Psychiatry 3

Dr. familar

Antidepressants 1.2


LEGENDS:
IMPORTANT
SIDENOTES Some antidepressants may apparently produce
restlessness or psychomotor agitation before any
2 General Classifications of Antidepressants: improvement in depressive symptom is seen
Cyclic Antidepressants most commonly used in practice In children, adolescents and adults younger than
Monoamine Oxidase Inhibitors age 24, a small (2-3%) risk of suicidal ideation or
hostility may be present in some who take
PHARMACOLOGIC CLASS DRUG antidepressants
CYCLIC ANTIDEPRESSANTS Antidepressants from different classes may be
combined if partial response or refractory cases are
Selective Serotonin Citalopram, Fluoxetine,
seen, but caution against serotonin syndrome
Reuptake Inhibitors (SSRI) Paroxetine, Escitalopram,
resulting from drug interactions
Fluvoxamine, Sertraline
Tolerance to different antidepressants is seen in 10-
Norepinephrine Dopamine Bupropion
20% of patients in spite of compliance to treatment
Reuptake Inhibitor (NDRI)
probably because of CNS adaptation, unrecognized
Selective Serotonin- Venlafaxine,
rapid cycling or increase in severity of disorder.
Norepinephrine Reuptake Desvenlafaxine, Duloxetine

Inhibitor (SNRI)
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)
Serotonin-2 Trazodone, Nefazodone
Chemical class Generic name Trade Dosage
Agonist/Serotonin Reuptake
name forms &
Inhibitor (SARI)
strength
Serotonin-1A Agonist/ Vilazodone
s
Serotonin Reuptake Inhibitor
Phthalene Citalopram Celexa Tab/cap
Noradrenergic/Specific Mirtazapine
derivative 10, 20,
Serotonergic Agent (NaSSA)
30, 40
Nonselective Cyclic Agents Desipramine, Amitriptyline, mg
(Mixed Reuptake Nortriptyline, Imipramine Oral
Inhibitor/Receptor Blockers) disintegr
MONOAMINE OXIDASE INHIBITORS ating tab
Reversible MAO-A Inhibitor Moclobemide Oral
(RIMA) solution
Irreversible MAO (A & B Phenelzine, Escitalopram Lexapro Tab/cap
inhibitors) (MAOIs) Tranylcypromine, (most common 5, 10, 20
Maprotiline DOC for MDD) mg
Irreversible MAO-B Inhibitor Selegiline Oral
solution
Common MOA: reuptake inhibition of Serotonin Bicyclic Fluoxetine Prozac Capsule
Leads to accumulation of serotonin -> SEROTONIN 10, 20,
SYNDROME 40 mg
Oral
The specificity of the cyclic antidepressants reuptake of solution
neurotransmitters somehow determines each drugs spectrum Fluoxetine/Olan Symbya Caps
of activity and adverse effects. zapine x 25/3, 6,
(Combination for 12 mg
Therapeutic Effects of Antidepressants MDD with Caps
Elevated mood most important effect psychotic 50/6, 12
Improved sleep & appetite features) mg
Better memory (for pseudodementia in MDD) Monocyclic Fluvoxamine Luvox Tabs 25,
Increased physical activity (for anhedonia, 50, 100
bradykinesia, hypokinisia in MDD) mg
Improved clarity of thinking Phenylpiperidine Paroxetine Paxil Tabs 10,
Decreased feelings of guilt, worthlessness, 20, 30,
helplessness & inadequacy 40 mg
Decrease in delusional preoccupation & ambivalence Oral
If it is MDD with psychotic features (i.e., with suspensi
delusions of grandeur or paranoia), give on
antidepressants + antipsychotics Controlle
d-release
Overview tab
In general, all antidepressants are equally efficacious Tetrahydronaphthyl Sertraline Zoloft Cap/tab
at reducing the symptoms of depression methylamine 25, 50,

