Antidepressants Flashcards
DSM-5 Diagnostic Criteria – Major Depressive Episode (MDD)
Major
Depressive
Episode
Depressed
mood
Weight change
Sleep disturbances
Agitation/retardation
Fatigue
Guilt
Decreased
concentration
Suicidal ideation Loss of interest
or pleasure
Symptoms present most
of the day, nearly every day
Symptoms present > – weeks
and represent a change from
previous functioning
2
Must have > – symptoms
5
DSM-5 Diagnostic Criteria – MDD
(4)
- symptoms cause clinically
significant distress or
impairment in social,
occupational, or other
important areas of functioning - not attributable to the
physiological effects of a
substance or another medical
condition - not better explained by
another psychiatric illness - has never been a manic
episode or a hypomanic
episode
Monoamine
Hypothesis of
Depression
* Depression due to
deficiency of
monoamine neurotransmitters (NT)
– norepinephrine
– serotonin
Monoamine
Hypothesis of
Depression
Evidence
– Depletion of NT induces depression
(2)
– Antidepressants increase levels of NT
– Onset of antidepressant activity
(decrease in depressive symptoms) is
correlated with down-regulation of
receptors
Oral Side Effects Associated with
Antidepressants
* Common
(2)
– Xerostomia (96%)
– Dysguesia (65%)
Oral Side Effects Associated with
Antidepressants
* Less Common
– Hypersalivation, stomatitis,
dysphagia, bruxism, glossiitis,
tardive dyskinesia, hairy
tongue, salivary gland
enlargement, tongue edema,
gingivitis, halitosis, ulcers, jaw
stiffness, candidiasis, sinusitis,
erythema multiforme, Steven-
Johnson syndrome, gumline
erosion, periodontal disease,
tooth disease
Monoamine Oxidase Inhibitors
(MAO-I)
(2)
- phenelzine (Nardil)
- tranylcypromine
(Parnate)
Monoamine Oxidase Inhibitors
* drug-drug and
drug-food interactions
(2)
– hypertensive crisis
– serotonin syndrome
Common Side Effects of MAO-I
(7)
- Dry mouth
- Nausea, diarrhea or constipation
- Headache
- Drowsiness or Insomnia
- Dizziness or lightheadedness
- Weight gain
- Sexual dysfunction
- Significant morbidity and mortality associated
with overdose
Hypertensive Crisis
* Defined by diastolic blood pressure > – mmHg
* Potentially fatal reaction characterized by:
(8)
120
– Occipital headache – may radiate frontally
– Palpitation
– Neck stiffness or soreness
– Nausea and/or vomiting
– Sweating
– Dilated pupils, photophobia
– Tachycardia or bradycardia
– Chest pain
Suggested Tyramine Dietary
Modifications for MAO-I
* Foods to AVOID
(6)
– Dried, aged, smoked,
fermented, spoiled, or
improperly stored meat,
poultry and fish
– Broad bean pods
– Aged cheeses
– Tap and nonpasteurized beers
– Marmite, sauerkraut
– Soy products/tofu
Suggested Tyramine Dietary
Modifications for MAO-I
* Foods ALLOWED
(5)
– Fresh or processed meat,
poultry and fish
– All other vegetables
– Processed and cottage
cheese, ricotta cheese,
yogurt
– Canned or bottled beers and
alcohol
– Brewer’s and baker’s yeast
Warnings:
Do not use if you are now taking a
prescription
monoamine oxidase inhibitor
(MAOI) (certain drugs for depression,
psychiatric or emotional conditions, or
Parkinson’s disease), or for 2 weeks after
stopping the MAOI drug. If you do not know
if your prescription drug contains an MAOI,
ask a doctor or pharmacist before taking this
product
Hypertensive Crisis –
Drug Interactions to AVOID
(4)
- Decongestants
- Stimulants
- Antidepressants with
NRI activity - Appetite suppressants
with NRI activity
- Decongestants
(4)
– phenylephrine
– ephedrine (ma huang,
ephedra)
– pseudoephedrine
– oxymetazoline
- Stimulants
(2)
– amphetamines
– methylphenidate
- Antidepressants with
NRI activity
(3)
– TCA
– SNRI (venlafaxine,
desvenlafaxine,
duloxetine)
– bupropion, mirtazapine
- Appetite suppressants
with NRI activity
(1)
– phentermine
Serotonin Syndrome
(3)
- Addition or increase of
known serotonergic agent to
an established medication
