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antidepressants Flashcards

1
Q

symptom dimensions of Major depressive episodes

A
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2
Q

DSM-5 Diagnostic Criteria – Major Depressive Episode (MDD)

A
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3
Q

Diagnostic Criteria – MDD
* symptoms cause?
* not attributable to?
* not better explained by?
* has never been?

A
  • 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
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4
Q

Monoamine Hypothesis of Depression

A
  • Depression due to deficiency of monoamine neurotransmitters (NT)
    – norepinephrine
    – serotonin
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5
Q
  • Evidence of monoamine hypothesis
A

– Depletion of NT induces depression
– Antidepressants increase levels of NT
– Onset of antidepressant activity (decrease in depressive symptoms) is correlated with down-regulation of receptors

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6
Q

Heterocyclic Tertiary Amines (TCA)

A

Amitriptyline (Elavil)
Imipramine (Tofranil)
Doxepin (Sinequan)

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7
Q

Heterocyclic Tertiary Amines (TCA) moa

A

Mixed NE and 5HT reuptake inhibition

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8
Q

Amitriptyline (Elavil)

moa and dosage

A

Mixed NE and 5HT reuptake inhibition

50-300 mg

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9
Q

Imipramine (Tofranil)

moa

A

Mixed NE and 5HT reuptake inhibition

tertiary TCA

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10
Q

Doxepin (Sinequan)

moa and dosage

A

Mixed NE and 5HT reuptake inhibition

50-300 mg

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11
Q

Heterocyclic Secondary Amines (TCA)

A

Nortriptyline (Pamelor)
Desipramine (Norpramin)

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12
Q

Heterocyclic Secondary Amines (TCA) moa

A

NE>5HT reuptake inhibition

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13
Q

Nortriptyline (Pamelor) moa

A

NE>5HT reuptake inhibition

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14
Q

Desipramine (Norpramin) moa

A

NE>5HT reuptake inhibition

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15
Q

Selective Serotonin Reuptake Inhibitors (SSRI)

A

Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil, Paxil CR, Pexeva)
Fluvoxamine (Luvox, Luvox CR)
Citalopram (Celexa)
Escitalopram (Lexapro)

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16
Q

SSRI moa

A

5HT»>NE reuptake inhibition

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17
Q

Fluoxetine (Prozac)

moa and dosage

A

5HT»>NE reuptake inhibition

10-80 mg

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18
Q

Sertraline (Zoloft)

moa and dosage

A

5HT»>NE reuptake inhibition

50-200 mg

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19
Q

Paroxetine (Paxil, Paxil CR, Pexeva)

moa and dosage

A

5HT»>NE reuptake inhibition

10-40 mg

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20
Q

Fluvoxamine (Luvox, Luvox CR)

moa and dosage

A

5HT»>NE reuptake inhibition

50-300 mg

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21
Q

Citalopram (Celexa)

moa and dosage

A

5HT»>NE reuptake inhibition

20-40 mg

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22
Q

Escitalopram (Lexapro)

moa and dosage

A

5HT»>NE reuptake inhibition

10-20 mg

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23
Q

Serotonin Norepinephrine Reuptake Inhibitors (SNRI)

A

Venlafaxine (Effexor)
Desvenlafaxine (Pristiq, Khedezla)
Duloxetine (Cymbalta)
Levomilnacipran (Fetzima)

