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1_Psychiatry Royal College 2017 > Mood > Flashcards

Mood Flashcards

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1
Q
A
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2
Q

According to the CANMAT bipolar guidelines, what are the 4 first line agents for maintenance therapy?
How about for rapid cycling?

A

The agents are: Lithium, Divalproex, Olanzapine and Lamotrigine (if patient has mild manias and mainly depression). For
rapid cycling, only divalproex and lithium are 1st line (olanzapine monotherapy is 2nd line)

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3
Q

ADs with increased risk of manic switch?

A

TCAs and venlafaxine

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4
Q

Anxious distress severity

A

* Mild - 2 sx * moderate - 3 sx * mod-severe: 4-5 sx * severe: 4-5 sx + agitation

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5
Q

Anxious distress

A

≥ 2 sx: * tense * restless * diff. [] 2nd worry * fear something bad will happen * fear might lose control of self

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6
Q

Atypical features specifier - DSM criteria

A

* mood reactivity * ≥ 2 of {wt gain/increased appetite, , hypersomnia, leaden paralysis, long-standing rejection sensitivity} * NO melancholia or catatonia in same episode

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7
Q

BD comorbidities

A

 Anxiety Disorders (most frequent, in 75% of individuals)
o Increased risk of suicide, longer time to recovery, increased risk of relapse.
 Alcohol Use Disorders (More than 50% of individuals with bipolar I, F>M, females with bipolar I or II disorder have much higher rates of alcohol use disorder than females in the general population)
 Other Substance Use Disorders (5xRR nicotine use disorder)
 ADHD
 Conduct Disorder
 Eating Disorders, both Anorexia and Bulimia Nervosa (F>M)
 Borderline Personality Disorder
 Medical Conditions: type 2 diabetes, metabolic syndrome (2xRR),
cardiovascular disease (5x RR), hypertension (5x RR), migraine (nearly 25%,
bipolar II > bipolar I)

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8
Q

BD course and prognosis

A

 90% of individuals with a single manic episode go on to have recurrent mood
episodes.
 Untreated manic episode lasts about 3 months (K&S) or 13 weeks (CANMAT)
 As the disorder progresses, the time between episodes often decreases and
there is less inter-episodic remission - after about five episodes the interepisode
interval often stabilizes at 6 to 9 months.
o 5-15% will be classified as rapid cyclers

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9
Q

BD in the elderly

A

Have greater levels of cognitive dysfunction than age-matched control subjects.
 In post-hoc subgroup analyses, quetiapine is effective in mania
 Open-label study found adjunctive lamotrigine to be effective in bipolar I and
bipolar II depressive symptoms

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10
Q

BD prognostic factors

A

 Manic episode with psychotic features is predictive of subsequent episodes with
psychotic features.
o Incomplete inter-episode recovery is more common with moodincongruent psychotic features.
 Mixed episode is associated with:
o Poor outcome, increased suicidal risk, and substance abuse/
 Lifetime risk of suicide is estimated to be 15-times that of the general
population, may account for 25% of all completed suicides.
o Lifetime risk of suicide is 15% (London Review)
o Past history of suicide attempt, percent days spent depressed in the
past year, alcohol use, and comorbid anxiety disorder are associated
with greater risk of suicide attempts or suicide completion.
o Patients w/ bipolar II disorder may have greater risk of both attempting
and completing suicide than patients with Bipolar I and MDD (K&S)
 Individuals perform more poorly than healthy individuals on cognitive tests.
Cognitive impairment occurs throughout the lifespan even during euthymic
periods.
o Even when euthymic cognition 0.7 SD below age matched controls
(London Review)
o Cognitive deficits especially in the domains of attention, verbal memory,
executive function, and information processing speed.
o Cognitive impairment in bipolar II is as severe as in bipolar I, with the
exception of memory and semantic fluency.
 Occupational impairment - 30% show severe impairment in work role function,
individuals with bipolar disorder have lower socioeconomic status despite
equivalent levels of education.
 Functional recovery lags behind recovery of symptoms
 Low level of comorbidity and later onset predict a better outcome

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11
Q

BD treatment in children

A

 Lithium approved ≥ age 12
 Atypical antipsychotics improved include:
o Quetiapine for acute manic/mixed episodes in pediatric populations
o Risperdal
o Aripiprazole
o Olanzapine (?second line due to metabolic effects)
 Anticonvulsants are not approved by the FDA
o Divalproex has increased risk of PCOS in females under 20 years

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12
Q

Before prescribing antidepressants, explain:

A

(1) Time lag to antidepressant effect
(2) Common and serious adverse events
(3) Need to continue medication even when feeling better

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13
Q

Bipolar I avg age of onset

A

18yo

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14
Q

Bipolar I course

A

* >90% recurrence of mood episodes * ~60% of manic episodes occure right before MDE * high income > low income countries * FHx - strongest risk factor * psychotic features predict future psychotic features * mood-incongruent psychosis –> incomplete recovery

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15
Q

Bipolar I epi (12mo prevalence, gender ratio)

A

* 12mo prevalence: 0.6%

* M:F = 1.1 : 1

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16
Q

Bipolar I OR II specifiers

A

* anxious distress * mixed features (≥3 sx of MDE most days during (hypo)manic episode) * rapid cycling (≥4 episodes of any mood in 12 months) * melancholic features (for MDE or mixed) * atypical features (MDE or mixed) * psychotic features * catatonia * peripartum onset * seasonal pattern

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17
Q

Bipolar II age of onset

A

avg age mid-20s

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18
Q

Bipolar II course

A

* often starts with MDE * higher lifetime episodes than BD I

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19
Q

Bipolar II prevalence

A

* 12mo prev: 0.3-0.8%

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20
Q

Bipolar II risk/prognostic factors

A

* FHx of BD II (not so much MDE/BD I) most predictive * rapid-cycling –> worse prognosis * younger, less severe –> return to baseline fxn * education, less duration, married –> assoc with recovery * F more likely to have mixed or rapid-cycling * 1/3 suicide attempts; more lethal than in BD I

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21
Q

Candidate genes for BD

A

COMT (psychotic symptoms), BDNF (cognitive
impairment and rapid cycling) , DISC1, CLOCK,

Replicated GWAS studies have implicated CACNA1C (an L-type calcium
channel) and ANK3 (a voltage gated sodium channel)

