Mood disorders

Major depressive disorder what can cause it?

• Life Events

• Crucial life events (particularly death or loss of loved

one) can precede onset of depression

• Biological Theories

• Neurotransmitters – hypothesis is that depression is

caused by a neurotransmitter deficiency and that

antidepressant exert their clinical effect by targeting

this imbalance; primarily norepinephrine, serotonin,

dopamine

• Neuroendocrine factors – cortisol, thyroid, etc

• Early life stress

ACEs- adverse childhood experiences

• Genetics? Lots of controversy here

MDD signs and symptoms

Major Depressive Episode

• Depressed mood or loss of interest/pleasure that predominates for at least 2 weeks, nearly every day, most of the time

• Also 3-4 other symptoms including weight/appetite changes, sleep disturbances, psychomotor changes,decreased energy, worthlessness/guilt, concentration/decision making, suicidality

• Symptoms must cause significant distress/impairment

• Symptoms must not be due to a substance or medical condition

Anhedonia

• Inability to enjoy usual activities; almost universal

among depressed patients

• Rare to have only anhedonia and not depressed

mood

Lab diagnosis for MDD

MDD is a clinical diagnosis, not a laboratory diagnosis.

Tests are mainly there to rule out mimics/contributors, particularly things like thyroid disease, anemia, metabolic problems, and substance-related causes.

What is the course of illness for MDD

it can be single or recurrent

common is early 20s for females or late 20s for males

Symptoms typically develop over days to weeks; can follow acute stressor but not always

• Course is variable

• About 50% of patients with one depressive episode will have a recurrence, 90% of patients who have 3 episodes

can be expected to have a 4th

What can also present similar to MDD?

Bipolar depression

• CRITICAL because treatment is SO DIFFERENT

• Careful evaluation of manic/hypomanic symptoms

• Psychotic disorders

• With MDD 12-20% can have psychotic symptoms

• Psychiatric comorbidities

• Comorbid anxiety, PTSD, substance use disorder

• Medical comorbidities

MDD – Treatment

active, continuation, and maintenance phases

• Goal in active phase is to achieve remission

• Continuation/maintenance phases are to prevent early and late relapse

• Multifactorial

• Should be frequently evaluated and personalized

Acute treatment of MDD

• SSRIs are most prescribed antidepressants for MDD

• Fluoxetine, paroxetine, sertraline, citalopram, escitalopram, fluvoxamine

• Potently and selectively block reuptake of serotonin by presynaptic serotonergic neurons

• Side effects: nausea, dry mouth, weight change, agitation, anxiety, tremor, headache, sexual dysfunction, sweating

• SNRIs

• Desvenlafaxine, duloxetine, venlafaxine

• Dopamine Reuptake Inhibitor

• Bupropion ( can have less sexual side effects)

• Atypical antidepressants

• Mirtazapine

• Trazodone

Serotonin Syndrome

• Severe but low prevalence

• Agitation, muscle twitching, high fever

• Be careful of prescribing:

• TCAs

• Antimigraine meds like carbamazepine, triptans

• Pain meds like Demerol, oxycodone, tramadol

• Lithium

• OTC cold meds with dextromethorphan

• Herbal supplements like st john’s wort

• Zofran

• Linezolid

• Ritonavir

• When in doubt, I do the interaction checker on UTD – BETTER SAFE

THAN SORRY

SSRIs what drugs are they

• Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

SSRIs drugs side effects:

• nausea, dry mouth, weight changes, agitation, anxiety, tremor, headache; tend to be short-term and go away with time

• Sexual dysfunction and sweating can be persistent; can trial dosage decrease but may need to switch to bupropion/mirtazapine if sexual dysfunction is of high concern to patient

Antidepressant withdrawal syndrome

• After long term SSRI therapy about 10-15% of patients may experience a withdrawal syndrome, especially if they stop rapidly

• Paresthesia, dizziness, irritable/anxious mood, nausea, insomnia, tremors, vivid dreams

• Can last up to 3 weeks

• Tapering rather than sudden discontinuation can minimize this

SNRIs drugs

• Venlafaxine, desvenlafaxine, duloxetine

SNRIs what do they target

serotonin and norepinephrine

SNRI side effects

Very similar side effects to SSRIs; also

tachycardia, increased BP

Dopamine Reuptake Inhibitor drug

• Bupropion

• Good first line med for patients with severe anhedonia, lack of energy, poor concentration, hypersomnia

