or at least for 14 days after MAOI • 60-80 mg for bulimia
stopped. • The long half lives of fluoxetine and its active metabolites mean that
o May displace high protein bound drugs. dose changes will not be fully reflected in plasma for several weeks,
o Via CYP450 2D6 inhibition lengthening titration to final dose and extending withdrawal drom
! interfere with analgesia, codeine, and increase the treatment.
plasma levels of some beta blockers and of • Active metabolite (norfluoxetine) has 2 week half life
atomoxetine • 2-3 day half life
o Via CYP450 2D6 • Inhibits CYP450 2D6
! increase concentration of Thioridazone can cause • Inhibits CYP4503A4
cardiac arrythmia • Inhibits CYP450 3A4
o May increase levels of alprazolam, buspirone and triazolam
Escitalopram Oxalate o Increase concentrations of certain cholesterol lowering HMG
• Class: SSRI CoA which can increase rhabdomyolysis
• Prescribed for: o Increase the comcentrations of prizodone and can caue QTc
o Major Depressive Depression prolongation and dangerous cardiac arrythmia
o Prementrual dysphoric disorder (PMDD) • Inhibits CYP450 2D6
o Obsessive compulsive disoder (OCD) o Via CYP450 2D6 inhibition- interfere with analgesia, codeine,
o Panic Disorder and increase the plasma levels of some beta blockers and of
o Generalized anxiety disorder atomoxetine
o Post traumatic disorder (PTSD) o Via CYP450 2D6 increase concentration of Thioridazone can
o Social anxiety disorder ( Social phobia) cause cardiac arrythmia
• Mode of action: o Fluoxetine
o Boosts neurotransmitter serotonin • May be first line choice for atypical depression
o Blocks serotonin reuptake pump • Actions of 5HT2C receptors may explain in part of fluoxetine efficacy
o Desentizes serotonin receptors, especially serotonin 1A in combination of bipolar depression and treatment resistance
receptors depression
o Presumably increase serotogenic neurotransmission
• As escitalopram has no known important secondary phramacologic Sertraline
properties, its side effects are presumambly all mediated by its • Class: SSRI
serotonin reuptake blockade. • Prescribed for:
• 5, 10, 20 mg o Depression
• Half-life: 27-32 hours o Prementrual dysphoric disorder (PMDD)
• No significant actions CYP450 enzymes o Obsessive compulsive disoder (OCD)
• Most tolerated anti-depressants o Panic Disorder
• R- citalopram may interfere with the binding of S- citalopram at the o Post traumatic disorder (PTSD)
serotonin transporter o Social anxiety disorder ( Social phobia)
• For this reason, S- citalopram may be twice more potent than R- o Generalized Anxiety Disorder

  “I call you her, cuz you’re my tear.”

- Outro : Her, 방탄소년단 Page  2  of  3  
• Mode of action:
o Boosts neurotransmitter serotonin
o Blocks serotonin reuptake pump
o Desentizes serotonin receptors, especially serotonin 1A
o Presumably increase serotogenic neurotransmission
o Sertraline also has some ability to block dopamine reuptake
pump (dopamine transporter), which could increase dopamine
neurotransmission and contribute to its therapeutic actions
o Sertraline also has mild antagonist actions at sigma receptors
• Increasing serotonin can cause diminished dopamine release and
might contribute to emotional flattening, cognitive slowing, and apathy
in some patients, although this could theoretically be diminished in
some patients by sertraline’s dopamine reuptake blocking properties.
• 50 mg
• Usual dose: 50-200 mg
• Depression and OCD: 50- 200 mg
• Panic and PTSD: initial 25 mg may increase to 200 mg
• Sertraline
• Half life: Parent drug- 22- 36 hours
o Metabolite half life- 62-104 hours
• Inhibits CYP450 2D6 (weakly at low dose)
• Inhibits CYP450 3A4 (Weakly at low dose)

  “I call you her, cuz you’re my tear.”

- Outro : Her, 방탄소년단 Page  3  of  3