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22
Q

Carbamazepine dosing

A

 Initial: 200mg PO BID
 Range: 400mg - 1600mg
 Maximum: 1600mg per day

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23
Q

Carbamazepine side effects

A

Mild:

(1) Sedation
(2) Headache
(3) Nausea, Vomiting, Diarrhea
(4) Dizziness
(5) Tremor (3%)

Serious:
(1) Leukopenia
 Tends to occur in the first three months of initiating treatment
 Estimated incidence is 10-20% during this period
 Usually resolves on carbamazepine cessation
(2) Agranulocytosis and aplastic anemia
 Rarer than leucopenia
 Occur in an unpredictable pattern with a more rapid onset
(3) Hyponatremia
 SIADH likely main cause
(4) Acute Hepatitits
 Immune-mediated
 Tends to occur early in treatment (within first eight weeks)
(5) Stevens-Johnson Syndrome (<10%) / SJS/TEN Overlap Syndrome (10-30%) / Toxic
Epidermal Necrolysis (>30%)
 Prodromal flu-like systemic symptoms
 Mucosal surfaces affected
 Characteristic lesions with target-like appearance

 1.4 / 10 000 (incidence: lamotrigine > carbamazepine > divalproex)
(6) Osteoporosis / Reduced Bone Density
(7) Drug interactions, including OCP. Recommend using IUD or barrier methods
Mild Weight Gain

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24
Q

Clinical features predictive of BD

A
  • Early age of onset
  • Psychotic depression before 25 years old
  • Postpartum depression, especially with psychotic features
  • Rapid onset and offset of depressive episodes of short duration (<3m)
  • Recurrent depression (more than 5 episodes)
  • Depression with marked psychomotor retardation
  • Atypical features (reverse vegetative signs)
  • Seasonality
  • Bipolar family history
  • High density, three generation pedigrees
  • Trait mood lability (cyclothymia)
  • Hyperthermic temperament
  • Hypomania associated with antidepressants
  • Repeated (at least 3 times) loss of efficacy of antidepressants after initial response
  • Depressive mixed state (with psychomotor excitement, irritable hostility, racing thoughts and sexual arousal during major depression)
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25
Q

Comorbidities in MDD

A

Substance Use Disorders, especially Alcohol Use Disorder
 Anxiety Disorders, especially panic disorder, social phobia and GAD
 OCD
 Eating Disorders, both Anorexia and Bulimia Nervosa
 Borderline Personality Disorder

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26
Q

Contraindications to lithium

A

 Significant renal impairment
 Severe dehydration or electrolyte imbalance
 Significant Cardiac Impairment
 Psoriasis - Relative Contraindication

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27
Q

Contraindications to psychotherapy in acute phase MDD

A

Severely suicidal patient

Psychotic depression

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28
Q

Contraindications to rTMS

A

o Presence of ferromagnetic material in head (cochlear implants, brain
stimulators, electrodes, clips, plates, etc.)
o Cardiac pacemakers
o Increased ICP
o Severe Cardiovascular Disease
o Epilepsy
o Serious Medical Conditions

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29
Q

Contraindications to valproate

A

Hepatic disease

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30
Q

Cyclothymic d/o course

A

insidious onset, persistent course

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31
Q

Cyclothymic d/o criteria

A

* >2 yrs of numerous periods of hypomanic or depressive Sx not meeting criteria for episode * Sx periods present for >50% of the time *

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32
Q

Cyclothymic d/o epi

A

* lifetime prev: 0.4-1% * M=F

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33
Q

Cyclothymic d/o risk factors

A

* MDD, BD I and II in 1st degree relatives * increased familial risk of substance use

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34
Q

DBS - how is it applied?

A

 Involves stereotactic neurosurgical implantation of electrodes under MRI
guidance
 Following surgery, need to wait 7-14 days before the device is switched on to
allow the localized edema to resolve
 Subcallosal cingulate gyrus (SCG) is site that has been evaluated the most
 Two additional sites, the nucleus accumbens and ventral caudate / ventral striatum
region have also been examined

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35
Q

DBS level of evidence

A

Level 3 acute efficacy, Level 3 relapse prevention, Level 3 safety and tolerability

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36
Q

DDx of MDD (medical, substance, psychiatric, other)

A

(1) Medical Conditions: Especially
A. Hypothyroidism
B. Cushing’s Disease or Addison’s Disease
C. Anemia, Vitamin B12 or Folate Deficiency
D. Infectious Etiology: Mononucleosis, HIV, etc.
E. Pancreatic cancer, brain tumours and other neoplasms
F. Epilepsy (especially with right-sided focus)
G. CVA (especially left frontal)
H. Multiple Sclerosis
I. Parkinson’s Disease

(2) Substance Induced
A. Stimulants (catecholamine depletion, withdrawal): Amphetamine, MDMA, Cocaine
B. Sedatives: Alcohol, Benzodiazepines, Barbiturates
C. Medications: Glucocorticoids, Tetrabenazine, centrally acting antihypertensive
(reserpine, methyldopa), sedative-hypnotics, antiparkinsonian drugs (e.g. L-Dopa)

(3) Normal Sadness
(4) Adjustment Disorder with Depressed Mood
(5) Dysthymia
(6) Bipolar I and Bipolar II Disorder
(7) Schizoaffective Disorder

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37
Q

Differential diagnosis for BD

A

(1) Medical Conditions: Especially
A. Hyperthyroidism
B. Cushing’s Disease
D. Infectious: HIV, Syphilis
F. Epilepsy (especially with left-sided focus)
G. CVA (especially right frontal)
H. Multiple Sclerosis

(2) Substance Induced
A. Stimulants: Amphetamine, Methamphetamine, Cocaine, Caffeine, Nicotine
B. Sedatives: Alcohol, Benzodiazepines, Barbiturates (withdrawal)
C. Medications: Glucocorticoids, Antidepressants, ECT, rTMS

(3) Attention Deficit Hyperactivity Disorder: Many symptoms overlap with mania
including rapid speech, racing thoughts, distractibility and less need for sleep. Double
counting of symptoms can be avoided by determining whether symptoms represent a
distinct episode and noticeable increase over baseline must be present. Furthermore,
onset of symptoms is in childhood in ADHD, whereas childhood onset is rare in bipolar
disorder.

(4) Borderline Personality Disorder: Mood lability and impulsivity are common in both
conditions. Symptoms must represent a distinct episode and noticeable increase over
baseline must be present. Diagnosis of a personality disorder should not be made during
an untreated mood episode.

