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Antidepressants (Week 3/4) Flashcards

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1
Q

Monoamine hypothesis of depression

A

Hypothesis involving deficiency of monoamine neurotransmitters

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2
Q

Neurotransmitter receptor hypothesis of antidepressant action

A

hypothesis involving monoamine neurotransmitters and their receptors

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3
Q

Mnemonic for depressive disorders

A

S: Sleep
I: Interest
G:Guilt
E: Energy
C: Concentration
A: Appetite
P:psychomotor activity
S: suicide

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4
Q

Indications for prescribing antidepressants

A

-Unipolar and bipolar depression(acute phase)
-organic mood disorders
-schizoaffective disorder
-anxiety disorders involving obsessive compulsive disorder
-Panic disorders
-Socia phobia
-PTSD
-PMDD
-impulsivity associated with personality disorders.

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5
Q

General side effects of SSRI’s

A

-Central nervous system effects:
Headache, Dizziness, Tremors, Anxiety, Insomnia
-Hyponatremia: low sodium, mainly in older patients
-Sexual dysfunction: 50% of patients (decreased libido, erectile dysfunction, inability to achieve orgasm)
-Excessive sweating: 20% of patients.
-Gastrointestinal symptoms: Nausea, Diarrhea, Loose stools, weight loss or gain
-Anticholinergic effects: not as common as in Tricyclic Antidepressants
Dry mouth
Sedation
-Discontinuation Syndrome: agitation, nausea, disequilibrium and dysphoria

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6
Q

Fluoxetine General prescribing info:

A

FDA Approved: Major Depressive Disorder, Obsessive Compulsive Disorder, Panic Disorder, Social Anxiety Disorder, Treatment resistant major depressive disorder, Bipolar I disorder, acute depressive phase
Off label use: Cataplexy
Formulation: Tab and weekly cap
Dosing: 20-80mg daily
Long half-life (2-4 days)
Releases NE and DA

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7
Q

Fluoxetine clinical indications

A

Clinical Indications
Useful for depressed patients with reduced positive affect, apathy, fatigue
Decreased incidence of discontinuation syndromes
May be used in combination with olanzapine
Good for patients with medication noncompliance issues

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8
Q

Sertraline (Zoloft)

A

FDA Approved:
Major Depressive Disorder, Obsessive Compulsive Disorder, Panic Disorder, Premenstrual Dysphoric Disorder
Off label use: Bulimia
Formulation: Tab
Dosing: 50mg-200mg daily
Short half life
Dopamine transporter (DAT) inhibition
Less sedating than paroxetine

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9
Q

Sertraline Clinical Indications

A

Clinical Indications
Useful for depressed patients with low energy and mood reactivity
May be used with other antidepressants
Must take on full stomach
Increased number of GI adverse drug reactions

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10
Q

Paroxetine:

A

FDA Approved:
Major Depressive Disorder, Panic Disorder, Obsessive Compulsive Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post Traumatic Stress Disorder
Dosing: 20-50mg daily
Formulation: Tabs and continuous release (CR)
Short half life
Sedating properties (dose at night)
Limited norepinephrine (NET) inhibitory properties
Mild anticholinergic properties

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11
Q

Paroxetine clinical indications

A

Clinical Considerations
Sedating, weight gain, more anticholinergic effects
Discontinuation syndrome is likely

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12
Q

Fluvoxamine(Luvox)

A

FDA Approved:
Obsessive Compulsive Disorder
Off label use: Social Anxiety Disorder
Dosing: 50mg-100mg bid
Shortest ½ life
Binds to Alpha-1 receptors
Action is more potent than sertraline
GI distress, headaches, sedation, weakness

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13
Q

Fluvoxamine clinical indications

A

Useful for management of obsessive-compulsive disorder and anxiety disorder
May be used for psychotic and delusional depression
May have analgesic properties

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14
Q

Citalopram

A

FDA Approved:
Major Depressive Disorder
Off label use: Obsessive Compulsive Disorder
Dosing: 20mg-40mg daily
Intermediate ½ life
Has mild antihistaminic properties, H1Antagonist

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15
Q

Citalopram Clinical Indications

A

Clinical Indications
Well-tolerated
Useful for management of depression in elderly populations.
Dose-dependent QT interval prolongation with doses of 10-30mg daily. Doses of >40mg/day not recommended!

