Depression

Highlighted = RAT

How many adults over the age of 18 experience at least 1 episode of depression in the US in any given 2-week period?

>17.3 million

What % of individuals over 20 years of age in the US experience depression at any given 2-week period?

8.1%

What causes depression?

probably multifactorial

•  genetic predisposition, psychological stressors, and underlying pathophysiology

1st degree relatives are ___ x more likely to develop MDD

2-4x

T/F: Stress always leads to depression

False

• Acute stressors may precipitate depression

• Chronic stressors cause longer duration of episodes and are more likely to lead to relapse and recurrence

Describe the biogenic Amine and Receptor hypothesis

Deficiency of NE, DA or 5-HT at the synapse

• Suggests that depression is related to upregulation of monoamine neurotransmitter receptors in response to depletion of monoamine NTs

• Chronic administration of antidepressants alters receptor sensitivity causing desensitization or downregulation of monoamine NTs → therapeutics response

What are other neurobiological hypothesis of depression?

• Neutrophy + other growth factors (i.e., BDNF)

  • BDNF is decreased in depression (antidepressants reverse this)

• HPA

  • Regulation is impaired in depression (antidepressant attenuate the neuroendocrine response)

• Proinflammatory cytokines including IL-1B, IL-6, TNF-a

  • Increased levels in depression (antidepressants suppress the synthesis of these cytokines)

What are symptoms of depression?

Need 5+ S/S within a 2-week period and change is noticed to = depression

• Depressed mood**

• Markedly diminshed interest/pleasure in usual activites**

• Increased/decrease in appetite or weight gain

• Increased/decrease in amount of sleep

• Increased/decrease in psychomotor activity (ex: Agitation, retardation)

• Fatigue or loss of energy

• Feelings of worthlessness or guilt

• Diminished ability to think, concentrate, or make decisions

• Recurrent thoughts of death, suicidal ideation, or suicide attempt

**either one or the other MUST be present

Which conditions may coexist with MDD?

• Anxiety disorders

• Eating disorders

• Personality disorders

• Substance use disorders

Which medical conditions have a strong coreelation with MDD?

• Diabetes

• Coronary artery disease (CAD)

• Hypothyroidism

• Cancer

• Anemia

• Electrolyte disturbances

• Folate deficiency

• Neurologic disorders

• CVD

• Respiratory disease

Which medications are associated with depression?

• CNS depressants

  • Alcohol

  • Benzos

  • Opioids

• Corticosteroids

• Lots more…

What are the goals of treatment?

• Resolution of S/S

• Return to euthymia

• Prevention of relapse/recurrence of S/S

• Prevent suicide and suicide attempts

What nonpharmacologic therapies are available for individuals with depression?

• Interpersonal and cognitive behavioral therapy 

• Psychotherapy

• Electroconvulsive Therapy (ECT)

• Light therapy

• Vagus Nerve Stimulation

• Transcranial Magnetic Stimulation

• Physical exercise

What are potential adverse effects of Serotonin reuptake inhibiton?

• Anxiety

• Insomnia

• Sexual Dysfunction

  • Paroxetine > Fluvoxamine > Sertraline > Fluoxetine, escitalopram, citalopram

• Anorexia

• Nausea

• Gi problems

What are potential adverse effects of Norepinephrine reuptake inhibiton?

• Tremor

• Tachycardia

• Sweatting

• Jitteriness

• Increased BP (due to NE effects)

What are potential adverse effects of Alpha 1 adrenergic receptor blockade?

• Orthostatic hypotension

• Dizziness

• Reflex tachycardia

What are potential adverse effects of Histamine 1 receptor blockade?

• Sedation

• Weight gain

What are potential adverse effects of Muscarinic cholinergic receptor blockade?

• Dry mouth

• Blurred vision

• Constipation

• Urinary hesitancy

• Sinus tachycardia

• Memory problems

What are examples of TCAs?

• Despiramine

• Nortriptyline

• Imipramine

• Amitriptyline

What are examples of SNRI's?

