8 - Depression Flashcards
List the symptoms of depression
SPACE DIGS
- Suicide
- Psychomotor
- Appetite/weight
- Concentration decreased
- Energy decreased
- Depressed mood
- Interest decreased (anhedonia)
- Guilt/worthlessness
- Sleep affected
What is the criteria for major depression ?
- Presence of symptoms for > 2 weeks
- At least 5 symptoms present; at least 1 depressed mood or loss of interest/pleasure
- Symptoms occur nearly every day
- Symptoms cause significant distress or impairment of functioning
- Symptoms not due to bereavement or last > 2 months
What are some additional emotional symptoms?
- Anxiety
- Irritability
What are some additional cognitive symptoms?
- Decreased concentration
- Indecisiveness
- Poor memory
What are some additional psychotic symptoms?
- Bizarre behavior
- Hallucination
- Delusions
What are some additional physical symptoms?
- Somatic complaints
- Fatigue
- Decreased libido
- Decreased hygiene
- Crying spells
What are some secondary causes of depression ?
Medical disorders:
- Thyroid disorder
- Malignancy
- Stroke
- CHF/MI
- Parkinson’s
- MS
- AIDS
- TB
Psychiatric disorders:
- Alcoholism
- Schizophrenia
- Anxiety
What are 4 non-pharms for depression ?
1) Cognitive behavioural therapy:
- Change distorted thinking
- Alteration of target thoughts
- Change erroneous assumptions
- Promote self control over thinking
2) Interpersonal
3) Bright Light therapy - for seasonal affective disorder
4) Exercise
Response
50% reduction in symptoms
Remission
symptoms go away
Recovery
remission (symptoms go away) lasting 6-12 months
Treatment goals of depression
- shorten episode
- decrease symptoms (want a response)
- restore function
- eliminate symptoms (remission)
- prevent relapse
- minimize adverse effects of treatment
- minimize drug interactions
- promote adherence to therapy
When is treatment urgent ?
- severe depressive symptoms
- severely impaired functioning
- psychotic symptoms
- suicidal
Describe the symptom response rate to Antidepressant treatment:
Anxiety, insomnia
few days
Describe the symptom response rate to Antidepressant treatment:
Energy, somatic symptoms
2-3 weeks
Describe the symptom response rate to Antidepressant treatment:
Sleep patterns
several weeks
Describe the symptom response rate to Antidepressant treatment:
Depressed mood, sexual dysfunction
4 weeks
Can starting antidepressants make someone suicidal and want to harm themselves?
**POSSIBLY
Antidepressants can cause adverse effects. They are called agitation-type adverse events that can be coupled with self-harm or harm to others.
We should monitor them every 2 weeks within starting therapy to make sure that they are okay and not getting more irritable and making suicidal or harmful plans.
What are some neurotransmitters ?
- Norepinephrine
- Serotonin
- Dopamine
Depression is a ______ in neurotransmitters.
decrease
Depression has an ______ number of receptors (upregulation).
enhanced
Antidepressants ________ neurotransmitters available at the receptor
increase
MOA of SSRIs
*selective serotonin reuptake inhibitors
increase serotonin by inhibiting the reuptake of serotonin
MOA or SNRIs
*selective serotonin and NE reuptake inhibitors
increase serotonin and NE by inhibiting the reuptake of serotonin and NE
MOA of NDRI’s
*norepinephrine and dopamine reuptake inhibitors
increase NE and dopamine by inhibiting the reuptake of NE and dopamine
MOA of NaSSA’s
*Noradrenergic and specific serotonergic antidepressant
increase serotonin and NE
MOA of TCA’s
*tricyclic antidepressants
increase serotonin and NE
MOA of MAOi’s
*monoamine oxidase inhibitors
increase serotonin, NE and dopamine
MOA of RIMA
*reversible inhibitor of monoamine oxidase
increase serotonin, NE and dopamine
Why do anti-depressants take 4-6 weeks to work ?
Because we are altering neurotransmitters and that takes a long time
What is the 1st line option for antidepressants for an uncomplicated, physically healthy outpatient without any CI to a specific class of antidepressants?
SSRI (the choice of which one depends on multiple factors)
What do you do if a patient responds to SSRI or has remission?
Maintain for at least 4-9 months for continuation and if necessary, 12-36 months for maintenance
What do you do if patient has partial response to SSRI (after maximizing dose) ?
Consider augmentation
-(non-SSRI antidepressant, lithium, thyroid hormone, atypical antipsychotic)
OR
-switch to alternative agent (different SSRI or non-SSRI antidepressant)
If they have a failed trial after switching, what do you do?