• Good if sexual side effects are limiting factor for SSRIs/SNRIs

Bupropion side effects

• Headache, insomnia, dizziness, agitation, decreased appetite/weight loss, dry mouth, nausea, constipation,tachycardia, pharyngitis

• CAN LOWER SEIZURE THRESHOLD; ContraIndicated for patients with seizure disorders

• Also ContraIndicated for patients with eating disorders, brain tumors, TBI, AV malformations, severe stroke

• CAN CAUSE FALSE POS FOR AMPHETAMINE AND METHAMPHETAMINE ON Urine drug analysis

TCAs whcih are the tertiary and secondary drugs

• Tertiary: amitriptyline, clomipramine, doxepin, imipramine

• Secondary: desipramine, nortritpyline, protryptyline

Excessive stopping of TCAs can cause what?

a withdrawal syndrome including excessive salivation, headache, vivid

dreams

• Before SSRIs became available, TCAs were number one med causing death by overdose

MAOIs drug examples

• Selegiline, phenelzine, etc

MAOIs common side effects

dry mouth, nausea, diarrhea, constipation, orthostatic hypotention, sexual

dysfunction

Main concern for MAOIs is?

hypertensive crisis – headache, diaphoresis, anxiety, high BP, neck stiffness;

can lead to cerebral hemorrhage/death

Ketamine/Esketamine

• NMDA antagonist

• Nasal spray given under direct observation of

medical provider in office/clinic

• Typically given twice weekly for first 4 weeks, then

tapered down for maintenance

• Treatment resistant MDD

different types of Psychotherapeutic Interventions

CBT-cognitive behavioral therapy

Interpersonal therapy

brief psychodynamic therapy

DBT- dialectical behavior therapy

family/couples therapy

Cognitive behavioral therapy what is it ?

“Change your thoughts → change your behaviors → feel better.”

Thoughts + behaviors

Interpersonal therapy (IPT) what is it?

“What is happening in your relationships that is affecting your mood?”

Relationships

Brief psychodynamic therapy what is it?

“What unconscious/emotional patterns from your past are affecting you now?”

Unconscious patterns + past experiences

Dialectical behavior therapy what is it?

“Learn skills to handle intense emotions and difficult situations.”

Emotional/behavioral skills

Family/couples therapy what is it?

“Let's improve the relationship/system around the patient.”

Family/partner relationships

ECT: Electroconvulsive Therapy

ECT has NO absolute contraindications, but certain brain, heart, and structural conditions increase the risk of complications.

First line treatment for MDD (mild depression)

Mild Depression:

•Psychotherapy alone (CBT or interpersonal therapy)

•Evidence-based psychological procedures are recommended as first-line before medications

treatment for moderate to severe depression

SSRI (fluoxetine, sertraline, paroxetine, or citalopram) PLUS psychotherapy

•SSRIs are first-line due to efficacy and favorable side effect profile

DSM-5 diagnosis

(≥5 symptoms for ≥2 weeks)

Persistent Depressive Disorder(dysthymia)

• NO history of a major depressive episode

• Persistently depressed mood for at least 2 years

• Never symptom free for at least 2 months

• At least 2 additional symptoms (same as MDD symptoms)

• Can be diagnosed independently of MDD

Persistent Depressive Disorder(dysthymia) first line treatment

SSRI and therapy

Premenstrual Dysphoric Disorder PMDD

• Cyclic reoccurrence of symptoms beginning in luteal phase and resolving with onset of menses

• Symptoms interfere with functioning

• Symptom free interval in first half of menstrual cycle

Premenstrual Dysphoric Disorder PMDD treatment

First line is SSRIs (sertraline or fluoxetine are ACOG’s drugs of choice); can be taken continuously or luteal phase only

• Drospirenone containing contraceptives (Yaz, Slynd, Nextellis)

May not help with mood symptoms

• Refractory cases: GnRH agonists with hormonal add back therapy (not recommended for adolescents) or bilateral salpingo-oophorectomy

Seasonal Affective Disorder

• Characterized by more than 5 of the 9 depression

symptoms present nearly every day for over two weeks,

for most of the day, causing significant functional impairment

• Occurs most commonly in seasons of lower light ie winter

Seasonal Affective Disorder treatment

• Antidepressants (SSRIs, SNRIs)

• Psychotherapy

• SUNLIGHT (real or fake)

Cyclothymic Disorder

• Chronic mood disorder characterized by cycling

between hypomanic symptoms and depressive

symptoms that don't meet full criteria for manic,

hypomanic, or major depressive episodes,

lasting ≥2 years in adults (≥1 year in children)

• 15-50% of cyclothymic patients will progress to

bipolar I or II disorder

• Often goes undiagnosed due to milder symptom

severity

• Chronic mood instability with fluctuations

between up and down periods; cause functional

impairment but never reach threshold for full

BPD or MDD

Cyclothymic Disorder no symptom free period longer than ___ months?