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16
Q

Escitalopram

A

FDA Approved:
Major Depressive Disorder
Off label use: Obsessive Compulsive Disorder
Dosing: 20mg-40mg daily
Intermediate 1/2 life
SERT inhibition
No antihistaminic properties
More effective than citalopram in acute response and remission

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17
Q

Escitalopram Clinical indications

A

Clinical Indications
Well-tolerated
Useful for patients with tendency to have QT prolongation
Dose-dependent QT interval prolongation with doses of 10-30mg daily
Nausea, headache

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18
Q

Vilazodone(Viibryd)

A

FDA Approved: Major Depressive Disorder
Formulation: Tabs
Dosing: 20mg to 40mg po daily
-combined SSRI and 5HT1A receptor partial agonist
Metabolized in CYP-450 3A4, Use cautiously with 3A4 inhibitors

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19
Q

Vilazodone Clinical Indications

A

-May be helpful in treatment-resistant or treatment-refractory patients
-May increase bleeding in patients taking anticoagulants or medications that increase likelihood of bleeding
-GI disturbance most common side effect (nausea, diarrhea, constipation, abdominal pain)
-Other side effects: insomnia, sexual dysfunction, dry mouth, dizziness, rare hyponatremia/SIADH
Must take with food

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20
Q

Vortioxetine(trintellix)

A

FDA Approved: Major Depressive Disorder
Formulation: Tabs
Dosing: 10mg po daily
-SSRI-Serotonin Receptor Modulator and stimulator (glutamate modulation)
-SERT inhibition (targets multiple serotonin receptors)
Metabolized in CYP-4502D6, Use cautiously with 2D6 inhibitors/inhibitors

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21
Q

Vortioxetine clinical indications

A

Clinical Indications
May be helpful in treatment-resistant or treatment-refractory patients
Improves the cognitive effects of depression
May increase bleeding in patients taking anticoagulants or medications that increase likelihood of bleeding
May cause seizures, mydriasis, sexual side effects and headache
GI disturbance most common side effect (nausea, diarrhea, constipation, abdominal pain

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22
Q

Common SSRI drug interactions

A

-MAOI’s: Serotonin syndrome
-Lithium: increases lithium level
-Antipsychotic: increases EPS
-Benzodiazepines: increases half-life of benzodiazepines
-TCA: Increases TCA serum level

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23
Q

Overview of major SNRI’s

A

-Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
CYP 2D6, “Dual Action”, Combine SERT inhibition and the Norepinephrine transporter (NET) inhibition,
Increase serotonin, norepinephrine, and also dopamine in the prefrontal cortex
-Clinical Indications:
Used to treat depressive disorders and other conditions, Useful for patients with pain syndromes, Debatable if they achieve higher remission rates than SSRIs.
-General Side Effects: Nausea, dizziness, insomnia, excessive sweating, constipation, dry mouth, decreased appetite, headache, sexual side effect

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24
Q

Venlafaxine

A

FDA Approved:
Major Depressive Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder
Off label use: Cataplexy, Migraine Headache, prophylaxis, PTSD
Formulation: cap and ER cap
Dosing: 75mg-225mg daily
Inhibits reuptake of both, serotonin (SRI) and norepinephrine transporter (NET)
SRI actions are seen with lower doses
NRI actions are seen with dose increases
-Available in extended-release and immediate-release forms
-Minimal drug interactions and almost no P450 activity
Short half-life and fast renal clearance

