Mood Flashcards

Question

Comorbidities in MDD

Answer 1

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

Answer 2

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

Answer 3

Severely suicidal patient Psychotic depression

Answer 4

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

Answer 5

Hepatic disease

Answer 6

insidious onset, persistent course

Answer 7

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

Answer 8

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

Answer 9

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

Answer 10

 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

Answer 11

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

Answer 12

(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

Answer 13

(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

Answer 14

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

Answer 15

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

Answer 16

ODD (give Dx of DMDD) Bipolar disorder (give dx of BD) Intermittent explosive disorder Note: CAN coexist with conduct d/o, MDD, ADHD etc

Answer 17

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

Answer 18

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

Answer 19

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

Answer 20

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)

Answer 21

``` 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) ```

Answer 22

(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

Answer 23

* *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

Answer 24

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)

Answer 25

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)

Answer 26

Quetiapine and Quetiapine XR

Answer 27

Lithium Lamotrigine Quetiapine

Answer 28

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

Answer 29

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

Answer 30

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

Answer 31

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

Answer 32

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.

Answer 33

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)

Answer 34

(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**

Answer 35

CBT, MBCT (2016)

Answer 36

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

Answer 37

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

Answer 38

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

Answer 39

 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**

Answer 40

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

Answer 41

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

Answer 42

75% of thetime in women, 67% of the time in men

Answer 43

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

Answer 44

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

Answer 45

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

Answer 46

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

Answer 47

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

Answer 48

(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

Answer 49

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

Answer 50

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

Answer 51

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

Answer 52

 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

Answer 53

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

Answer 54

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

Answer 55

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

Answer 56

\* 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

Answer 57

\* 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

Answer 58

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

Answer 59

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

Answer 60

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)

Answer 61

40% 1st degree relatives: 2-4x chance of having MDD one parent: 10-25% risk, both: 20-50%

Answer 62

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)

Answer 63

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

Answer 64

\* 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}

Answer 65

\* ≥ 3 manic sx during most of MDE

Answer 66

 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)

Answer 67

 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

Answer 68

Structural:  Decreased hippocampal volume Functional:  Increased activity in Amygdala and Medial Prefrontal Cortex  Reduced activity in Dorsolateral Prefrontal Cortex

Answer 69

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

Answer 70

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

Answer 71

\* 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

Answer 72

\* 12mo prevalence: 2-6%

Answer 73

stress, trauma, seasonal changes, no OCP

Answer 74

\* 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} \*

Answer 75

 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)

Answer 76

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

Answer 77

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)

Answer 78

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

Answer 79

* 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

Answer 80

•: 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?

Answer 81

* 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

Answer 82

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

Answer 83

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

Answer 84

BDI-II HAM-D MADRAS Zung Self-Rating Depression Scale PHQ-9

Answer 85

\* 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

Answer 86

 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

Answer 87

 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

Answer 88

 Lithium  Lamotrigine  Divalproex  Combinations

Answer 89

Divalproex combinations

Answer 90

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

Answer 91

(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)

Answer 92

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

Answer 93

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

Answer 94

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

Answer 95

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

Answer 96

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

Answer 97

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

Answer 98

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

Answer 99

\* 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

Answer 100

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)

Answer 101

Clozapine  Tamoxifen / Adjunctive Tamoxifen ## Footnote 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

Answer 102

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)

Answer 103

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

Answer 104

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

Answer 105

Long-term psychodynamic psychotherapy

Answer 106

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

Answer 107

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

Answer 108

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

Answer 109

 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

Answer 110

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

Answer 111

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

Answer 112

Quetiapine at 300 mg daily.

Answer 113

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)

Answer 114

Hypothyroidism Substance use Female gender

Answer 115

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

Answer 116

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

Answer 117

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

Answer 118

- 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

Answer 119

\<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

Answer 120

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

Answer 121

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)

Answer 122

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

Answer 123

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.

Answer 124

mixed episode or history of rapid cycling