1
Q
Anxious Distress Specifier for Bipolar Disorder or MDD
A
Criteria for mania/hypomania/MDE + >/= 2 of:
-Feeling keyed up or tense
-Feeling unusually restless
-Difficulty concentrating b/c of worry
-Fear that something awful may happen
-Feeling that the individual may lose control
*EXCLUDES sleep issues, irritability, muscle tension (from GAD dx crit)
2
Q
Mixed Features Specifier of Manic/Hypomanic Episode
A
Criteria for mania/hypomania + >/= 3 of:
-Prominent dysphoria or depressed mood
-Anhedonia
-Psychomotor retardation
-Fatigue or loss of energy
-Feelings of worthlessness or excessive or inappropriate guilt
-Recurrent thoughts of death, recurrent SI w/o plan, suicide attempt, plan for suicide
*EXCLUDES: Concentration, Appetite (from MDE crit)
3
Q
Mixed Features Specifier of MDE
A
Criteria for MDE met + >/= 3 of:
-Elevated or expansive mood
-Inflated self-esteem OR grandiosity
-Talkativeness or pressured speech
-Flight of ideas OR subjective experience that thoughts are racing
-Increased energy OR goal-directed activity (socially, work, school, sexual)
-Impulsivity
-Decreased need for sleep
*EXCLUDES: Distractibility (from mania crit)
4
Q
Rapid Cycling Specifier for Bipolar Disorder
A
Presence of at least FOUR mood episodes in the previous 12 months that meet criteria for manic, hypomanic, or MDE in BPI OR that meet criteria for hypomanic or MDE in BPII
*Episodes are demarcated by either partial or full remissions of at least 2mos OR a switch to an episode of the opposite polarity
5
Q
Duration of Assessment Orders
A
- 5 to 30 days
- Can be extended by 30 days, to a maximum of 60 days total
6
Q
Section of Criminal Code related to Fitness to Stand Trial
A
Section 2
7
Q
Section of Criminal Code related to Not Criminally Responsible due to a Mental Disorder
A
Section 16
8
Q
Melancholic Features Specifier
(DSM 5TR)
A
> /= 1 of:
-Loss of pleasure in all, or almost all, activities
-Lack of reactivity to usually pleasurable stimuli
AND >/= 3 of:
-Profound despair, despondency or empty mood
-Anorexia or weight loss
-Diurnal variation (depressed mood worse in the morning)
-Early morning awakenings
-Excessive or inappropriate guilt
-Psychomotor agitation or retardation
9
Q
With Atypical Features Specifier
(DSM 5TR)
A
- Mood reactivity
AND >/= 2 of:
-Hypersomnia
-Increased appetite or weight gain
-Leaden paralysis
-Longstanding pattern of interpersonal rejection sensitivity
10
Q
With Peripartum Onset (MDE, mania, hypomania)
(DSM 5TR)
A
Onset of a mood episode during pregnancy or during the 4wks following delivery
11
Q
With Seasonal Pattern (MDE, mania, hypomania)
(DSM 5TR)
A
A) There has been a regular temporal relationship b/t the onset of manic/hypomanic/MDE and a particular time of year in BPI or BPII
B) Full remissions (or a change in polarity) also occur at a characteristic time of year
C) In the last 2yrs, the episodes have demonstrated a seasonal relationship and NO nonseasonal episodes of that polarity have occurred
12
Q
Factors A/W Increased Risk of Suicide Attempts in Bipolar Disorder
(2018 CANMAT BD Guidelines)
A
-Female
-Younger; older (higher lethality)
-Racial minorities (youth only)
-Single, divorced, single parents
-Younger age of onset
-Predominant depressed polarity
-Current depressed or mixed episode
-Other episode characteristics: mixed features, greater number/severity of episodes, rapid cycling, anxiety, atypical features, SI
-Psychiatric comorbidities: SUD, cigarette smoking, coffee intake, anxiety d/os, eating d/os, BPD
-Obesity, high BMI
-First-degree FHx of mood d/os, bipolar d/o or suicide
-Prior suicide attempts
-Childhood abuse, early life stress
-Psychosocial precipitants - interpersonal or occupational probs, bereavement, social isolation
-Sexual dysfunction
13
Q
Factors A/W Increased Risk of Suicide Completion in Bipolar Disorder
(2018 CANMAT BD Guidelines)
A
-Male*
-First degree FHx of suicide*
-Older (higher ratio of deaths/attempts)
