Mood Disorders

Compiled By

Salina Chan, R3

Asia Karakoc, R2

2013

Today We’ll Talk About…Major Depressive Disorder

Treatments

BipolarTreatments

Persistent depressive disorder (dysthymia)

Cyclothymia

Adjustment d/o

Major Depressive Disorder

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.

Major Depressive DisorderM - SIGECAPSM - SIGECAPS

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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

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

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

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

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

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

MDD Videohttps://www.youtube.com/watch?v=4YhpWZCdi

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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

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

Depressive Symptoms d/t…

Medical Conditions

MS

Stroke

Hypothyroidism

Anemia

Medications

Anticonvulsants

Beta blockers

CCB

Estrogen

Opioids

MDD TreatmentLifestyle

nutrition, exercise, socialize, Omega 3s

Meds SSRIs SNRIs NDRI Mirtazapine Tricyclics, MAOIs

Psychotherapy Cognitive-Behavioral Therapy, Interpersonal Therapy,

Family

ECT

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”

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.

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

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)

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

Common adverse effects of antidepressants

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

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

Psychotherapy Details with Anxiety

lecture! *Cognitive Behaviour

Therapy

Family Therapy

Supportive Therapy

*Interpersonal therapy

Dialectic Behavior Therapy

Psychodynamic Therapy

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

BIPOLAR

:):

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

GST PAID by Bipolar Buyer

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

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

Bipolar DisordersBipolar Type I

At least one manic episode

Bipolar Type IIAt least one Major Depressive Episode and

one Hypomanic Episode

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

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

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

Bipolar MSESpeech & Thought

Form

Pressured speech

Flight of ideas

Distractibility

Tangential

Thought Content

Grandiosity

Paranoia

Religious preoccupation

Bipolar Videohttps://www.youtube.com/watch?v=zA-fqvC02o

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

Other TreatmentsPsychotherapy

Re: medication compliance

ECTFor prolonged or severe maniaBipolar depression

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

The Dysthymia Dog CHASES its Tail

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

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

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.

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

Thank-you! QUESTIONS?

:):

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)

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)

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