Depression/Antidepressants Flashcards
Which ADs don’t give SIADH?
Mirtazapine
Bupropion
Neurobiology MDD
Decreased hippocampus volume Increased activity HPA axis (no suppression of cortisol with dexamethasone test) Decreased somatostatin in CSF Short allele 5HTT transporter NO PROLACTIN CHANGES
Sleep changes in MDD
DECREASED SLOW WAVE SLEEP
DECREASED REM LATENCY (get to REM sleep quicker)
INCREASED TOTAL REM TIME + DENSITY
INCREASED REM IN FIRST PART OF NIGHT
Serotonin anti-REM so most antidepressants suppress REM sleep
Most common presenting symptom of MDD?
Insomnia
Fatigue
MDD epidemiology?
Prevalence 7%
1.5-3 F : 1 M
Heritability 40%
RR 2-3 with first degree relative
Timing for remission specifier of MDD?
2 months partial vs. complete
MDD specifiers?
With anxious distress (2)
Mixed characteristics (3) RISK FACTOR FOR DEVELOPING BAD
Melancholia (Anhedonia + 3)
Atypical (Mood reactivity + 2)
Psychosis (mood congruent vs. incongruent)
Catatonia (3)
Peripartum characteristics (up to 4 weeks PP)
Seasonal characteristics (2 episodes in last 2 years and no non-seasonal episodes…can happen in lifetime but outnumbered by seasonal ones)
Persistent depressive disorder criteria?
Depressed mood for most of the day for more days than not x 2 years
(ONE YEAR IN CAP)
Never without symptoms for more than 2 MONTHS
At least TWO Appetite change Sleep change Low energy Low self-esteem Low concentration Hopelessness
Persistent depressive disorder specifiers?
Early vs. late onset based on 21 YEARS OLD
Pure dysthymic syndrome (if no MDD in 2 years)
With persistent or intermittent MDD episodes
Same others as MDD including peripartum!
Except SEASONAL
MORE PSYCHIATRIC CO-MORBIDITIES THAN MDD
Persistent depressive disorder conversion rates?
TO MDD = 20%
TO BAD 2 = 15%
TO BAD 1 = < 5%
Which disorders cannot be diagnosed with DMDD?
ODD
IED
BAD
What disorders typically developed by kids with DMDD?
MDD and anxiety
NOT BAD
DMDD criteria?
Temper outbursts at least 3 TIMES PER WEEK for AT LEAST 12 MONTHS and never without symptoms for more than 3 MONTHS
In 2-3 settings and SEVERE in at least 1
Criteria for hypomania/mania never for more than 1 day
Difference between DMDD and IED?
Need only 3 months for IED
vs.
Need 12 months for DMDD
Irritability usually doesn’t persist in between outbursts in IED
Premenstrual dysphoric disorder criteria?
In the majority of menstrual cycles in the past year
At least FIVE symptoms with particular pattern of onset and disappearance.
PROVISIONAL DIAGNOSIS UNTIL GET DAILY RATINGS WHICH CONFIRM IN AT LEAST 2 SYMPTOMATIC CYCLES
Premenstrual dysphoric disorder treatment?
Mild to moderate = non-pharmaco
Moderate to severe =
1st line = SSRI during LUTEAL phase or continuous
2nd line = clomipramine, Xanax
3rd line = OCP
4th line = surgical or chemical menopause (GnRH agonist)
First neuropsychiatric symptom of Huntington’s?
Depression
Precedes motor and cognitive impairments
Atypical MDD
Mood reactivity + 2
- Increased weight
- Hypersomnia
- Leaden paralysis
- Pattern of interpersonal rejection
Also known as HYSTEROID DYSPHORIA
RESPOND BETTER TO MAOI & SSRI
Starts earlier, psychomotor slowing more severe
Panic/substance/somatization co-morbidities
Peripartum MDD
3-6%
50% start DURING pregnancy
Up to 4 weeks post-partum
With psychotic features most common in
- primiparous
- prior post-partum mood episode
- history of mood d/o (especially BAD1)
- family history of BAD
R/o post-partum delirium
Risk of recurrence 30-50%
Seasonal pattern MDD
In last 2 years = 2 seasonal episode and NO non-seasonal ones
Non-seasonal episodes can happen in lifetime but do not outnumber the seasonal ones
Higher in BAD2
Winter type associated with younger people and higher altitude
Treat with light therapy (65% remission)
Wellbutrin 1st line
Prozac/Moclobemide 2nd line
State effect?