(5) Major Depressive Disorder: Sometimes also accompanied by subthreshold hypomanic
or manic symptoms, should be differentiated from bipolar disorder. Also need to ensure
that patients presenting with MDD have not had history of mania or hypomania.

(6) Other Bipolar Disorders: Need to differentiate bipolar I from bipolar II as well as
cyclothymia, other specified bipolar disorders, etc.

(7) Generalized Anxiety Disorder: Anxious ruminations may be mistaken for racing thoughts.

(8) Disruptive Mood Dysregulation Disorder: Severe irritability in children and
adolescents is not diagnostic of mania, distinct episode is needed

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38
Q

Disruptive mood dysregulation disorder - criteria

A

temper outbursts: - severe and recurrent - ≥ 3x/week - inconsistent with dev. level - irritable most of the time - >12 months - >2-3 settings _ 6-18yo - no manic symptoms >1 day

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39
Q

Divalproex side effects

A

Mild:

(1) Sedation
(2) Nausea, Vomiting, Diarrhea
(3) Weight Gain
(4) Hair Thinning / Loss (up to 12%)
(5) Tremor
(6) Benign Rash
(7) Benign hepatic transaminase elevation

Serious:
(1) Thrombocytopenia
 Dose-dependent - occurs at higher doses and blood levels
 Develops over months after initiating treatment
 Tends to resolve with dose reduction
 Clinically significant bleeding with severe thrombocytopenia <50 000
(2) Hepatotoxicity
 Non-immune mediated
 Occurs within first 3-6 months of treatment
 More common in young children
(3) Acute Pancreatitis
 Presents with abdominal pain, abdominal distension, vomiting, or fever
 Can be fatal
(4) Hyperammonemic Encephalopathy
 Symptoms include confusion, reduced LOC, irritability, agitation, vomiting,
lethargy, and seizures
 Develops within days or weeks typically, but can even occur after years
 Unrelated to valproate dose or serum levels
 Can be fatal, need to discontinue drug to treat
(5) Polycystic Ovary Syndrome
 Hyperadrogenism (hirsutism, acne, alopecia)
 Chronic Anovulation (oligomenorrhea or amenorrhea)
 Polyscystic Overaies on Ultrasonography
 Can lead to infertility and metabolic syndrome
 Risk of 10.5% in women treated with divalproex
 NICE guidelines recommend avoidance of valproate use in women under 18
(6) Stevens-Johnson Syndrome (<10%) / SJS/TEN Overlap Syndrome (10-30%) / Toxic
Epidermal Necrolysis (>30%)
 Prodromal flu-like systemic symptoms
 Mucosal surfaces affected
 Characteristic lesions with target-like appearance
 0.4 / 10 000 new users (incidence: lamotrigine > carbamazepine > divalproex)
(7) Osteoporosis / Reduced Bone Density
(8) Interaction with aspirin and warfarin
 ASA increases free fraction of serum valproate and decreases clearance - up to 4-fold increase in valproate level and valproate increases unbound fraction of warfarin
 Valproate can also effect platelet aggregation, which further excerbates these interactions

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40
Q

DMDD cannot coexist with the following diagnoses

A

ODD (give Dx of DMDD)

Bipolar disorder (give dx of BD)

Intermittent explosive disorder

Note: CAN coexist with conduct d/o, MDD, ADHD etc

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41
Q

Does combining ECT and ADs increase therapeutic effect?

A

No

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42
Q

ECT - how do you calculate the initial stimulus, best dose, sz threshold?

A

Full age method, use mC = age * 5, half age method mC = age * 2.5
o Seizure threshold increases during the course of ECT from 25 to
200%
o Men and older adults have higher seizure thresholds
o Doses of three times the threshold are the most rapidly effective
(K&S)
o Minimal suprathreshold dose causes the fewest and least severe
cognitive adverse events

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43
Q

ECT contraindications

A

No absolute contraindications
o Heart - pre-ECT ECG for everyone, cardiology consultation in high risk pt
 Recent Myocardial infarction - high risk, although risk greatly
diminished two weeks after MI and even more so after 3 months
 Hypertension should be stabilized with antihypertensives before
ECT is administered
 Cardiac Arrhythmias
 Abdominal Aortic Aneurysm
o Brain - neurosurgery consultation recommended in high risk patients
 Space occupying lesion - increased risk for edema & herniation
after ECT
 Increased ICP - at risk for bleeding during ECT due to increased
cerebral blood flow during the seizure, need to control blood
pressure
o Anaesthetic Hypersensitivity

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44
Q

ECT electrode placement - positions, effects

A

Bitemporal - 1.5 to 2.5 times threshold, faster in improving symptoms
and more effective than unilateral but associated with more cognitive
effects. Also some evidence that right unilateral suprathreshold is as
effective and associated with fewer side effects.
o Bifrontal - 1.5 to 2.5 times threshold, as effective as bitemporal and
associated with less cognitive side effects
o Unilateral - 6 times above seizure threshold, fewer side-effects

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45
Q

ECT indications

A

Level 1 Indications:
 Acute Suicidal Ideation (level 1)
 MDE with psychotic features (level 1)
 Treatment resistant depression (level 1)
o Level 3-4 Indications:
 Catatonia (level 3)
 Prior Favourable Response (level 3)
 Repeated Medication Intolerance (level 3)
 Rapidly Deteriorating physical status (level 3)
 Patient choice (level 3)
 During pregnancy for any of these indications (level 3)

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46
Q

ECT stimulus parameters

A 
o Current (500 to 800 mA)
o Frequency (20 to 120 Hz)
o Pulse Width (0.25 to 2 ms)
o Duration (0.5 to 8 or more seconds)
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47
Q

Factors supporting long-term (>2 years to lifetime) antidepressant maintenance

A

(1) Older age
(2) Recurrent Episodes (3 or more)
(3) Chronic episodes
(4) Psychotic Episodes
(5) Severe episodes
(6) Difficult to Treat Episodes
(7) Significant Comorbidity (psychiatric or medical)
(8) Residual Symptoms
(9) History of recurrence during discontinuation of antidepressant

Some evidence maintenance dose should be same as dose that led to improvement

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48
Q

FASTER-D (bipolar sx)

A
  • *F**light of ideas
  • *A**ctivity that is goal-directed increased or Agitated psychomotor-wise
  • *S**leep Need Decreased
  • *T**alkative or pressured speech
  • *E**steem increased or grandiosity
  • *R**isky Behaviours
  • *D**istractible
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49
Q

Finding the site for optimal stimulation for rTMS?

