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PHAR 253 > Major Depressive Disorder (MDD) > Flashcards

Major Depressive Disorder (MDD) Flashcards

1
Q

What is major depressive disorder?

A

low mood, characterized by feelings of sadness, emptiness or irritability and accompanied by other somatic or cognitive changes that significantly affect the individuals capacity to function

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2
Q

How much does genetics come in to play for MDD?

A

twin studies show 40-50% heritability

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3
Q

what is the monoamine hypothesis of MDD?

A

dysfunction in monoamine production
dysregulation in monoamine activity

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4
Q

what are monoamines?

A

serotonin, norepinephrine, dopamine

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5
Q

What is the neuroplasticity hypothesis of MDD?

A

downstream effects lead to altered cell growth and adaptation leading to lower levels of BDNF

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6
Q

What is BDNF?

A

brain derived neurotrophic factor: growth factor that regulates survival of neurons, important for structural integrity and neuroplasticity

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7
Q

According to the neuroplasticity hypothesis, which drugs are needed to help depression?

A

drugs that restore balance to glutamate/GABA

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8
Q

How might endocrine and immune system abnormalities cause depression?

A

increased plasma cortisol, increased peripheral cytokine concentrations
chronic stress model – involves the HPA axis

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9
Q

how might structural and functional alterations in brain regions involving emotional processing cause depression?

A

reduced volume or hyperactivity in prefrontal cortex, cingulate cortex, hippocampus, amygdala

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10
Q

What percent do personality disorders play a role in depression?

A

30%

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11
Q

What amount of people with depression have other medical comorbidities?

A

85%

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12
Q

What are the emotional, neurovegetative and neurocognitive symptoms of depression according to the DSM?

A

emotional:
depressed mood
anhedonia
feelings of worthlessness or guilt
suicidal ideation, plan or attempt

neurovegetative:
fatigue or loss of energy
sleep increase or decrease
weight or appetite increase or decrease

neurocognitive:
decreased ability to think or concentrate or indecisiveness
psychomotor retardation or agitation

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13
Q

How many symptoms of depression according to the DSM-5 are needed to be considered severe?

A

nearly all symptoms, significant functional impairment or motor impairment

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14
Q

What criteria must be met to be diagnosed with depression according to the DSM-5?

A

(A) at least 5 symptoms, at least 1 symptom must be depressed mood or anhedonia; present nearly every day for at least a 2 week period
(B) symptoms cause clinically significant distress or impairment in social, occupational, or other areas of functioning
(C) episode is not attributable to direct physiologic effects of a substance of another medication
(D) MDD is not better explained by a different mental illness
(E) there has never been a manic or hypomanic episode

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15
Q

What does SIG: E. CAPS stand for?

A

symptoms of depression:
Sleep changes: increase during day or decreased sleep at night
Interest (loss): of interest in activities that used to interest them
Guilt (worthless): depressed elderly tend to devalue themselves

Energy (lack): common presenting symptoms (fatigue)

Cognition/concentration: reduced cognition and/or difficulty concentration
Appetite (wt. loss); usually declined, occasionally increased
Psychomotor: agitation (anxiety) or retardations (lethargic)
Suicide/death preocp.

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16
Q

What is MDD with anxious distress?

A

MDD diagnosis PLUS 2+ of: tension, worried, restlessness, afraid of losing control, impaired concentration

not a full anxiety diagnosis

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17
Q

What is MDD with mixed features?

A

subthreshold mania/hypomania

MDD diagnosis PLUS 3+ symptoms of mania most days

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18
Q

What is MDD with catatonic features?

A

MDD diagnosis PLUS 2+ of: catalepsy, excessive purposeless motor activity, extreme negativism, peculiar voluntary movements, echopraxia

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19
Q

What is MDD with melancholic features?

A

Severe form of depression

MDD diagnosis PLUS 3+ of: nonreactive “empty” mood, increase morning severity, early morning awakening, psychomotor agitation or retardation, significant weight loss, excessive guilt

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20
Q

What is MDD with atypical features?

A

MDD diagnosis with reactive mood, oversleeping, overeating, leaden paralysis, sensitive to rejection

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21
Q

What is Peripartum onset depression?

A

MDD during pregnancy or within 4 weeks postpartum

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22
Q

What is MDD with psychotic symptoms?

A

MDD diagnosis with delusions or hallucinations

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23
Q

What is dysthymia?

A

Persistent depressive disorder

depressive mood for 2 or more years with symptoms free period no greater than 2 months
2+ additional depressive symptoms (not full criteria for MDD)
no MDD episode in first 2 years of onset – depressive episodes can be superimposed after

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24
Q

What is substance/medication induced depressive episode?