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 Psychiatry 3 topic

100, 150, Mechanism of Action of SSRIs
200 mg Exact MOA is unknown
Oral Inhibition of serotonin reuptake
solution Increased concentration of serotonin in the synapse
Downregulation of postsynaptic receptors
All are in oral forms.
Some SSRIs can also affect other neurotransmitters
SSRI Indications SSRI Other actions
Mood Disorders Citalopram & Most selective serotonin
MDD Escitalopram reuptake inhibitor
MDD, recurrent, prophylaxis
Depression in bipolar I & treatment-resistant Fluoxetine Weakly inhibits
depression norepinephrine reuptake and
Premenstrual dysphoric disorder binds to 5-HT2c receptors
Dysthymia Sertraline Weakly inhibits
Atypical depression norepinephrine & dopamine
MDD in medical or other psychiatric disorders reuptake
Postpartum depression Paroxetine Significant anticholinergic
Eating Disorders activity at higher doses
Bulimia nervosa
Binge-eating disorder Pharmacokinetics of SSRIs
Anxiety & Related Disorders Absorbed relatively slowly but completely
Panic disorder with or without agoraphobia Time to peak plasma concentration 3-8 hours
Social phobia Undergo little first-pass effect
GAD Highly bound to plasma protein and may even
OCD displace other drugs from protein binding but this is
PTSD not clinically significant: FLUOXETINE,
Others PAROXETINE, SERTRALINE
Pain management Metabolism primarily by the liver
Trichotillomania All affect CYP450 and will affect metabolism of
Premature ejaculation other drugs metabolized by this system
Body dysmorphic disorder Least: CITALOPRAM and ESCITALOPRAM
Schizophrenia, negative symptoms Clearance of ALL SSRIs is reduced in patients
Tardive dyskinesia with cirrhosis
FLUOXETINE and PAROXETINE decrease their
Currently approved indications of SSRIs in US/Canada own metabolism
Disor Fluo Fluvo Paro Sertr Cital Escital FLUOXETINE, as well as its active metabolite,
der xetin xamin xetin aline opra opram NORFLUOXETINE, have the longest half-lives (70
e e e m and 330 hours, resp.)
MDD A/P - A A A A Peak plasma concentration of SERTRALINE is
GAD - - A - - A 30% higher when taken with food, as first pass
OCD A/P A/P A A/P - A metabolism is reduced
Panic A - A A - -
disord The most important drug-to-drug interactions
er involving the SSRIs occur as a result of inhibition or
PTSD - - A A - - slowing by the SSRI of the metabolism of co-
Social A - A A - - administered medications.
anxiet
y Drug Characteristi Interaction Thro
disord c with ugh
er Fluvoxamine Most Theophylline CYP
Bulimi A - - A - - notorious 1A2
a marked effect Clozapine CYP
nervo on several 1A2
sa CYP enzymes Alprazolam/Clo CYP
Prem A - A A - - nazepam 3A4
entru Fluoxetine & Significant Opiates such CYP
al Paroxetine effects as codeine & 2D6
Dysp hydrocodone
horic by blocking
Dso. conversion into
their active
Pediatric indications for: forms
MDD - Fluoxetine Sertraline/ Least likely
OCD Fluoxetine, Fluvoxamine, Sertraline Citalopram/ for
Escitalopram interaction