-Current depressed, mixed or manic w/ psychotic episode
-Prior suicide attempt
-Comorbid anxiety d/o
-Hopelessness
-Psychomotor agitation
-First-degree FHx of mood d/os, bipolar d/o or suicide
-Psychosocial precipitants
*** - guideline also says that only these 2 are actually associated with suicide deaths
14
Q
Factors associated with the eventual development of BP in youth dx with MDD
(2018 CANMAT BD Guidelines)
A
-FHx of BP
-Earlier age of onset
-Presence of psychotic sxs
15
Q
Antidepressants with lower risk of manic switch
(2018 CANMAT BD Guidelines)
A
-SSRIs
-Bupropion
16
Q
Treatment for AUD comorbid with BD
(2018 CANMAT BD Guidelines)
A
Combination lithium + divalproex
17
Q
Treatment of Stimulant Use Disorder (cocaine, amphetamine, methamphetamine) comorbid with BD
(2018 CANMAT BD Guidelines)
A
-Adjunctive Citicoline (level 2)
-Quetiapine (level 3)
18
Q
Most common personality disorder comorbid with BD
(2018 CANMAT BD Guidelines)
A
OCPD
19
Q
Symptomatic relief for Borderline Personality Disorder comorbid with BD
(2012 CANMAT Task Force/
2018 CANMAT BP Guidelines)
A
-Divalproex (level 3)
-Lamotrigine (level 4)
20
Q
GAD and Panic Disorder comorbid with BD - tx
(2018 CANMAT BP Guidelines)
A
Quetiapine monotherapy
(level 2)
21
Q
Treatment of ADHD comorbid with BD
A
-Amphetamine mixed salts (lv 3)
-Methylphenidate (lv 3)
-Atomoxetine (lv 4)
-Bupropion (lv 4)
-Lisdexamphetamine (lv 4)
22
Q
Baseline laboratory investigations in pts with BD
A
-CBC
-Fasting glucose
-Fasting lipid profile (TC, vLDL, LDL, HDL, TG)
-Plts
-Lytes + calcium
-Liver enzymes
-Serum bilirubin
-PT & PTT
-U/A
-Urine tox for substance use
-Creatinine
-24hr creatinine clearance (if hx of renal disease)
-TSH
-ECG (>40yrs or if indicated)
-Preg test (if relevant)
-Prolactin
23
Q
Lithium treatment in BD is a/w a reduced risk of what comorbid medical conditions?
A
-Stroke
-Cancer
-Dementia
24
Q
What mood stabilizers affect the efficacy of OCP?
A
-Lamotrigine
-Carbamazepine
25
Monitoring for lithium treatment
At 6mos then annually:
-Thyroid function
-Kidney function (eGFR, creatinine)
-Plasma calcium (for hyperparathyroidism)
26
Monitoring for valproic acid treatment
Every 3-6mos during first year, then annually:
-LFTs
-CBC (hematology profile)
-Menstrual hx (evaluate for PCOS)
27
What should you educate patients on (risk) re lamotrigine and carbamazepine?
-Risk of skin rashes, especially Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
28
Monitoring for antypical antipsychotics
Monthly for first 3mos, then every 3mos thereafter:
-Weight
At 3mo, 6mo then annually:
-Lipid profile
-Fasting glucose
-Blood pressure
29
Monitoring lithium levels
A) When to draw?
B) How frequently to draw?
C) Targets
A) 12hrs post-dose (lithium trough); should be drawn 5 days after dose adjustment
B) Two consecutive serum levels in acute phase, then every 3-6mos, or more frequently
C) Targets:
Adult Acute - 0.8 - 1.2
Adult Maintenance 0.6 - 1
Older Adult Acute - 0.4 - 0.8
30
Monitoring valproic acid levels
A) When to draw?
B) How frequently to draw?
C) Targets
A) 12hrs post-dose (valproic acid trough); should be drawn 3-5 days after dose titration
B) Two consecutive serum levels in acute phase, then every 3-6mos or more frequently
C) Target: 350 - 700
31
Lithium is associated with what renal concerns?
-Nephrogenic diabetes insipidus (NDI)
-Chronic tubulointerstitial nephropathy
-Acute tubular necrosis
32
Factors leading to increase susceptibility of decreased GFR and CKI with lithium treatment
-Higher plasma lithium level
-Multiple daily dosing
-Concurrent medications (NSAIDs, ARBs, ACEIs, diuretics)
-Somatic illnesses (DM, CAD, HTN)
-Older age
-Lithium toxicity
33
When to consult nephrology in context of lithium treatment?
-Rapidly declining eGFR (>5 in 1yr; >10 in 5yrs)
-If eGFR falls below 45 in two consecutive readings
-If clinician is concerned
34
New onset neurological sxs in a patient on valproic acid should raise suspicion for?