A

prominent, persistent disturbance in mood predominates the clinical picture with diminished interest in almost all activities
symptoms develop or shortly after substance intoxication or withdrawal and the substance is known to cause disturbance

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25
Q

How do you rule out Bipolar depression when diagnosing MDD?

A

completely mood disorders questionnaire to rule out history of mania/hypomania

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26
Q

How to rule out anxiety when diagnosing MDD?

A

complete GAD-7

may co-occur with MDD

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27
Q

What is part of the differential diagnosis of MDD?

A

Bipolar depression
anxiety (no co-occur)
substance use disorder (may co-occur)
another medical condition
grief
PMS
irritable or labile emotions
feeling sad

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28
Q

What prescription medications might cause depression?

A

CV agents: clonidine, methyldopa, reserpine
anticonvulsants: phenobarbital, topiramate, vigabatrin
hormonal agents: corticosteroids, GnRH agonists, tamoxifen
immunologic: IFN alpha
other: benzos, BB (?), opioids, anti-thyroid

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29
Q

which standardized rating scales for MDD can be completed by the patient?

A

PHQ-9, QIDS, Beck depression inventory

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30
Q

Which standardized rating scales for MDD are administered by a physician?

A

QIDS (also a self administered version), HAM-D, MADRS

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31
Q

What questions are on PHQ-9?

A
  1. little interest or pleasure in doing things
  2. feeling down, depressed, or hopeless
  3. trouble falling or staying asleep, or sleeping too much
  4. feeling tired or having little energy
  5. poor appetite or overeating
  6. feeling bad about yourself - or that you are a failure or have let yourself or your family down
  7. trouble concentrating on things, such as reading the newspaper or watching TV
  8. moving or speaking so slowly that other people could have noticed? or the opposite - being so fidgety or restless that you have been moving around a lot more than usual
  9. thoughts that you would be better off dead or hurting yourself in some way
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32
Q

What does your PHQ-9 score mean?

A

20-27 = severe
15-19 = moderately severe
10-14 = moderate
5-9 = minimal
<5 = no symptoms

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33
Q

what improvement in PHQ-9 score is considered a response to treatment? what is considered remission?

A

Response = 50% or more reduction in score
remission = score 5 or lower

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34
Q

What questions are on the PHQ-2?

A
  1. little interest or pleasure in doing things
  2. feeling down, depressed or hopeless
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35
Q

What is considered a positive score for the PHQ-2

A

3+

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36
Q

what is the lifetime risk of suicide in untreated MDD?

A

20%

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37
Q

what are suicide risk factors?

A

IS PATH WARM

Ideation
Substance use

Purposelessness
Anxiety
Trapped (feelings of no way out)
Hopelessness

Withdrawal
Anger
Recklessness
Mood changes (dramatic)

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38
Q

What is the response rate to antidepressants vs response to placebo?

A

40-60% to antidepressants; 30-50% to placebo

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39
Q

T or F
response/remission declines with each subsequent treatment trial

A

True

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40
Q

what percentage of people will experience a recurrance?

A

25-40% in 2 years, 50-80% have more than one episode in lifetime

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41
Q

What is considered a partial remission?

A

continued presence of some symptoms but full criteria not met

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42
Q

What is the difference between remission and recovery?

A

full remission is the absence of significant symptoms and recovery is full remission for at least 2 months

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43
Q

what is the difference between a relapse and a recurrance?

A

a relapse is a new episode before recovery, and a recurrence is new episode any time after achieving recovery

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44
Q

What is considered chronic depression?

A

full criteria for MDD met for a minimum of 2 years

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45
Q

What is considered to be treatment resistance?

A

episode that has failed to response to 2 separate trials of different antidepressants of adequate dose and duration

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46
Q

What are some predictors of remission?

A

female sex, white race, employment, higher level of education, higher income

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47
Q

what is the goal of acute treatment?

A

symptom remission and restoration of premorbid functioning within 8-12 weeks
prevent hard ongoing
restore optimal functioning within 8-12 weeks

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48
Q

what HAM-D scores are considered remission? response?

A

remission: HAM-D score 7 or less
response: HAM-D 50% or more reduced from baseline

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49
Q

What is the goal with maintenance treatment of MDD?

A

prevent recurrences of mood episode

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50
Q

What are some non pharm treatments of MDD?

A

positive lifestyle changes
natural products
psychological treatment
neurostimulation
physical interventions: acupuncture, massage, yoga
bright light therapy
music therapy
spiritual care
vagal nerve stimulation

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51
Q

What is St. John’s Worts MOA in MDD?

A

weak non selective MAO, inhibits 5-HT, NE, DA transporter

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52
Q

What is St. John’s Wort used for?

A

monotherapy for mild to moderate depression symptoms

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53
Q

what are some AE’s of St. John’s Wort?