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 Psychiatry 3 topic

Drug Effect on sleep
Drug Bioavaila Prot Pea Elimina Therap Fluoxetine Insomnia
bility (%) ein k tion eutic Sertraline/Fluvoxamine Insomnia <-> Somnolence
bindi plas half-life dose Citalopram/Paroxetine Somnolence
ng ma (%) range Escitalopram More likely insomnia
(%) level (mg)
(%) Case reports of cognitive impairment (short-term
Citalopr 80 80 4 23-45 10-40 memory and attention affected)
am Rarely tremor, EPS, and fine tremor
Escitalo 80 54 4-5 27-32 10-20
pram Anticholinergic effects
Fluoxeti 72-85 94 4-8 24-144 10-80 Mild dose-dependent dry mouth, constipation and
ne (parent) sedation: PAROXETINE
200-
330 Hematologic effects
(metab Easy bruising, excess or prolonged bleeding
olite) without reduced platelet count
Fluvoxa 60 77- 2.5-4 9-28 50-300 Caution with concomitant use of aspirin and
mine 80 NSAIDs
Paroxeti >90 95 5.2 3-65 10-60
ne Sexual dysfunction
Sertralin 70 96 6 22-36 50-200 Most common side effect caused by all SSRIs,
e (parent) associated with long-term treatment
62-104 Result of increased serotonergic transmission
(metab through 5-HT2c receptor that results in reduced
olite) dopaminergic transmission and acetylcholine
blockade
Onset & Duration of Action of SSRIs Affects all phases of sexual cycle
Long acting Reducing dose may help in some, Sildenafil has
Can be given in single daily dose, usually in helped some, too
morning
Fluvoxamine and sertraline may cause sedation GI effects
and may have to be given at night Very common, resulting from activation of 5-HT2
Adequate clinical activity and saturation of the receptors
transporters Nausea, vomiting, diarrhea, anorexia, flatulence,
Most patients with depression respond to the initial and dyspepsia
dose Most severe symptoms are caused by
As a rule, higher dosages do not increase SERTRALINE & FLUVOXAMINE
antidepressant effect but may increase the risk of Up to one-third of patients may gain weight that
adverse effects happens gradually and is resistant to diet and
Therapeutic effect seen in about 28 days but some exercise
may respond sooner Most weight gain is caused by PAROXETINE
Tolerance to effects may be seen after months of
treatment -> may lead to serotonin syndrome Glucose disturbance
Acute decrease in glucose, so caution to diabetics
Adverse Effects of SSRIs Long-term use may increase glucose levels
Incidence may be greater in the early days of
treatment CV effects
Patients may adapt to them over time All SSRIs can lengthen QT interval and cause QT
If there is intake of a previous drug, may have to rule syndrome even in the healthy, when taken in
out withdrawal from that drug overdose especially CITALOPRAM
Poses the greatest risk
CNS EFFECTS: Dose should not exceed 40 mg/day or 20 mg/day
Headache is common for those over 45, with liver failure, if combined
From FLUOXETINE mainly with CYP2C19 inhibitors or if taking Cimetidine
Or a worsening of migraines Do not give to those with congenital long QT
Generally effective prophylaxis for migraine & syndrome
tension headache Monitor ECG and serum electrolytes and correct
Seizure episodes in those previously diagnosed abnormal levels before prescribing
More frequent at the highest doses of the drug
Sedation or wakefulness Serotonin syndrome
Improved sleep is the major effect but 25% report Serious and possibly fatal syndrome of serotonin
trouble sleeping or excessive sleepiness overstimulation
With concurrent use of SSRI and MAOI or
lithium or L-tryptophan

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 Psychiatry 3 topic

Symptoms appear in the following order, till it SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITOR
worsens: (SNRI)
Diarrhea Chemical Drug name Trade Dosage
Restlessness class name forms &
Extreme agitation, hyperreflexia & autonomic strengths
instability with fluctuation in vital signs Bicyclic Venlafaxine Effexor Tab 25,
Myoclonus, seizures, hyperthermia, agent 37.5, 50,
uncontrollable shivering, and rigidity 75, 100 mg
Delirium, coma, status epilepticus, cardiovascular Effexor XR Extended
collapse, and death release
tab/cap
Withdrawal 37.5, 75,
Abrupt discontinuation of an SSRI with a shorter 150, 225
half-life such as Paroxetine or Fluvoxamine may mg
lead to dizziness, weakness, nausea, headache, Duloxetine Cymbalta Delayed-
rebound depression, anxiety, insomnia, poor release cap
concentration, upper respiratory symptoms, 20, 30, 60
paresthesias, and migraine-like symptoms mg
May occur only after at least 6 weeks of Desvenlafaxine Pristiq Extended
treatment, and disappears in 3 weeks release tab
spontaneously 50, 100 mg