Hyperammonaemic encephalopathy
*Discontinuation of valproic acid is critical to prevent morbidity and mortality in these cases
35
First-line treatment for acute mania
Acute mania first-line monotherapy:
-Lithium
-Quetiapine
-Divalproex
-Asenapine
-Aripiprazole
-Paliperidone (>6mg)
-Risperidone
-Cariprazine
*Loud Queens Do Acid And Party Really Crazy*
Acute mania first-line combo therapy:
-Quetiapine + Li/DVP
-Aripiprazole + Li/DVP
-Risperidone + Li/DVP
-Asenapine + Li/DVP
*Queens Aren't Really Angels*
36
Psychosocial interventions for bipolar disorder
MAINTENANCE:
-Psychoeducation (first-line)
-CBT and family-focused therapy are second-line
NO first line treatments for acute mania or acute depression
ACUTE DEPRESSION:
-CBT and FFT are second-line adjunctive treatments
37
Second-line treatment for acute mania
-Olanzapine
-Carbamazepine
-Olanzapine + Li/DVP
-Lithium + DVP
-Ziprasidone
-Haloperidol
-ECT
38
First-line treatment for acute bipolar I depression
-Quetiapine
-Lurasidone + Li/DVP
-Lithium
-Lamotrigine
-Carbamazepine
-Lurasidone (adjunct)
*Queens Lie Lots Leaving Crowds Laughing*
39
Second-line treatment for acute bipolar I depression
-Divalproex
-SSRIs/bupropion (adjunct)
-ECT
-Olanzapine-fluoxetine
-Lumateperone
40
First-line treatment for maintenance of bipolar I
-Lithium
-Quetiapine
-Divalproex
-Lamotrigine
-Asenapine
-Quetiapine + Li/DVP
-Aripiprazole + Li/DVP
-Aripiprazole PO
-Aripiprazole LAI
*Loud Queens Drink Lemonade And Quietly Add Alcohol*
41
Second-line treatment for maintenance of bipolar I
-Olanzapine
-Risperidone LAI
-Risperidone LAI (adjunct)
-Carbamazepine
-Paliperidone (>6mg)
-Lurasidone + L/DVP
-Ziprasidone + Li/DVP
42
First-line treatment for bipolar II depression
Quetiapine
43
Second-line treatment for bipolar II depression
-Lithium
-Lamotrigine
-Bupropion (adjunct)
-ECT
-Sertraline
-Venlafaxine
-Lumateperone
44
First-line maintenance for bipolar II
-Quetiapine
-Lithium
-Lamotrigine
45
Second-line maintenance for bipolar II
-Venlafaxine
46
First-line treatment for mania in CAP
-Lithium
-Quetiapine
-Asenapine
-Aripiprazole
-Risperidone
47
First-line treatment for depression in bipolar d/o CAP
Lurasidone
48
First-line maintenance for bipolar d/o CAP
-Aripiprazole
-Lithium
-Divalproex
49
First-line treatment for mania in geri
-Lithium
-Divalproex
50
First-line treatment for depression in bipolar d/o geri
-Quetiapine
-Lurasidone
-?try lithium or lamotragine before quetiapine
-ECT should be considered for treatment-resistant depression, suicidal patients, patients with inadequate food or fluid intake
51
First-line maintenance in bipolar d/o geri
-Lithium
-Lamotrigine
-Divalproex
52
What do you have to monitor in carbamazepine treatment
-Skin rashes
-Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
-Monitor serum sodium annually due to risk of hyponatremia
53
Levels of Evidence in CANMAT Depression Guidelines
Level 1 - High quality meta analysis w/ narrow CIs and/or 2 or more RCTs of adequate sample size, preferably placebo-controlled
Level 2 - Lower-quality meta analysis w/ wide CIs and/or 1 or more RCTs w/ adequate sample size
Level 3 - Small-sample RCTs or nonrandomized, controlled prospective studies or high-quality retrospective studies
Level 4 - Expert opinion/consensus
54
Lines of Treatment in CANMAT Depression Guidelines
First-Line - Level 1 or 2 evidence + clinical support
Second-Line - Level 3 evidence or higher + clinical support
Third-Line - Level 4 evidence or higher + clinical support
55
Lifetime prevalence of MDD
12%
56
Past year prevalence of MDD
5%
57
Risk factors for MDD
Static risk factors:
-Female sex
-Youth and middle age
-FHx of mood d/os
-Hx of ACEs (emotional abuse, parental loss, physical neglect, bullying)
-Death of a spouse
Dynamic risk factors:
-Periods of hormonal changes (e.g. puberty, pregnancy, postpartum, perimenopause)
-Alcohol use
-Cannabis use (esp during adolescence)
-Comorbid physical illnesses (chronic pain, IBS, DM, obesity, cancer, CVD, sleep d/os)
-Comorbid psychiatric illnesses (esp anxiety d/os)
-Sedentary lifestyle
-Shift work
-Screen time
-Bereavement
-Stressful life events
-Income inequality
-Gender dysphoria
58
Who should be screened for depression?
CANMAT recommends depression screening, using a validated scale, in primary and secondary care settings for those with risk factors - IF there are resources available for subsequent diagnostic assessment and treatment for those who screen positive
59
What depression screening tools should be used?
Patient Health Questionnaire (PHQ)
PHQ-2 followed by, if positive (>/=2), the PHQ-9 (>/= 10)
PHQ-2 asks about:
-depressed mood/hopelessnes/feeling down AND
-anhedonia/lack of interest over the past 2wks
60
What should an assessment for MDD include?
-Personalized assessment based on DSM5TR
-Collateral
-Medical Hx
-Physical Exam
-Bloodwork: CBC, TSH (Testost and VitD if indicated)
-Workup if indicated:
-->ECG --> if CVD and meds causing QTc prolongation
-->Neuroimaging --> if neurological signs, sudden change in personality/behaviour/mood, late-onset, new or persistent cog impairment
61
How long are the phases of treatment for MDD?