A

GI upset, sexual dysfunction, photosensitivity
increases risk of serotonin syndrome, bleeding
lots of drug interactions

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54
Q

What is S-Adenosyl Methionine used for?

A

adjunct for mild-moderate symptoms

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55
Q

What are some AE’s of S-Adenosyl-Methionine?

A

GI upset, flatulence, dry mouth

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56
Q

how might omega-3 fatty acids work in depression?

A

3-PUFA deficiency has been shown to be associated with depression

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57
Q

What is Omega-3 fatty acids used for?

A

monotherapy or adjunct to antidepressants

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58
Q

What is Folate L-methylfolate used for?

A

adjunct for antidepressants

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59
Q

When is psychological treatment used as monotherapy?

A

mild depression

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60
Q

What severity of depression is psychological treatment recommended in?

A

All

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61
Q

T or F
Psychological treatment is not found to be as successful as antidepressants in treating depression

A

False

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62
Q

What is transcranial magnetic stimulation (TMS)?

A

magnetic fields are used to stimulate nerve cells in regions of the brain involved in mood regulation and depression

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63
Q

What is TMS used for?

A

refractory depression

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64
Q

How long is the course of TMS treatment?

A

4-6 weeks

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65
Q

What are some AE’s of TMS?

A

headache, scalp discomfort

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66
Q

what is electroconvulsive therapy (ECT)?

A

electrodes placed on various scalp regions
electrical charge is applied to stimulate the brain and produce a seizure while patient under general anesthetic
seizure lasts 1 minute

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67
Q

what is ECT used for?

A

severe depression, depression with psychosis or catatonic features, severe SI

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68
Q

how long is the course of ECT treatment?

A

6-12 treatments

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69
Q

what medications should be minimized/avoided during ECT treatment?

A

anticonvulsant medications
benzos
lithium
buproprion

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70
Q

what are some AE’s of ECT?

A

confusion during post-ictal period
impaired memory after procedure
headache
muscle ache

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71
Q

What are the two landmark papers on MDD?

A

Cipriani network meta-analysis
STAR*D

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72
Q

what did the Cipriani show?

A

no strong evidence to conclude that any antidepressant is superior in efficacy

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73
Q

which antidepressants do meta-analyses show have the best efficacy/tolerability profile?

A

sertraline, escitalopram, vortioxetine, venlafaxine, mirtazapine

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74
Q

what did the STAR*D trial show?

A

no difference in remission rates or times to remission:
between medication strategies (switch or augmentation) at any treatment level
between any of the switching options between any of the augmenting options in step 2-4
between switch to CT vs meds or augment with CT vs meds

longer time to remission, greater number of treatment steps = higher relapse rates

prognosis better for those achieving remission prior to follow-up phase compared to those with adequate response without remission

no difference between remission/response between primary or psychiatric care setting

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75
Q

What is the success rate upon first treatment of antidepressants?

A

30% remission
10-15% show no response

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76
Q

what is the symptom response rate across all antidepressant trials?

A

40-60%

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77
Q

According to CANMAT, what is the 2nd line intervention to no response to antidepressants?

A

switch to alternate antidepressant
TMS
ECT
light therapy
omega-3

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78
Q

according to CANMAT, what is the 2nd line intervention to partial response to antidepressants?

A

augment with 1st line adjunct (aripiprazole, quetiapine, risperidone)
adjunctive exercise
light therapy, yoga, SAMe
adjunct St. John’s Wort, omega-3

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79
Q

According to CANMAT what are 3rd line interventions (AKA treatment resistance)?

A

augment with other AD or different med: brexpiprazole, buproprion, lithium, mirtazapine, modafinil, olanzapine, triiodothyronine, TCAs, MAOIs, ketamine
neurostimulation mono treatment or augmentation
adjunctive acupuncture

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80
Q

what are the patient factors to take into account while selection an antidepressant?

A

clinical features and dimensions
comorbid conditions
response and side effects during previous use of antidepressants
patient perference

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81
Q

according to CANMAT what are the first line antidepressants?

A

SSRIs: sertraline, escitalopram, fluoxetine, citalopram, paroxetine
SNRIs: duloxetine, venlafaxine
Mirtazapine
Buproprion

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82
Q

how many remit after first treatment? second? fourth?

A

1 = 1/2
2 = 1/3
4 = 2/3

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83
Q

what is the MOA of SSRIs?

A

inhibition of presynaptic 5-HT reuptake by inhibition of the 5-HT transporter CNS neurons (reuptake inhibition/transporter inhibition) = increased 5-HT in synaptic cleft

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84
Q

What is the onset of action of SSRIs?

A

1st few days: decrease agitation and anxiety, improved sleep and appetite

1-3 weeks: increased activity and sex drive, improved self-care, concentration, memory, thinking, movements

2-4 weeks: relief of depressed mood, return of experiencing pleasure, fewer hopeless feelings, subsiding suicidal thoughts

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85
Q

what are some AEs of SSRIs?