Endocrine and allergic reactions Potent reuptake inhibitors of serotonin and
Increased prolactin levels caused by SSRIs can norepinephrine
produce galactorrhea in both men and women Venlafaxine inhibits norepinephrine reuptake at
Rashes in some patients may generalize to involve doses above 150 mg
the pulmonary system, resulting in rare fibrotic Duloxetine has equal affinity to both serotonin and
damage and dyspnea NE receptors
Discontinue if with drug-related rashes
Indications of SNRIs
In children & adolescents no SSRI is approved for clinical Venlafaxine Duloxetine Desvenlafaxine
use in Canada
MDD

GAD -
Drug MDD OCD
Social - -
Fluoxetine Age 8-17 Age 7-17
Phobia
Fluvoxamine No data >age 7
Panic - -
Sertraline Efficacy not >age 6 Disorder
demonstrated in

clinical trials
Other indications
Paroxetine Efficacy not ?
Neuropathic pain
demonstrated in
Pain from fibromyalgia
clinical trials
Chronic musculoskeletal pain
Citalopram Efficacy not ? Pain due to osteoarthritis
demonstrated in Bipolar disorder: depressed phase
clinical trials Treatment resistant depression, dysthymia,
Escitalopram No data ? postpartum depression and melancholic depression
OCD
SSRIs have been associated with increased suicidal
ideation, hostility and psychomotor agitation in Dosing and Pharmacokinetics
clinical trials involving children, adolescents and Drug Thera Bioava Pro Pea Elimi Metab
young adults, which was not seen in those aged 24- peuti ilability tein k natio olizin
65 c (%) bin pla n g
They may even be protective for those over 65 dose din sm half- enzym
Monitor all patients for worsening of depression and (mg) g a life es
suicidal thinking (%) lev
el
In the Elderly (%)
Initiate lower dose and increase more slowly Venlafa 75- 11 27 2 5-7 1D6,
Elderly may take longer to respond and may need xine 375 (pare 3A4,
trials of at least 12 weeks before treatment response nt) 2C9,
is noted. 8-13 2C19
Higher doses of fluoxetine have been associated (meta
with delirium bolite)
SSRIs generally have low risk of CNS, anticholinergic Desven 50- 80 30 7.5 11 UGT
and cardiovascular effects lafaxine 100 1A4