-Acute phase --> 8-16wks, until sx remission
-Maintenance phase --> 6-24mos or longer
62
What is the risk of suicide attempts for pts with MDD compared to general population?
5x higher
63
When is risk of suicide in MDD higher in relation to pharmacotherapy?
The month after initiation AND discontinuation
64
What are some potentially modifiable factors a/w higher suicide risk in MDD
Symptoms and life events:
-SI w/ a well-developed plan and/or intent to act
-Hopelessness
-Anxiety
-Impulsivity
-Psychoti sxs
-Stressful life events (e.g. financial stress and victimization)
Comorbid conditions:
-PTSD
-SUD (esp. AUD)
-Personality d/os (esp. cluster B)
-Sleep d/os
-Chronic painful medical conditions (e.g. arthritis, migraines)
65
Describe lifestyle interventions for MDD
First-Line:
-Supervised exercise - low-mod intensity for 30-40mins 3-4x/wk for at least 9wks (MILD MDE)
-Light therapy - 10,000 lux white light x30mins/day (MDEs w/ seasonal patern)
Second-Line:
-Light therapy (mild non-seasonal MDE)
-Adj exercise (mod MDE)
-Adj light therapy (mod non-seasonal MDE)
-Adj sleep hygiene + CBTi
Third-Line:
-Adj healthy diet
-Adj Mediterranean diet
-Adj sleep deprivation (wake therapy)
66
When to do psychotherapy vs pharmacotherapy for MDD
Mild MDE w/ low safety risk
--> psychotherapy
Mod MDE w/ mod safety risk
--> psychotherapy OR pharmacotherapy
--> can do both
--> ADs more efficacious for low mood, SI, anxiety, somatic sxs
--> psychotherapy more efficacious at 6- and 12-mo F/U
Severe MDE w/o psychotic features
--> psychotherapy + pharmacotherapy
Severe MDE w/ psychotic features
--> antidepressant + antipsychotic
--> psychotherapy deferred until psychotic sxs resolve
Most severe MDE and/or life-threatening situations (e.g. severe suicide risk, physical deterioration)
--> ECT should be considered as first-choice option
67
Psychotherapies for MDD
First-line:
-CBT
-IPT
-BA
Second-line:
-Short-term psychodynamic
-MBCT
-Cognitive behavioural analysis system of psychotherapy (CBASP)
-Problem-solving therapy
Third-line:
-ACT
-Long-term psychodynamic psychotherapy
-Metacognitive therapy
-MI
68
How many sessions of psychotherapy should you receive for MDD? Frequency?
12-16 session
Twice weekly sessions for CBT and IPT show improved outcomes compared to once weekly
-there is little support for the efficacy of psychological treatment delivered less than once per week
69
When to assess for SEs with antidepressants in MDD
Before prescribing and w/i 2wks of starting
70
8 antidepressants found to be most efficacious
-Agomelatine
-Bupropion
-Escitalopram
-Paroxetine
-Mirtazapine
-Sertraline
-Venlafaxine XR
-Vortioxetine
71
First line medications for MDD
-SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
-SNRIs (venlafaxine XR, levomilnacepran, duloxetine, desvenlafaxine)
-Bupropion
-Mirtazapine
-Vortioxetine
-Vilazodone
-Agomelatine (not in Canada)
-Milnascipran (not in Canada)
-Mianserin (not in Canada)
72
Second line medications for MDD
-TCAs (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine)
-Reversible MAOI (moclobemide)
-Trazodone
-Quetiapine
-Dextromethorphan-bupropion (not in Canada)
-Nefazodone (not in Canada)
-Selegiline transdermal (not in Canada)
73
Third line medications for MDD
-Irreversible MAOIs (tranylcypromine, phenelzine)
-Reboxetine (not in Canada)
74
What antidepressant is worst for causing nausea
Venlafaxine XR
(second to milnacipran, which is not in Canada)
30% or higher
75
Antidepressants with greatest drug-drug interaction concerns
-Fluoxetine
-Fluvoxamine
-Paroxetine
76
Antidepressant with risk of QTc prolongation
Citalopram
77
Normal QTc intervals
Male: < 450
Female: < 460
78
Antidepressants with lower rates of sexual side effects
-Bupropion
-Mirtazapine
-Vortioxetine
-Vilazodone
-Desvenlafaxine
-Agomelatine
79
Medication options for MDE with mixed features
-Involve a psychiatrist
-General first-line from guidelines
-Second-line --> lurasidone
80
Antidepressants with superior efficacy for cognitive sxs of depression (problems with conc,memory and executive fxn)
First-line --> Vortioxetine
Second-line --> Bupropion, Duloxetine, SSRIs
81
Antidepressants with superior efficacy for comorbid pain
-Duloxetine
-SNRIs
82
Is there an association b/t antidepressant use and suicide?
-Acute tx w/ AD is a/w increased risk of suicidal behaviours among young adults below age 25
-Acute tx w/ AD is a/w decreased risk of suicidal behaviours among those age 65 and older
-No effect on suicidal behaviour for adults aged 25-65
83
When is suicidal behaviour highest in association with ADs?