A

Identify site for optimal stimulation of abductor pollicis brevis and then measure 5
cm anteriorly along the skull surface in a parasagittal line to locate site for
stimulation (DLPFC on either side)

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50
Q

First line for BD I depression

A

Monotherapy:
 Lithium
 Lamotrigine
 Quetiapine or Quetiapine XR (4 RCTs: BOLDER I+II, EMBOLDEN I+II)
Combinations and Adjuncts:
 Lithium and Divalproex
 Lithium or Divalproex + SSRI (except paroxetine)
 Lithium or Divalproex + Bupropion
 Olanzapine and SSRI (except paroxetine, esp. fluoxetine)

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51
Q

First line for BD II depression

A

Quetiapine and Quetiapine XR

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52
Q

First line in BD II maintenance

A

Lithium

Lamotrigine

Quetiapine

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53
Q

First line pharmacotherapy for BD I acute mania

A

Monotherapy:
 Lithium
 Divalproex or Divalproex ER
 Quetiapine or Quetiapine XR
 Olanzapine
 Risperidone
 Aripiprazole
 Ziprasidone
 Asenapine
 Paliperidone ER
Adjuncts:
 Atypical Antipsychotics except Ziprasidone and Paliperidone (negative level 2
evidence for these two) in addition to Lithium or Divalproex

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54
Q

First line psychotherapy for acute phase MDD

A

(1) Cognitive Behavioural Therapy (level 1)
(2) Interpersonal Therapy (level 1)

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55
Q

First-line add-on agents in MDD

A

Aripiprazole (level 1)
 Lithium (level 1)
 Olanzapine (level 1)
 Risperidone (level 2)

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56
Q

First-line antidepressants in breastfeeding

A

Citalopram
o Sertraline
o Paroxetine
o Nortriptyline
 Avoid fluoxetine as infants exposed to fluoxetine have higher risk of having
elevated serum levels

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57
Q

First-line antidepressants in children

A

In children, fluoxetine and citalopram are first-line antidepressants with the best
benefit-risk evidence
o Antidepressants carry 1.5-2 fold risk of increasing suicidal thoughts and
behaviors in children with NNH of 143 - 2004 blackbox warning has
been extended to young adults age 18-24.
o Venlafaxine has higher risk estimate for suicidality and is a third-line
antidepressant in children.
 Best outcomes in children have resulted from combining antidepressants with
CBT.

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58
Q

First-line for BD I maintenance

A

Monotherapy:
 Lithium
 Divalproex or Divalproex ER
 Quetiapine or Quetiapine XR
 Lamotrigine (effective at preventing depression)
 Olanzapine (effective at preventing mania)
 Aripiprazole (effective at preventing mania)
 Riperidone Consta / Long Acting Injection (effective at preventing mania)
 ? Ziprasidone (in text, but not in table 5.5, effective at preventing mania)
Combinations and Adjuncts:
 Adjunctive Quetiapine, Aripiprazole, Risperdal LAI, and ziprasidone (adjunctive
olanzapine and risperdal are second line)

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59
Q

First-line pharmacotherapy for MDD

(+ evidence of superiority)

A

(1) Agomelatine
(2) Bupropion
(3) Citalopram
(4) Desvenlafaxine
(5) Duloxetine,
(6) Escitalopram
(7) Fluoxetine
(8) Fluvoxamine
(9) Mianserin
(10) Milnacipran
(11) Mirtazepine
(12) Moclobemide
(13) Paroxetine
(14) Reboxetine
(15) Sertraline
(16) Tianeptine
(17) Venlafaxine

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60
Q

First-line psychotherapy for maintenance phase in MDD

A

CBT,

MBCT (2016)

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61
Q

First-line switch agents with evidence of superiority in MDD

A

Escitalopram (level 1)
 Sertraline (level 1)
 Venlafaxine (level 1)
 Mirtazepine (level 2)
 Milnaciprin (level 2)
 Duloxetine (level 2)

62
Q

Frequency and duration of rTMS?

A

Usually 5 sessions are delivered per week, most trials have been 4-6 weeks in
duration

63
Q

Frequency of acute phase ECT for MDD?

A

 3 times per week -> faster onset of action
 2 times per week -> less cognitive side effects

64
Q

Gender differences in BD I and II

A

 1.1:1 M:F ratio (DSM-5), 1:1 M:F(K&S)
o Females are more likely to have rapid cycling, mixed states, also more likely to have depressive symptoms and are also more likely to have bipolar II diagnosis

65
Q

How do you differentiate the Baby Blues from Post Partum Depression?

A

Baby Blues

30 to 75% of women who give birth

Onset after 3 – 5 days post partum

Lasts days to weeks

No identifiable stressors

No family history

No personal history of mood disorder

No anhedonia

Absent or mild guilt

Rarely infanticidal and suicidal thoughts

Occassional sleep disturbance

Postpartum Depression 10-15% of women who give birth Onset between 3 to 6 months Lasts months Lack of social supports is usually a stressors Often family history of mood disorders Often personal history of mood disorder Often anhedonia Guilt usually present and excessive Suicidal and infanticidal thoughts can be present Frequent sleep disturbance

66
Q

How is rTMS delivered?

A

rTMS is delivered in trains lasting for several seconds followed by inter-train
intervals, several trains can be delivered per session.

67
Q

How many patients with BD start with a depressive episode?

A

75% of thetime in women,

67% of the time in men

68
Q

Hypomanic episode criteria

A

* mood AND energy x >4 days * ≥3 of {grandiosity, sleep, talkative, flight of ideas, distractibility, goal-directed/agitation, painful consequences} * uncharacteristic change in fxn

69
Q

Initial measurements for monitoring in BD

A

tial Measurements:
 BMI (kg/m2) & Waist Circumference
 Blood Pressure
 Fasting Glucose
 Fasting Lipid Profile (Triglycerides, LDL, HDL, total cholesterol)
 CBC / Electrolytes / BUN and Creatinine
 Liver Function Tests
 Beta-HCG, also ensure appropriate contraception in all patients
 (Serum Levels of Lithium and Divalproex) <- if on Lithium or Divalproex
 (TSH) <- if starting lithium
 (Ca) <- if starting lithium
 (Coagulation studies, Urine Toxicology, Urinalysis, Prolactin, ECG if over 40) <- CANMAT

70
Q

Lab workup for MDD

A

Core workup: CBC, Electrolyes, Creatinine / BUN, Liver Enzymes, TSH, Beta-HCG (if
female)
Specific Workup:
 Urine Toxicology for Substance Abuse
 Blood Toxicology
 Serology for EBV or HIV
 Vitamin B12 and Folate
 24 hour urine cortisol
 Neuroimaging

71
Q

Lab workup in BD?