Decreased ability to register pleasure when depressed
Amygdala HYPOACTIVITY during positive memory recall
Trait effect?
Keep overacting to negativity even when recovered
Amygdala HYPERACTIVITY during negative memory recall
Suspect BAD when depressed if?
Atypical sx < 21 yo > 5 episodes Psychotic in < 25 yo Loss of response to antidepressants Hypomania due to Rx Post-partum Substance use disorder Mixte symptoms Rapid onset and remission (3 MONTHS) Psychomotor retardation Seasonal pattern Mood lability Hyperthymic temperament
Most frequent physical co-morbidity with MDD?
COPD
Depression following TBI
50% MDD
NOT LINKED TO SEVERITY
Linked to accumulated TBIs, age, SUD, personal and family history of psychiatric d/o, post-TBI amnesia, stressors, epilepsy post-TBI
Menopause tx?
1st line = PRISTIQ, CBT
2nd line = transdermal estradiol > Celexa, etc.
3rd line = mindfulness, supportive therapy
HOT FLASHES AND NIGHT SWEATS are risk factors for perimenopausal depression
Cardiovascular illness and MDD
20% cardiovascular patients have mood disorder
2F > 1M
Post-MI: RR 3-6 of mortality in 6-12 months if MDD co-morbid
NO association between beta-blockers and depression
Risk of MI if have depression is RR 4-5
Most predictive of white matter lesion (late-onset MDD) = HYPERTENSION
MDD Prognosis
33% don’t remit
50% remit at 3 months with treatment
30-50% relapse at 2 years
50-75% relapse at 5 years
5-10% switch to mania (average 32yo, after 2-4 depressive episodes)
6-13 month episodes if no Rx
3 month episodes if treated
Symptoms that respond well to Rx?
Mood
Suicidal ideations
Psychomotor retardation
Symptoms that tend to persist?
INSOMNIA Fatigue Somatic Anhedonia Concentration
HAM-D
Remission = 7
Out of 17 points
Mainly neurovegetative and somatic symptoms
MADRS
Remission = < 10-12
Mainly psychological symptoms
To monitor evolution
Sensitive to changes with Rx
STAR*D
33% response at 6 weeks with Celexa
Predicted response at 14 weeks
Therefore 66% don’t achieve remission with first AD trial
Cumulative remission rate of 67% in trial
Minimum trial 6 weeks, optimal 8-10 weeks
Augment after 14 weeks
Choosing Rx based on symptoms not needed
Psychotherapy tx in MDD
Acute: COMBO > CBT = Rx
Maintenance: CBT = Rx (but less relapse with CBT)
Increased efficacy with increased FREQUENCY of sessions rather than increased total number of sessions (same result for 8 than 16)
INDIVIDUAL > group
CBT efficacious in resistant MDD
Acute
1st line = CBT, IPT, behavioural activation
Maintenance
1st line = CBT, mindfulness (adjuvant to Rx)
Pharmacotherapy tx in MDD
Superiority: Cipralex, Effexor XR, Mirtazapine, Sertraline
Trazodone and TCAs second line because of tolerability
Moclobemide (reversible MAOI) second line but other MAOIs third line because of tolerability and diet necessary
Adjunct:
1st line = Abilify, Seroquel, Risperdal
2nd line = Wellbutrin, Mirtazapine, Lithium (target 0.5-1), Modafinil, Olanzapine, T3
When would monotherapy with stimulant be recommended in MDD?
In mildly depressed patient with physical illnesses
Suicidality and SSRIs warning
RR 1.5-2 increased suicidality in 14-18 yo (warning extended to include up to 24 yo)
Highest with Paxil and Effexor
Protective in > 24 yo
YOUNG ADULTS MORE LIKELY TO RESPOND TO SEROTONIN than noradrenaline
Pharmacotherapy in MDD with co-morbid alcohol use disorder?
