Depression and Treatment Flashcards
List the risk factors for major depressive disorder
- Past or family history
- chronic medical condition
- substance use
- psychosocial adversity
- high users of the medical system with many somatic complaints
List the good and poor prognostic features of depression
- 40% recover within 3 months and 80% recovery within 1 year
- those with 1 episode have 50% risk of relapse and those with two have 75%
Good - recent onset
- short duration of depression
Poor - chronic or severe depression
- psychotic features
- melancholic features
- anxiety
- personality disorder
- young age
- multiple episodes
List the MSIGECAPS diagnostic criteria
M: Mood that is depressed everyday or nearly every day
S: Sleep is increased or decreased
I: Interest is lost or loss in pleasure in almost all activities
G: Guilt/Worthlessness feelings everyday
E: Energy is lost or severely decreased
C: Concentration is decreased
A: Appetite is increased or decreased
P: Psychomotor retardation or agitation
S: Suicide recurrent thoughts of death with or without plan
List the diagnostic criteria for a major depressive episode
- > =5 of the MSIGECAPS symptoms for at least two weeks where mood or interest must be included
- symptoms must cause distress and impair functioning
- not due to substances or medical condition
- not another psychotic disorder
- no manic or hypomanic episode
List the specifiers for major depressive disorder
- mixed features when 3 manic or hypomanic symptoms are present
- anxious distress
- melancholic features when have loss of pleasure and at least 3 of (PAGE MD):
- psychomotor agitation or retardation
- anorexia
- guilt
- early morning awakenings
- morning worsening of depression
- different quality of depressed mood
- atypical features when have reactive mood and 2 of the following (WILL):
- weight gain
- increased sleep
- leaden paralysis
- longstanding pattern of intepersonal rejection
- with psychotic features
- with catatonia when have greater than 2 of the following (SPENT):
- stupor/motor immobility
- peculiar voluntary movements
- echolalia
- negativism
- too much motor activity
List the investigations for major depressive disorder
- CBC for anemia or infection
- electrolytes
- Metabolic work up (Ca, Glucose, B12)
- kidney function
- liver function
- TSH
- albumin
List common medical conditions and substances that can cause depression
Medical conditions - stroke - Parkinsons - hypothyroidism - cancer - anemia - coronary artery disease - HIV - SLE - OSA Substances - alcohol - sedativ - opioid - steroids
List the diagnostic criteria for persistent depressive disorder (dysthymia)
>=2 years of depressed mood for most days with >=2 of the following (ACHEWS) - appetite change - concentration decreased - hopelessness - energy decreased - worthlessness - sleep change Not symptom free for >2 months No manic or hypomanic episode Not other psychotic disorder or susbtance Cause distress and impair function
List the diagnostic criteria for premenstrual dysphoric dirsorder
Cyclical pattern of depressed mood coinciding with menstrual cycle
- Present in majority of cycles with >=5 symptoms
- Group 1: affective liability, irritability, depressed mood, anxiety
- Group 2: Sleep, interest, energy, concentration, appetite, physical symptoms
- must have 1 symptoms from group 1 and group 2
- symptom onset week prior to menses and subside few days after menses
- symptoms cause distress and impair functioning
- confirmed by prospective daily rating of at least 2 symptomatic cycles
Discuss the pathophysiology of depression
Have insufficient mono-amine neurotransmitter resulting in upregulation of neurotransmitter receptors -> decreased gene expression and abnormal mood state
List the function of each of the primary neurotransmitters have on symptoms of depression
Psychomotor activity - serotonin - norepinephrine - dopamine Mood - serotonin - norepinephrine - dopamine Sleep - serotonin - norepinephrine - dopamine Appetite and Weight - serotonin Guilt and Worthlessness - serotonin Suicide - Serotonin Interest - Norepinephrine - dopamine Energy - Norepinephrine - dopamine Executive function - norepinephrine - dopamine