A

HANDS:
Headache
Anxiety
Nausea
Diarrhea and other GI upset
Sleep disturbances: insomnia or sedation

anticholinergic: dry mouth, constipation, blurred vision

sexual dysfunction

emotional blunting/detachment

tremor, yawning, sweating, enuresis

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86
Q

What is SIADH?

A

syndrome of inappropriate antidiuretic hormone secretion
body makes too much antidiuretic hormone (vasopressin)
causes body to retain too much water

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87
Q

What are some causes of SIADH?

A

pain, vomiting, CNS injury, inflammation, lung injury, carbamazepine, opioids, SSRIs, NSAIDs, SNRIs, mirtazapine

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88
Q

what are the s/sx’s of SIADH?

A

lethargy, change in mental status, Na <135 mEq/L, hyperosmolar urine (>300 mosmol/kg)

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89
Q

what is the management of SIADH?

A

usually inpatient care, d/c offending agent, water restrictions

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90
Q

what are some precautions with SSRIs?

A

increased risk of suicide in children, adolescents, and young adults <24 years old

increased fracture risk and decreased bone mineral density (especially elderly)

citalopram, escitalopram have dose dependent risk of QTc prolongation

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91
Q

which SSRIs seem to be most sedating?

A

mild sedation: sertraline and citalopram
most: paroxetine

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92
Q

Which SSRI has the most weight gain?

A

paroxetine

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93
Q

which SSRI is the most stimulating?

A

fluoxetine

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94
Q

Which SSRI has the longest half life?

A

fluoxetine

95
Q

Which SSRIs have the highest rates of nausea/diarrhea?

A

fluvoxamine and sertraline

96
Q

which SSRI has been shown to be the least tolerable?

A

fluvoxamine

97
Q

which SSRIs have the most DIs?

A

fluoxetine, paroxetine, fluvaoxamine

98
Q

what are some DIs of SSRIs?

A

NSAIDs, antiplatelets, anticoagulants: increased bleeding risk secondary to decreased platelet aggregation effects of SSRIs

serotonergic agents: increased risk of serotonin syndrome

99
Q

which SSRI has better bioavailability with food?

A

sertraline

100
Q

which SSRIs form active metabolites? when would this be a concern?

A

fluoxetine, citalopram and sertraline

concern if liver cannot metabolize these efficiently

101
Q

What is the dosing of SSRIs?

A

all taken once daily

102
Q

what is the MOA of vorioxetine?

A

serotonin reuptake inhibitor
5HT1A receptor agonist
5HT1B receptor partial agonist
5HT3+7 5Ht1D receptor agonist

103
Q

what are some AE’s of vortioxetine?

A

headache, nausea, vomiting, diarrhea, sexual dysfunction

seems to be better tolerated than other ADs

104
Q

Which SNRIs are available in Canada?

A

venlafaxine
desvenlafaxine
duloxetine
levomilnacipran (not first line)

105
Q

what is the MOA of SNRIs?

A

inhibit presynaptic 5-HT and NE reuptake by inhibiting 5-HT and NE transporters in CNS neurons

106
Q

T or F
SSRIs are thought to be more antidepressive and more pro-cognitive compared to SNRIs

A

False
SNRIs are thought to be more antidepressive and more pro-cognitive than SSRIs

107
Q

what does of venlafaxine binds to only 5-HT? which does binds to both 5-HT and NE?

A

only 5-HT = <150 mg/day
NE and 5-HT = >150 mg/day

108
Q

T or F
at high doses, venlafaxine inhibits DA transport?

A

True
at doses >450 mg/day it weakly inhibits DA transporter

109
Q

which SNRIs have equal affinity for NE and 5-HT?

A

duloxetine and desvenlafaxine

110
Q

what is the onset of action of SNRIs?

A

1st few days: decreased agitation and anxiety, improved sleep and appetite

1-3 weeks: increased activity and sex drive, improved self-care, concentration, memory, thinking, movements

2-4 weeks: relief of depressed mood, return of experiencing pleasure, fewer hopeless feelings, subsiding suicidal thoughts

111
Q

What are the AE’s of SNRIs?

A

similar to SSRIs
“HANDS”

anticholinergic like effects (dose related): related to increased NE - dry mouth, constipation, sedations, urinary retention

sexual dysfunction

SIADH

risk of serotonin syndrome, AD-induced suicidality

dose related increased BP and HR and sweating due to NE action

less emotional blunting than SSRIs

112
Q

T or F
SNRIs are associated with increased risk of fractures

A

False

113
Q

which SNRIs have more risk of sexual dysfunction?