Suicidal behaviour is highest in the month before AD initiation, remains high in the month after AD initiation and then declines
The month after d/c an AD is also a/w elevated risk of suicidal behaviour
84
Increased risk of what with SSRIs?
-Fractures and falls in the elderly
-GI bleeds if combined w/ NSAIDS (can be mitigated w/ PPIs)
-Hyponatremia if combined w/ diuretics, esp in the elderly
Rare but serious adverse effect of ADs is drug-induced liver injury, which can occur up to 6mo after initiation
-agomelatine, bupropion, duloxetine and nefazodone are more likely to cause this
-citalopram and escitalopram are least likely
85
Increased risk of what with SNRIs?
-Increased BP
-GI bleeds if combined w/ NSAIDS (can be mitigated w/ PPIs)
-Hyponatremia if combined w/ diuretics, esp in the elderly
Rare but serious adverse effect of ADs is drug-induced liver injury, which can occur up to 6mo after initiation
-agomelatine, bupropion, duloxetine and nefazodone are more likely to cause this
-citalopram and escitalopram are least likely
86
Impact on Fluoxetine on CYP isoenzymes
Potent 2D6 inhibitor
87
Impact on Paroxetine on CYP isoenzymes
Potent 2D6 inhibitor
88
Impact on Fluvoxamine on CYP isoenzymes
Potent 1A2, 2C19 & 3A4 inhibitor
89
Why are MAOIs third-line for depression
Can cause serious life-threatening interactions
--> serotonin syndrome and hypertensive crisus
--> if combined with detromethorphan products, SSRIs, St. John's wart, foods containing high levels of tyramine (cured meats, mature cheeses, fermented products)
90
What are some CAM tx options for depression?
First-Line:
-St.John's wort for mild MDE
Second-line:
-Acupuncture for mild MDE
-St. John's wort for mod MDE
-Adj acupuncture for mod MDE
-Adj folic acid (L-methyl folate) for mild-mod MDE
Third-line:
-DHEA for mild MDE
-Omega-3 FAs for mild MDE
-Saffron, lavendar or roseroot for mild MDE
-Adj SAM-e for mild-mod MDE
91
Concerns with St. John's wort
-Potent 3A4 inducer
-1A2 inducer
-Can cause serotonin syndrome when combined with serotonergic agents
92
Are digital health interventions (DHIs) recommended for MDD?
First line:
-Guided iCBT DHIs for mild MDE
-Adj guided iCBT DHIs for mild-mod MDE
Second line:
-Adj self-directed DHIs for mild-mod MDE, when supported by clinicians
-Adj guided iBA DHIs for mild-mod MDE
Third line:
-Self-directed DHIs or mild MDE when no other clinical interventions are available
Insufficient evidence:
-Chatbots and conversational agents
93
Explain early improvement, response and remission according to CANMAT guidelines
Early improvement --> Reduction of symptoms on symptom scale by 20% or greater w/i 2-4wks after tx initiation
Response --> 50% or greater improvement
Remission --> Indicated by a specific threshold score for each scale (e.g. 7 or less on HAM-D); DSM-5 defines remission as the absence or near absence of sxs for at least 2mo
94
How long to take medication for MDD after achieving remission?
Continue for 6-12mos after sx remission
95
What are the most robust risk factors for recurrence of a MDE?
-Residual sxs
-History of childhood maltreatment or abuse
Other, less robust, risk factors for recurrence are:
-Poor social support
-Chronic depressive sxs
-Greater severity of depressive episodes
-Presence of medical comorbidities (psychiatric or nonpsychiatric)
-Greater # of previous episodes
-Persistent stressful life events
96
What are the symptoms of discontinuation syndrome?
-Flu-like sxs
-Insomnia
-Nausea
-Imbalance
-Sensory disturbances
-Hyperarousal
FINISH mnemonic
97
Antidepressants with highest risk of discontinuation syndrome
-Paroxetine
-Venlafaxine
98
What factors contribute to a poor response to initial treatment in MDD
Clinical factors:
-Incorrect dx
-Demographic and illness characteristics (e.g. older age, female, younger age of onset, higher severity, increased number/duration of episodes, trauma hx)
-Psychiatric comorbidities (e.g. ADHD, personality d/os, SUDs, anxiety d/os)
-Nonpsychiatric comorbiditis (e.g. anemia, sleep apnea, obesity, thyroid disease)
-Acute or chronic stressors
Treatment factors:
-Inadequate dose of tx
-Inadequate duration of tx
-SEs masking as sxs
-Poor adherence to tx
-Pharmacogenetic variability (e.g. rapid or slow metabolism of drugs)
98
What to do when there is poor response to first tx in MDD?
-Re-evaluate the dx
-Assess comorbidities
-Assess tx adherence
-May consider lab investigations to r/o medical factors
-May consider pharmacogenetic testing
Strategies include:
-Optimizing dose --> important first step
-Switching to another AD
-Adding an adjunctive medication
-Incorporating psychological and/or neuromodulation txs
99
When to switch to another medication vs add and ajunctive medication in MDD?