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25
Venlafaxine Clinical Indications
Used for depression, and individuals with treatment-resistant depression Approved and used for management of anxiety disorders Can cause a 10-15 mmHG dose-dependent increase in diastolic BP. May cause significant nausea, primarily with immediate-release (IR) tabs Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration Noted to cause QT prolongation Sexual side effects in >30%
26
Desvenlafaxine
FDA Approved: Major Depressive Disorder Formulation: ER tab Dosing: 50mg daily Greater NET inhibition Serotonin, Norepinephrine and Dopamine Reuptake Inhibitor Minimal drug interactions Short half-life and fast renal clearance avoids build-up
27
Desvenlafaxine Clinical Indications
Clinical Indications Used for depression Useful to treat vasomotor symptoms, especially in women with depression and peri and post-menopausal GI distress in 20%+ Dose related increase in total cholesterol, LDL and triglycerides Dose related increase in BP
28
Duloxetine
FDA Approved: Major Depressive Disorder, Generalized Anxiety Disorder, Diabetic Peripheral Neuropathy, Fibromyalgia, Chronic Musculoskeletal Pain Formulation: caps Dosing: 60mg daily, max dose 120mg daily Greater SERT inhibition, Lesser NET inhibition Usually prescribed once a day, but it can be increased to twice a day as needed Data to suggest efficacy for the physical symptoms of depression Less BP increase as compared to venlafaxine Clinical Indications Cannot break capsule, as active ingredient not stable within the stomach
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Norepinephrine Dopamine Reuptake Inhibitor(NDRI)
-The prototypical agent is bupropion -Mechanism of action remains unclear -A main hypothesis points out that it inhibits the reuptake of dopamine (dopamine transporter or DAT inhibitor) -Inhibits reuptake of norepinephrine (norepinephrine transport or NET inhibitor) -Considered an active drug and a precursor for other active drugs
31
Bupropion (Wellbutrin/Zyban)
-Activating, decreased appetite -Can be problematic for patients with anxiousness/irritability -Can produce false-positive urine test results for amphetamines -No sexual side effects (can reverse sexual side effects of other antidepressants) -Improves concentration -Side effects: Agitation, insomnia, headache, nausea, vomiting, tremor, jerks, tachycardia, dry mouth, weight loss. -Rare risk: Seizures (higher dosages, rapid dose increase), avoid in patients with binge/purge behavior
32
SARI(Serotonin Antagonist and reuptake inhibitor
Clinical Indications Useful for treatment of depression Used to manage insomnia in patients with major depression It can augment the efficacy of other antidepressants Block serotonin 2A (5HT 2A) and 2C (5HT 2C) receptors Also increases reuptake of serotonin
33
Serotonin Modulators
5HT2 inhibitors Both antagonist and agonist of serotonin Less effect on norepinephrine Affects multiple serotonin receptors Less sexual dysfunction, anxiety or insomnia Side effects: orthostatic hypotension, drowsiness, dry mouth, blurred vision, nausea, vomiting Examples: Mirtazapine (Remeron), Trazodone (Desyrel) Nefazodone (Serzone), Vilazodone (Viibryd), Vortioxetine (Trintellix)
34
Trazodone
FDA Approved: Major Depressive Disorder Off label Use: Insomnia Formulation: immediate release and controlled released Dosing: 50mg-100mg MDD, 25-50mg Insomnia Short half-life Antagonist of 5HT2A and 5HT2C Has both antidepressant and sedative effect Less sexual disfunction, anxiety or insomnia Side effects: orthostatic hypotension, priapism, drowsiness, dry mouth, blurred vision, nausea, vomiting
35
Nefazodone(Serzone)
FDA Approved: Major Depressive Disorder Off label use: Premenstrual Syndrome Dosing: 150mg-300mg tabs Lower SERT inhibition, also NET inhibition Side effects: orthostatic hypotension, less risk of priapism, drowsiness, dry mouth, blurred vision, nausea, vomiting
36
Tricyclic Antidepressants (overview)
Block reuptake of norepinephrine transporter Some TCAs have greater serotonin inhibition, others more selected norepinephrine inhibition High protein binding, high lipid solubility Many side effects have been identified (anticholinergic, antihistaminic, antiadrenergic) Cause increased sedation Cause increased anticholinergic actions Can cause postural hypotension and dizziness Can be lethal in an overdose (QT prolongation) Amitriptyline (Elavil) Clomipramine (Anafranil) Imipramine (Tofranil) Doxepin (Sinequan) Nortriptyline (Pamelor)
37
Amitriptyline (Elavil)
Tricyclic: FDA Approved: Major Depressive Disorder Off label use: neuropathic pain, fibromyalgia, migraine headache, post-herpetic neuralgia Dosing: 50mg-150mg qhs Potent sedative Side effects: Increased weight gain, black tongue unpleasant taste, anticholinergic effects, weight gain (particularly at doses below 45mg), decrease sex drive, decrease urination, erectile dysfunction, cardiac changes. -Beers Criteria: avoid in elderly
38
Clomipramine (anafranil)
Tricyclic FDA Approved: Obsessive Compulsive Disorder Off label use: cataplexy, confusional arousals, sleep terrors, sleep walking Dosing: 150mg-250mg qhs caps Closely related to antipsychotic drugs (phenothiazines) Side effects: dry mouth, constipation, blurred vision, mydriasis, metallic taste, urinary retention, sedation, weight gain, no sexual side effects;
39
Nortriptyline(Pamelor)
Tricyclic FDA Approved: Major Depressive Disorder Dosing: 50mg-150mg qhs Metabolite of amitriptyline
40
Doxepin (Sinequan)