• Desvenlafaxine

• Venlafaxine

• Duloxetine

• Levomilnacipran

T/F: Duloxetine causes increase in LFTs

True

What are potential adverse effects on Dopamine reuptake inhibiton?

• Insomina

• Euphoria

• Pyschomotor activation

• Aggravation of psychosis

What are potential adverse effects of Mirtazipine?

• Histamine 1 receptor blockade: sedation, weight gain

• 5-HT2c receptor blockade: Increased appetite, weight gain

Which antidepressants have less likelihood of causing sexual side effects? 

• Bupropion

• Mirtazepine 

• Nefazodone 

• Vortioxetine

Which antidepressant should not be received in someone having a seizure disorder?

Bupropion (TDD < 450mg)

• C/I in patients with CNS lesion, seizure hx, head trauma, anorexia, bulimia

Which antidepressants may increase blood pressure at higher doses?

SNRIs (venlafaxine, desvenlafaxine)

Which antidepressant should not be prescribed to someone having chronic liver disease?

SNRI (Duloxetine)

Which antidepressant is used primarily for sleep?

Trazodone

Which antidepressant may cause priapism (prolonged erection lasting >4 hrs)?

Trazodone (rare)

Which antidepressants have a relatively short half-life compared with other agents?

• Paroxetine

• Nefazodone (2-4hr)

• Venlafaxine (5hr)

Which antidepressant has a long half-life?

• Fluoxetine (4-6 days) → 5-week washout for MAOIs or 2-week washout for other serotonergic agents

• Vortioxetine (66hr)

What are the symptoms of serotonin syndrome?

• Confusion

• Restlessness

• Fever

• Abnormal muscle movements

• Hyperreflexia

• Sweating

• Diarrhea

• Shivering

What is the approximate response rate of each antidepressant?

50-75%

According to the APA and VA/DoD guidelines, which antidepressants are recommended first-line for Mild-Mod major depressive disorder?

• Psychotherapy

• SSRI (Not fluvoxamine)

• SNRI

• Bupropion

• Mirtazipine

According to the APA and VA/DoD guidelines, which antidepressants are recommended first-line for Severe major depressive disorder?

• Pharmacotherapy + Psychotherapy

According to the APA and VA/DoD guidelines, which antidepressants are recommended second-line for major depressive disorder?

• Alternative 1st line agent

• Add psychotherapey, bupropion, buspirone, lithium, or SGA (2nd gen)

According to the APA and VA/DoD guidelines, which antidepressants are recommended third-line for major depressive disorder?

• MAOIs

• TCAs

How do we select an antidepressant?

Use response hx and side effects (efficacy, AEs, patient satisfaction, 1st degree relatives hx to CNS depressants)

How long does it take an antidepressant to start working?

• Physical Symptoms (i.e., appetite, sleep, energy): 1-2 weeks

• Emotional Symptoms (i.e., sadness, anhedonia): 2-4 weeks (up to 6-8 weeks for full effect)

How is partial response managed?

1/3 do not respond satisfactory to their first antidepressant

• Clinician must evaluate: dosage, duration, adherence, verification of patient diagnosis, reconsideration of clinical factors that may be blocking successful treatment (current medical conditions, comorbid psychitaric conditions or substance use disorders)

• Treatment recommendations

• Extending trial and/or using higher doses within the recommended dosage range

• Augmentation therapy

  • Adding a non-antidepressant such as lithium, buspirone, or triiodothyronine, SGA, stimulants, lamotrigine

How long should an antidepressant be continued when treating the 1st depressive episode?

6-9 months (acute phase is 6-12 weeks)

What are the symptoms of antidepressant withdrawl?

• Sleep disturbances

• Anxiety

• Fatigue

• Mood changes

• Malaise

• GI issues

• HA

• NA

• Lightheadedness

• Chills and body aches

• Insomnia 

• Paresthesias

Which antidepressants are chosen frequently for geriatric depression?