A

Core workup Plus: CBC, Electrolyes, Creatinine / BUN, Liver Enzymes, TSH, BetaHCG (if female) + BMI (kg/m2) & Waist Circumference, Blood Pressure, Fasting
Glucose, Fasting Lipid Profile (Triglycerides, LDL, HDL, total cholesterol)
 (Serum Levels of Lithium and Divalproex) <- if on Lithium or Divalproex
 (TSH) <- if starting lithium
 (Ca) <- if starting lithium
 ECG for patients over 40 <- if starting lithium

Specific Workup:
 Urine Toxicology for Substance Abuse
 Blood Toxicology
 Serology for HIV and Syphilis
 24 hour urine cortisol
 Neuroimaging
 EEG

72
Q

Lamotrigine dosing

A

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid:
o 25mg PO daily Weeks 1 and 2
o 50mg PO daily Weeks 3 and 4
o 100mg PO daily Week 5
o 200mg PO daily Week 6 and maintenance

Regimens containing valproic acid:
o 12.5mg PO daily or 25mg every other day Week 1 and 2
o 25 mg PO daily Weeks 3 and 4
o 50mg PO daily Week 5
o 100mg PO daily Week 6 and maintenance

73
Q

Lamotrigine side effects

A

(1) Benign Rash
 8.3% of patients
(2) Stevens-Johnson Syndrome (<10%) / SJS/TEN Overlap Syndrome (10-30%) / Toxic
Epidermal Necrolysis (>30%)
 Prodromal flu-like systemic symptoms
 Mucosal surfaces affected
 Characteristic lesions with target-like appearance
 Occurs in 2.5/10 000 new users (incidence: lamotrigine > carbamazepine > divalproex)
 Concurrent valproate increases levels of lamotrigine due to its inhibition of hepatic glucuronidation, this increases risk of SJS
 Also more likely in children under 16 years
(3) Sedation
(4) Nausea / Vomiting / Diarrhea

Weight Neutral

74
Q

Lifetime risk of suicide in BD

A

15%

Evidence indicates that patients with bipolar II are at greater risk of both attempting and completing suicide tha patients with bipolar I and MDD

75
Q

Lithium and ECT - effects, management

A

Lithium may increase post-ictal confusion and delirium, most
practitioners omit one or two doses prior to each ECT session

76
Q

Lithium dosing and target levels

A

Dosing - Guided by Plasma Levels
 Initial: 300mg PO BID or TID
 Range: 900 - 1800mg (once daily or divided BID - QID)
 Maximum: 1800mg (UptoDate) 2400 mg (CHOP-D (daily or divided BID - QID)

Usual target lithium levels are
 0.8-1.2 mmol/L for treatment of acute mania
 0.6-1.0 mmol/L (some recommend 0.8-1.2 as well) for maintenance treatment
 Levels should not exceed 1.5, which is the range for toxicity (although toxicity is
a clinical diagnosis and can occur at any serum lithium level)
 ≥ 2.5 mmol/L is a medical emergency

77
Q

Lithium monitoring

A

 2 consecutive therapeutic lithium levels (5 days after dose titration and 12
hours after last dose) to establish therapeutic dose
 Levels q3-6 months
 Renal Function Tests q3-6 months
 TSH, Ca, Weight at 6 months and then qYear
 Also monitor for signs of lithium toxicity

78
Q

Lithium side effects

A

Mild:

(1) Sedation
(2) Nausea / Vomiting / Diarrhea
(3) Fine Tremor
(4) Dry mouth , Excessive Thirst (Polydipsia)
(5) Acne
(6) Cognitive Impairment

Severe:
(1) Chronic Renal Disease
 Glomerular and Tubulointerstitial Nephropathy, Nephrotic Syndrome, Renal
Failure.
 Longer duration and higher cumulative doses may be risk factors, in addition
to hypertension, DM, use of other nephrotoxic drugs, prior lithium toxicity,
and nephrogenic diabetes insipidus
(2) Nephrogenic Diabetes Inspidius:
 Impaired renal concentrating capacity due to distal renal tubule insensitivity to
ADH
 Manifests as polyuria and polydipsia
 Causes nephrogenic DI through dysregulation of aquaporin 2
 Longer duration of treatment and use of other psychotropic agents are risk
factors.
 Lithium is the most common cause of acquired nephrogenic diabetes inspidus
(3) Hypothyroidism:
 female gender and pre-existing thyroid auto-antibodies are risk factors.

 Association between lithium and hyperthyroidism is less clear.
(4) Hyperparathyroidism:
 Confirm hypercalcemia by repeated measurements, then can measure PTH
 Causes renal calculi, arrhythmias, osetopenia, mental state disturbances (stones,
bones, groans, psychiatric overtones)
(5) Weight gain
 +3.8 kg over one year
(6) ECG Changes
 Bradycardia and sick sinus syndrome are worrisome complications
 20-30% have benign T-wave changes (flattening or inversion) and widening QRS
at therapeutic doses
(7) Psoriasis Exacerbation

79
Q

Lithium toxicity symptoms

A

 Coarse tremor
 Drowsiness
 Lethargy
 Weakness
 Agitation
 Muscle Fasciculation
 Ataxia
 Dysarthria
 Vomiting, Diarrhea
 Dizziness, Syncope Arrhythmias
 Polyuria, Polydypsia

80
Q

Major depressive disorder - criteria

A

* 2 weeks + change of previous fxn * 5 of {mood, interest, sleep, wt, psychomotor, energy, guilt/worthlessness, [], SI}

81
Q

Manic episode criteria

A

* elevated/irritable mood AND increased energy x >1wk * ≥3 of {grandiosity, dec. sleep, talkative, flight of ideas/racing thoughts, distractibility, goal-directed activity/agitation, painful consequences} * marked impairment or hospitalization or psychosis

82
Q

MDD - course

A

* variable course *

40% recover in 3mo, 80% in 1yr *

poor prognosis: episode duration, psychosis, anxiety, personality d/o, severity *

