Depressive Disorders (Andress)

How do symptoms progress

Symptoms are gradual

At what PHQ-9 test score do you begin treatment

10-14: moderate

What are some risk factors for depression

• Women > Men

• Prior episodes or suicide attempts

• Comorbid medical or substance related disorders

• Lack of support

• Psychological events or stress

• Genetic and enviornmental factors

Phases of Treatment

• Acute Phase

  • 6-12 weeks

  • Goal = Remission

• Continuation Phase

• Maintenance Phase

What is first line therapy for mild-moderate depression

Nonpharm therapy

Electroconvulsive Therapy (ECT)

• Safe and effective

• Pts are candidates if rapid response is needed

  • Severe suicidality

  • Nutritional deficiency

  • Cationic symptoms

What should patients receiving Bright Light Therapy do

Should receive routine eye exams

When should expected symptom remission be seen in pharm therapy

• Some improvement in 1-3 weeks

• May take 4-8 weeks before max efficacy is seen

TCA agents to know

• Amitriptyline (Tertiary)

• Doxepin (Tertiary)

• Nortriptyline (Secondary)

Secondary more selective for NE

Tertiary more effective but worse side effects (increased anticholinergic properties)

TCA

• MoA

• Metabolism

• Overdose

• Potentiate activity of NE and 5-HT by blocking reuptake

  • Nortriptyline used in patients with migraine HA, neuropathic pain, or fibromyalgia

• Hydroxylation via CYP2D6 (watch for DDIs)

• 1200mg Imipramine can be toxic

TCA Adverse Effects and who should not receive

• Anticholinergic effects (elderly)

• Orthostatic hypotension

• Cardiac conduction abnormalities (cardiac pt)

• Sexual dysfunction

• Lower seizure threshold (epilepsy/head injury)

• Hepatic (liver problems)

• Weight gain (T2DM pt)

• LETHAL IN OVERDOSE

Who should caution when taking TCA

• Elderly

  • side effect is FALLS

• Cardiac Problems

• Suicide risk

• Interactions

  • MAOIs require 2 week washout period

MAOI

• MoA

• Nonselective drugs

• Selective drugs

• Who should take these drugs

• Increase NE, 5-HT, DA within nuronal synapse through inhibition of MAO enzyme

  • MAO-A = found in GI tract

  • MAO-B = Brain

• Phenelzine and Traylcypromine

  • Inhibit MAO-A and B

• Selegiline (patch)

  • Selective for MAO-B

• Should be restricted to pts who are unresponsive to other treatments due to safety concerns

MAOI Adverse Effects

• Orthostasis

• Dizziness

• Anticholinergic

• Sedation/Insomnia

• Increased risk of hypertensive crisis

• Sexual dysfunction

• Weight gain

• Hepatic complications

Hypertensive Crisis

• Can culminate in CVA and death

• Sx

  • Occipital HA

  • Stiff neck

  • N/V

  • Sweating and sharply elevated BP

• Food Restrictions

  • Tyramine (aged food)

  • Results in HA, tachycardia, N, HTN, cardiac arrhythmias and stroke

MAOI Med Restrictions and D/I

• Amphetamines

• Buspirone

• Carbamazepine

• Cocaine

• Cyclobenzaprine

• Decongestants (topical and systemic)

• Sumatriptan

Avoid drugs that increase 5-HT, NE, Epi, or DA

SSRI

• MoA

• Tapering?

• Discontinuation

• Inhibit reuptake 5-HT (increase 5-HT)

• 1st line drugs

  • Safety in OD and improved tolerability

• Taper off slowly

• Electronic shock sensations at D/C (withdrawal)

Fluoxetine Metabolism

• CYP2D6 substrate and inhibitor

• Most Activating

What SSRI is most sedating

Paroxetine

Fluvoxamine

• PK

• Treatment

• CYP1A2 and 2C19 inhibitor

• Approved for treatment of OCD only

• Sedating

• Rarely used

Citalopram

• PK

• Warning

• CYP3A4, 2C19, and 2D6 (minor)

• QT Prolongation

Escitalopram v Citalopram

• Less side effects than Citalopram

• Still has QT Prolongation

What SSRI is preferred in Cardiac risks

Sertraline

SSRI Adverse Effects

• Nervousness

• Anxiety

• Akathisia

• Serotonin Syndrome

• Discontinuation Syndrome

Vilazodone

• Class

• With or without food

• Advantage

• SPARI (SSRI and 5-HT1A partial agonists)