regimen - Other etiologies (infectious,
metabolic, substance abuse
or withdrawal) have ruled
out. - Antipsychotic has not been
started or increased prior to
the onset of sign/symptoms
Serotonin Syndrome
* Three of more of the
following symptoms:
– Agitation
– Diaphoresis
– Diarrhea
– Fever
– Hyperreflexia
– Incoordination
– Mental status changes
(confusion, hypomania)
– Myoclonus
– Shivering
– Tremor
Serotonin Syndrome –
Drug Interactions to AVOID
(4)
- Antidepressants
- Other TCA structure
drugs - Pain Medication
- Cough Suppressants
- Antidepressants
(4)
– SSRI
– TCA (clomipramine)
– SNRI
– Mirtazapine
- Other TCA structure
drugs
(2)
– Cyclobenzaprine
– Carbamazepine
- Pain Medication
(5)
– Meperidine
– Tramadol ✔
– Methadone
– Propoxyphene
– Fentanyl
- Cough Suppressants
(1)
– Dextromethorphan
MAO-I: Summary
Advantages
(1)
- May be useful in
treatment refractory
depression
MAO-I: Summary
Disadvantages
(7)
- Tolerability
- Significant risk of
morbidity and
mortality associated
with overdose - Oral side effect – dry
mouth - Dietary restrictions
- Significant drug
interaction risk - Hypertensive crisis
- Serotonin syndrome
Tricyclic Antidepressants (TCA)
(2)
- Tertiary TCA
– amitriptyline (Elavil) - Secondary TCA
– nortriptyline (Pamelor)
Side Effect Profile of TCA
(4)
- cardiac conduction disturbances - QTc prolongation
- seizures
- sexual dysfunction
- significant risk of morbidity and mortality associated with
overdose
Drug Interactions with TCA
- TCA + CNS Depressants (ex. opioid pain
medication) = additive CNS depressant effects
TCA: Summary
Advantages
(2)
- May be useful in
treatment refractory
depression - More commonly used
for chronic pain
(diabetic peripheral
neuropathic pain,
fibromyalgia, chronic
musculoskeletal pain)
and insomnia
TCA: Summary
Disadvantages
(4)
- Tolerability
- Significant risk of morbidity
and mortality associated
with overdose - Oral side effect – dry
mouth - Overall high side effect
burden – including weight
gain, sedation and sexual
dysfunction - Significant risk for drug
interactions (additive CNS
depressant effects)
Selective Serotonin Reuptake
Inhibitors (SSRI)
(5)
- fluoxetine (Prozac)
- paroxetine (Paxil, Paxil CR,
Pexeva) - sertraline (Zoloft)
- citalopram (Celexa)
- escitalopram (Lexapro)
Mechanism of Action and
Side Effect Profile of SSRI
(2)
– minimal to no effect on
H1, M1 or alpha1
receptors
– side effect profile - GI
upset, headache,
insomnia, restlessness,
anxiety, weight gain,
sexual dysfunction
Side Effects Important in Dentistry
(2)
- Increased risk for
bleeding and bruising - Bruxism
Drug Interactions with NSAID
* Pharmacodynamic
interactions
(2)
– SSRI – decrease
platelet aggregation
* INCREASED RISK FOR
BLEEDING
Drug Interactions with Opioid Medications
(codeine, hydrocodone and oxycodone)
(4)
- Pharmacokinetic interaction
- Drugs that INHIBIT CYP450 2D6
PREVENT the metabolism of
codeine, hydrocodone and
oxycodone to an active medication. - OUTCOME: pain relieving effects
are REDUCED - Antidepressants
– Paroxetine (Paxil)
– Fluoxetine (Prozac)
SSRI: Summary
Advantages
(4)
- (+) safety associated
with overdose - Recommended 1st line in
all depression treatment
algorithms - (+) safety profile in
patients with medical
illnesses - Relatively well tolerated
SSRI: Summary
Disadvantages
(4)
- Tolerability
- Oral side effect –
bruxism, increased
risk for bleeding - Long term side effects
– weight gain and
sexual dysfunction - Significant risk for drug
interactions
Side Effect Profile -
Venlafaxine and Duloxetine
* Side effect profile
(2)
– no effect on H1, M1 or
alpha1 receptors
– side effect profile -
nausea, elevated BP,
weight gain, sexual
dysfunction
SNRI: Summary
Advantages
(4)
- (+) Safety profile in
overdose - Recommended 1st line in
all depression treatment
algorithms - Used to treat depression
and pain (diabetic
peripheral neuropathic
pain, fibromyalgia, chronic
