Antidepressants Flashcards
Tricyclic Antidepressants (TCA):
amitriptyline (Elavil), desipramine
Selective Serotonin Reuptake Inhibitors (SSRI):
fluoxetine, paroxetine, sertraline, (2nd gen)
Serotonin & Norepinephrine Reuptake Inhibitors (SNRI):
venlafaxine (2nd gen)
Monoamine Oxidase Inhibitors (MAOI):
phenelzine
Atypical antidepressants (tetracyclic and
unicyclic antidepressants):
mirtazapine (tetracyclic), bupropion (unicyclic)
What are the 4 domains/Sx’s of depression?
Emotional:
- Reduced pleasure, reduced interest in usual activities
- Pessimistic outlook
- Anxiety
Physical:
- Fatigue, sleep disorders (insomnia), appetite disturbances
Cognitive:
- Poor concentration, slow thinking, poor short-term memory, confusion
Psychomotor:
- Agitation
- Slowed speech
What is the Serotonin hypothesis?
Depression is related to reduced synaptic levels of serotonin
- 1950’s – Reserpine caused depression in 15% of patients (can downreg. serotonin)
- Most antidepressant drugs appear to work by enhancing synaptic monoamines
What are the functions of serotoninergic system?
- Mood
- Memory processing
- Cognition
- Sleep
What are the 5 steps of Serotonin neurotransmission?
- Synthesis
- Storage
- Release
- Bind to receptors
- Degradation / termination *
- Uptake by presynaptic serotonin transporter(SERT)
- Monoamine oxidase (MAO)
What is the main target of current Antidepressants?
Degradation / termination
- Uptake by presynaptic serotonin transporter(SERT)
- Monoamine oxidase (MAO)
Antidepressants have a _______ onset
SLOW
it takes at least 2 weeks to generate therapeutic effects
What is the action site of TCA’s?
Inhibit serotonin and norepinephrine uptake similarly (therapeutic);
Anti-muscarinic, anti-histaminic and anti-adrenergic (α) actions (adverse effects).
What are the therapeutic uses of TCA’s?
depression; chronic pain
What are the adverse effects of TCA’s?
Sexual dysfunction
Antagonize muscarinic r’s (CNS: confusion, ANS: constipation, dry mouth)
Antagonize a-adrenergic r’s (orthostatic hypo, reflex tachy)
Antagonize histamine (sedation, weight gain)
Overdoses are potential problems (–> coma, resp. depression, seizures & cardiac arrhythmias)
Interact with SSRIs (CYP2D6 inhibitor)
Interact with sedatives, sympathomimetics, antimuscarinics
NOT recom., for elderly pt’s
What are the action sites of SSRI’s?
inhibit serotonin reuptake.
What are the therapeutic uses of SSRI’s?
First-line treatment (Are safer than TCAs and MAOIs; not more effective than TCAs and MAOIs);
Depression; Anxiety (GAD, PTST, OCD..);
Fluoxetine for bulimia.
What are the adverse effects of SSRI’s?
Safer in general;
Sexual dysfunction, weight gain;
Interact with β blockers and TCAs, interact with MAOIs (serotonin syndrome)
What are the action sites of SNRI’s?
Inhibit both serotonin and NE reuptake;
What are the therapeutic uses of SNRI’s?
depression; anxiety;
What are the adverse effects of SNRI’s?
Sexual dysfunction;
Sympathetic symptoms;
Interact with MAOIs (serotonin syndrome)
What are the action sites of MAOI’s?
Inhibit monoamine oxidase (metabolism enzyme) → increase monoamines.
What are the therapeutic uses of MAOI’s?
depression; usually reserved for patients who don’t respond to other agents.
What are the adverse effects of MAOI’s?
sexual dysfunction; weight gain; overdose
Interact with SSRIs, SNRIs, TCAs (serotonin syndrome); interact with foods containing tyramine.
What are the action sites of Atypical’s?
Mirtazapine (Remeron)
Action sites:
- Structurally a tetracyclic compound
- Increasing norepinephrine and serotonin release
- Potent blocker of histamine H1 receptors
Bupropion:
Action sites:
- Structurally an unicyclic compound
- Largely unknown; No direct effects on the serotonin system.
What are the therapeutic uses of Atypical’s?
Mirtazapine (Remeron)
- Depression that is unresponsive to SSRI and SNRI
- Might be added to an SSRI or SNRI to augment
antidepressant benefit
Bupropion:
- Might be added to an SSRI or SNRI to augment antidepressant→ benefit if monotherapy is unsuccessful.
- Smoking cessation.
- Have some benefits in treating obesity.
What are the adverse effects of the Atypicals?
Mirtazapine (Remeron)
- Sedation
– Drug interactions: may be additive with those of CNS
depressants such as alcohol and benzodiazepines
- Weight gain
- not commonly associated with sexual effects.
Bupropion:
- Can include headache, dizziness, insomnia, seizures: much lower incidence than TCA’s
- No sexual dysfunction, no weight gain, and no sedation adverse effects
- Drug interactions: inhibit CYP 2D6
– Interact with many drugs such as β blockers and TCAs
→ increase plasma β blockers and TCAs levels.
How long do Antidepressants take to generate therapeutic effects?
take at least 2 weeks
SSRIs are…
first-line agents for MDD and anxiety disorders.
SNRI’s are…
also first-line agents for MDD.
TCAs and MAOIs:
- second- or third-line treatments for MDD.
- is reserved for patients who have been unresponsive to other agents.
Mirtazapine and bupropion:
- Mirtazapine: SSRI or SNRI non-responders
- Added on drugs for an SSRI or SNRI
- No sexual dysfunction adverse effects.