BD more likely if mixed features, psychosis, FHx of BD

83
Q

MDD Age of onset, age differences in symptoms and prevalence

A

Incidence peaks in 20s (in Canada 15-45yo)

Likelihood decreases after puberty but can still have first onset in late life

Prevalence in 18-30 = 3x Prevalence >60 (decreases with age)

Younger: hyper-somnia & -phagia

Older: melancholic sx, esp psychomotor

84
Q

MDD gender distribution

A

1.5-3:1 F:M ratio (DSM-5), 2:1 F:M (K&S)

Difference decreases with age

85
Q

MDD genetic markers (genes & alleles)

A

5HTTLPR short allele + stressful life events

If long allele - better response to SSRIs with fewer side effects (but not nortriptyline)

BDNF - met/met + stressor high risk (cf val/met and val/val)

86
Q

MDD heritability

A

40%

1st degree relatives: 2-4x chance of having MDD

one parent: 10-25% risk, both: 20-50%

87
Q

MDD Prevalence (lifetime, 12mo, US and Canada)

A

Lifetime: U.S. - 16.9 % (NCS), Canada - 10.8% (CCHS 1.2)

12-Month: U.S. - 6.8% (NCS), 7% (DSM-5), Canada - 4.0% (CCHS 1.2)

88
Q

MDD- specifiers

A

* anxious distress * mixed features * melancholic features * atypical features * mood-congruent psychotic features * mood-incongruent psychotic features * catatonia * peripartum onset * seasonal pattern

89
Q

Melancholic features

A

* during most severe period of MDE: * 1 of {anhedonia or lack of reactivity to pleasurable stimuli} * ≥ 3 of {despair/empty mood, worse in AM, AM awakening, psychomotor agitation or retardation, we loss , excessive guilt}

90
Q

Mixed features in MDD

A

* ≥ 3 manic sx during most of MDE

91
Q

Monitoring for divalproex or carbamazepine

A

 2 levels to establish therapeutic dose (4 weeks apart for CBZ), then as clinically indicated
 Weight*, CBC LFT, menstrual history* q3 months (monthly for CBZ for first 3 months) for first year than annually (*Divalproex only), lytes + RFTs - CBZ
 Bone densitometry if risk factors
 Monitor for Rash (and for lamotrigine)

92
Q

Monitoring when treating with atypical antipsychotics

A

 Weight monthly for first 3 months, than q3months
 BP and fasting glucose q3months for first year than annually
 Fasting lipid profile after 3 months and then annually
 ECG and prolactin level as clinically indicated

93
Q

neuroimaging findings in MDD

A

Structural:
 Decreased hippocampal volume

Functional:
 Increased activity in Amygdala and Medial Prefrontal Cortex
 Reduced activity in Dorsolateral Prefrontal Cortex

94
Q

Persistent depressive d/o - epidemiology

A

* 0.5% 12mo prevalence for dysthymia * 1.5% for chronic MDD * early, insidious course

95
Q

Persistent depressive disorder

A

* >2 years depressed mood (1yr for child) * 2 sx of {appetite change, sleep change, fatigue, low self-esteem, poor [] or decision making, hopelessness} *

96
Q

Persistent depressive disorder - specifiers

A

* all specifiers as MDD * early/late onset (21yo) * pure dysthymic syndrome (no MDE in past 2 years) * persistent MDE (meets criteria for full 2 years) * intermittent MDE, with/ wi/o current episode * severity

97
Q

PMDD prevalence

A

* 12mo prevalence: 2-6%

98
Q

PMDD risk factors

A

stress, trauma, seasonal changes, no OCP

99
Q

Premenstrual dysphoric disorder

A

* most cycles in past 1 yr , ≥5 sx in final wk, improve in a few days * ≥ 1 of {affective lability, irritability, depressed mood/hopelessness, anxiety/tension/keyed up}\ * ≥ 1 of {anhedonia, []. energy, appetite, sleep, overwhelmed, phys. sx} *

100
Q

Prevalence of BD I and II

A

 Lifetime: 1.0% bipolar I, 1.1% bipolar II (NCS-R)
 12-Month: 0.6% bipolar I (NCS-R & DSM-5), 0.8% bipolar II (NCS-R)

101
Q

Putative biomarkers for BD

A

Structural (London Review):
 White Matter Hyperintensities
 Anterior cingulate cortex is reduced in volume
 Lateral and 3rd ventricles are larger

Functional (London Review):
 Increased activity in Amygdala and Parahippocampal Gyrus in mania during emotional tasks, normal activation during euthymia
 Hypoactivation of ventrolateral prefrontal cortex during emotional and cognitive tasks

MR Spectroscopy (London Review):
 Increased Glutamate Levels
 Decreased NAA levels

102
Q

Putative biomarkers in MDD

A

BDNF - decreased; antidepressant tx reverses this

Proinflammatory cytokines, eg IL-6 and TNF-alpha: increased

HPA axis regulation impaired:

dexamethasone non-suppression (not specific)

and hypercortisolemia (40-60% of depressed inpatients, 20-40% of depressed outpatients)

103
Q

Rank the risk factors for postpartum psychosis (greatest to least)

A

a. History of postpartum psychosis (70%)
b. History of postpartum depression (50%)
c. History of bipolar disorder (20-50%)
d. History of MDD (30%)

104
Q

Rapid cycling course and treatment

A
  • Less likely to be symptom free in 2-5 year follow-up studies (usually have shortening of cycles for 4-6 episodes before stabilization)
  • Lithium vs. Valproate study Calabrese 2005: The hypothesis that divalproex would be more effective than lithium in the longterm management of rapid cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid cycling bipolar disorder (Am J Psychiatry 2005)
  • Cites several guidelines including “Evidence based guidelines for treating bipolar disorder revised second edition recommendations from British association for psychopharmacology
  • Firstline: Minimize or eliminate potential cycling-promoting agents (subclinical hypothyroidism, substance abuse, steroids, stimulants, antidepressants, activities that interfere with sleep-wake cycle). Lithium or valproate monotherapy.

Second-Line: Lithium or valproate + lamotrigine. Combine two traditional mood stabilizers (#1 valproate + lithium), #2 carbamazepine + lithium). Add Risperdal Constan (Macfadden 2009), Add olanzapine or quetiapine

105
Q

Rapid cycling risk factors

A

•: 3F>M,

earlier age of onset of illness,

premorbid cyclothymic temperament,

bipolar II> I (inconsistent),

hypothyroidism ? (inconsistent),

comorbid substance abuse,

longterm use of antidepressants (especially TCAs),

abrupt discontinuation of medications?,

childhood physical or sexual abuse?