-Switching should be considered first when there is no response to the initial AD or when the first medication has troublesome SEs
-Adjunctive strategies should be considered first when there is a partial response to the initial AD and there are minimal or no tolerability issues with the first medication
100
When are adjunctive treatment options for MDD?
First-line:
-Aripiprazole (2-10mg)
-Brexpiprazle (0.5-2mg)
Second-line:
-Bupropion (150-450mg)
-Quetiapine XR (150-300mg)
-Olanzapine (2.5-10mg)
-Risperidone (1-3mg)
-Cariprazine (1.5-3mg)
-Mirtazapine/Miancerin (30-60,g/30-90mg)
-Intranasal esketamine (56-84mg)
-IV racemic ketamine (0.5-1mg/kg)
-Lithium (600-1200mg; therapeutic serum level 0.5-0.8)
-Modafinil (100-400mg)
-Triiodothyronine (25-50mcg)
Third-line:
-Other ADs, including TCAs
-Stimulants
-Lamotrigine (100-300mg)
-Pramipexole (1-2mg BID)
-Ziprasidone (20-80mg BID)
-Non-IV racemic ketamine
101
What is the response rate for ECT for MDD?
65-75%
102
What patient population/symptom constellation is ECT most effective for in MDD
-Older patients
-Psychotic features
-Catatonic features
103
Timeline/logistics of ECT for MDD
-6-12 sessions 2-3x/wk
104
What medications cause issues with ECT?
Lithium worsens cognitive side effects
*RC MCQ*
Cannabis also worsens cognitive SEs
Antidepressants should be continued during ECT as it improves outcomes
105
Rate of recurrence for MDD with ECT
60-80% at 6mo F/U
106
What medications are superior for relapse prevention after ECT?
Lithium with either nortriptyline or venlafaxine XR
*RC MCQ, repeated*
107
Recommendations for ECT from CANMAT
First-line:
-Brief pulse, bifrontal (1.5x sz threshold) *RC MCQ*
-Brief pulse, RUL (6x sz threshold) *RC MCQ*
-Ultrabrief pulse, RUL (6x sz threshold)
Secon-line:
-Brief pulse, bitemporal (1.5x sz threshold)
-Ultrabrief pulse, bifrontal (1.5x sz threshold)
108
Timeline/logistics of rTMS for MDD
20-40min sessions daily, 5 days/wk for 4-6wks
109
rTMS response rate for MDD
40-50%
110
Placement of high vs low frequency
High-frequency --> LEFT DLPFC
Low-frequency --> RIGHT DLPFC
DLPFC = dorsolateral prefrontal cortex
111
What clinical features are a/w lower remission rates from rTMS
-Higher baseline severity of depressive and anxious sxs
-Greater # of failed AD trials
112
Types of Theta Burst Stimulation
--> Intermittent TBS (iTBS) --> INCREASES cortical excitability
-2s train of TBS q10s for 190s
--> Continuous TBS (cTBS) --> DECREASES cortical excitability
-continuous 40s train
113
What is transcranial direct current stimulation?
Modulates cortical excitability through the delivery of a constant, weak electrical current via surface scalp electrodes
-can be delivered at home
Current evidence DOES NOT SUPPORT use of tDCS for those w/ severe depression or DTD
Considered third-line adjunctive for mild-mod MDE
114
What is magnetic seizure therapy?
MST was developed to mitigate cognitive SEs of ECT. Instead of placing electrodes directly on the scalp as with ECT, MST uses vertex of frontal placement of single or paired circular coils to deliver transcranial magnetic stimulation
-the high intensity and frequency of TSM induces an electrical field and elicits a generalized seizure
MST is considered INVESTIGATIONAL as per CANMAT due to limited evidence
115
Recommendations for rTMS from CANMAT
First-line:
-iTBS to LEFT DLPFC
-High-frequency rTMS to LEFT DLPFC
-Low-frequency rTMS to RIGHT DLPFC
Second-line:
-Sequential bilateral rTMS to DLPFC (right low frequency then left high frequency)
-Accelerated iTBS to LEFT DLPFC
-Sequential bilateral TBS to DLPFC (right continuous then left intermittent TBS)
116
What does vagus nerve stimulation involve?
-Surgically implanting an electrode around the LEFT vagus nerve in the mid-cervical neck region, connected to a pulse generator implanted subcutaneously in the chest wall
117
What area does vagus nerve stimulation target?
-Low-level intermittent electrical stimulation of the left vagus nerve is believed to stimulate the...
NUCLEUS TRACTUS SOLITARIUS
118
What areas are frequently studied in deep brain stimulation
-Subcallosal cingulate cortex
-Ventral capsule/striatum
-Nucleus accumbens
-Anterior limb of the internal capsule
-Medial forebrain bundle
119
Summary of recommendations for neuromodulation treatments by CANMAT
First-line:
-ECT for severe MDE (w/ severe psychotic or catatonic features, severe SI or deteriorating physical condition)
-rTMS for TRD
Second-line:
-ECT for DTD
Third-line:
-Adjunctive tDCS for mild-mod MDE
-VNS for DTD
Investigational:
-DBS for DTD
-MST for DTD
120
Features of depression that increase suspicion of bipolar disorder?