• Lower starting doses and slow upward titrations are recommended

  • Favorable AE profiles and low toxicity

  • Most TCAs are avoided – anticholinergic, CV, and sedative properties

    • Desipramine and nortriptyline are more tolerable and may be used in this population

• Other newer antidepressants are recommended 

  • SNRIs, bupropion, vortioxetine, mirtazapine

  • The SSRIs are chosen frequently for geriatric depression because of their overall favorable adverse effect profiles and low toxicity

Which antidepressants are considered initially in the pediatric population?

SSRIs (lexapro, prozac)

Which antidepressants have significant toxicity risk on overdose?

TCAs and MAOIs

What drugs are activating?

• Buproprion

• SNRIs

• Fluoxetine/Setraline

• Escitalopram/Citalopram (50/50 split)

What drugs are sedating?

• Mirtazipine

• Paroxetine

What drugs cause sexual dysfinction?

• SSRIs

• SNRIs

• TCAs

What drugs cause weight gain?

• Mirtazipine

• TCAs

• Paroxetine

What drugs can cause seizures?

• Bupropion

• TCAs

• Though all antidepressants can lower the seizure threshold

Counseling points for antidepressants

• Take medication exactly as prescribed in order to have desired effects

• May take several weeks to see benefit

• Duration of therapy typically 6-12 months after response (for 1st episode)

• Medication should be continued after symptoms improve & should not be stopped w/out alerting provider

• Avoid alcohol

• Depression is a biological disorder, not a character weakness or personality flaw

• Although medication affects certain chemicals in the brain, it is not addicting 

• Mention common adverse effects + what to do if they occur

• Risk of suicidality – be alert to symptoms of worsening depression

How do you switch antidepressants?

Direct switches:

• Can be considered when converting between drugs in the same class

Cross tapering / cross titration:

• Full D/C of treatment

• Complete washout is required if an overlap of 2 antidepressants is contraindicated because of severe drug interactions

According to guidelines, what is the recommended 1st line treatment for depression?

• SSRIs

• SNRIs

• Bupropion

• Mirtazipine

• Vilazodone

• Vorioxetine

According to guidelines, what is the recommended 2nd line treatment for depression?

• TCAs

• Trazadone

• Quetiepine

• Dextromethorphan-bupropion

• Selegiline transdermal

According to guidelines, what is the recommended 3rd line treatment for depression?

• Phenelzine

• Tranylcypromine

____ has FDA indications for

• Depression

• GAD

• Social anxiety disorder

• Panic disorder

Venlafaxine

______ has FDA indications for

• Depresion

• Diabetic neuropathic pain

• GAD

• Fibromyalgia

• Chronic musculoskeletal pain

Duloxetine

_____ is an SNRI developed to target fatigue and lack of energy

Levomilnacipran (Fetzima)

What antidepressant has FDA indications for:

• Depression

• Seasonal affective disorder

• Smoking cessation

Bupropion

What are common antidepressants used for treating depression in pregnancy>

1. Sertraline

2. Escitalopram

If a TCA needs to be used, what kind would you chose first?

secondary amines (Despiramine, nortriptyline)

• Less sedative and anticholinergic effects

What is the MOA of Vilazodone (Viibryd)?

5-HT reuptake inhibition, 5HT1A partial agonist

What are adverse effects of Vilazodone?

• GI upset (high)

• Sexual dysfunction (low)

• Sedation, activation, weight gain, weight loss (minimal)

What is FDA approved for treatment-resistant depression (adjunct) depressive symptoms in adults with MDD with acute suicidal behavior or ideation?

Esketamine (Spravato)

• CIII

What is used for postpartum depression?

Brexalonone (Zulresso)

• Positive allosteroic modulator of GABAa

• CIV

Zuranolone (Zurzuvae)

• Positive allosteroic modulator of GABAa

What antidepressants are used for PTSD?

1st line: Fluoxetine, paroxetine, sertraline, venlafaxine

2nd line: Mirtazapine, Imipramine, Phenelzine