Switch to another agent (non-SSRI antidepressant)
If they have a partial response (after maximizing dose) after switching, what do you do?
consider augmentation (non-SSRI antidepressant, lithium, thyroid hormone, atypical antipsychotic)
What is the FIRST THING you do if patient fails trial of SSRI due to nonresponse of limiting adverse effect?
ENSURE MEDICATION ADHERENCE
If patient fails trial of SSRI due to nonresponse of limiting adverse effect, and after ensuring medication adherence, what is the next step ?
switch to alternative agent (different SSRI or non-SSRI antidepressant)
List some combination therapies that are possible
- Venlafaxine and buproprion
- SSRI and buproprion
- SSRI and TCA
-TCA and MAOi (very cautiously !!)
What combo is NEVER EVER EVER allowed ?
SSRI and MAOi
What are types of augmentation treatment?
- T4
- T3
- VPA
- Atypical antipsychotics
- Lithium
How long is treatment usually?
4-9 months after remission
Who gets lifelong treatment?
<40 and had 2+ episodes
any age and had 3+ epidoes
What is poop-out syndrome? How common is it?
Some drugs lose effectiveness over time and may require a switch or add-on therapy
20-30% at 18 months
Who are candidates for ECT (electroconvulsive treatment) ?
- rapid response (suicidal, psychotic)
- history of poor response to meds
- pregnancy
What is ECT ?
It’s like a shock to the system. Just enough to elicit a seizure and kind of reset the neurotransmitters. Can come out of depression really quickly but can also relapse quickly so require maintenance therapy
Describe the course of ECT
- 6-12 treatments
- Unilateral or bilateral
- 2-3 times weekly
What are some adverse effects of ECT ?
- confusion
- memory loss months pre and post ECT
- CV dysfunction
- headache
- nausea
What are some factors that affect the choice of antidepressant ?
- Past Hx
- Family Hx
- Subtype of depression (ex. if it’s seasonal, look at bright light therapy)
- Medication Hx, concurrent meds
- Potential for drug interactions
- SE profile
- Cost
- Mechanism of antidepressant action
List examples of SSRI’s
- fluoxetine
- sertraline
- paroxetine
- fluxoamine
- citalopram
- escitalopram
“Ine’s and Pram’s”
SSRI’s:
Advantages?
Decreased side effect profile vs. TCA’s
-lack alpha1, M1, and H1 effects
SSRI’s:
What are some serotonin type adverse effects ?
- activating effects: agitation, nervousness, restlessness
- insomnia/drowsiness (paroxetine, fluvoxamine)
- GI effects initially
- weight gain (less than TCA’s)
- initial loss then gain in some
- sexual dysfunction (60%)
*LOTS OF DRUG INTERACTIONS WITH SSRI’S
SSRI’s:
What are some toxic effects?
- tremor
- sinus tachycardia
- N/V/D
- obtundation (less than full alertness)
- seizures
- serotonin syndrome
- mild bradycardia
- increase in vagal tone ?
SSRI’s:
What is the treatment for toxic effects?
charcoal + supportive care
SSRI’s:
Describe the symptoms of serotonin syndrome
1) Cognitive/behavioural:
- agitation
- mental status changes
- confusion, hypomania
2) Autonomic dysfunction:
- diaphoresis
- diarrhea
- fever
- shivering
3) Neuromuscular abnormalities
- Incoordination tremor
- Myoclonus (jerky muscle movements)
- Hyperreflexia
What are some of the drugs that can cause serotonin syndrome ?
1) Drugs that inhibit breakdown of 5-HT:
- MAOi
2) Drugs that block reuptake of 5-HT:
- SSRI
- Clomipramine
- Dextromethorphan
- Meperidine
- Cocaine
- Venlafaxine
- Trazodone
- Pentazocine
3) Drugs that are 5-HT precursors or agonists:
- Lithium
- Buspirone
- Psilocybin
- L-tryptophan
- LSD
4) Drugs that enhance 5-HT release
- MDMA (ecstasy)
How do you treat serotonin syndrome?
- Supportive care (d/c agent and it should resolve)
- Benzos to treat neuromuscular symptoms
- Tylenol and cooling blankets to treat increased temp
- Dantrolene for severe rigidity
- Cyproheptadine, serotonin antagonists for severe symptoms
- watch anticholinergic and antihistaminic properties
What are some risks for serotonin syndrome?