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24
Q

SNRI moa

A

mixed based on the agents

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25
Venlafaxine (Effexor) | moa
5HT >NE>>DA reuptake inhibition
26
Desvenlafaxine | moa
5HT=NE reuptake inhibition
27
Duloxetine (Cymbalta) | moa
5HT=NE reuptake inhibition
28
Levomilnacipran (Fetzima) | moa
NE>5HT reuptake inhibition | SNRI
29
Monoamine Oxidase Inhibitors (MAOI)
Phenelzine (Nardil) Tranylcypromine (Parnate) Selegiline Transdermal patch (EMSAM)
30
MAOI moa
Nonselective MAO A and B inhibition
31
Phenelzine (Nardil) | moa and dose
Nonselective MAO A and B inhibition | 15-90 mg 10-60 mg
32
Tranylcypromine moa
Nonselective MAO A and B inhibition
33
Selegiline Transdermal patch (EMSAM) moa and dose
Selective MAO B inhibition Nonselective MAO A and B inhibition 6 mg/24hrs 9 mg/24hrs 12 mg/24hrs
34
Atypical Antidepressants
Bupropion (Wellbutrin, Forfivo) Mirtazapine (Remeron) Trazodone Nefazodone (Serzone) Vilazodone (Viibryd) Vortioxetine (Trintellix)
35
Bupropion (Wellbutrin, Forfivo) moa
NE and DA reuptake inhibition
36
Mirtazapine (Remeron) moa
Alpha2-NE 5HT2 presynaptic antagonist 5HT2/3 postsynaptic antagonist
37
Trazodone moa
5HT2 antagonist / Selective 5HT reuptake inhibitor
38
Nefazodone (Serzone) moa
5HT2 antagonist / Selective 5HT reuptake inhibitor
39
Vilazodone (Viibryd) moa
Selective 5HT reuptake inhibitor/partial 5HT1A agonist
40
Vortioxetine (Trintellix) moa
5HT3/1D/7 antagonist 5HT1B partial agonist 5HT1A agonist
41
Novel Antidepressants
Esketamine (Spravato) Brexanolone (Zulresso
42
Esketamine (Spravato) moa
Non-selective, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor
43
# Brexanolone (Zulresso) moa
Positive allosteric modulation of GABAA receptors
44
Common oral side effects of antidepressants
– Xerostomia (96%) – Dysguesia (65%
45
less common oral side effects of antidepressants
* 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
46
Monoamine Oxidase Inhibitors (MAO-I) drug and food interactions
– hypertensive crisis – serotonin syndrome NE increaed with MAOI and can be further increaed thru tyramine in diet
47
Common Side Effects of MAO-I: * oral? * GI * head? * other side effects * od?
* **Dry mouth** * Nausea, diarrhea or constipation * Headache * Drowsiness or Insomnia * Dizziness or lightheadedness * Weight gain * Sexual dysfunction * **Significant morbidity and mortality associated with overdose**
48
Hypertensive Crisis
* Defined by diastolic blood pressure > 120 mmHg * Potentially fatal reaction characterized by: – Occipital headache – may radiate frontally – Palpitation – Neck stiffness or soreness – Nausea and/or vomiting – Sweating – Dilated pupils, photophobia – Tachycardia or bradycardia – Chest pain
49
Suggested Tyramine Dietary Modifications for MAO-I * Foods to AVOID
– 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
50
Suggested Tyramine Dietary Modifications for MAO-I * Foods ALLOWED
– 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
51
what common rx should be avoided with MAOI? what is the protocol?
52
Hypertensive Crisis – Drug Interactions to AVOID with MAOI
cold meds are big cause
53
decongestants causing HTN crisis with MAOi
– phenylephrine – ephedrine – pseudoephedrine – oxymetazoline
54
stims causing HTN crisis with MAOi
– amphetamines – methylphenidate
55
AD's causing HTN crisis with MAOis
* Antidepressants with NRI activity – TCA – SNRI (venlafaxine, desvenlafaxine, duloxetine) – bupropion, mirtazapine
56
appetite Rx causing HTN crisis with MOAi
* Appetite suppressants with NRI activity – phentermine
57
Serotonin Syndrome
* 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
58
SS signs and symptoms
Three of more of the following symptoms: – Agitation – Diaphoresis – Diarrhea – Fever – **Hyperreflexia** – Incoordination – Mental status changes (confusion, hypomania) – Myoclonus – Shivering – Tremor
59
Serotonin Syndrome – Drug Interactions to AVOID with MAOI
tramadol and dextromethorphan increase 5HT
60
AD's associated with SS and MAOi's
– SSRI – TCA (clomipramine) – SNRI – Mirtazapine
61