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Duloxet 60- 70 25 6 6-19 1A2, Panic disorder, GAD, social anxiety disorder
ine 120 2D6 Sexual dysfunction, SSRI-induced
Serotonin syndrome
Desvenlafaxine is the major active metabolite of
venlafaxine which is not metabolized by CYP2D6. Mechanism of Action of NaSSA
This may result in its reduced risk of interaction with Antagonism of central presynaptic 2-adrenergic
other drugs. receptors increased firing of norepinephrine and
Venlafaxine & desvenlafaxine are well absorbed from serotonin neurons
GIT and food has no effect on absorption Blockade of post synaptic serotonin 5 HT2 and 5 HT2
Duloxetine may or may not be given with meals receptors decrease anxiety, relieve insomnia, and
Therapeutic effect typically seen after 28 days or stimulate appetite
sooner in some Potent antagonism of H1 receptors and moderate
Clinical trials among children have shown associated antagonism of 1 adrenergic and muscarinic
increased suicidal ideation, and psychomotor cholinergic receptors
agitation; close monitoring needed if depression Reduces sleep latency and prolongs sleep
worsens and suicidal thoughts are noted. duration due to H1 and 5-HT2A/C blockade
This may be helpful in treating depression with
Side Effects of SNRIs prominent insomnia or agitation
Generally dose-dependent Has mild anxiolytic effect at low doses
Safety and tolerability of Venlafaxine is similar to the Increases both norepinephrine and serotonin through
SSRIs a mechanism other than reuptake blockade (as in the
Nausea is most common; headache, too case of SSRI and TCA), or monoamine oxidase
Other common ones include dry mouth, dizziness, inhibition (as in the case of phenelzine or
somnolence, constipation and sweating moclobemide)
Rise in BP noted with higher doses of venlafaxine;
duloxetine, too Pharmacologic Actions of NaSSA
For those with diabetes or are high risks, increase in Orally administered
blood sugar and hemoglobin A1C levels are noted Rapidly and completely absorbed
with long-term treatment Half-life of about 20-40 hours
Hepatic problems may ensue with duloxetine use, so Peak concentration in 2 hours of ingestion
avoid giving to those who abuse alcohol Steady state after 6 days
Fatal overdoses have been documented with Plasma clearance impaired by liver disease and renal
venlafaxine in combination with alcohol, other drugs disease
or both Plasma clearance slowed in the elderly
Avoid duloxetine in those with severe renal Food slightly decreases absorption rate
insufficiency and liver disease Protein binding about 85%
Do not use SNRI in those with uncontrolled Extensively metabolized by CYP1A2, 2D6, and 3A4
hypertension Therapeutic effect seen after 28 days but effects
Serotonin syndrome may occur on sleep and appetite are seen sooner
May induce mania in those with bipolar disorder Remeron SolTabs dissolve on tongue within 30
seconds and can be swallowed with or without water,
Discontinuation syndrome manifesting as chewed or allowed to dissolve
Dizziness Dry mouth Sweating Incoordination
Lethargy Diarrhea Chills Insomnia Side effects of NaSSA
Nausea Headache Malaise Nervousness Side effect Percentage affected
Vomiting Fever Anorexia Sensory Somnolence 54
disturbances Dry mouth 25
Increased appetite 17
These medications should be withdrawn gradually Constipation 13
over several weeks after prolonged use!!! Weight gain 12
Dizziness 7
NORADRENERGIC/SPECIFIC SEROTONERGIC Myalgias 5
ANTIDEPRESSANT (NaSSA) Disturbing dreams 4
Chemical Drug name Trade Dosage
class name form & Hypotension, hypertension, tachycardia and
strengths palpitations are rare
Tetracyclic Mirtazapine Remeron Tab 7.5, 15, No significant ECG changes
agent 30, 45 mg Sexual dysfunction occurs occasionally
Remeron Oral Risk increased with age, higher doses and
Soltab disintegrating concomitant medications
tab 15, 30,
Monitor all patients for worsening depression and
45 mg
suicidal thoughts with treatment

Low liability for toxicity in overdose if taken alone
Indications of NaSSA
May induce manic reactions in those with bipolar
MDD (with or without comorbid anxiety)
disorder