-Earlier age of onset (<25y/o)
-Highly recurrent depressive episodes (>/= 5)
-FHx of BP
-Depression w/ psychotic features
-Psychomotor retardation
-Psychomotor agitation
-Lability of mood
-Irritability
-Racing thoughts
-Pathological guilt
-Atypical features (leaden paralysis; hyperphagia; hypersomnia; rejection sensitivity)
-Post-partum depression and psychosis
-Past suicide attempts
-Antidepressant-induced manic sxs
-Rapid cycling
121
Rapid cycling is a/w...
-Hypothyroidism
-Antidepressant Use
-Substance Use
122
How long do the effects of IV ketamine take for MDD, and how long do they last?
A single infusion of IV ketamine has rapid antidepressant effects that peak w/i 24hrs and last 3-7 days.
Relapse usually occurs w/i 10 days
123
What are the recommended assessments prior to initiation of ketamine tx?
-Physical exam
-Weight & BMI
-Vital signs (temp, HR, BP)
-ECG
-Urinalysis
-UDS (if indicated by hx or PE)
-Outcome rating scales for measurement-based care
-Cognitive testing (if indicated by hx or PE)
-Informed consent
124
What is monitored during ketamine infusion, and how often?
Measured at baseline, midway through infusion, infusion endpoint, and 1hr post-infusion:
-HR
-BP
-RR
-Oximetry
-Dissociative sxs
125
Who should not receive ketamine tx?
Pts with serious risk of HTN, such as those with increased intracranial pressure or increased intraocular pressure
Relative contraindications...
-Psychotic sxs
-Poorly controlled HTN
-Unstable medical conditions (e.g. cardiovascular or respiratory disease)
-Substance use/dependence
-Pregnancy
-Breastfeeding
126
What cognitive dysfunctions are a/w depressive disorders?
Disturbances in...
-Attention
-Memory
-Processing speed
-Executive functioning
127
Perinatal maternal depression is a/w what adverse outcomes in children?
-Problems w/ emotional regulation
-Internalizing d/os
-Insecure attachment
-Adolescent depression
-Negative effects on cognitive development
-Hyperactivity
-Reduced social competence
-Behavioural disorders
128
Patient with MDE has cognitive dysfxn as residual sx. What medication do you choose?
First-line:
-Vortioxetine
Second-line:
-Bupropion
-Duloxetine
-SSRIs
129
Patient w/ MDE has sleep disturbance as residual sx. What do you choose?
First-line:
-Agomelatine
Second-line:
-Mirtazapine
-Quetiapine-XR
-Trazodone
130
Patient w/ MDE has somatic symptoms as residual symptoms. What medication do you choose?
First-line:
-Duloxetine (pain)
-Bupropion (fatigue)
Second-line:
-Duloxetine (fatigue)
-Other SNRIs (pain)
-SSRIs (fatigue)
131
What ADs have efficacy for superior response?
-Agomelatine
-Bupropion
-Escitalopram
-Mirtazapine
-Paroxetine
-Sertraline
-Venlafaxine-XR
-Vortioxetine
132
How does rTMS compare to ECT?
-rTMS is less effective than ECT, especially for pts w/ psychosis
-rTMS response rates are poor in pts who failed ECT
Takeaway:
-rTMS should be considered prior to pursuing ECT
-Pts who have not responded to ECT are unlikely to respond to rTMS
133
Most common adverse effect of rTMS
-Scalp pain during procedure (40%)
-Transient headache after stimulation (30%)
134
Most serious rTMS adverse effect
Seizure induction
Seizure incidence w/ rTMS is ~0.01-0.1%, compared to 0.1-0.6% on ADs and 0.07-0.09% spontaneous incidence in the gen pop
135
Contraindication to rTMS
Absolute contraindications:
-Seizure history (considered absolute CI by most rTMS practitioners)
-Metallic hardware (e.g. cochlear implants; aneurysm clips, electrodes) anywhere in the head, except the mouth
Relative contraindicatons:
-Cardiac pacemakers
-Implantable defibrillator
-Hx of epilepsy
-Presence of brain lesion (vascular, traumatic, neoplastic, infectious, metabolic)
136
Absolute contraindications for ECT
None
137
Relative contraindications for ECT
-Increased intracranial pressure
-Unstable vascular aneurysm or malformation
-Recent MI
-Recent cerebral hemorrhage
-Space occupying cerebral lesion
-Pheochromocytoma
-Class 4 or 5 anesthesia risk
138
Most common maintenance/continuation ECT scheduling/frequency
After course of ECT...