other TCA structure rx associated with SS and MAOi
– Cyclobenzaprine – Carbamazepine
62
pain meds that can cause SS when used with maoi
– Meperidine – Tramadol ✔ – Methadone – Propoxyphene – Fentanyl
63
cough suppressant associated with SS and MAOi
Dextromethorphan
64
MAO-I: Summary Advantages
* May be useful in treatment refractory depression
65
MAO-I: Summary * tolerable * OD * oral? * diet * ddi?
66
TCA forms | and action sites
67
Mechanism of Action of TCA
Mixed NE and 5HT reuptake inhibition | mainly used for refactory depression and neuropathic pain
68
Side Effect Profile of TCA | based on?
based on effected receptors h1: weight gain, xerostomia, drowsy m1: constipation, xero, blurred vision, drowsy a: dizzy, hypotension
69
TCAs and cardiac function
cardiac conduction disturbances - QTc prolongation
70
other TCA side effects
* seizures * sexual dysfunction * **significant risk of morbidity and mortality associated with overdose**
71
Drug Interactions with TCA
* TCA + CNS Depressants (ex. opioid pain medication) = additive CNS depressant effects
72
TCA advantages * May be useful in? * More commonly used for ?
* May be useful in treatment refractory depression * More commonly used for chronic pain (diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain) and insomnia
73
TCA disadvantages * Tolerability * Significant risk of? * Oral? * side effects? * ddis?
* Tolerability * Significant risk of **morbidity and mortality associated with overdose** * Oral side effect – **dry mouth** * Overall **high side effect burden** – including w**eight gain, sedation and sexual dysfunction** * **Significant risk for drug interactions** (additive CNS depressant effects)
74
Mechanism of Action and Side Effect Profile of SSRI
only 5HT reuptake inhibited= increased tolerability | weight gain is less than TCAs, 65% sex dysfunc, these tend to remain
75
Side Effects Important in Dentistry for SSRIs
* Increased risk for bleeding and bruising, 5HT reduces this * Bruxism related to 5HT
76
what rx can SSRI interact with to increase bleeding
Drug Interactions with NSAID * Pharmacodynamic interactions – SSRI – decrease platelet aggregation * INCREASED RISK FOR BLEEDING
77
SSRI and opioids
* Pharmacokinetic interaction * Drugs that INHIBIT CYP450 2D6 PREVENT the metabolism of codeine, hydrocodone and oxycodone to an active medication. – Paroxetine (Paxil) – Fluoxetine (Prozac) * OUTCOME: pain relieving effects are REDUCED due to decreaed opioid activation | also buprion
78
# SSRI * overdose? * Recommended? * safety in patients with medical illnesses? * tolerable?
* (+) safety associated with overdose * Recommended 1st line in all depression treatment algorithms * (+) safety profile in patients with medical illnesses * Relatively well tolerated
79
# SSRI disadvantages * Tolerable? * Oral side effect? * Long term side effects? * Significant risk for?
* Tolerability * Oral side effect – bruxism, increased risk for bleeding * Long term side effects – weight gain and sexual dysfunction * Significant risk for drug interactions
80
Venlafaxine (Effexor) and Duloxetine (Cymbalta) structure
SNRIs (DPI with venlafaxin) ## Footnote good for neuropathic pain
81
Mechanism of Action of SNRI:
both NTs affected
82
Side Effect Profile - Venlafaxine and Duloxetine
**NO ORAL SIDE EFFECTS**
83
SNRI: *OD * Recommended? * Used to treat? * tolerated?
* (+) 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
84
SNRI Tolerabler? * oral side effects? * Long term side effects? * ddi?
Tolerability * No specific oral side effects * Long term side effects – weight gain and sexual dysfunction * Low risk for drug interactions
85
Bupropion (Wellbutrin) moa
NDRI
86
Side Effect Profile of Bupropion
* no effect on H1, M1 or alpha1 receptors * side effect profile -insomnia, seizures (less common) **– low risk of sexual dysfunction – low risk of weight gain**
87
Bupropion contraindications – hx of what dx's/events * caution use in ?
– seizure history – history of significant head trauma – anorexia or bulimia (electrolyte imbalances) * caution use in psychosis
88
bupropion and opiates