musculoskeletal pain) - Relatively well tolerated
SNRI: Summary
Disadvantages
(4)
- Tolerability
- No specific oral side
effects - Long term side effects –
weight gain and sexual
dysfunction - Low risk for drug
interactions
Side Effect Profile of
Bupropion
* contraindications
(3)
* caution use in —
* no effect on (3)receptors
* side effect profile -
(3)
– seizure history
– history of significant head trauma
– anorexia or bulimia
psychosis
H1, M1 or alpha1
– insomnia, seizures (less common)
– low risk of sexual dysfunction
– low risk of weight gain
Drug Interactions with Opioid Medications
(codeine, hydrocodone and oxycodone)
(4)
- Pharmacokinetic interaction
- Drugs that INHIBIT CYP450 2D6
PREVENT the metabolism of
codeine, hydrocodone and
oxycodone to an active medication. - OUTCOME: pain relieving effects
are REDUCED - Antidepressants
– Paroxetine (Paxil)
– Fluoxetine (Prozac)
– Bupropion (Wellbutrin)
NDRI - Bupropion: Summary
Advantages
(5)
- Recommended 1st line in
depression treatment
algorithms - Low risk of sexual
dysfunction - Low risk risk for weight
gain - Used for smoking
cessation - Relatively well tolerated
NDRI - Bupropion: Summary
Disadvantages
(4)
- Tolerability
- No specific oral side
effects - Potential for seizures
associated with
overdose - Significant risk for drug
interactions
Side Effect Profile of Mirtazapine
(3)
- no effect on M1 or alpha1 receptors
- (+) effect on H1 receptors
- side effect profile
– Sedation
– dry mouth
– weight gain
– low risk of sexual dysfunction
Presynaptic Alpha2 Antagonist - Mirtazapine:
Summary
Advantages
(3)
- (+) Safety profile in
overdose - Recommended 1st
line in depression
treatment
algorithms - Low risk for sexual
dysfunction
Presynaptic Alpha2 Antagonist - Mirtazapine:
Summary
Disadvantages
(4)
- Tolerability
- Oral side effect –
dry mouth - Long term side
effects - weight
gain, sedation - Low risk for drug
interactions
Goals of Antidepressant Therapy
(7)
- REMISSION = resolution of depression
symptoms - Improve functioning
- Reduce risk of relapse
- Increase quality of life
- Decrease depression morbidity
- Decrease depression mortality
- Decrease healthcare costs
Definitions of Response and Remission
% Reduction in Score
Remission
Response
Partial Response
Nonresponse
≥75%
50% - 74%
25% - 49%
<25%
Selection of Antidepressant Therapy
Empiric selection of antidepressant therapy:
(5)
- past history of AD response
- family history of AD response
- concurrent disease states/drug therapy
- adverse effect profile
- cost
Selection of Antidepressant Therapy
* Treatment Guidelines (APA 2019)
(5)
- Psychotherapy can be used alone for mild-moderate
depression - Pharmacotherapy can use used alone for mild-
moderate depression - Pharmacotherapy +/- psychotherapy for moderate-
severe depression - SSRI, SNRI, bupropion and mirtazapine are
recommended as 1st line therapy - Only complimentary therapy recommended 1st line is
St. John’s wort (CANMAT 2016, VA/DoD 2016)
Efficacy
of AD
(3)
- All antidepressants demonstrate equivalent
efficacy - 70%. - onset - days to weeks (depending on type of
symptom) - therapeutic trial - 6-8 weeks
Nonremission is Common
* —% remission
* —% response with residual symptoms
* –% partial response
* –% nonresponse
* –% intolerant
35–45
10–20
15
25
7–15
Symptom Remission
first week (3)
- Decreased Anxiety
- Improvement in Sleep
- Improvement in Appetite
Symptom Remission
1-3 Weeks (3)
- Increased Activity,
Sex Drive, Self-care,
and Memory - Thinking and Movements
Normalize - Sleeping and Eating
Patterns Normalize
Symptom Remission
2-4 Weeks (3)
Relief of Depressed
Mood
* Less Hopeless/
Helpless
* Thoughts of Suicide
Subside
Maintenance Antidepressant
Therapy
* first episode -
* second episode -
* > 2 episodes -
* elderly patients -
continue AD for 9-12 months
continue AD for 5 years
continue AD for lifetime
consider continuing AD
for longer; maybe indefinitely
