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Mood Disorders
Compiled By
Salina Chan, R3
Asia Karakoc, R2
2013
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Today We’ll Talk About…Major Depressive Disorder
Treatments
BipolarTreatments
Persistent depressive disorder (dysthymia)
Cyclothymia
Adjustment d/o
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Major Depressive Disorder
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Major Depression StatsPublic Health Agency of Canada/ Statistics Canada:
Lifetime prevalence of major depression: 12.2%, past-year episodes: 4.8%
The peak annual prevalence occurred in the group aged 15 to 25 years.
Female to male ratio 2:1
Worldwide, major depression is the leading cause of years lived with disability.
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Major Depressive DisorderM - SIGECAPSM - SIGECAPS
MoodMoodSleepSleepInterestInterestGuiltGuiltEnergyEnergyConcentratioConcentratio
nnAppetiteAppetitePsychomotor Psychomotor Suicidal Suicidal
ideationideation
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Major Depressive DisorderCriteria
Depressed Mood; OR Markedly diminished
Interest/pleasure 4 other symptoms
(5/9 total)
Most of the day, almost every day
2 weeks duration
Other Symptoms Weight or appetite changes
Fatigue or loss of energy
Feelings of worthlessness or excessive or inappropriate guilt
Diminished ability to think/concentrate or indecisiveness
Insomnia or hypersomnia
Psychomotor agitation or retardation
Recurrent thoughts of death, recurrent SI, SA
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Major Depressive DisorderChange from previous function
Symptoms cause clinically significant distress or impairment in social, occupation or other important area of functioning
Episode not attributable to physiological effects of a substance or to another medical condition
Not better accounted for by SczA, Scz, delusional d/o or other psychotic d/o
Never been manic or hypomanic episode
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Major Depressive Episode Specifiers
Melancholic
Loss of pleasure or lack of mood reactivity + 3 of: Distinct depressed mood,
worse in morning early awakenings psychomotor changes weight loss guilt
Atypical
Mood Reactivity + 2 of: Chronic rejection
hypersensitivity leaden paralysis hypersomnia increased appetite
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Major Depressive Episode Specifiers
Peri-Partum Onset of episode during pregnancy or within 4 weeks
postpartum
With Seasonal Pattern Onset and offset at particular times of year MDE never in a different season in past 2 years
With Psychotic Features Hallucinations or delusions
With Anxious Distress Feeling 2 or more of keyed/tense, restless, difficulty
conc b/c of worries, fearing something awful may happen, feeling might lost control
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Major Depressive Episode MSE
Appearance
Normal to Poor kempt/hygiene
Psychomotor retardation or agitation Objective or subjective
Mood & Affect
May deny being sad but look it
“depressed”, “down in dumps”, “sad”, “hopeless”, “discouraged”, “blah”, “have no feelings”, “anxious”
Irritability, down, depressed, low, heavy, anxious, tense
Lability, Range restriction
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Major Depressive Episode MSE
Speech & Thought
Latency (may be long!)
Circumstantial
may be preoccupied with somatic complaints, death, hopelessness, personal defects
Ruminations about past failings
Delusions of guilt
guilt/responsibility not limited to being sick and not meeting occupational/interpersonal responsibilities
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MDD Videohttps://www.youtube.com/watch?v=4YhpWZCdi
Zc
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MDD DifferentialManic episode with irritable mood or mixed
episodes
Mood d/o due to another medical condition
Substance/medication-induced depressive disorder
ADHD
Adjustment d/o with depressed mood
Normal sadness
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BereavementBereavement MDE
Primary feelings
Emptiness/ loss Depressed mood, loss of pleasure
Timing Waves of grief, ↓intensity
Persistent low mood
Thoughts Preoccupation with deceased
Self-critical, pessimistic
Self-esteem Preserved Worthlessness/self-loathing
Suicide “joining deceased” Worthless, hopeless, pain
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Depressive Symptoms d/t…
Medical Conditions
MS
Stroke
Hypothyroidism
Anemia
Medications
Anticonvulsants
Beta blockers
CCB
Estrogen
Opioids
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MDD TreatmentLifestyle
nutrition, exercise, socialize, Omega 3s
Meds SSRIs SNRIs NDRI Mirtazapine Tricyclics, MAOIs
Psychotherapy Cognitive-Behavioral Therapy, Interpersonal Therapy,
Family
ECT
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Antidepressants: SSRIsSSRI – Selective Serotonin Reuptake inhibitor
Fluoxetine (Prozac): 10 to 60 mgFluvoxamine (Luvox): 50 to 300 mgSertraline (Zoloft): 25 to 250 mgParoxetine (Paxil): 10 to 60 mgCitalopram (Celexa): 10 to 60 mgEscitalopram (Cipralex): 10 to 20 mg
First line: any, escitalopram- some evidence for superiority, or “select one based on patient’s presentation & med SE profile”
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Common SEs of SSRIsHeadaches or dizziness
Weight/appetite fluctuations
Nausea, loss of appetite, diarrhea.