Additive serotonin effects:
- PK interaction
- dosage of drug
- amount and duration of 5-HT response
- ability of drug to cross BBB
What is a washout period ?
The time between stopping a drug and starting another.
Allows time for first drug to be cleared before administering the second drug to avoid “carry over” or “over lap”
Onset of serotonin syndrome?
Rapid (2-72 hours)
Describe the ‘FINISH’ pneumonic for SSRI withdrawal symptoms
- Flu-like symptoms
- Insomnia
- Nausea
- Imbalance
- Sensory disturbance (parenthesis, electric shock, visual)
- Hyperarousal
When do SSRI withdrawal symptoms occur and how long do they last ?
-within 1-3 days (up to 1 week)
- lasts up to 7-14 days (may be several weeks)
- depends on half life, dose, active metabolites and Act effects
What is the treatment for SSRI withdrawal symptoms ?
- Prevent with gradual tapering
- If appears - increase dose and taper more slowly
- If severe - switch to fluoxetine !
Why do we not usually use fluoxetine in adults? Why do we use it in children?
- Don’t usually use in a adults because it has a really long half life and takes longer to start and stop
- Use in children bc we have more data in children
What drugs can increase SSRI levels?
- Divalproex increases fluoxetine levels
- Cimetidine increases sertraline and paroxetine levels
- Clarithromycin increases fluoxetine levels
- Grapefruit juice increases fluvoxamine and sertraline levels
List examples of SNRI’s (there are only 2)
- Venlafaxine
- Duloxetine
Adverse effects of venlafaxine ?
- blood pressure increases
- dose related GI side effects and dizziness
- sexual dysfunction
- dry mouth, constipation
List example of NDRI (there is only 1)
Bupropion
D/c bupropion 2 days prior to ____
ECT
Drug interactions with bupropion ?
- Bupropion increases concentration of imipramine and desipramine
- Bupropion conc decreases when taken with carbamazepine
Adverse effects of bupropion ?
- agitation, restlessness, anxiety, tremor, insomnia
- seizures @ high dosages
- dry mouth, headache, N&V, constipation, tremor, rash
Advantages of bupropion ?
- little sexual dysfunction
- little weight gain
Why does bupropion not cause sexual dysfunction?
*sexual dysfunction is associated with serotonin and this is an NDRI
List an example of NaSSA (there is only 1)
Mirtazapine
What receptors does a NaSSA bind to and what affect do they have?
- 5-HT (2A, 2C, and 3)
- Histamine 1
- Alpha 2
- it enhances release of NE and 5-HT
- it blocks 5-HT 2A and 2C to minimize anxiety, insomnia, and sexual dysfunction
- blocking histamine causes weight gain and sedation
- anticholinergic (dry mouth, constipation)
Advantages of Mirtazapine?
- Little sexual dysfucntion
- Less serotonergic effects
What receptors does a TCA bind to and what affect do they have?
- NRI
- SRI
- alpha
- Histamine 1
- Muscarinic 1
- blocks serotonin and NE reuptake
- blocks histamine, muscarinic and alpha adrenergic receptors
TCA’s:
In usual doses, cardiac effects include ?
- HTN, tachycardias
- slowed cardiac conduction
- antiarrhythmic properties
- orthostatic hypotension
TCA’s:
Who are high risk patients for cardiac effects?
- elderly
- CV disease
- Drug interactions: increased levels
- Overdose cases
TCA’s:
List examples of Tricyclic Tertiary amines
- Amitriptyline
- Imipramine
- Clomipramine
TCA’s:
List examples of Tricyclic Secondary amines
- Desipramine
- Nortriptyline
TCA’s:
What are some central anticholinergic effects ?
- agitation
- hallucinations
- confusion
- sedation
- coma
- seizures
TCA’s:
What are some peripheral anticholinergic effects?
- hypertension
- tachycardia
- hyperthermia
- mydriasis
- dry, flushed skin
- decreased GI motility
- urinary retention
TCA’s:
What are some antihistaminic effects?
- sedation
- weight gain
TCA’s:
What are some alpha adrenergic effects?
-Orthostatic hypotension
TCA’s:
What are some Toxic Effects in Overdose ?
CV:
- intraventricular conduction delay
- sinus tachycardia
- ventricular arrhythmias
- hypotension
CNS:
- coma
- delerium
- myoclonus
- seizures
Other:
- hyperthermia
- ileus
- urinary retention
TCA’s:
What is the withdrawal syndrome due to?
cholinergic and adrenergic rebound
TCA’s:
What are the symptoms of withdrawal?