List the mechanism of action of SSRI and a few examples
- act at dendrite synapses of the pre-synaptic neuronto increase serotonin in the synapse Examples - paroxetine (paxil) - fluoxetine (prozac) - citalopram (celexa) - sertraline (zoloft) - cipralex (escitalopram)
List the side effects of SSRIs
- transient increase risk of suicide that decreases after few weeks Common (HANDS) - headache - anxiety and agitation - nausea - diarrhea - sexual dysfunction and sleep disruption Rare - upper GI bleed, especially when used with NSAID - Syndrome of inappropriate ADH release - Osteoporosis - Serotonin syndrome
List the features of SSRI discontinuation syndrome
- Occur 3 days after discontinuation
- Greatest risk with paxil and effexor
FINISH - flu-like symptoms
- insomnia
- nausea
- imbalance
- sensory disturbance
- hyperarousal
List the contraindications to starting a SSRI
- use of a MAO inhibitor, triptan or other serotonergic drug due to risk of serotonin syndrome
- pregnancy
- bipolar
Discuss the mechanism of action of NDRI and provide an example
- norepinephrine and dopamine are prevented from reuptake at pre-synaptic neuron
Example - Bupropion (wellbutrin)
List the side effects of NDRI
SHAARES
- seizures (cannot use with bulimia or electrolyte disturbance)
- headaches, hypertension
- Agitation
- Anticholinergic symptoms
- flushing
- dry mouth
- blurred vision
- delirium
- hyperthermia
- urinary retention and constipation - rash
- emesis
- sleep disruption
Discuss the mechanism of action and provide examples of SNRI
- blockade of serotonin at lower doses
- blockade of serotonin and norepinephrine at mid doses
- blockade of serotonin, norepinephrine and dopamine at high doses
Examples - Venlafaxine (effexor)
- Duloxetine (cymbalta)
Discuss the mechanism of action and provide examples of NaSSA (noradrenergic and specific serotonergic antidepressants)
- block alpha 2 auto receptor on norepinephrine receptor and heteroreceptor on 5HT neurons increasing release of norepinephrine and serotonin
- also block 5HT2 so not sleep or sexual side effects, 5HT3 so no GI side effects and H1 histamine receptor leading to sedation and weight gain
Example - Mirtazepine (remeron)
List the side effects of NaSSA
Common (WADE) - weight gain - anticholinergic effects - drowsiness - equilibrium problem Rare - neutropenia - serotonin syndrome - hepatoxicity - SIADH
Discuss the mechanism of action and provide examples of SARI (Serotonin 2A antagonist reuptake inhibitor)
- weak serotonin reuptake inhibitor
- block 5HT2A so no sleep disruption or sexual dysfunction
- block H1 histamine so sedating
- block alpha 1 so orthostatic hypotension
Example - trazodone (desyrel)
List the side effects of SARI
- headache
- sedation
- orthostatic hypotension
- vivid dreams
- dry mouth
- priapism
- serotonin syndrome
Discuss the mechanism of action and provide examples of TCA
- block all three monoamine reuptake
- block 5HT2 so no sex or sleep side effects
- block H1 histamine, muscarinic, alpha 1 adrenergic, and sodium channels in heart and brain
Examples - amitriptyline
List the side effects of TCAs
Common
- weight gain
- sedation
- anticholinergic
- orthostatic hypotension
- prolonged QTc
Rare
- serotonin syndrome
- Torsade de Pointes
- Before starting: ECG to rule out bradycardia or prolonged QTc, electrolyte imbalance, taking type 1 or 3 antiarrhythmic
- SIADHDiscuss the mechanism of action and provide examples of MAOI (Monoamine oxidase inhibitor)
- irreversible bind and inhibit MAO thereby increasing 5HT, NE and DA levels
- irreversible inhibition last for 2 weeks
Examples - moclobemide
List the rare side effects of MAOI
3Hs
- hyperthermia due to serotonin syndrome
- Hypertensive crisis
- Hepatotoxicity
- Teratogenicity
- Blood dyscrasia
Discuss the features of serotonin syndrome
HARMED
- hyperthermia