Anxiety or irritability.
Problems sleeping or drowsiness.
Loss of sexual desire or ability.
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Serotonin SyndromeResults from excess serotonergic activity centrally
(5HT1a, 5HT2)
Onset within 24 hours of initiating a serotonergic agent
Signs and Symptoms Cognitive: agitation, delirium, hallucinations, coma Autonomic: shivering, diaphoresis, hyperthermia,
hypertension, tachycardia, diarrhea Neurologic: myoclonus, hyperreflexia, tremor
Untreated or unrecognized may lead to rhabdomyolysis, renal failure, seizures
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Serotonin SyndromeSymptoms are self-limited with removal of
offending agent(s)
Supportive treatment targeting specific symptoms or medical consequencesCooling, hydration, antihypertensives,
anticonvulsants, Benzodiazepines to manage agitationSerotonin receptor antagonists (cyproheptadine)
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Other AntidepressantsSNRI: Serotonin Norepinephrine Reuptake Inhibitor
Venlafaxine (Effexor): 37.5mg to 450mg Desvenlafaxine (Pristiq): 50-400mg Duloxetine: (Cymbalta): 60 mg
NDRI: Bupropion (Wellbutrin) Bupropion SR 100 mg to 450 mg Bupropion XL 150 mg to 400 mg
NaSSA: Mirtazapine (Remeron) 15mg to 60 mg
Serotonin-2 antagonist/reuptake inhibitor: Trazadone: 50 to 400 mg
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Common adverse effects of antidepressants
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Old AntidepressantsMAOIs
Not first line
SE Hypertensive Crisis; if combined with foods containing tyramine (unpasteurized cheese, herring, unpasteurized meats, some beers and wines)
Phenelzine (Nardil): 15 mg BID to TID
Tranylcypromine (Parnate): 10 mg BID to TID
Meclobemide (Mannerix) – reversible MAOI
TCAs
Not first line
SE include: dizziness, sedation, blurred vision, urinary retention, constipation, dry mouth
Risk of cardiac arrhythmias if OD
Nortriptyline, Amitriptyline
Desipramine, Imipramine
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Starting MedicationsStart low, go mod-slow , aim for lowest
efficacious dose, hold & assess, go up if still symptomatic, don’t go beyond usual highest doseEscitalopram: start at 5mg x 1-2 weeks, then
increase to 10mg.Sertraline: start with 25mg and increase by 25mg
every week until 150-200mgVenlafaxine: start 37.5mg and increase by 37.5mg
per week till 150mg
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Psychotherapy Details with Anxiety
lecture! *Cognitive Behaviour
Therapy
Family Therapy
Supportive Therapy
*Interpersonal therapy
Dialectic Behavior Therapy
Psychodynamic Therapy
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ECTGold Standard treatment for depression
Most efficacious with least side effects
Main side effects: memory loss
1st line for acute catatonia/psychosis/ suicidality/patient’s preference
Also used for refractory cases
May take up to 15 sessions before effect seen
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BIPOLAR
:):
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Bipolar Disorder CriteriaAbnormally elevated, expansive or irritable
mood
and
Persistently increased goal-directed activity or energy
Plus 3 (4 if mood = irritable) of possible associated symptoms
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GST PAID by Bipolar Buyer
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GST PAID
Bipolar Disorder
Grandiosity (inflated self esteem)
Sleep (less)
Talkative (Pressured speech or talking more)
Pleasurable activities with painful consequences spending, sex, speed, substances, foolish investments, gambling
Activity increased (Goal-directed or psychomotor agitation)
Ideas, Flight of (or racing thoughts)
Distractable
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Bipolar DisorderManic
>7 days marked impairment in
social/occupational functioning OR hospitalization
Possible psychotic features
Hypomanic
>4 days Not severe enough to
cause marked impairment/psychosis .
No hospitalization needed
No psychotic features
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Bipolar DisordersBipolar Type I
At least one manic episode
Bipolar Type IIAt least one Major Depressive Episode and
one Hypomanic Episode
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Q: What is a Mixed Episode?