2

Cyclothymic Disorder symptoms must ______ functioning

impair

Cyclothymic Disorder treatment

confirm diagnosis

• Psychoeducation/therapy

• CBT, interpersonal therapy, family focused therapy

• Lifestyle Interventions

• Mood Stabilizer (no FDA approved meds specifically for cyclothymia)

First line mood stabilizer for cyclothymia

Lamotrigine, Lithium, Valproate

second line mood stabilizer for cyclothymia

Quetiapine, aripirazole

Bipolar I Disorder

At least 1 manic episode (greater than or equal to 7 days or

any duration requiring hospitalization) with persistently

elevated/irritable mood, increased energy, and >3 DIG-FAST

symptoms (4 if mood only irritable)

• Manic episodes cause severe functional impairment and may

include psychotic features

• Common to also have depressive episodes but NOT

REQUIRED FOR DIAGNOSIS

• mood episodes alternate between mania, hypomania, and

depression with periods of stable mood; can switch directly

from one pole to the other without intervening euthymia

DIG FAST stand for?

Distractibility

Impulsivity or irresponsibility such as risky behaviors

Grandiosity

Flight of ideas

Activity

Sleep decreased

Talkativeness

Acute Mania Treatment

First line: Lithium, valproate, carbamazepine

• Remember lithium works well but requires close monitoring

• Valproate/carbamazepine have faster onset, monitor LFTs

• If needed, add second gen antipsychotic: quetiapine, olanzapine, risperidone, aripiprazole

Acute mania is a _____________; consider hospitalization if patient is a danger to self or others or is unable to care for themselves

psychiatric emergency

Acute Bipolar Depression

• Still need to avoid SSRI monotherapy because of risk of rapid cycling into mania

• Quetiapine, lurasidone, Lamictal, lithium

Maintenance Phase for acute bipolar depression

• Continue acute phase meds

• Lithium reduces recurrence by 50% at optimal doses

• Valproate/carbamazepine useful for rapid cycling or mixed states

• Best practice is to combine antipsychotic with mood stabilizer

Bipolar II Disorder

• Requires 1 or more depressive episodes and at least one hypomanic episode lasting more than 3 days;

NO manic episodes

• Often misdiagnosed as MDD since patients typically present during depressive episodes

• Depressive episodes more frequent, longer-lasting, and more severe than in bipolar I

Mania (Bipolar I)

• Severe impairment and/or psychotic features present

• Lasting at least 7 days or any duration if hospitalization required

Hypomania (Bipolar II)

• No severe impairment, no psychotic features

• Lasting at least 4 days

Acute Bipolar II Depression treatment

• Only quetiapine monotherapy is FDA approved specifically for bipolar II depression

• Lamotrigine, pramipexole, modafinil, armodafinil show efficacy in trials

• AVOID ANTIDEPRESSANT MONOTHERAPY – risk unmasking mania/hypomania and destabilizing illness

Acute Bipolar II Depression for maintenance therapy

Mood stabilizer: lithium, valproate, lamotrigine

• Add second gen antipsychotic if mood stabilizer monotherapy ineffective

• Lamotrigine particularly useful for preventing depressive episodes

• Psychoeducation and psychotherapy

• Treatment resistant patients: ECT, TMS

Disruptive Mood Dysregulation Disorder (DMDD)

• Childhood specific diagnosis; children ages 6-18 yo

• Chronic, persistent severe irritability and temper outbursts lasting at least 12 months

• Symptoms/outbursts present in at least 2 settings

• More common in males; typically first presents in school age children

• Common co-morbidities

• Conduct disorder

• Impulse control disorders

• Disruptive behavior disorders

• ASD

Disruptive Mood Dysregulation Disorder (DMDD)

First line is Psychotherapy focusing on emotional regulation, coping skills, problem solving, frustrationtolerance

• Parent Management Training (PMT)

• Consistent consequences, positive reinforcement, predictable routines, reducing reinforcement of outbursts

• School interventions

• Treat comorbid disorders

• If severe irritability; second gen antipsychotics like risperidone, aripiprazole