- agitation and autonomic instability (tachy, diarrhea)
- rigidity and reflexes increased
- myoclonus
- encephalopathy
- diaphoresis
List the indications for treatment in depression
- medication indicated for mild to moderate if patient prefer over psychotherapy
- medication required in moderate to severe with or without psychotherapy or ECT
- psychotic depression require ECT or antidepressant and antipsychotic
List the first line medications and how they are started
First Line
- SSRI: escitalopram or sertraline
- SNRI: venlafaxine or duloxetine
- NaSSA: mirtazapine
Starting
- begin at lowest possible dose and increase weekly until:
- intolerable side effects
- full response
- maximum dose
- usually do not find subjective benefit until 4-6 weeks, objective benefit after 2 weeksList the starting and target doses for the common medications from each class
SSRI - Escitalopram 10mg/10-20mg - Fluoxetine 20mg/20-80mg - Sertraline 50mg/50-200mg SNRI - Venlafaxine 75mg/75-375mg - Duloxetine 60mg/60-120mg NDRI - Buproprion 150mg/150-300mg NaSSA: - Mirtazapine 30mg/30-60mg MAOI/RIMA - Moclobemide 300mg/300-600mg SARI: - Trazadone 150-200mg/150-300mg TCA - Nortriptyline 25mg/150-250mg
Discuss response after assessing at 4 weeks following achievement of therapeutic dose
Remission
- maintain antidepressant for 1 year post-remission months
- if more severe depression may require continued therapy for 2 years
Little to No Improvement (<20% reduction in score)
- re-evaluate diagnosis
- switch to another antidepressant with evidence of superiority
- if no benefit with switch then add-on another agent
- or combine with atypical antipsychotic or lithium
List the indications for ECT
- severe major depressive disorder when lack of response to medication, intolerant to medication or require fast improvement
- mania in bipolar
- mixed state
- catatonia
- psychosis
List the predictors of good outcome with ECT
- older age
- shorter duration of symptoms
- unipolar depression
- depression with psychotic features
- adequate seizure of adequate duration
Discuss the mechanism of action of ECT
- use electricity to ellicit seizure that results in
- neurotransmitter theory: ECT enhances action of monoamines
- neuroendocrine theory: ECT releases prolactin, TSH, ACTH, endorphines, brain derived neurotrophic factor (BDNF) and BDNF-R in frontal cortex
- neurogenesis: ECT increases neuroplasticity via BDNF increasing neuron connection and growth
- anticonvulsant theory: ECT alters GABA
List the investigations required before ECT
- CBC, electrolytes
- creatinine, BUN
- liver function
- drug levels
- pregnancy
- ECG
- CXR
Discuss the ECT procedure
- Anesthesia to establish airway and provide bite block and induction
- EEG to assess seizure quality
- beta blocker (esmolol) to prevent tachycardia
- Electrodes placed on patient along bilateral temporal temporal or bifrontal or right unilateral temporal (ranked in greatest effectiveness and increasing side effects)
- Monitor EEG for recruitment (low amplitude, high frequency), tonic (high amplitude, high frequency, spike and poly-spike activity), clonic (high amplitude, spike and slow wave complexes) termination (slow wave amplitude and frequency) and post ictal silence
Discuss the treatment regimen for ECT
- provided for 8-12 sessions where receive ECT 2-3 times per week
- have high relapse rate following conclusion so must continue with medication
List the side effects of ECT
Common - headache - nausea - muscle pain Severe - cardiovascular: vagal stimulation leading to bradycardia/asystole, sympathetic discharge leading to tachycardia and hypertension or rebound parasympathetic effect causing secondary bradycardia - prolonged seizure (>3 minutes) - prolonged apnea Cognitive - amnesia which is transient and disappear within 6 months - delirium post-ictal
List the contraindications for ECT
Relative
- brain disease (space occupying lesion, subdural hematoma, raised ICP)
- cardiovascular disease (recent MI/stroke or aortic stenosis)
- retinal detachement
- pheochromocytoma
