Major Depressive Disorder (MDD) Flashcards
What are the types of depressive disorder?
- Major Depressive Disorder
- Persistent Depressive Disorder
- Substance/Medication-Induced Depressive Disorder
- Premenstrual Dysphoric Disorder
- Depressive Disorder due to another medical condition
- Other specified depressive disorder
- Unspecified depressive disorder
What are the DSM-5 Criteria for Major Depressive Disorder?
Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning
What are the symptoms of Major Depressive Disorder?
- Depressed mood
- Sleep
- Interest
- Guilt
- Decreased energy
- Decreased concentration
- Appetite (weight loss or weight gain)
- Psychomotor changes
- Suicidal thoughts
What are medications that can induce major depressive disorder?
- Acyclovir
- Alcohol
- Antiepileptic medication
- Antiretrovirals
- Barbiturates
- BB/CCB
- Corticosteroids
- Interferon-a & b
- Isotretinoin
- Levonorgestrel implants
- Montelukast
- Opioids
- Varenicline
What is the onset of MDD?
- Late 20’s but first episode can develop at any age
- Can develop over days to weeks or suddenly
What is the duration of MDD?
- Median time to recovery is 20 weeks with adequate treatment
- 15% of patients never achieve remission (chronic depression)
What is the recurrence of MDD?
- 50% with a single episode will recover without recurrence
- Risk of recurrence increases with number of episodes
Remission
Absence of depressive symptoms or only 1 or 2 symptoms to a mild degree of > 2 months
Monoamine Hypothesis
Depressive symptoms related to deficiencies in serotonin (5-HT), Norepinephrine (NE), and Dopamine (DA)
Dysregulation Hyopthesis
Depression results from dysregulation of neurotransmitters that leads to alteration in pre & post receptors
Neuroendocrine Hypothesis
Dysregulation of thyroid and HPA axis results in sustained in sustained depression
What is the mechanism of action SSRIs?
Inhibit the reuptake of serotonin (5HT) in the presynaptic neuron of the CNS–> increased serotonin in the synaptic cleft
SSRI
- First line treatment for MDD
- Well tolerated
- Low risk of toxicity
What is the CYP450 metabolism of fluoxetine?
2D6
What is the CYP450 Metabolism of fluvoxamine?
- 1A2
- 2C19
What is the CYP450 metabolism of paroxetine?
2D6
What is the longest half-life SSRI?
Fluoxetine (norfluoxetine: ~4-6 days)
What are the adverse effects of SSRIs?
Common:
* Nausea and/or vomiting
* Headache
* Sleep changes
* Increased in anxiety/agitation or sedation
Serious:
* Hyponatremia
* Increased bleeding/bruising
* Serotonin syndrome
List the SSRIs from most actvivating to most sedation
- Fluoxetine
- Setraline
- Escitalopram & citalopram
- Fluvoxamine
- Paroxetine
What are some clinical pearls of citalopram?
- Max daily dose not to exceed 40 mg (QTc prolongation)
- Lower max dose of 20 mg is recommended for elderly (> 60 years), significant hepatic impairment, interacting medications
- Sedating
- Starting dose can also be maintenance dose
What is the clinical pearl of escitalopram?
- Also has a risk of QTc prolongation, but no boxed warning
- Starting dose can also be maintenance dose
What are the clinical pearls of fluoxetine?
Longest half life (1-3 days) with longer half life for metabolite (4-16 days)
What are the clinical pearls of setraline?
Non-selective–> can affect serotonin in gut and cause more diarrhea and nausea
What are the clinical pearls of fluvoxamine?
- OCD, NO FDA approval in depression
What are the clinical pearls of Paroxetine?
- “Dirtiest SSRI” (anticholinergic & histaminic, more sexual dysfunction)
- Most weight gain
- Short half-life–> withdrawal
What are the clinical pearls of vortioxetine?
Brand only
What is the mechanism of action of Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs)?
Inhibits the reuptake of serotonin and norepinephrine presynaptically
SNRIs
- Well tolerated
- Low risk of toxicity
- Additional mechanism (norepinephrine)
What is the CYP metabolism Duloxetine (Cymbalta)?
CYP1A2
-Inactive: CYP2D6
What is the CYP450 metabolism of Levomilnacipran (Fetzima)?
CYP3A4
What are the common side effects of SNRIs?
- Nausea and/or vomiting
- Sleep changes
- Increased agitation/anxiety
- Sexual dysfunction
- Dose-dependent blood pressure elevation
- Constipation
What are the serious adverse effect of SNRIs?
- Hyponatremia
- Increased bleed/bruising
- Serotonin Syndrome
What are the clinical pearls of Venlafaxine?
- Doses > 225 mg/day needed for NE activity, but this dose is also very nauseating
- Also inhibits dopamine reuptake at higher doses (>300 mg)
- Withdrawal risk high due to half-life, do not use IR formulation
What are the clinical pearls of Desvenlafaxine?
- Active metabolite of venlafaxine
- Renal dose adjustment needed for CrCl < 50 mL/min
- $$$
What are the clinical pearls of Duloxetine?