106
Q

Response/remission rates in rTMS

A
  • Response rates are 25% for treatment resistant depression
  • w/o maintenance relapse is common, median 3 months
  • w/ maintenance rTMS - better outcomes; sustain remission in 60% of responders, 70% of remitters
107
Q

Risk factors for MDD

A

Core:
 Early-Onset Adversity/Childhood Maltreatment (esp. losing a parent before 11)
 Stressful Life Events (esp. loss of a spouse & unemployment which has 3-fold
relative risk of depression versus people who are employed)
o Stressful life events more often precede the first rather than
subsequent episodes of mood disorders both in MDD and Bipolar I.
 Family History (first degree relatives have 2-4x greater chance of having MDD)
Specific:
 Female Gender
 Temperament: Neuroticism (negative affectivity)
 Chronic Medical Conditions
 Substance Use especially Alcohol Use
 Anxiety Disorders
 Borderline Personality Disorder

108
Q

rTMS stimulus calculation?

A

Stimulus is based on individual motor threshold (stimulus required to produce
twitches), usually 90 to 120% of motor threshold

109
Q

Scales for MDD

A

BDI-II

HAM-D

MADRAS

Zung Self-Rating Depression Scale

PHQ-9

110
Q

Seasonal pattern

A

* regular temporal relationship w/ season ( not psychosocial stressors) * full remissions or (hypo)mania * in last 2yrs, 2 MDE w/ temporal relationship and no MDE out of season * seasonal > non-seasonal episodes

111
Q

Second line for BD I depression

A

 Lurasidone (1 RCT in AJP positive for monotherapy in bipolar I depression -
found improvement in depressive symptoms as early as week two vs. placebo)
 Divalproex
Adjunct:
 Lurasidone (in addition to Lithium or Divalproex)
 Quetiapine + SSRI
 Lithium or Divalproex + Lamotrigine
 Adjunctive Modafinil

112
Q

Second line for BD I maintenance

A

 Carbamazepine (similar efficacy to lithium maintenance for rates of relapes, but
more dropouts due to adverse effects with carbamazpeine, also difficult to
combine with other psychotropics so second line)
 Paliperidone ER
Adjunct:
 Lithium and Divalproex (BALANCE study - combination therapy was not
significantly more effective than lithium alone, but more effective than divalproex
monotherapy in preventing relapse)
 Adjunctive Olanzapine, Risperidone

113
Q

Second line for BD II depression

A

 Lithium
 Lamotrigine
 Divalproex
 Combinations

114
Q

Second line for BD II maintenance

A

Divalproex

combinations

115
Q

second line pharmacotherapy for BD I acute mania

A

 Haloperidol
 Carbamazepine or Carbamazepine ER
 ECT
 Lithium + Divalproex

116
Q

second line psychotherapy for acute phase MDD

A

(1) Bibliotherapy (level 1)
(2) Behavioural Activation (level 2)
(3) Cognitive-behavioural analysis system of psychotherapy (CBASP) (level 2)
(4) Computer-Assisted CBT (level 2)
(5) Telephone-delivered CBT and IPT (level 2)
(6) Combination of CBT or IPT with medication is second line (level 1)

117
Q

Second line psychotherapy for maintenance phase MDD

A

(1) Interpersonal Therapy (IPT) (level 2)
(2) Behavioural activation (level 2)
(3) Cognitive-behavioural analysis system of psychotherapy (CBASP) (level 2)

118
Q

Second line switch agents in MDD

A

Amitriptyline (level 2)
 Clomipramine (level 2)
 MAOIs (level 2)

119
Q

Second-line add-on agents in MDD

A

Bupropion (level 2)
 Mirtazapine (level 2)
 Mianserin (level 2)
 Quetiapine (level 2)
 Triiodothronine (level 2)
 Other antidepressant (level 3)

120
Q

Second-line pharmacotherapy for MDD

A

(1) Tricylcic Antidepressants
(2) Quetiapine XR
(3) Selegiline Transdermal
(4) Trazodone

121
Q

Side effects of ECT

A

o Mortality is very low (0.2/100 000 treatments), approximates risk of
general anaesthesia
o Nausea
o Headache
o Muscle Pain / Persistent Myalgia
o Marked confusion in up to 10 percent of patients within 30 minutes of
the seizure (K&S)
o Memory impairment - can be both anterograde and retrograde including
deficits in autobiographical memory, most often reported by patients
who have experienced little improvement with ECT (K&S)
 Can reduce cognitive impairment by reducing frequency to two per
week, using right unilateral or bifrontal positioning of electrodes,
and using lower dose stimuli

122
Q

Side effects of rTMS?

A

o No evidence of cognitive impairment
o Headaches and scalp pain are most common short-terms side-effects.
o Should use ear plugs due to concerns about hearing loss during process.
o Case reports of seizures

123
Q

SSRI discontinuation symptoms

A

FINISH (flu-like, insomnia, nausea, imbalance, sensory disturbance, hyperarousal)

124
Q

Substance/Medication induced bipolar and related d/o

A

* prominent mood disturbance: elevated/irritable OR depressed OR anhedonia * related to intox or withdrawal of substance capable of producing the Sx * NOTE: ?? no need for full criteria of (hypo)mania/MDE

125
Q

Target areas for rTMS?

A

o Left DLPFC -> high frequency stimulation (most evidence)
o Right DLPFC -> low frequency stimulation
Recommendations from CANMAT:

First-line
o Start with high frequency rTMS to left DLPFC (level 1)
o Superior outcome for 20 vs. 10 sessions (level 2)
o Minimal evidence for maintenance and relapse prevention (level 3)

Second-line

bilateral (left high-freq, right low-freq)

126
Q

The only neurostimulation
method with level 1 evidence for relapse prevention?