No longer a Dx
Now a mixed features specifier for MDD or Bioplar
MDD> 3 manic/hypomanic symptoms that don’t
overlap with symptoms of major depression
Hypomania/Maniathe presence of at least three symptoms of
depression in concert with the episode of mania/hypomania
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Bipolar disorder statsBipolar I disorder: 12mo prev 0.6%, mean age
18
Bipolar II disorder: 0.8%, early 20s
Male: female ratio 1.1:1 (BPI)
Females: more rapid cycling, mixed episodes, depressive symptoms
12% of originally diagnosed MDE bipolar
5-15% of bipolar II bipolar I
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Bipolar MSEAppearance
Flamboyant, better hygiene than normal
Psychomotor activity: exaggerated hand gestures, getting up from chair frequently
Intense eye contact
Mood & Affect
“anxious”, “happy”, “angry ”
Elevated, ecstatic, euphoric, irritable, worried
Quick liability between extremes
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Bipolar MSESpeech & Thought
Form
Pressured speech
Flight of ideas
Distractibility
Tangential
Thought Content
Grandiosity
Paranoia
Religious preoccupation
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Bipolar Videohttps://www.youtube.com/watch?v=zA-fqvC02o
M
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Bipolar Disorder Differential
Bipolar I
MDD
Anxiety d/o
Substance/Medication-induced
ADHD
Personality d/o
Disorders with prominent irritability
Biopolar II
Bipolar II MDD
Cyclothymic disorder
Scz spectrum & oter related d/o
Anxiety d/o
Substance-use d/o
ADHD
Personality d/o
Bipolar I
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Bipolar Disorder TreatmentLifestyle
eat well, exercise, socialize, SLEEP!!!
Meds Mood Stabilizers Antipsychotics Lamotrigine – for depression only + SSRIs (usually with a mood stabilizer or anti-
psychotic)
Psychotherapy Case Management, Mental Health Teams
ECT
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Mood Stabilizers Lithium, Valproic Acid, Carbamazepine
Drugs of choice for bipolar disorder, schizoaffective disorder and cyclothymia
Acute mania and prophylaxis of mania and depression in bipolar disorders
Less effective for bipolar disorder depression
Sometimes used for impulse control disorders, aggressive behaviour and mood management in personality d/o
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LithiumUsed in Bipolar mania, but also popular as an
antidepressant augmenter (especially resistant)
Forms: regular, slow release, liquid
300-1200mg total daily dose (OD or BID dosing) Start with 300mg OD/BID
Dose increased over 7 to 10 days until plasma level 0.8 to 1.2 mEq/L (0.8 to 1.2 mMol/L) for acute mania
Lower in elderly (0.4 –1.0) 0.6 to 0.8 mEq/L for maintenance Usual dose range: 900 mg/day to 2100 mg/day Make sure to measure levels 12 hrs after the preceding
dose
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LithiumBaseline Labs: BUN, Creat, lytes, FBG, TSH, fT4,
ECG>40yrs or cardiac disease
Effects: 2 weeks, need 4-8 weeks for trial (7-14 days for acute mania)
Levels: drawn on day 5, usually weekly for first 1-2 month, then q2-4wks.
Watch TSH and Creat q6months
For side effects relief always think sustained release or spreading the dose aroundFor tremor consider beta blocker
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Predictors of Lithium Response
Previous or family history of response
Few previous manic episodes
“Classic mania” (not mixed)
Lack of rapid cyclingLess effective than Valproic Acid in rapid cycling
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Lithium: SEsAcute SE
GI (nausea, diarrhea)
Neuro (drowsiness, cognitive dulling, fine hand tremor)
Metabolic (wt gain)
Derm (rash, worsening of psoriasis, acne)
GU (polydipsia/polyuria, DI)
Hematologic (mild leukocytosis common)
Long-term SE
Hypothyroidism (20%)
GU: impaired concentration of urine, DI, renal parenchymal changes, rare kidney failure
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Lithium: Toxicity/OverdoseSymptoms:
Mental status changesNausea/VomitingIncontinenceCourse hand tremorDysarthriaGait ataxiaCardiac: depressed ST segments, T wave inversions, arrhythmias
CAN BE FATAL
Causes:
Dehydration, NSAIDs, ACEi, diuretics can increase Li levels
Management: Stop lithium Supportive medical care Draw lithium levels Dialysis if serum level >
4 or if clinically indicated
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Valproic AcidEffective for bipolar disorder, schizoaffective
disorder, cyclothymia
More effective than lithium for rapid cycling and mixed state episode bipolar disorder
Can also be used for impulse control disorders, aggression and Cluster B personality disorders
May take up to 14 days to see antimanic effect
Trial of 4 to 6 weeks should be completed
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Valproic Acid - Dosing Starting dose: 20 mcg/kg for rapid stabilization
of maniaApprox: 500 mg TID or 750 mg BID
Titrate up to serum level of 50 to 125mg/mL (350 – 700) = Avg maintenance dose: 1500 to 3000mg/day Available in once daily or divided doses
Elderly require approximately half that of younger adults
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Valproic AcidLabs
Baseline: CBC, LFTs
Serum levels, CBC, platelet count, and PT/PTT should be done weekly during first month
Serum levels, CBC, LFTs Q3-6months
SEs