A

venlafaxine similar rates of SSRIs
desvenlafaxine and duloxetine less than SSRIs

114
Q

Which SNRI has the highest SIADH risk?

A

venlafaxine

115
Q

T or F
SNRIs are not effected by food

A

True

116
Q

T or F
you do not have to adjust SNRI dose in renal impairment

A

False

117
Q

which SNRIs are hepatically metabolized?

A

venlafaxine and duloxetine

118
Q

what are some DIs with SNRIs?

A

CYP interactions:
duloxetine: moderate inhibitor and substrate
venlafaxine: weak inhibitor and substrate
desvenlafaxine: no significance

NSAID, antiplatelets, anticoagulants - caution only: increased bleeding risk secondary to decreased platelet aggregation effects serotonin reuptake inhibition (less risk than SSRIs)

serotonergic agents: increased risk of serotonin syndrome

119
Q

what are some precautions with SNRIs?

A

duloxetine CI in narrow angle glaucoma

increased suicide risk if <24 years

monitor for increased BP

caution if history of HTN or narrow angle glaucoma

avoid abrupt withdrawal

duloxetine: avoid in hepatic impairment or heavy ETOH use; risk of urinary retention

120
Q

which SNRI has the worst withdrawal symptoms?

A

venlafaxine

121
Q

which SNRI is particularly useful for menopausal vasomotor symptoms?

A

desvenlafaxine

122
Q

what is the MOA of bupropion

A

inhibits NE and DA transporters increasing concentrations in the synapses

123
Q

T or F
bupropion has effects on 5-HT

A

False

124
Q

T or F
bupropion is similar in structure to amphetamine

A

True

125
Q

in what situations may bupropion be beneficial?

A

useful in patients with psychomotor retardation, hypersomnia, ADHD type symptoms

can be used to augment SSRI or SNRI in treatment resistant cases

much less risk of sexual dysfunction and in some cases may alleviate symptoms when used as adjunct

possibly useful in stimulant use disorder to reduce illicit use and cravings

126
Q

What are some AEs with bupropion?

A

activating: agitation, insomnia, tremor and anxiety - may need to avoid if hx of anxiety

sweating due to NE reuptake inhibition

GI upset

psychosis/exacerbation of psychosis

urticaria and anaphylactoid reactions

seizures: dose dependent

127
Q

how is bupropion activated?

A

metabolized in liver by CYP2B6 to active metabolite hydroxybupropion

128
Q

T or F
Bupropion is renally eliminated

A

true
dose adjustments may be needed in renal impairment

129
Q

What are some DIs of bupropion?

A

Zyban: same drug

concurrent MAOI therapy CI: hypertensive crisis

potent CYP2D6 inhibitor

130
Q

What is the difference between bupropion SR and bupropion XL?

A

SR = OD or BID dosing
XL = OD dosing

131
Q

what are some CIs of bupropion?

A

seizure disorder

eating disorders

abrupt discontinuation of alcohol or sedatives

132
Q

what are some precautions with bupropion?

A

increased risk of suicide if <24 years

precaution in:
dependence on opioids, cocaine, stimulants
concurrent use of seizure threshold lowering drugs
head trauma history
HTN
unstable CVD/CAD
psychosis
anxiety
insomnia
overdose lethality

133
Q

what is the MOA of mirtazapine?

A

antagonism at 5-HT2a, 5-HT2c, 5-HT3, a2-adrenergic, H1

134
Q

what does antagonism of presynaptic central alpha2 adrenergic autoreceptors in mirtazapine use do?

A

increased release of NE and 5HT

135
Q

at what dose does mirtazapine need to be at to cause antagonism of a2-adrenergic autoreceptors?

A

> 15 mg/day

136
Q

what is 5HT2a/2c receptor antagonism linked to in mirtazapine use?

A

linked to lower anxiety, antidepressive, pro-cognitive
lower 5HT related AEs

137
Q

what is 5HT3 receptor antagonism linked to in mirtazapine use?

A

lower GI side effects (helps relieve N/V)

138
Q

What is H1 receptor antagonism linked to in mirtazapine use?

A

sedation, weight gain

139
Q

at what dose does mirtazapine antagonize histamine receptors?

A

doses <30 mg

140
Q

in what situations might mirtazapine be useful?

A

useful as monotherapy and adjunctive treatment

consider patients with insomnia, anxiety, reduced appetite

benefit for antipsychotic induced akathisia

possibly useful in stimulant intoxication or opioid withdrawals

141
Q

What are some AEs with mirtazapine?

A

CNS: sedation

endocrine: increased TGs and weight gain due to increased appetite

GU: less sexual dysfunction

142
Q

which antidepressants have the least sexual dysfunction?

