Antidepressants Flashcards
Where is the monoamine system located
Upper brainstem and limbic system
What are the NT involved in the monoamine system
NE,5HT, DA
What is the purpose of NE
Study and get things done
What is the purpose of 5HT
Everyday life NT- appetite, mood, emotion, sleep
What is the purpose of DA
Joy of life, feel good and party, attention
What other receptors are involved in the monoamine system
5HT3,2
H1
Alpha 1adrenergic
M- cholinergic
5HT3
Agonist- N/V/D
Antagonist- anti emetic
5 HT2
Agonist- insomnia, anxiety, akathesia, sexual dysfunction
H1
Weight gain and sedation
M cholinergic
Antagonist- constipation, dry mouth, drowsiness and confusion
Alpha 1 adrenergic
Orthostatic hypotension
Rules for diagnosing depression
Must have 5 of the SIGECAPS symptoms (1 of them must be from the interest category), change from normal functioning, and must rule out physical problems- tsh, hgb, b12
SIGECAPS
S- sleep- insomnia or hypersomnia
I- interest- depressed mood or adhedonia
G- guilt- feelings of worthlessness
E- energy- decreased energy
C-concentration- inability to make decisions or focus
A-appetite- wit changes or loss of enjoyment of food
S-suicidie- recurring thoughts of suicide
Who is most successful at suicide
Older men
What questions should you ask about suicide and when should you’ve concerned?
Always be concerned
Be especially concerned and make sure to ask if they have a plan
Etiologic hypothesis of depression
Stress diathesis- threshold for depression, environment determines if we exceed it
Biological hypothesis- aided by fact that drugs help
Catecholamine hypothesis- body runs out of NE AND 5HT
Dsregulation hypothesis- imbalance between NE and 5HT
Role of psychotherapy and CBT
Used in mild to moderate depression- works synergistically with antidepressants.
Takes longer to help but has a lower rate of remission
When do you use pharmacotherapy for depression
In severe depression
ECT
Safe for pregnant and elderly
Very quickly down regulates beta receptors in the brain which correspond to a decrease in depression.
Use if patient has depression that is refractory to 2-3 drugs that have been used for at least 12 weeks
Pharmacotherapy
Takes 4 -6 weeks to see mood changes
Changes in mood correspond to decrease in beta receptor density not changes in hormone or NT levels
Pharmacotherapy AE
Transient insomnia, anxiety, and jitteriness
Sexual dysfunction occurs but this is not transient
Types of drugs used to tx depression
SSRI TCA MOA venlafaxine Duloxetine Nefazodone Trazodone Bupropion Mirtazapine
SSRI- drug names
Fluoxetine Citalopram Paroxetine Sertaline Fluvoxamine Escitalopram
SSRI MOA
Blocks serotonin reuptake
5HT2 agonist
Down regulation of beta receptors
SSRI AE
Insomnia, anxiety, diarrhea
Sexual dysfunction
Serotonin syndrome
How is sexual dysfunction Dealt with
PDE5 inhibitor
What is serotonin syndrome
Occurs when have excess serotonin, have taken to many drugs that stimulate serotonin
Fishing, wheezing, hyperthermia, N/V/D
Hypertension, myoclonus, headache, seizure, ataxia
Treat by stopping the serotonin drugs, cooling blankets, nifedipine for HTN, clonazepam for the myoclonus, and anti convulsants for the seizures
SSRI withdrawal
Shooting electric pains, anxiety, flu like symptoms
Headache, insomnia, dizziness
Must titration down the dosage especially if using SSRIs with a short half life ie paroxetine or venlafaxine
Fluoxetine doesn’t have to be titrated down BC it has a long half life and active metabolite
Fluoxetine
SSRI with very long half life and most psychomotor activating of the SSRI so good for pts with motor depression
Citalopram
Least psychomotor activating of the SSRI so good for pts with psychomotor activation
Paroxetine
Short half life,must be tapered down
Do not give to pregnant woma
What SSRI do you not give in pregnancy
Paroxetine
Sertaline
SSRI USE
DOC for depression with comorbid anxiety
Can change between them if one doesn’t work another might
TCA drug names
Imipramine –> desipramine
Amotryptaline–> nortriptaline
Dsipramine and nortriptaline are metabolites
TCA- MOA
Inhibit NE AND 5HT reuptake
Muscarinic, alpha 1, and H1 antagonists
TCA AE
Orthostatic hypotension, Weight gain, and anti cholinergic
Sexual dysfunction
Serotonin syndrome if given with other antidepressants
Lowers the seizure threshold
Cardiac events
OD- can kill
Mechanism of cardiac toxicity for TCA
Block the NA Channels causing prolonged QT interval leading to torsades des pointes –> vfib–> death
Tx OD with NAHCO3 BC it act on NA channels
TCA’s and teratogenicity
The non metabolite TCA (Imipramine and amitriptalline) can cause heart failure, tachycardia, seizures, and urinary retention in newborns.