Favourable SE profile and lower toxicity compared to Lithium
Nausea, diarrhea, headache, sedation, fine tremor, weight gain, alopecia, leukopenia, neutropenia, thrombocytopenia, elevated LFT’s – in rare cases liver failure and/or pancreatitis
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Lamotrigine Anticonvulsant
Indicated for bipolar depression
More effective in the treatment of bipolar depression compared to other mood stabilizers
Also used in treatment resistant unipolar depression
Used as monotherapy or adjuncive tx to other mood stabilizers and/or antidepressants
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Lamotrigine – DosingInitial dose: 25 mg OD, increased weekly by 25
mg/week until you reach 200 mg/day
Up to 400 mg may be required to treat depression
Once or twice daily dosing usually qhs
Therapeutic effect may be seen in 2 to 4 weeks
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LamotrigineLabs
Baseline: renal and hepatic fx (both involved in excretion)
Serum levels not useful as therapeutic window not yet determined
SEs
Very well tolerated by most patients
HA, somnolence, nausea, diarrhea, dizziness, ataxia, diplopia, blurred vision
RASH (10%): limbs
Steven – Johnson (0.3%): chest, neck, face, oral mucosa
If rash of any sort advise pt to DC and see MD immediately
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CarbamazepineAnticonvulsant
Used in pts who do not respond to lithium
Starting dose: 200 mg BID
Maintenance dose: 800 to 1600 mg/dayDivided BID or TID to minimize SE
Serum level 25 to 60 mM
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Carbamazepine – SEsAgranulocytosis and aplastic anemia (1 in 20
000)
Induction of liver enzymes: effects most psych meds, decreased effectiveness of OCP, auto–induction (half life and serum level decrease with time)
SJS reported (rare)
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Second Generation Antipsychotics:
Evidence for efficacy as monotherapy and add-on mood stabilizers for:Risperidone, Olanzapine, Quetiapine
Same doses as treating psychotic d/oRisperidone 4-8mg/dOlanzapine 15-35mg/dQuetiapine 600-900mg/d
More info about antipsychotics with Psychosis lecture
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Other TreatmentsPsychotherapy
Re: medication compliance
ECTFor prolonged or severe maniaBipolar depression
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Persistent Depressive Disorder (Dysthymia)
Depressed Mood most of the day, for more days than not, for > 2 yrs Children: mood can be irritable & > 1 yearNot without symptoms for > 2 months at a
time
> 2 of 6 following (CHASES):Concentration, poor or difficulty making
decisionsHopelessnessAppetite, poor or increasedSleep, decreased or increasedEnergy lowSelf-esteem low
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The Dysthymia Dog CHASES its Tail
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CyclothymiaNumerous periods of Hypomanic symptoms and
Numerous periods of depressive symptoms for 2 years.
No full manic, hypomanic or major depressive episode
Not symptom-free for > 2 months
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Adjustment DisorderEmotional or behavioural symptoms in response
to an identifiable stressorOccurs within 3 months of onset of stressorMarked and excessive distressSig impairment in important areas of functioningSymptoms don’t persist > 6 months after stressor
or its consequences have ended
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Adjustment Disorder Specifiers
With depressed mood
With anxiety
With mixed anxiety and depressed mood
With disturbance of conduct*
With mixed disturbance of emotions and conduct
Unspecified *abnormal conduct violating the rights of others or
going against societal norms. Ie. truancy, vandalism, reckless driving, fighting, or defaulting on legal responsibilities.
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SummaryDepression:
Bereavement exclusion gone, but use clin judgement
MAOi/TCAs rarely usedAnti-depressants equally efficacious S/E profileWatch for serotonin syndrome
Bipolar disorder:New criteria: mood PLUS energy/ goal-directed
activityWatch for lithium toxicity
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Thank-you! QUESTIONS?
:):
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Hypertensive Crisis: “the cheese reaction”
Tyramine causes a potent release of NE
In the absence of an MAO-I, tyramine is broken down by MAO-A in the gut, liver and any NE released is broken down in the synaptic cleft
Normally a person can ingest 400mg of tyramine with no increase in BP (a high tyramine meal only has 40mg)
Drug-drug interactions can also lead to hypertensive crises (decongestants, stimulants, SNRIs)
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TCA OverdoseMost symptoms related to anticholinergic load:
delirium, tachycardia, dilated pupils, ileus
Seizures and coma (mechanism poorly understood)
Cardiotoxicity mediated via the Na channel blockadeArrhythmias ECG changes: QT prolongation, widening of the
QRS, AV blockade, V tach
Severe hypotension (a-adrenergic blockade)
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TCA Overdose Management
Hospitalization, cardiac monitoring (continue for 24 hours after signs of toxicity have resolved)
Charcoal
IV fluid resuscitation
Bicarb infusion to treat acidosis
Psychiatric consult