A

bupropion and mirtazapine

143
Q

T or F
half life of mirtazapine is significantly longer in men compared to women

A

false
significantly longer in women

144
Q

T or F
mirtazapine dose needs to be adjusted in renal AND hepatic impairment

A

False
but use with caution as it may accumulate

145
Q

What is the typically dosing on mirtazapine?

A

initially: 15 mg PO HS
may increase q1-2 weeks up to a max of 45mg PO HS

146
Q

What dose of mirtazapine is best to balance andepression and insonmia?

A

around 22.5mg

147
Q

what are some precautions in mirtazapine?

A

increased suicide risk if <24 years

caution:
agranulocytosis cases reported (rare)
orthostasis
hyponatremia in elderly

148
Q

What are CANMATs second line agents?

A

TCAs: amitriptyline, clomipramine, noritryptaline, etc.
SNRI: levomilnacipran
reversible MAOI: moclobemide
Serotonin reuptake inhibitor/5Ht2 antagonist: trazodone
atypical antipsychotic: quetiapine
serotonin reuptake inhibitor/5HT1a partial agonist: vilazodone

149
Q

which TCAs are available in Canada?

A

tertiary amines:
amitriptyline
clomipramine
doxepin
imipramine

secondary amines:
notritryptaline
desipramine

150
Q

what is the MOA of TCAs?

A

inhibit presynaptic 5HT and NE reuptake by inhibiting 5HT and NE transporters in CNS neurons

151
Q

T or F
tertiary amine TCAs have more NE activity while secondary amine TCAs have more 5HT activity

A

false
the opposite is true

152
Q

T or F
secondary amines are typically better tolerated

A

true

153
Q

in which situations might TCAs by useful in?

A

MDD with:
insomnia
anxiety
chronic, non-cancer pain (low back, neuropathic)
migraines/headaches
OCD (clomipramine)

154
Q

what are some CIs with TCAs?

A

acute MI, heart block, CHF

severe liver impairment

155
Q

what are some conditions where TCAs should be taken with caution?

A

any CVD
suicidal ideation (limit quantity dispensed)
QT prolongation
seizure history/risk
risk of harm associated with anticholinergic effects
elderly
bipolar disorder

156
Q

what are some AEs of TCAs

A

common: sedation, anticholinergic, CV

CV effects:
cardiotoxicity is primary mechanism of OD
orthostatic hypotension
tachycardia
right bundle branch block
QT prolongation

weight gain

tremors

sexual dysfunction

urine discolouration (amitriptyline)

rash; anticonvulsant hypersensitivity cross reaction (rare)

seizures, SIADH, fractures

157
Q

T or F
TCAs have a high risk of lethal OD

A

true

158
Q

what are some DIs on TCAs?

A

many potential interactions related to additive CNS depression, serotonin activity, neurotoxicity w lithium, seizure risk, arrhythmias

most are substances of CYP2D6
clomipramine: 1A2

159
Q

what is the MOA of trazodone?

A

weak inhibitor of SERT and NET
5HT2a and 2c (doses 200mg or more) receptor antagonism
antagonism at a1 adrenergic receptors and H1 histamine receptors

160
Q

what are some AEs of trazodone?

A

CNS: dizziness, sedation, headache, akathisia, myalgia, tremor

CV: orthostatic hypotension, syncope, prolonged QT interval, arrhythmias, CI is recent or acute MI

GI: nausea, constipation, dry mouth

rare: can cause priaprism, sexual dysfunction, seizures, suicidal ideation, serotonin syndrome, bleeding

161
Q

what is the dosing of trazodone in MDD?

A

initial: 50 mg BID taken after a meal
may be increased by 50mg/d every 3-7 days

usual dose range: 200-400mg

162
Q

what is the dosing of trazodone for a sedative?

A

50-200 mg HS

163
Q

what are some DIs of trazodone?

A

CYP 3A4 inducers or inhibitors

antihypertensives: trazodone causes hypotension

164
Q

what is the MOA of quetiapine?

A

antagonism of 5HT1 and 2, D1 and2, H1, a1 and 2

165
Q

what is the dosing of quetiapine in MDD?

A

start at 50 mg PO daily
increase to 150mg PO on day 3

usual dose range = 150-300mg/day
max daily dose for MDD = 300-600mg

166
Q

what are the reversible MAOIs available in canada?

A

moclobemide

167
Q

what is the MOA of reversible MAOIs?

A

short acting reversible inhibition of MAO-A to decrease metabolism of 5HT, NE and DA

168
Q

what are the irreversible MAOIs available in canada?

A

selegiline, phenelzine, tranycypromine

169
Q

what is the dosing of moclobemide?

A

300mg/d div into 2 doses

170
Q

at what dose of moclobemide is specificity for MAO-A lost? what are the consequences of this?

A

over 600mg/d

caution regarding tyramine is required

171
Q

which foods are rich in tyramine?

