Antidepressants (Week 3/4) Flashcards
Monoamine hypothesis of depression
Hypothesis involving deficiency of monoamine neurotransmitters
Neurotransmitter receptor hypothesis of antidepressant action
hypothesis involving monoamine neurotransmitters and their receptors
Mnemonic for depressive disorders
S: Sleep
I: Interest
G:Guilt
E: Energy
C: Concentration
A: Appetite
P:psychomotor activity
S: suicide
Indications for prescribing antidepressants
-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.
General side effects of SSRI’s
-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
Fluoxetine General prescribing info:
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
Fluoxetine clinical indications
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
Sertraline (Zoloft)
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
Sertraline Clinical Indications
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
Paroxetine:
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
Paroxetine clinical indications
Clinical Considerations
Sedating, weight gain, more anticholinergic effects
Discontinuation syndrome is likely
Fluvoxamine(Luvox)
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
Fluvoxamine clinical indications
Useful for management of obsessive-compulsive disorder and anxiety disorder
May be used for psychotic and delusional depression
May have analgesic properties
Citalopram
FDA Approved:
Major Depressive Disorder
Off label use: Obsessive Compulsive Disorder
Dosing: 20mg-40mg daily
Intermediate ½ life
Has mild antihistaminic properties, H1Antagonist
Citalopram Clinical Indications
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!
Escitalopram
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
Escitalopram Clinical indications
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
Vilazodone(Viibryd)
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
Vilazodone Clinical Indications
-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
Vortioxetine(trintellix)
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
Vortioxetine clinical indications
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
Common SSRI drug interactions
-MAOI’s: Serotonin syndrome
-Lithium: increases lithium level
-Antipsychotic: increases EPS
-Benzodiazepines: increases half-life of benzodiazepines
-TCA: Increases TCA serum level
Overview of major SNRI’s
-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
Venlafaxine
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