-Weekly ECT for 4wks, then
-Biweekly ECT for 8wks, then
-Monthly thereafter
139
Protocol for light therapy, and CANMAT recommendations
10,000 lux for 30mins each morning for up to 6wks
First-line monotherapy for MDE w/ seasonal patter
Second-line monotherapy for nonseasonal MDE mild severity
Second-line augment for nonseasonal MDE of moderate severity
140
MOA of light therapy for depression
-Alteration of circadian rhythms
-Modulation of serotonin and catecholamine systems
141
Protocol for sleep deprivation (wake therapy) for depression and CANMAT recommendation
Sleep deprivation for up to 40hrs ("total sleep deprivation")
Sleep deprivation occurs 2-3x in one week, typically total sleep deprivation interspersed between partial sleep deprivation (allowed to sleep for 3-4hrs) and normal (recovery) sleep
Third-line adjunct
142
MOA of sleep deprivation (wake therapy) for depression
-Increased activity of all neurotransmitters
-Synaptic potentiation
-Glial signalling
143
MDD in children and adolescents --> CANMAT tx recommendations
Generic MDE
-1st line --> CBT or IPT (internet-based if no in-person)
-2nd line --> FLUOXETINE, Escitalopram, Sertraline, Citalopram
-3rd line --> Venlafaxine, TCA (only for >12yo)
Nonresponse
-1st line --> Add SSRI to psychotherapy
-2nd line --> Switch to another SSRI (if unresponsive to fluoxetine)
-3rd line --> Venlafaxine, TCA (only for >12yo)
Tx Resistant
-1st line --> Psychotherapy + SSRI
-2nd line --> Switch to another SSRI (if unresponsive to fluoxetine)
-3rd line --> Venlafaxine, TCA, Neurostimulation (ECT, rTMS) (only for >12yo)
***suicide/adverse events must be monitored during SSRI tx --> weekly F/U during first 4wks
***citalopram not recommended for pts w/ congenital long QT syndrome, congenital heart disease, or hepatic impairment
144
Dosing medication for children and adolescents w/ MDE schedule
-Initial dose is at lower end of therapeutic range
-Maintain initial dose for 4wks
-If only partial response by 12wks, at adequate dose, should consider changing tx
145
How long should adults take their medications in the context of an MDE?
Take for 6-12mos after sx remission
If risk factors for recurrence (see below), then take for >/=2yrs
Risk factors for recurrence:
-Frequent, recurrent episodes
-Severe episodes (psychosis, suicidality, severe impairment)
-Residual sxs
-Difficult-to-treat episodes
-Presence of comorbid psychiatric or other medical conditions
-Chronic episodes
146
How long should children and adolescents take their medications re MDE?
Children and adolescents should continue their AD for 6-12mos following sx remission
For pts w/ hx of 2 depressive episodes or 1 severe or chronic episode, AD should be continued for >/=1yr
147
Prevalence of women having unipolar MDE during pregnancy
7.5%
148
Risks of untreated MDE in pregnancy/postpartum
-Poorer nutrition
-Poorer prenatal care
-Smoking
-Substance use
-Obstetrical complications
-Neonates small for gestational age
-NICU admissions
-Infant sleep disturbance
-Impairments in mother-infant bonding
-Mild developmental delay
-Eventual cognitive, behavioural or emotional problems in the offspring
149
Treatment recommendations for MDE during pregnancy (CANMAT 2016)
First-line --> CBT or IPT
Second-line --> Citalopram, Escitalopram, Sertraline
Third-line --> Structured exercise, acupuncture, Bupropion, Desvenlafaxine, Duloxetine, Fluoxetine, Fluvoxamine, Mirtazapine, TCAs, Venlafaxine, ECT (for severe, psychotic or treatment-resistant depression), therapist-assisted CBT...
***For severe major depressive disorder, pharmacotherapies each move up one recommendation line
150
Prevalence of anxiety disorders
31%
151
Risk factors for developing anxiety d/os
-Female
-FHx of mood or anxiety d/os
-Personal hx of mood or anxiety d/os
-Personal hx of stressful life events (childhood abuse)
-Loneliness
-Lower education
-Adverse parenting
-Chronic somatic illness (e.g. CVD, DM, asthma, obesity)
-Behavioural disinhibition
152
Lifetime prevalence of Panic Disorder
5%
153
Lifetime prevalence of Agoraphobia
1.4%
154
Duration required for dx of Panic Disorder
1mo
155
Duration required for dx of Agoraphobia
6mos
156
Pharmacotherapy for Panic Disorder
1st Line (PPEFFS-CV)
-Paroxetine
-Paroxetine CR
-Escitalopram
-Fluoxetine
-Fluvoxamine
-Sertraline
-Citalopram
-Venlafaxine XR
2nd Line:
TCAs --> clomipramine, imipramine
Benzos --> alprazolam, clonazepam, diazepam, lorazepam
Mirtazapine
Reboxetine
Not recommended:
-Buspirone
-Propranolol
-Trazodone
-Tiagabine
157
5 key features that define schizophrenia spectrum d/os
1) Delusions
2) Hallucinations
3) Disorganized thoughts (inferred from speech)
4) Disorganized or abnormal behaviour
5) Negative sxs
158
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