A

cheese, wine, meats, chocolate, smoked, pickled foods

172
Q

what happens in tyramine overdose?

A

increased NE leading to a hypertensive crisis

173
Q

how long before starting an MAOI must you stop taking other ADs?

A

2 weeks
fluoxetine: 5 weeks

174
Q

T or F
MAOIs must be stopped for at least 2 days prior to local or general anesthesia

A

true

175
Q

what are some AEs of moclobemide?

A

tachycardia, hypotension, sleep disturbance, agitation, nervousness, anxiety

less common: N/V/D, sexual dysfunction, anticholinergic effects

176
Q

what is the MOA of irreversible MAOIs?

A

nonspecifically irreversibly binds MAO-A and MAO-B

177
Q

what are some CIs for irreversible MAOIs?

A

pheochromocytoma
concurrent use of serotonergic or sympathomimetic agents
tyramine containing foods
d/c at least 10 days prior to surgery

178
Q

what are some important DIs of irreversible MAOIs?

A

antihistamines
opioids
carbamazepine
linezolid
methylene blue
stimulants

179
Q

which receptors/channels does ketamine inhibit?

A

NMDA
HCN channels
calcium channels
voltage gated sodium channels
BK channels

180
Q

which receptors/channels does ketamine activate?

A

opioid receptors
AMPA receptors
GABAa receptors

181
Q

what does inhibition of NMDA in ketamine use do?

A

dissociative anesthesia, amnesia
analgesia, inhibited sensory perception

182
Q

what does activation of opioid receptors in ketamine use do?

A

central antinociception; potential acute euphoric effects

183
Q

what does activation of AMPA receptors in ketamine use do?

A

rapid antidepressant effects

184
Q

which receptor is responsible for the antidepressant effect of ketamine?

A

AMPA

185
Q

what is the MOA of ketamine in MDD?

A

chronic stress theory
chronic stress induces neuronal remodeling and glial deficit –> results in decreased glutamate reuptake, increased extrasynaptic glutamate, leads to excitotoxicity –> in prefrontal cortex this leads to neuronal synaptic hypoconnectivity (decreased dendritic length and synaptic density/strength) –> decrease in certain receptors and synaptic strength

ketamine upregulates neurotrophic signaling –> increased synthesis and restoration or synaptic connectivity in the prefrontal cortex

186
Q

what is the official indication of racemic ketamine?

A

anesthesia

187
Q

what is the official indication of esketamine?

A

intranasal spray for TRD

188
Q

what is the official indication of arketamine?

A

no official indication

shows promise for more potent and longer lasing antidepressant effects with fewer side effects

189
Q

what are some AEs of ketamine at TRD doses?

A

CNS: dissociation, dizziness, feeling drunk, sedation, headache, anxiety, vertigo, cognitive impairment

GU: frequent daytime urination, dysuria, ulcerative or interstitial cystitis

dermatological: hyperhidrosis

CV: increased BP/HR

GI: nausea

190
Q

how do you manage nausea and stomach upset as a side effect of ADs?

A

divided doses/decrease SSRI dose if patient is stable
take the medication with small amount of food
ginger (?)

191
Q

which antidepressants are the worse for nausea as a side effect?

A

venlafaxine > SSRI > bupropion > moclobemide > mirtazapine

192
Q

which SSRI is linked to the highest rates of constipation?

A

paroxetine

193
Q

what is the association of AD use and suicidality across different age groups?

A

> 18: possible association
18-24: ambiguous
25-64: neutral to protective
64: possible protective effect

194
Q

which ADs have an increased frequency of sexual side effects?

A

SSRIs, SNRIs, TCAs

195
Q

what are the 5 possible management strategies for sexual side effects of ADs?

A
  1. no intervention
  2. decrease dose
  3. drug holidays or eliminating doses for a few days prior to sex
  4. using medication to adjunct sexual s/e
  5. switching AD (bupropion or mirtazapine)
196
Q

which ADs are at the highest risk for QT prolongation?

A

TCAs at highest risk

citalopram, escitalopram, venlafaxine, desvenlafaxine and mirtazapine

197
Q

T or F
serotonin syndrome is not life threatening

A

False

198
Q

what is the triad of symptoms with serotonin syndrome?

A

mental status change: confusion, agitation, lethargy, coma

autonomic hyperactivity: hyperthermia, tachycardia, mydriasis, diaphoresis, nausea and vomiting, diarrhea

neuromuscular abnormalities: hyperkinesia, hyperflexia, trismus, myclonis, cogwheel rigidity

199
Q

how long after changing a drug or dose will serotonin syndrome occur?

A

6-24 hours

200
Q

what is the treatment for serotonin syndrome?