1st line = MIRTAZAPINE, NALTREXONE, NALTREXONE + SERTRALINE
2nd line = Antabuse adjunct
3rd line = Cipralex, TCAs, Epival, Memantine
Pharmacotherapy in MDD with co-morbid ADHD?
1st line = WELLBUTRIN, ANTIDEPRESSANT + LONG-ACTING STIMULANT, ANTIDEPRESSANT + CBT
2nd line = TCAs, Effexor
3rd line = antidepressant + Strattera, antidepressant + short-acting stimulant
IF NOT IN ACUTE DEPRESSIVE EPISODE, USE FIRST LINE TREATMENTS FOR ADHD (regardless of whether maintenance treatment for MDD or not)
Which SSRI inhibits dopamine recapture?
SERTRALINE (increases dopamine)
Which SSRI is least linked to proteins?
CIPRALEX
Which SSRIs are most linked to proteins?
PAXIL
PROZAC
SERTRALINE
At what does do we get NE effects from Effexor?
> 150mg
Noradrenergic and specific serotinergic (NASSA)
MIRTAZAPINE
- Alpha 2 antagonist
- 5HT 2a (sexual side effects), 2c (weight), 3 (nausea) antagonist
NO EFFECT OF SEROTONIN REUPTAKE
Risk of AGRANULOCYTOSIS
MAO enzymes?
MAO-A: metabolizes serotonin, norepinephrine, epinephrine
MAO-B: metabolizes dopamine and tyramine
MAOI frequent side effects?
Orthostatic hypotension Weight gain Edema Insomnia Sexual dysfunction
NO ANEMIA
NO ICTERIA
Moclobemide
Reversible MAO-A inhibitor (return to normal activity 24-48H after last dose)
(but at doses higher than 600mg/d can block MAO-B as well and therefore needs tyramine-free diet)
Selegiline
MAO-B inhibitor (so increases dopamine)
Parkinson’s treatment
TCAs
2ry = desipramine (most specific noradrenergic), nortriptyline (only one with a therapeutic window)
3ry = clomipramine (most serotonergic), doxepin (most histaminic), amitriptyline (can be used for sialorrhea), imipramine (can be used for enuresis)
MEN respond better than woman overall
Contraindications
- QTc > 450ms
- Seizure risk
- Closed angle glaucoma
Compared with SSRIs:
- less sexual side effects
- less weight gain
- less sleep disturbance
Wellbutrin
Inhibits reuptake of NOREPINEPHRINE + DOPAMINE
Trazodone
SARI
Serotonin antagonist and reuptake inhibitor
Priapism
Hepatotoxicity
Orthostatic hypotension
Buspirone
5HT1A pre-synaptic AGONIST
5HT1A post-synaptic partial agonist
Cipriani study
Efficacy:
Mirtazapine > Cipralex > Effexor > Sertraline > Celexa > …
Tolerability
Cipralex > Sertraline > Wellbutrin > Celexa > Prozac > …
Sexual dysfunction with SSRIs
50-80% with SSRI, tends to persist with Rx tx
Worst with Sertraline, Paxil, Prozac, Luvox
Better with Wellbutrin and Mirtazapine, Moclobemide
SSRIs and pregnancy?
Celexa
Cipralex
Sertraline
Risk of withdrawal in 15-30% of babies
But not dangerous and resolves spontaneously in 2-14 days
SSRIs and breastfeeding?
Celexa
Cipralex
Sertraline
rTMS
1st line if don’t respond to AT LEAST ONE antidepressant
3rd line in maintenance
Target = DLPFC
1-4cm deep
Stimulate 2-10 seconds at 10-60 second intervals for 15-45 minutes
5x / week for up to 20-30 sessions
25% response
17% remit
Same cost as ECT but less efficacious
Need to use ear plugs (LOUD)
Contraindication: METAL IN HEAD (except in mouth), pacemaker, epilepsy, cerebral lesion
Deep brain stimulation
SUBCALLOSAL GYRUS
Surgical for MDD?
