Treatment Resistant Depression (Behave)

What is the general order of medications fore treatment of MDD

1st - SSRIs

2nd - SNRIs

3rd - Atypical antidepressant or SSRI + Serotonin Modulator

MOA of TCAs

Inhibits the reuptake of serotonin AND especially norepinephrine (more effect on norepinephrine than these other neurotransmitters)

Blocks histaminic, alpha and muscarinic receptors

Blocks the action of acetylcholine

SE of TCAs

Central anticholinergic side effects (sedation, dizziness)

Peripheral anticholinergic side effects (i.e.: constipation, blurred vision, urinary retention etc.)

Lower seizure thresholds

How are TCAs metabolized

Liver, cytochrome system

Why is TCA overdose frequently lethal

Prolongs QT → Arrhythmia

Due to lipophilic nature, unable to be dialyzed out

Clomipramine (Anafranil)

A TCA not approved for MDD but is for OCD

Amitriptyline (Elavil)

TCA

Nortriptyline (Pamelor)

TCA

Doxepin (Silenor, Sinequan)

TCA

Imipramine (Tofranil)

TCA

Desipramine (Norpramin)

TCA

Which TCAs are worst for anticholingeric effects

Doxepin (Silenor, Sinequan)

Amitriptyline (Elavil)

What TCAs have the strongest side effects

Amitriptyline (Elavil)

Doxepin (Silenor, Sinequ

Which TCAs do not have effect on sex drive

Nortripytline (Pamelor)

Desipramine (Norpramin)

What is considered a prolonged QT

(>450 ms in males,

‘ >460 ms in females

At what QT length is Torsades a high risk

Greater than 500

Other than MDD, what other uses do TCAs have

Chronic pain/neuropathic pain

Migraine prophylaxis

Anxiety

Insomnia

Eneuresis

What TCA is given to help with insomnia

doxepine (Silenor, Sinequan)

What TCA is given to help with Eneuresis

imipramine (Tofranil)

Indications for amitriptyline (Elavil)

Insomnia

Neuropathic pain

IBS

Migraines

Indications for doxepin (Silenor, Sinequan)

Insomnia

Refractory pruritis

Indications for nortriptyline (Pamelor)

cannot tolerate GI side effects from serotonin as it has far less affinity for serotonin than any other TCA

Most sensitive and specific screener for Bipolar

Rapid Mood Screener

What are indictors that a patient is suffering from bipolar rather than depression

Family history of bipolar disorder (8x greater risk)

Age of first depressive episode <25 yo

More depressive episodes (≥ 5)

Shorter depressive episodes

Mood reactivity

Early morning insomnia/ hypersomnia

What medical conditions can worsen MDD

HypoThyroid

Anemia

Vitamin D deficiency

Pancreatic Cancer

Inflammatory Conditions

What psych conditions can worsen MDD

Anxiety

PTSD

ADHD

OCD

Sleep Disorder

Substance Use Disorder

What are some general issues to address with treatment resistant depression

Medication noncompliance

Isolation

Interpersonal conflict/ situational stressors

Substance use

Poor sleep hygiene

Treatment resistant depression

failing 2 or more antidepressants

What is considered a “true failure” for antidepressants when discussing treatment resistant depression

a therapeutic dose should be used for an amount of time where a response should be seen

options for treatment resistant depression

Augmentation (also helpful for partial responses)

Esketamine (Spravato)

Electroconvulsive Therapy (ECT)

Rapid Transmagnetic Stimulation (r-TMS)

Last resort- Monoamine oxidase inhibitors (MAOI’s)

What treatment is the absolute last choice for treating MDD

MAOIs

What medications can be used to augment SSRI/SNRI treatment of depression

Atypical antidepressant

Atypical antipsychotic

esketamine (Spravato)

A ketamine isomer

MOA for esketamine (Spravato)

Opioid receptor agonist

(AMPA) receptor stimulation

(NMDA) receptor antagonist

reduce the symptoms of treatment resistant major depressive disorder, including suicidal ideation

Route for esketamine (Spravato)

nasal

Indications for esketamine (Spravato)

Treatment resistant major depressive disorder in which other recommended therapies have been exhausted

Restricted distribution program

SE of esketamine (Spravato)

Sedation

Potential for abuse/misuse

Suicidality

Indication for ECT

all mood disorders when patients are unresponsive to medications

What is needed prior to administring ECT

medical clearances (medical and anesthesia)

Electroconvulsive Therapy (ECT)

Involves induction of a generalized seizure by passing a current of electricity across the brain

Seizure lasts approximately 25-60 seconds

Contraindications for ECT

Cardiac dysrythmias

Increased ICP

How is ECT done

Premedication given followed by general anesthesia and a muscle relaxant before seizure induction

Inpatient → 6-12 treatments over a 2-4 week period

Maintenance ECT is done after (outpatient once a week, eventually taper down)

SE of ECT

Amnesia (anterograde)

When does amnesia from ECT resolve

6 months

Repetitive Transmagnetic Stimulation (r-TMS)

Direct short repetitive pulses from an MRI-strength magnet to the prefrontal cortex (usually left)

Indication for r-TMS

patients who have failed at least one medication treatment (but is often used after that) for depression

Benefits of r-TMS over ECT

Requires no anesthetic or sedation

Able to target specific area (much more controlled)

Proving to be effective when used with medications

Very minimal adverse effects

SE of r-TMS

Discomfort from stimulation of facial nerve

Contraindications for r-TMS

increased risk for seizure,

implanted metallic hardware/ medical devices

cochlear implants

, local tattoos with ferromagnetic-containing ink,

unstable general medical disorders

What was the first MAOI

Isoniazid (INH)

SE of MAOIs

Fatigue

Hypotension

Dry mouth

Headache

Myoclonic jerks

Can cause lethal hypertension

How does MAOIs cause lethal HTN

Tyramine metabolism gets blocked by MAOIs

Tyramine causes excessive release of norepinephrine

Norepinephrine is not degraded (usually done by MAO-A)

Norepinephrine causes vasoconstriction and elevates BP

What foods are high in tyramine

cheeses,

cured meats,

alcohol,

fruits

If transitioning a patient from SSRIs to MAOIs, what must be done

Should be separated by >2+ weeks form SSRI/SNRI (“washout period”)

May need 4 weeks in those with longer half-life (fluoxetine)

What medications should be avoidied on MAOIs

Cold medication

Asthma meds

Pain meds

Antihistamines

Isocarboxazid (Marplan)

MAOI

Phenelzine (Nardil)

MAOI

Selegiline (Eldepryl, Emsam transdermal patch)

MAOI

Tranylcypromine (Parnate)

MAOI

Who guides MAOI treatment of MDD

psychiatrist

Psilocybin

prodrug and is converted to psilocin in the body.

MOA of Psilocybin for MDD

Serotonergic

Alters perception, mood, and cognition while promoting neuroplasticity and changes in brain network connectivity.

increases global brain connectivity, allowing regions that normally do not communicate to interact.