Drug treatment for Depression Flashcards
Depressed mood most of the time or persists for a long time
Mood disorder
Causes of Major Depressive Disorder
Endogenous (no apparent external cause)
Reactive (identifiable external cause)
Biochemical basis of Depression
Neurotrophic Hypothesis & Monoamine Hypothesis
Explain the Neurotrophic Hypothesis
stress and pain are associated with a drop in BDNF levels
Essentially, lower BDNF = depression
What is BDNF (Brain Derived Neurotrophic Factor)
responsible for nerve growth factor and emotional regulation
Two evidences that support the Neurotrophic hypothesis
Direct infusion of BDNF into the brain of rodents has antidepressant effects
Antidepressants are associated with an increase in BDNF
Explain the Monoamine Hypothesis
Deficit in function or amount of biogenic amines
Evidences of Monoamine Hypothesis
Reserpine treatment is associated w/ depression
All available antidepressants appear to have significant effects of the monoamine system
Administration of NE synthesis inhibitor is associated with relapse
MOA of TCAs (Amitryptiline, Desipramine, Imipramine, Clomipramine, Nortryptiline, Protryptiline, Doxepin, Lofepramine)
Blocks the neuronal reuptake of NE and 5HT
All are equally effective in relieving depression, although some patients respond better to one drug than to another
Side effects of TCAs (Amitryptiline, Desipramine, Imipramine, Clomipramine, Nortryptiline, Protryptiline, Doxepin, Lofepramine)
Antihistamine (Sedation)
A-1 adrenoreceptor blocker
Antimuscarinic
Acute poisoning (manifests as suicidal ideation) - generally recommended that no more than a week’s supply should be given at any time to acutely depressed patient
Cardiac arrhythmias
Weight gain (most common)
Confusion, impaired memory and cognition
Lower the seizure threshold
Examples of TCAs
AMITRYPTILINE
DESIPRAMINE
IMIPRAMINE
CLOMIPRAMINE
NORTRYPTILINE
PROTRYPTILINE
DOXEPIN
LOFEPRAMINE
MOA of TeCAs (Amoxapine, Quetiapine, Mianserin, Mirtazapine, Maprotiline, Setiptiline)
blocks neuronal reuptake of NE and 5HT
Alternative for patients who are unresponsive to other antidepressants
Examples of TeCAs
Amoxapine & Quetiapine - four rings are not fused together
Mianserin - First second generation, lacks cardiotoxic and anticholinergic S/E,
sedative, postural hypotension, weight gain, and causes blood dyscrasias
Mirtazapine - derivative of Mianserin that lacks blood dyscrasias and adverse effects,
(Noradrenergic & Specific Serotonergic
Antidepressant)
Maprotiline & Setiptiline - both are NaSSA
MOA of SSRIs (Fluoxetine, Paroxetine, Fluvoxamine, Sertraline, Citalopram, Escitalopram, Vilazodone, Vortioxetine)
Selectively block the neuronal reuptake of serotonin and have much less effect on the reuptake of NE
SSRIs are
the most widely used drugs of depression an certain anxiety disorders
as effective as TCAs - fewer autonomic side effects and less sedation
safer than TCAs - less likely to cause arrhythmia and seizures
Examples of SSRIs
FLUOXETINE
PAROXETINE
FLUVOXAMINE
SERTRALINE
CITALOPRAM
ESCITALOPRAM
VILAZODONE
VORTIOXETINE
Side effects of SSRIs
N&V
Diarrhea/constipation
Tremor
Dizziness
Sexual dysfunction
HA
MOA of SNRIs (Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran)
Block the neuronal reuptake of serotonin and norepinephrine
SNRIs tend
to be favored over the TCAs in the treatment of MDD
Examples of SNRIs
DULOXETINE
VENLAFAXINE
DESVENLAFAXINE
MILNACIPRAN
MOA of NaRIs (Reboxetine, Atomoxetine, Viloxazine)
Block the neuronal reuptake of norepinephrine
*Also indicated for ADHD
Examples of NaRIs
REBOXETINE
ATOMOXETINE
VILOXAZINE
MOA of Unicyclic Antidepressant (Bupropion)
Block the neuronal reuptake of NE and DA
*Adjunct therapy for patients who are attempting to quit smoking cigarettes
MOA of MAOIs (Moclobemide, Selegiline, Rasagiline, Tranylcypromine, Isocarboxazid, Phenelzine)
Inhibits Monoamine Oxidase thereby increasing biogenic amines
Substrates of MAO - A
Norepinephrine, Epinephrine, Serotonin
Substrates of MAO - B
Dopamine, Tyramine
Examples of MAOIs
MOCLOBEMIDE - reversible inhibitor of MAO-A
SELEGILINE & RASAGILINE - irreversible inhibitor of MAO-B
Non selective MAOIs:
TRANYLCYPROMINE
ISOCARBOXAZID
PHENELZINE
Examples of serious interactions of MAOIs
MAOIs + Tyramine-rich food
MAOIs + Adrenergic Drugs
MAOIs + Serotonergic Drugs
MOA of Serotonin Receptor Modulators (Trazodone, Nefazodone)
Mild inhibition of serotonin reuptake
Examples of 5HT receptor Modulators
TRAZODONE
NEFAZODONE
Neither drugs is effective for severely depressed people
Trazodone is strongly sedative which can improve sleep of depressed patients
Isolated from Hypericum officinalis/ perforatum
Contains HYPERICIN and FLAVONES
St. John’s Wort
MOA of St. John’s Wort
Blocks neuronal reuptake of 5HT
Have fewer side effects than other antidepressants but is not as effective as prescription antidepressants
Adverse effects of Antidepressants
Some potential adverse effects
are common to all
antidepressants, most of their
adverse effects are specific to
subclass of agents and to their
pharmacodynamic effects
FDA warning applied to all
antidepressants is the risk of
increased suicidality in patients
younger than 25. Association
with suicidal ideation and
gestures but not completed
suicide