Tricyclic FDA Approved: depression, anxiety Off label use: insomnia, alcohol dependence, chronic urticaria Dosing: 150mg-300mg qhs
41
Imipramine(Tofranil)
Tricyclic: FDA Approved: Major Depressive Disorder (MDD) Off label use: treatment resistant generalized anxiety disorder, chronic pain, confusional arousals, sleep terrors, sleep walking, nocturnal enuresis (older than 6 years) Dosing: 150mg-300mg qhs MDD Closely related to antipsychotic drugs (phenothiazines) Side effects: dry mouth, constipation, blurred vision, mydriasis, metallic taste, urinary retention, sedation, weight gain, no sexual side effects; rare agranulocytosis/neutropenia
42
Mirtazepine (remeron)
Tetracyclic Antidepressant FDA Approved: Major Depressive Disorder Formulation: tabs and oral disintegrating tablet (ODT) Dosing: 15mg-45mg MDD Can be utilized as a hypnotic at lower doses May be a good medication to augment with antidepressant Cons Increases serum cholesterol and triglycerides Very sedating at lower doses, activating at doses 30mg and above Associated with weight gain (particularly at doses below 45mg Side effects: Somnolence, increased appetite, weight gain, no sexual side effects; rare agranulocytosis/neutropenia
43
Serotonin Syndrome may occur if SSRI is combined with:
Tryptophan SNRIs MAOIs TCAs Bupropion Amphetamines, Lysergic acid diethylamide (LSD), ecstasy, cocaine Opioids, opiates, dextromethorphan St. John’s Wort, ginseng, nutmeg Tegretol, lithium, valproic acid
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Serotonin Syndrome mneumonic
ARMS: A: anxiety, R: restlessness, M: myoclonus, S: sweating
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Serotonin Syndrome Symptoms
Symptoms can be from mild to severe Cognitive effects: confusion, hypomania, hallucinations, agitation, coma. Autonomic effects: shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea. Somatic effects: ataxia, myoclonus, twitching, hyperreflexia, rigidity, tremor. Treatment: Stop SSRI, stabilize temperature, benzodiazepine for muscle relaxation, beta-blocker for tachycardia.
46
MAOI Clinical Indications
Clinical Indications Used to manage depression, primarily due to inhibition of MAO-A Antidepressant efficacy is also believed to be achieved due to concurrent inhibition of both MAO-A and MAO-B MAOIs are also used to manage Parkinson’s Disease
47
MAOI clinical indications
Action: Inhibit enzyme responsible for the metabolism of serotonin, dopamine, norepinephrine, and tyramine. Increases levels of norepinephrine and serotonin in the CNS Interacts with food -- low tyramine diet Non-selective Monoamine Oxidase Inhibitors Particularly effective for ”atypical depression”: overeating, oversleeping, rejection sensitivity, mood reactivity
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MAOI prescribing guidelines/considerations
Switching with serotonergic agents A complete washout of a serotonergic agent is required For most serotonergic agents is 5 to 7 days For fluoxetine, the washout period should be 5 weeks If switching an MAOI to a SSRI, 14 days must be allowed to start an MAOI.
49
Dietary Restrictions with MAOI's.
Dietary Restriction: Avoid high tyramine, tryptophan, phenylalanine, or tyrosine (aged cheese, cured meats, fava or broad bean pods, tap/draft beers, marmite, sauerkraut, soy sauce, over-ripe fruit, spoiled foods) to avoid a Hypertensive Crisis.
50
Additional MAOI prescribing Considerations:
-Hypertensive Crisis: Systolic blood pressure > 120 mmHg, occipital headache, palpitations, neck stiffness, nausea, vomiting, sweating, dilated pupils, tachycardia or bradycardia, may be associated with chest pain -Medication Avoidance: Other antidepressants, stimulants, sympathomimetics, dextromethorphan, meperidine, disulfiram -Main Side effects: dizziness, headache, orthostatic hypotension, dry mouth, constipation, drowsiness (Nardil), tremor, sweating, peripheral edema, sexual side effects, weight gain (Nardil) -Do not use within 5 weeks of Fluoxetine and 2 weeks of other antidepressants; -Washout period= Wait 2 weeks after stopping MAOI to start other antidepressant
51
Manic Switch
Sometimes referred to as a psychiatric event Especially concerning when there is a family history of bipolar disorder Screen patients for hypomania or mania prior to prescribing If signs of mania or worsening of a pre-existing illness occur, dose reduction or discontinuation may be considered
52
Discontinuation Syndrome
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Tyramine Rich foods
Beverages Beverages with caffeine Red wine and sherry Homemade beer Foods All strong or mature cheese Smoked/processed meats Sour cream Yogurt Avocado Soy Sauce Chocolate
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No Response (R's of depression)
Improvement of <25%
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Partial Response
Partial Response: Improvement of 25-49%
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Response
Response: Improvement of >=50%
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Remission
Remission: Complete resolution of symptoms
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Relapse
Relapse: Return of depression symptoms within 6 months of remission
59
Recovery
Recovery: Absence of symptoms for at least 6 months following remission
60
Recurrence
Recurrence: New episode after recovery
61
Resistant
Resistant: Failure of two or more trials
62
Refractory
Refractory: Highly resistant to treatment and do not respond

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