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Early data suggests no teratogenic effects in humans Contraindicated in patients with history of
Higher rate of spontaneous abortions and preterm anorexia or bulimia, undergoing alcohol or
births reported benzodiazepine withdrawal
Secreted into breast milk in low concentrations
Adverse effects of NDRI
Discontinuation syndrome Primarily a result of effects on dopamine and
Withdraw gradually after prolonged use because of norepinephrine
manifestations of dizziness, lethargy, nausea, Insomnia, headache, tremor, nausea, dry mouth
vomiting, diarrhea, headache, fever, sweating, chills, are most common
incoordination, and others Vivid dreams and nightmares
Agitation, anxiety, irritability
NOREPINEPHRINE DOPAMINE REUPTAKE INHIBITOR Can exacerbate psychotic symptoms
(NDRI) Reported to exacerbate symptoms of OCD
Chemical Drug name Trade Dosage Seizures with abrupt dose increases or high daily
class name form & dose above 450 mg
strength Most notable in the absence of significant drug-
Monocyclic Bupropion Wellbutrin Tabs 75, induced orthostatic hypotension, weight gain, daytime
agent 100 mg drowsiness and anticholinergic effects
(aminoketone) Wellbutrin Sustained
SR release tab SEROTONIN-2 ANTAGONIST/REUPTAKE INHIBITORS
100, 150, (SARI)
200 mg Chemical class Drug name Trade Dosage
Wellbutrin Extended name form &
XL release tab strength
150, 300, Phenylpiperidine Nefazodone Serzone Tabs 50,
450 mg 100, 150,
200, 250
Indications of NDRI mg
MDD Triazolopyridine Trazodone Desyrel Tabs 50,
Prophylaxis for recurrent MDD 68.25, 100,
Bipolar disorder, depressed phase 150, 300
Smoking cessation (Zyban, extended-release tablet) mg
Seasonal affective disorder Oleptro Extended
release tab
Mechanism of action of NDRI 150, 300
Inhibits reuptake of primarily norepinephrine and mg
to a lesser extent, dopamine, into the presynaptic
neurons Indications of SARI
Hydroxybupropion, the major metabolite, is 10- to MDD
20-fold higher than bupropion and blocks only MDD, recurrent, prophylaxis
norepinephrine reuptake Bipolar disorder, depressed phase
May have lower switch rate to mania or hypomania Agoraphobia with panic disorder
than other antidepressants Dysthymia
May enhance energy and motivation early in Social phobia
treatment due to effects on norepinephrine and PTSD
dopamine
Reported to improve neurocognitive function in Mechanism of action of SARI
patients with depression Exact MOA is unknown
Does not potentiate the sedative effects of alcohol Cause downregulation of -adrenergic neurons
Least likely of all antidepressants to impair sexual Trazodone inhibits reuptake of serotonin and
functioning induces changes in 5-HT presynaptic receptor
adrenoceptors
Pharmacologic action of NDRI Nefazodone inhibits neuronal reuptake of
Rapid absorption: peak concentration in 3 hours serotonin and norepinephrine
Protein binding 80-85%
Metabolism primarily by liver, through CYP2B6 Adverse effects of SARI
Both bupropion and hydroxybupropion inhibit CNS: Result of antagonism at histamine H1 receptors
CYP2D6 isoenzyme and 1 adrenoceptors
Elimination half-life 11-14 hours; longer with chronic Occur frequently
dosing Drowsiness: most common
Decreased clearance reported in elderly Weakness, lethargy, fatigue
Therapeutic effect usually after 28 days Anticholinergic: Result of antagonism by muscarinic
Caution with use in those with hepatic and renal receptors
impairment Dry eyes, blurred vision, constipation, and dry mouth
May lower seizure threshold

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 Psychiatry 3 topic

CV: Result of antagosim at 1 adrenoreceptors,
muscarinic, 5-HT2AC and H1 receptors, and inhibition
of sodium fast channels
More common in elderly
Dizziness, orthostatic hypotension, and syncope
Bradycardia: Nefazodone
Exacerbate transient ischemic attacks
GI: Result of inhibition of 5-HT uptake and M1
receptor antagonism
Peculiar taste, glossitis
Beware of discontinuation syndrome
Use caution in combination with drugs prolonging QT
interval

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SHORT QUIZ RECALLS (NON-VERBATIM)

CASE A:
Ate gurl suffers from insomnia and MDD, unable to take care of her
child and was fired from her job because shes no longer productive.

DOC, justification and what would you advise the patient/cautionary
use:
a. Paroxetine (SSRI)
Justification: AE includes somnolence, so it would
normalize the sleep-wake cycle of the patient
Caution: Take note of her diet because it causes weight
gain and she may feel anti-cholinergic AEs (dry mouth,
constipation, etc.)
b. Citalopram (SSRI)
Justification: SAME
Caution: may cause CV problems (QT prolongation)
c. Mirtazapine (NaSSA)
Justification: reduces sleep latency and prolongs sleep
duration due to H1 and 5-HT2A/C blockade, SAME
Caution: may cause dry mouth, increased appetite, etc.

CASE B:
Manong suffers from MDD and has a history of hypertension and
angina attacks.

DOC:
ANY DRUG EXCEPT CITALOPRAM because it causes CV problems (QT
prolongation).

Dont know the details of the other cases.

CASE C:
Surgeon yada yada with insomnia.

DOC, justification:
PLEASE FOLLOW CASE A ANSWERS.

CASE D:
Preggers near term yada yada.

According to Doc Familiar, ANY DRUG WILL DO.

Answer if patient is not yet term:
ANY DRUG EXCEPT MIRTAZAPINE (NaSSA) because it causes
spontaneous abortion and preterm delivery.

Transcribed by: orquia, pat