A

ECT

127
Q

Third line pharmacotherapy for acute mania

A

Clozapine
 Tamoxifen / Adjunctive Tamoxifen

Not Recommended:
 Lamotrigine
 Gabapentin
 Topiramate
 Verapamil
 Tiagabine
Meta-analysis showed that haldol was more effective than lithium, divalproex,
quetiapine, aripiprazole ziprasidone, carbamazepine, asenapine and lamotrigine/ Given this strong data it has been upgraded to second line, but should only be used on a short term basis to treat acute mania since long-term use increases risk of depressive episode

128
Q

Third-line add-on agents in MDD

A

Buspirone (level 2) (-)ve RCT, less favourable outcomes STAR*D
 Modafinil (level 2)
 Stimulants (level 3) two RCTs of methylphenidate showed no
difference in outcome vs. placebo, Cochrane review equivocal
 Ziprasidone (level 3)

129
Q

Third-line pharmacotherapy for MDD

A

(1) Phenelzine (Nardil)
(2) Tranylcypromine (Parnate)

130
Q

Third-line psychotherapy for acute phase MDD

A

(1) Acceptance and commitment Therapy (ACT) (level 3)
(2) Motivational Interviewing (level 4)
(3) Psychodynamic therapy (level 2)
(4) Emotion-focused therapy (level 2)

131
Q

Third-line psychotherapy in maintenance phase MDD

A

Long-term psychodynamic psychotherapy

132
Q

Types of rTMS stimuli

A

o Low frequency (below 5 Hz): transient reduction in cortical excitability
o High frequency (above 5 Hz): transient increase in cortical excitability

133
Q

Valproate dosing and target levels

A

Dosing:
 Initial: 250mg-375mg PO BID
 Range: 1000-3000mg daily or divided BID
 Maximum: 3000mg daily (60mg/kg/day)

Valproate Levels:
 Therapeutic level is from 400-700 mmol/L

134
Q

VNS - how is it applied?

A

Wire connected to subclavicular pulse generator which delivers intermittent
electrical signals to left vagus nerve (chosen due to its limited cardiovascular
effects)

135
Q

VNS - most common side effect

A

 Hoarseness (54-68%) is most common side-effect
 Many side-effects are related to stimulation parameters and can be minimized by
reducing the intensity of the stimulus being delivered

136
Q

VNS level of recommendation

A

Level 3 acute efficacy, Level 2 relapse prevention, Level 2 safety and tolerability

137
Q

VNS response rate

A

In RCT, response rate of 15% compared with 10% sham treatment

138
Q

What antipsychotic is now first-line in the CANMAT bipolar guidelines for acute bipolar depression & what
is the recommended target dose?

A

Quetiapine at 300 mg daily.

139
Q

What are 10 factors that are predictive of Bipolar Disorder?

A

a. Early onset mood symptoms
b. Psychotic depression prior to age 25
Study Notes 2008
Page 24 of 61
c. Post-partum depression (especially if psychotic features present)
d. Rapid onset and offset of depressive symptoms
e. Depression with psychomotor retardation
f. Antidepressant induced hypomania
g. Repeated loss of efficacy of antidepressants
h. Family history of bipolar disorder
i. Trait mood lability or hyperthymic temperament
j. Seasonality of mood symptoms
k. Atypical depressive symptoms (reverse vegetative symptoms)

140
Q

What are 3 risk factors for rapid-cycling bipolar disorder?

A

Hypothyroidism

Substance use

Female gender

141
Q

What are recurrence rates for major depression at 6 months, 2 years and 5 years?

A

i. 6 months – 25%
ii. 2 years – 50%
iii. 5 years – 70%

142
Q

What are risk factors for depression following abortion (MCQ question)?

A

a. Prior psychiatric history (e.g. MDD)
b. Younger age at time of abortion
c. Second trimester > first trimester
d. Lack of social supports
e. Sociocultural groups antagonistic to abortion
*Psychological problems immediately post-abortion is not a risk factor

143
Q

What are the best acute treatment options for rapid-cycling bipolar disorder?

A

a. Valproic acid
b. Olanzapine
c. ECT
d. If no other options, use lithium & valproic acid combination

144
Q

What are the Melancholic Features for Major Depressive Disorder?

A
  • Lack of pleasure in all activities OR lack of reactivity to pleasurable stimuli
  • 3 of 6 of the following
  • Distinct quality of depressed mood
  • Early morning awakening
  • Worse mood in AM
  • Guilt is excessive or inappropriate
  • Anorexia or weight loss
  • Psychomotor retardation
145
Q

What are the ranges for the BDI-II in terms of depression?

A

<7-10 is nondepressed
10-14 is mildly depressed
15-22 is moderately depressed
23+ is severely depressed

Note: CES-D (Centre for Epidemiologic studies scale for depression) is another validated self-report scale. It is a 20-item
scale scored from 0-3 with scores ranging from 0-60. Scores of 16 or higher indicates depressive illness. Designed for
community samples as opposed for psychiatric patient populations, which is the case for the BDI

146
Q

What are the scoring ranges for the HAM-D

A

a. 0-7 = no depression
b. 8-13 = mild depression
c. 14-18 = moderate depression
d. 19-22 = severe depression
e. >23 = very severe depression

147
Q

What is a self-report and clinician administered rating scale for mania?

A

a. Mood disorder questionnaire (MDQ)
i. Self-report
ii. 3 questions - Question 1 has 13 yes-no items
iii. Positive test = Q1 at least 7/13 + Q2 “yes” (all at same time) + Q3 at least moderate problems
iv. Informs you to screen more closely for mania and bipolar disorder
b. Young Mania Rating Scale (YMRS)
i. Clinician rated
ii. 11 items with 7 items 0-4 and 4 items 0-8
iii. Scoring cut-offs: <13 = not significant symptoms, 13 = minimal severity, 20 = mild, 26 =
moderate and 38 = severe (max = 60)

148
Q

What is first-line treatment for acute bipolar II depression in CANMATS?

A

None. Lithium, DVP, LTG, quetiapine, antipsychotic + antidepressant, Li + DVP and Li/DVP + antidepressant are all 2nd
line. LTG and Li are recommended for bipolar II disorder maintenance

149
Q

What proportion of patients with BD only have manic episodes?

A

10-20%

150
Q

What to do in failure to induce seizure in ECT?

A

Check contact between electrodes
o Increase intensity by 25 to 100%
o Change anaesthetic agent to minimize increases in seizure threshold
o Hyperventilation lowers seizure threshold
o IV caffeine sodium benzoate 500-2000mg 5 to 10 minutes before the
stimulus also lowers seizure threshold.

151
Q

When to avoid antidepressants in BD I?

A

mixed episode or history of rapid cycling

1_Psychiatry Royal College 2017 (6 decks)

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