Anterior cingulectomy
Sub-caudal tractotomy
34-62% response
Luminotherapy
1st line mono therapy if seasonal
2nd line mono/adjunct if mild-moderate MDD
10 000 lux 30 minutes daily x 6 weeks
Exercise
1st line mono therapy in mild-moderate MDD
2nd line adjunct in moderate-severe MDD
30 minutes 3x/week moderate intensity x 9 weeks
Aerobic = anaerobic
Yoga
2nd line adjunct mild-moderate MDD
Acupuncture
3rd line adjunct mild-moderate MDD
Millepertuis
1st line mono therapy in mild-moderate MDD
2nd line adjunct in moderate-severe MDD
Contains HYPERICINE and HYPERFORINE
REUPTAKE INHIBITOR OF SEROTONIN, DOPAMINE AND NOREPINEPHRINE
Main side effect = SKIN PHOTOSENSITIVITY
Reduced OCP EFFECTIVENESS
Omega-3
2nd line mono/adjunct in mild-moderate MDD
2nd line adjunct in moderate-severe MDD
Can INCREASE COUMADIN levels
SAM-e
2nd line adjunct all MDDs
Risk of serotonin syndrome
Can induce mania
DHEA/Acetyl-L-carnitine/Crocus Sativus/L-methylfolate/Lavender
3rd line monotherapy/adjunct in mild-moderate MDD
What alternative/complementary medicine not recommended?
Tryptophan
Inositol
ECT recommendations
1st line in acute SI, psychotic depression and resistant depression (level 1)
1st line in catatonia, past response to ECT, intolerance to medication, PREGNANCY and physical deterioration (level 3)
1st line in patient preference (level 4)
ECT contraindications
NO ABSOLUTE
Relative
- recent MI or CVA
- dental problems
- irreversible MAOI (need to stop x 2 weeks)
- clozapine (prolonged seizures)
- increased ICP
- cerebral bleeding
- retinal detachment
ECT efficacy
70-80% response
40-50% remission
Superior to Rx acutely
Equal to Rx in maintenance
Aim for seizure length of 20-25 seconds
ECT parameters
1st line = BIFRONTAL
RIGHT UNILATERAL BRIEF
2nd line = bitemporal (gold standard but many side effects), ultra brief (less side effects but SLOWER improvement)
Bilateral = 1.5 - 2x seizure threshold RUL = 5-8x seizure threshold
SINUSOIDAL = memory problems
ECT side effects
HEADACHE (most common) Nausea Muscular pain Dental lesions Mania (IN 10-30% BAD PATIENTS) Delirium Amnesia (BENZOS, LITHIUM, CLOZAPINE) Increased prolactin Hypertension, tachycardia, ST changes 24-H post-ECT
HYPERVENTILATION does not influence cognitive troubles
Mortality 0.01% for each patient
Same risk as general anesthesia and delivery
LESS mortality than with antidepressants
ECT stimulus threshold
1/2 of age
Increases with treatment by 25-200%
Good response:
- post-ictal suppression
- ictal amplitude
Child and adolescent depression
Relapse 20-60% @ 2 yrs, 70% @ 5 yrs
Conversion 20-40% to BAD (compared to 5-10% in adults)
Geriatric depression
1st line = Cymbalta, Mirtazapine, Nortriptylline
Suicide
DEMENTIA DOES NOT INCREASE THE RISK
Most common psychiatric diagnoses:
- mood disorder
- schizophrenia
- substance use disorder
Pseudocholinesterase deficiency
CAUTION ECT
Succinulcholine is acetylcholine receptor blower so this interferes = apnea; use non-depolarizing anesthetic instead
Maintenance Rx after ECT?
Lithium + nortriptyline
ECT for which symptoms in Parkinson’s?
BOTH MOTOR AND MOOD
CORE study?
Antidepressant failure does NOT predict lower ECT response rates.
Lithium + nortriptyline in ECT-responsive patients
Most specific and sensitive sleep change in MDD?
INCREASED REM DENSITY