A

supportive, d/c serotonergic agents (usually resolve within 24-72 hours)

cyproheptadine (serotonin antagonist): 12 mg once, followed by 2 mg q2h until sx resolve

201
Q

what are the causes of serotonin syndrome?

A

antidepressants: MAOIs, TCAs, venlafaxine, st Johns wort
other: linezolid, DM, meperidine, tramadol, opioids

202
Q

which are the worst ADs for discontinuation syndrome?

A

venlafaxine and paroxetine

203
Q

at what duration of treatment do you have a higher risk for discontinuation syndrome?

A

> 6-8 weeks

204
Q

which SSRI has the lowest risk of discontinuation syndrome and why?

A

fluoxetine because of its long t1/2

205
Q

what are the symptoms of discontinuation syndrome?

A

FINISH

Flu like sx: fatigue, lethargy, malaise, muscle aches
Insomnia
Nausea
Imbalance
Sensory disturbances: paresthesia, electric shock sensations
Hyperarousal: anxiety, agitation

206
Q

how long after stopping ADs does discontinuation syndrome occur?

A

24-72 hours

207
Q

how long does discontinuation last for?

A

1-2 weeks
may persist for weeks to months for some pts

208
Q

what do you do if symptoms of discontinuation syndrome occur during treatment what do you do?

A

consider restarting at original dose and taper slowly

209
Q

what can you do if a slow taper off SSRIs is not well tolerated?

A

consider substituting fluoxetine

210
Q

how often should you follow up with patients after they start ADs?

A

week 1-4: follow up q1-2 weeks
week 2-8: follow up q2-4 weeks

suicidal ideation: ensure someone is monitoring daily until resolved

211
Q

when is it best to augment vs switch in treatment nonresponse?

A

if no response: switch

if partial response: augment

212
Q

what is the definition of treatment resistant depression?

A

lack of improvement (<20% decrease in depression scores) following adequate trials of 2 or more AEs

213
Q

What options do you have with TRD?

A

switch to another AD - again

may choose to use augmentation therapy

or combining ADs

214
Q

how do you switch between SSRIs and SNRIs?

A

can switch directly
similar MOA but will still often cross taper

215
Q

How would you switch from another AD to an MAOI?

A

“wash out” period of 2 weeks
5 days in fluoxetine

216
Q

What are the first line adjunct medications options in MDD?

A

2nd generation antipsychotics (aripiprazole, quetiapine, risperidone, olanzapine, brexpiprazole)

217
Q

what are the second line adjunct medication options in MDD?

A

bupropion
mirtazapine
lithium
T3

218
Q

what are the third line adjunct medication options in MDD?

A

lisdexamphetamine
TCAs

219
Q

Describe lithium as an adjunct therapy in TRD

A

has AD effect and is one of the most investigated augmented strategies
should see response by 3-4 weeks: if patient responds continue the combo for at least 6-9 months

220
Q

describe thriiodothyronine (T3) as an adjunct therapy in TRD

A

improves and accelerates AD effects in some studies
25-50 mcg/day is recommended and rarely affects peripheral thyroid measures at this dose
recommended trial is 2 weeks at 50mcg

221
Q

describe atypical antipsychotics as adjunct therapy in TRD

A

augmentation with olanzapine, quetiapine and risperidone as well as aripiprazole and brexpiprazole
usually at lower doses than for schizophrenia or bipolar

222
Q

what are the 3 phases of treatment in MDD?

A

response
continuation
maintenance

223
Q

when does the acute phase of MDD move into the continuation phase?

A

with clinically significant improvement in sx (preferably remission of sx)

224
Q

who is maintenance phase treatment of MDD recommended for?

A

pts with chronic sx or with a hx of 3 or more depressive episodes

225
Q

what is the general rule for AD use in elderly?

A

start low, go slow and use less drugs
consider maintenance therapy

226
Q

which ADs are on the BEERS list?

A

SSRIs, SNRIs, TCA, mirtazapine

227
Q

which ADs are best in elderly?

A

duloxetine
bupropion
sertraline

228
Q

which ADs are indicated for children <18?

A

none approved by HC
FDA: fluoxetine, escitalopram
off label: sertraline, citalopram

229
Q

which ADs should be avoided in children?

A

SNRIs and TCAs

230
Q

what is the preferred treatment of mild depression in pregnancy?

A

psychotherapy

231
Q

what is the treatment of moderate to severe treatment of depression in pregnancy?

A

use lowest effective dose
agents with few metabolites, higher protein binding, few DIs

232
Q

which ADs are used in pregnancy?

A

SSRIs first: most safely with sertraline, citalopram and escitalopram
paroxetine has risk of cardiac malformations of fetus

233
Q

which ADs are used during breast feeding?

A

citalopram, nortriptyline, sertraline and paroxetine are first line
breast feeding not a CI to any AD

PHAR 253 (6 decks)

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