* 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
89
Bupropion * Recommended? * Low risks for? * Also used for? * tolerated?
* 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
90
Bupropion * Tolerable? * oral? * Potential for? * ddi?
* Tolerability * No specific oral side effects * Potential for seizures associated with overdose * Significant risk for drug interactions
91
Mirtazapine moa
A2 antagonsit that increases 5HT and NE, however reuptake pumps work normally. A2 responsible for signaling when there are adequate amts of NT in synapse= antagonizes this cause no signal and increased NTs
92
Side Effect Profile of Mirtazapine * no effect on? * (+) effect on? * side effect profile?
* no effect on M1 or alpha1 receptors * (+) effect on **H1 receptors** * side effect profile – Sedation – dry mouth – weight gain – low risk of sexual dysfunction
93
which Ad classes cause xerostomia
mirtazapine TCAs MAO-i
94
Mirtazapine * od? * Recommended? * Low risk for?
* (+) Safety profile in overdose * Recommended 1st line in depression treatment algorithms * Low risk for sexual dysfunction
95
Mirtazapine * Tolerability? * Oral side effects? * Long term side effects? * risk of ddi?
* Tolerability * Oral side effect – dry mouth * Long term side effects - weight gain, sedation * Low risk for drug interactions
96
Goals of Antidepressant Therapy * REMISSION? * Improve ? * Reduce risk of ? * Increase ? * Decrease ? * healthcare costs
* REMISSION = resolution of depression symptoms * Improve functioning * Reduce risk of relapse * Increase quality of life * Decrease depression morbidity and mortality * Decrease healthcare costs
97
Definitions of Response and Remission
98
Selection of Antidepressant Therapy Empiric selection of antidepressant therapy:
* past history of AD response * family history of AD response * concurrent disease states/drug therapy * adverse effect profile * cost
99
Selection of Antidepressant Therapy: Treatment Guidelines (APA 2019) * Psychotherapy can be used alone for? * Pharmacotherapy can use used alone for? * Pharmacotherapy +/- psychotherapy for? * 1st line therapies? * Only complimentary therapy recommended 1st line is?
* 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
100
Efficacy of AD * % efficacy? * trial period?
101
non remission with AD's * % remission * % response with residual symptoms * % partial response * % nonresponse * % intolerant
* 35–45% remission * 10–20% response with residual symptoms * 15% partial response * 25% nonresponse * 7–15% intolerant
102
Symptom Remission timeline | 1st week, weeks 1-3, weeks 2-4
103
first week improvements with ADs
Decreased Anxiety * Improvement in Sleep * Improvement in Appetite
104
weeks 1-3 improvements with ADs
Increased Activity, Sex Drive, Self-care, and Memory * Thinking and Movements Normalize * Sleeping and Eating Patterns Normalize
105
weeks 2-4 improvements with ADs
* Relief of Depressed Mood * Less Hopeless/ Helpless * Thoughts of Suicide Subside
106
Maintenance Antidepressant Therapy * first episode - * second episode - * > 2 episodes - * elderly patients -
* first episode - continue AD for 9-12 months * second episode - continue AD for 5 years * > 2 episodes - continue AD for lifetime * elderly patients - consider continuing AD for longer; maybe indefinitely
107
neruotransmitter receptor hypothesis of AD action
* in depressive state receptors will upregulate due to decreased NT * with AD there are increased NT's (5HT and NE) * increased NTs will sensitize receptors and downregulate them over time
108
delayed AD onset diagrammed
109
Amitriptyline (Elavil) Imipramine (Tofranil) Doxepin (Sinequan)
Heterocyclic Tertiary Amines (TCA)
110
Mixed NE and 5HT reuptake inhibition
Heterocyclic Tertiary Amines (TCA) moa
111
Mixed NE and 5HT reuptake inhibition | 50-300 mg
Amitriptyline (Elavil) | moa and dosage
112
Mixed NE and 5HT reuptake inhibition | 50-300 mg
Imipramine (Tofranil) | moa and dosage
113
Mixed NE and 5HT reuptake inhibition | 50-300 mg
Doxepin (Sinequan) | moa and dosage
114
Nortriptyline (Pamelor) Desipramine (Norpramin)
Heterocyclic Secondary Amines (TCA)
115