• Taken with food

• Fewer sexual side effects than SSRIs

Vortioxetine (Trintellix)

• PK

• ADRs

• Advantage

• Atypical Antidepressant

• Metabolized by CYP2D6

• ADRs similar to other SSRIs

• Fewer sexual side effects than SSRIs

A pt experiencing insomnia, what would be the best recommendation for an SSRI for them

Paroxetine

SNRI

• MoA

• Treatment

• Higher rates of response and remission with SNRIs

• Inhibit the reuptake of 5-HT and NE

• Also used to treat pain and other disorders

Venlafaxine

• MoA

• PK

• ADR

• 5-HT inhibition at low doses

  • NE also inhibited at high doses

• CYP2D6

• Nausea, sexual dysfunction, activating, increased HR

  • increase in diastolic BP at high doses

Desvenlafaxine Adverse Effects

• Increases in BP and HR

• Ghost tablet

Levomilnacipran (Fetzima)

• PK

• ADR

• Adjust in renal impairment (CYP3A4)

• Increased risk of seizures

What are some class traits of SNRI

• Nausea

• Increase in diastolic BP

• Increase in HR

Triazolopyridines Agents

• Nefazodone

  • only generic available in US

  • Hepatotoxicity → inhibits CYP3A4

• Trazodone

What drug is available as ODT

What are the adverse effects of this drug

• Mirtazapine (Remeron)

  • weight gain

  • increased appetitie

  • minimal sexual dysfunction

Bupropion

• MoA

• ADR

• C/I

• SR v XR

• Other uses

• Weak DA and NE reuptake inhibitor

• Tremor, decreased appetite, insomnia, dry mouth, less sexual side effects than SSRIs, and seizures

  • Seizures are dose related or predisposing factors

• C/I in pt w/ eating disorders

  • Anorexia or Bulimia

• SR formulation do not exceed 400mg/day

• XR formulation do not exceed 450mg as a single dose

• SR also used for smoking cessation

• Bupropion + Natrexone used for weight management

Is Ketamine FDA approved for depression

No

How is Esketamine administered

• Intranasal formulation

• Requires supervision in clinic self administration

  • 2 hours of in clinic observation after administration

• REMS program

What drug is FDA approved for postpartum depression

Brexanolone

• IV infusion

• REMS

Who would not receive Bupropion

• Seizure risk (head trauma and CNS tumor)

• Eating disorders

Alternative Meds

• St. Johns Wort used for mild-moderate MDD

• Omega-3 fatty acids

  • May increase bleeding risk

• S-Adenosyl-L-Methionine (SAMe)

• Levomefolate

  • Readily crosses BBB

BBW of Antidepressants

Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults

When do you assess for presence of suicidal thoughts

Always assess

Pharmacological Summary

• Allow 4-6 weeks for optimal response

• Start low and go slow

• Adequate trial means 6 weeks at max dose

• Allow washout period when switching from one antidepressant to another

• 3-4 weeks typically required before mood-elevating response seen

Withdrawal syndromes

• Occurs with abrupt disontinuation

• SSRIs/SNRIs

  • Irritability, HA, agitation, brain zaps

  • Less likely with Fluoxetine

Switching Antidepressants

• Consider pt symptoms

• Allow washout period

Is serotonin syndrome a medical emergency

Yes

First line for pregnancy

• Mild-moderate depression → psychotherapy

• Sertraline, Citalopram, Escitalopram (safe options)

First line for Elderly

• usually misdiagnosed and undertreated

• SSRIs first line

  • Citalopram, Escitalopram, Sertraline

• Bupropion, Mirtazapine, and Venlafaxine are chosen for milder anticholinergic and less frequent CV effects

FDA approved drugs for Pediatrics

• Fluoxetine

• Escitalopram

What is the cause of majority of treatment resistance cases

• Inadequate therapy

  • Low dose or short duration

3 approaches for Refractory cases

1. Stop current antidepressant and start unrelated agent

2. Augment current antidepressant

3. Addition of atypical antipsych to augment antidepressant response

   • Aripiprazole and Quetiapine (adjunctive therapy options)

Conclusions

• SSRIs/SNRIs considered first line

• Antidepressants take 4-8 weeks for full benefits to occur

• Transient side effects may last 2 weeks

• If adverse effects do not resolve, see if patient can tolerate or reassess therapy