TCA uses
Alternative to SSRI.
Used in depression with comorbid pain- fibromyalgia, Migraine, chronic pain, and atypical depression.
B/c NE IS THE NT OF PAIN
TCA contraindications
History of CAD, seizure history, BPH, dementia, or constipation
MOA- drugs
Isocarboxacid
Phenelzine
Tranycypromine
TCA MOA
Blocks MAOA (5Ht, NE, and Tyrammine) and MAOB (DA)
MAO AE
Orthostatic hypotension, weight gain, anti cholinergic
Sexual dysfunction
Serotonin syndrome if given with other antidepressants or meperidine, tramadol, or dextrometorphan
Wine and cheese syndrome
TERATOGENIC
Wine and cheese syndrome
Hypertensive crisis that leads to fatal hemmorhages
Wine and cheese have a lot of tyrammine, normally it’s cleared nfirst pass metabolism, if there is an mao inhibitor then it might not be cleared this causes excess release of NE from peripheral neurons.
Mao drug interactions
Meperidine, phenylephrine, and sympathmimetics
Lead to hypertension, fever, and delirium
MAO uses
Atypical depression for tx refractory depression
Other drugs have better safety profiles.
When switching to Mao from another antidepressant make sure to taper off it the previous drug for at least two weeks and 5-6 weeks if it is fluoxetine.
Venlafaxine MOA
At low doses acts as a 5HT reuptake inhibitor, at high doses acts as a NE reuptake inhibitor
Venlafaxine AE
At low doses has the same AE as SSRI, including withdrawal BC of the short half life
Be careful inpatients with uncontrolled HTN
Duloxetine MOA
Blocks NE AND 5HT reuptake at low doses
Duloxetine uses
Depression with pain , it is FDA approved for diabetic pain
Duloxetine AE
Drug interactions
Hepatotoxicity
Nefazodone MOA
Blocks 5HT and NE reuptake
5HT2A, H1, M antagonist
Nefazodone uses
Good for depression with anxiety and insomnia and sexual dysfunction
Nefazodone AE
Sedation, GI complaints, drumouth, constipation
Nefazodone- AE
Drug interactions
Hepatotoxicity
Trazodone- MOA
5ht reuptake inhibitor and 5HT2 antagonist
Blocks H1 and alpha 1
Trazode AE
Orthostatic hypotension
Very sedating
Priapism
Trazondone uses
Used for sedation to counter insomnia with other antidepressants and hypotonic
Bupropion MOA
Blocked NE AND DA reuptake
This is the same MOA AS COCAINE
Buproprion AE
CAN INCREASE SEIZURES AND SEXUAL FUNCTION
Psychomotor activation, headache, insomnia, psychosis,and anorexia
Can cause weight loss
Bupropion use
Help patients quit skiing and to counter sedation
Bupropion CI
Seizure history
Anxiety
Bulimia
Mirtazapine MOA
Antagonizes the presynaptic alpha 2 receptors increasing NE RELEASE
Block 5HT3 and 2,and H1
Mirtazapine uses
Good for DEPRESSION with comorbid anxiety, reduced sexual function and has a low risk of OD
This is the sleep, sex, and food antidepressant
Mirtapazine AE
Sedative effect, weight gain, neutropenia, and agranulocytosis
What to think about when prescribing antidepressants
Comorbid conditions
Which drugs has pt had success with, or their first degree relatives
Adverse events
Treating depression phases
Acute, continuation, maintenance
Acute phase
Week 1- Improvement in sleep and appetite
1-3 weeks- everyday life improvements- activity, sex drive, self care, sleeping and appetite normalization
2-6 weeks- suicide and depression subside
Continuation phase
4-9 months of maintaining the same dose as during the acute phase to keep it in remission
Maintenance phase
Long term therapy depends on the person and their circumstances
Treatment outcomes
Response- dec symptoms by 50%, this occurs in 60% of patients
Remission- attitude returns to normal, this occurs in 30% of patients, has a decreased chance of relapse
Treatment regimen in depression
Start with SSRI they are the safest, least AE, and most studied
If that doesn’t work can change meds, add bupropion or another agent, or augment to with- lithium, anticonvulsant, th, or buspirone.