NE>5HT reuptake inhibition
Heterocyclic Secondary Amines (TCA) moa
116
NE>5HT reuptake inhibition | 50-150 mg 75-300 mg
Nortriptyline (Pamelor) moa and dosage
117
NE>5HT reuptake inhibition 75-300 mg | 75-300 mg
Desipramine (Norpramin) moa and dosage
118
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil, Paxil CR, Pexeva) Fluvoxamine (Luvox, Luvox CR) Citalopram (Celexa) Escitalopram (Lexapro)
Selective Serotonin Reuptake Inhibitors (SSRI)
119
5HT>>>NE reuptake inhibition
SSRI moa
120
5HT>>>NE reuptake inhibition | 10-80 mg
Fluoxetine (Prozac) | moa and dosage
121
5HT>>>NE reuptake inhibition | 50-200 mg
Sertraline (Zoloft) | moa and dosage
122
5HT>>>NE reuptake inhibition | 10-40 mg
Paroxetine (Paxil, Paxil CR, Pexeva) | moa and dosage
123
5HT>>>NE reuptake inhibition | 50-300 mg
Fluvoxamine (Luvox, Luvox CR) | moa and dosage
124
5HT>>>NE reuptake inhibition | 20-40 mg
Citalopram (Celexa) | moa and dosage
125
5HT>>>NE reuptake inhibition | 10-20 mg
Escitalopram (Lexapro) | moa and dosage
126
Venlafaxine (Effexor) Desvenlafaxine (Pristiq, Khedezla) Duloxetine (Cymbalta) Levomilnacipran (Fetzima)
Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
127
mixed based on the agents
SNRI moa
128
5HT >NE>>DA reuptake inhibition | 37.5-225mg
Venlafaxine (Effexor) | moa and dose
129
which SNRI has 5HT=NE reuptake inhibition? | 50 mg
Desvenlafaxine (Pristiq, Khedezla) | moa and dose
130
5HT=NE reuptake inhibition | 30-120 mg
Duloxetine (Cymbalta) | moa and dose
131
NE>5HT reuptake inhibition | 40-120 mg
Levomilnacipran (Fetzima) | moa and dose
132
Phenelzine (Nardil) Tranylcypromine (Parnate) Selegiline Transdermal patch (EMSAM)
Monoamine Oxidase Inhibitors (MAOI)
133
Nonselective MAO A and B inhibition
MAOI moa
134
Nonselective MAO A and B inhibition | 15-90 mg 10-60 mg
Phenelzine (Nardil) | moa and dose
135
Nonselective MAO A and B inhibition | 10-60 mg
Tranylcypromine (Parnate | moa and dose
136
Selective MAO B inhibition Nonselective MAO A and B inhibition
Selegiline Transdermal patch (EMSAM) moa and dose
137
Bupropion (Wellbutrin, Forfivo) Mirtazapine (Remeron) Trazodone Nefazodone (Serzone) Vilazodone (Viibryd) Vortioxetine (Trintellix)
Atypical Antidepressants
138
NE and DA reuptake inhibition
Bupropion (Wellbutrin, Forfivo) moa
139
Alpha2-NE 5HT2 presynaptic antagonist 5HT2/3 postsynaptic antagonist
Mirtazapine (Remeron) moa
140
5HT2 antagonist / Selective 5HT reuptake inhibitor
Trazodone moa
141
5HT2 antagonist / Selective 5HT reuptake inhibitor
Nefazodone (Serzone) moa
142
Selective 5HT reuptake inhibitor/partial 5HT1A agonis
Vilazodone (Viibryd) moa
143
5HT3/1D/7 antagonist 5HT1B partial agonist 5HT1A agonist
Vortioxetine (Trintellix) moa
144
Esketamine (Spravato) Brexanolone (Zulresso
Novel Antidepressants
145
Non-selective, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor
Esketamine (Spravato) moa
146
Positive allosteric modulation of GABAA receptors
# Brexanolone (Zulresso) moa
147
which AD classes ARE NOT 1st line
TCAs and MAOi
148
# what can these lead to mixed with MAOi – phenylephrine – ephedrine – pseudoephedrine – oxymetazoline
decongestants causing HTN crisis with MAOi
149
# what can these lead to mixed with MAOi – amphetamines – methylphenidate
stims causing HTN crisis with MAOi
150
# what can these lead to mixed with MAOi – TCA – SNRI (venlafaxine, desvenlafaxine, duloxetine) – bupropion, mirtazapine
AD's causing HTN crisis with MAOis
151
# what can these lead to mixed with MAOi – phentermine
appetite Rx causing HTN crisis with MOAi
152
# what can these lead to mixed with MAOi – SSRI – TCA (clomipramine) – SNRI – Mirtazapine
AD's associated with SS and MAOi's
153
# what can these lead to mixed with MAOi – Cyclobenzaprine – Carbamazepine
other TCA structure rx associated with SS and MAOi
154
# what can these lead to mixed with MAOi – Meperidine – Tramadol ✔ – Methadone – Propoxyphene – Fentanyl
pain meds that can cause SS when used with maoi
155
# what can this lead to mixed with MAOi Dextromethorphan
cough suppressant associated with SS and MAOi

pharm 2 (20 decks)

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