Dizziness, nausea, diarrhea, anxiety, insomnia, restlessness, diaphoresis, hot or cold flashes, delirium, mania
Taper over 2-4 weeks
TCA’s:
Treatment for withdrawal symptoms ?
- Restart at low dosage
- Anticholinergic agent
Washout period is required for which antidepressant?
MAOi
Exception: add to TCA with caution
How long should the washout period be for:
Antidepressant to MAOi
5 half lives of the antidepressant
How long should the washout period be for:
MAOi to Antidepressant
10-14 days
Cheese has a lot of _____
tyramine
Describe the Cheese Reaction
Hypertensive crisis:
- indirect acting amines
- directa chino do not require MAO for their metabolism
- catabolized by COMT
Tyramine - major dietary amine - indirect acting aognist
- Peripheral effects (does not cross BBB)
- Causes NE release from peripheral noradergic neurons
What foods should you avoid if on MAOi?
- cheese
- alcohol
- fish
- meat (fermented/aged, salami)
- fruit (spoiled or overripe banana peels)
- yeasts
- sauerkraut
- beans
When are MAOi’s indicated?
- atypical depression
- resistant depression
What are adverse effects?
- orthostatic hypotension
- dry mouth
- constipation
- sexual side effects (impotence, increased libido)
- insomnia
- sedation
Drug interactions with MAOi’s can cause _____ ______
serotonin syndrome
MAOi’s: Watch OTCs and herbals such as ?
-dextromethorphan, appetite suppressants, decongestants, tryptophan, St. John’s Wort
Give an example of a RIMA (there is only 1)
*reverse inhibitor of MAO-A
Moclobemide
SE of Moclobemide
- HTN
- tachycardia
- orthostatic hypotension
- insomnia, headache
- stimulating
St. John’s wort used for ____ to ______ depression (level 1 evidence for first line use)
mild to moderate
*not effective for severe depression
Adverse effects of St. John’s Wort
serotonin syndrome, hypomania
List 3 other possible OTC antidepressants
- crocus sativus
- SAM-e
- omega 3 fatty acids
see slide 64/65 for Washout recommendations
ok
What antidepressants should you avoid in seizure disorders?
- bupropion
- TCAs
What antidepressants should you avoid if concerned about sexual dysfunction ?
- SSRI’s
- Venlafaxine
- TCA’s
- MAOi’s
Why don’t we use trazodone as an antidepressant?
It is super sedating!
What antidepressants should you avoid if you’re concerned about weight gain?
- TCA’s
- MAOi’s
- Mirtazapine
_____ should get lower initial dosages
Eldelry
What do we need to evaluate elderly for?
orthostatic hypotension
cognition
Which antidepressants will cause excessive sedation?
TCA’s, trazodone, mirtazapine
What antidepressants will cause urinary retention (anticholinergic) ?
TCA’s, mirtazapine
Cardiac patients:
_____ will increase BP with increased dose
venlafaxine
Cardiac patients:
______ effect of certain antidepressants will increase HR
anticholinergic
Cardiac patients:
Caution _____ in those with arrhythmias
TCAs
Cardiac patients:
Rare bradycardia with ______
SSRI’s
Cardiac patients:
_____ have been seen in overdose with venlafaxine
arrhythmias
In _____, we need to weigh the risks vs benefits
Pregnancy
Pregnancy:
Most evidence for safety of ________, and then _____.
Fluoxetine, TCA’s
Pregnancy:
Can you use ECT ?
yes
Pregnancy:
How do you handle depression after delivery?
- Watch for direct drug effects and transient withdrawal symptoms in infants
- No long term neurodevelopment effects
Breastfeeding:
Which ones have evidence?
paroxetime, sertraline, fluoxetine, clomipramine, and notriptyline
*monitor infant daily
Children:
What is first line for moderate to severe depression?
fluoxetine, citalopram
Children:
What is second line for moderate to severe depression?
other SSRI’s (paroxetine > adverse effects)
Children:
What is third line for moderate to severe depression?
venlafaxine
Children:
What therapy provides the best outcome ?
combining CBT with antidepressant
Children:
___ not recommended
TCA’s
Children:
Continue tx if effective for 6 months, gradually d/c over __ weeks
6
Children:
What 4 things do parents need to think about when their child is prescribed an antidepressant ?
1) There is a risk of suicidal thoughts or actions
2) How to try to prevent suicidal thoughts or actions in your child
3) You should watch for certain signs if your child is taking an antidepressant
4) There are benefits and risks when using antidepressants