- Contraindicated in hepatic disease
- FDA approved for diabetic peripheral neuropathy, musculoskeletal pain, fibromyalgia
What are the clinical pearl of Levomilnacipran?
- Brand only, $$$
- Renal adjustment needed for CrCl < 60 mL/min
What are the mechanism of action of Serotonin 2 Antagonist/Reuptake Inhibitors (SARIs)?
- 5-HT2A and 5-HT2C receptor antagonist (post-synaptic)
- Inhibits serotonin reuptake
What are the adverse effects of SARIs?
- Sedation
- Dizziness
- Orthostatic hypotension
- Priapism (rare)
What are the clinical pearls of trazodone?
- More commonly used for insomnia than MDD
- Doses > 200 mg/day required for treatment of MDD
- Doses for insomnia are subtherapeutic for the treatment of MDD
What are the clinical pearls of Nefazodone?
- Boxed warning: may cause liver failure
- Not first line due to toxicity
- Can be used in PTSD
What are the mechanism of action of Norepinephrine & Dopamine Reuptake Inhibitor (NDRI)?
Inhibits the reuptake of norepineprhine and dopamine
NDRIs
- First or second line treatment of MDD
What are the adverse effects of NDRIs?
- Activation (insomnia, agitation, tremor)
- Weight loss
- Headache
- Nausea/vomiting/constipation
What are the clinical pearls of NDRIs?
- Beneficial: Fatigue, poor concentration, smoking cessation interest
- Contraindicated: Bulimia, anorexia, seizure disorder
- Appetite suppression
- Lowers the seizure threshold
- Activating
What is the mechanism of action of the Noradrenergic & Specific Serotonergic Antidepressant (NaSSa)
- Primary–> alpha 2 agonist
- Secondary–> 5-HT2A, 5-HT2C, and 5-HT-3 antagonist, antihistamine
NaSSa
- Considered as a second line agent
What are the clinical pearls of NaSSa?
- Less sexual dysfunction
- Weight gain/sedation are worse at lower dose (7.5-15 mg)
What are the mechanism of action of Serotonin modulator?
- Serotonin reuptake inhibitor, 5-HT1A partial agonist
- Similar to SSRI and buspirone
What are the clinical pearls of serotonin modulator?
- Dose adjust with CYP3A4 inhibitor
- Must take with food to increase bioavailability
- Lowest incidence of sexual dysfunction
What is the mechanism of action of tricylic antidepressant?
- Presynaptic inhibition of norepinephrine and serotonin reuptake–> increase NE and 5-HT in the synaptic cleft
- Varying affinities for H1, alpha adrenergic, and muscarinic antagonist
What are the common adverse effects of tricyclic antidepressants?
- Anticholinergic
- Antihistaminergic
- Orthostasis
- Photosensitivity
What are the serious adverse events of tricyclic antidepressants?
- Cardiotoxicity (QTc prolongation and risk of MI)
- Decreased seizure threshold
What are the clinical pearls of amitriptyline?
- Most cholinergic and alphalytic
- More often used for chronic pain and migraine
What are the clinical pearls of clompramine?
- Most serotonergic
- FDA approved for OCD
What are the clinical pearls of desipramine?
- Most noradrenergic
- Low anticholinergic properties
What are the clinical pearls of doxepin?
Most antihistamine
What are the clinical pearls of imipramine?
- Used for GAD
- Best for panic disorder with agoraphobia
What are the clinical pearls of nortriptyline?
- Low anticholinergic properties
- Best tolerated TCA
What is the mechanism of action of Monoamine Oxidase Inhibitor (MAO-Is)?
Inhibition of monoamine oxidase enzymes (MAO-A & MAO-B) resulting in increased concentrations of norepinephrine, serotonin & dopamine in synapse
What are the adverse effects of MAOIs?
Common:
* Hypotension
* Dizziness
* Urinary retention, constipation, and xerostomia
Serious:
* Hypertensive crisis–> drug-food interactions
* Serotonin syndrome–> drug-drug interaction
Hypertensive Crisis
Diastolic blood pressure > 120 mm Hg
What are some presentations of Hypertensive crisis?
- Occipital headache
- Palpitations
- Neck stiffnes/soreness
- Nausea and/or vomiting
- Dilated pupils, photophobia
- Tachycardia or bradycardia
- Chest pain
What is the dietary modifications of hypertensive crisis?
Avoid tyramine
How do you treat hypertensive crisis?
Phentolamine (also nifedipine and chlorpromazine)
Which antidepressants should you avoid if you have hypertensive crisis?
- TCAs
- NRIs
- SNRIs
- NDRIs
What are some clinical pearls of Phenelzine?
- Increased weight gain
- May cause hepatoxicity (rare)
What are some clinical pearls of selegiline?
- Low doses selective for MAO-B (increases dopamine)
- No need for dietary restriction with 6 mg/24hr patch
- Drug-drug interactions are still a concern
What are some clinical pearls of Tranylcypromine?
- Structurally similar to amphetamine–> stimulating
- Can cause insomnia
- Transient hypertension
What is the Hunter’s Criteria of Serotonin Syndrome?
- Spontaneous clonus
- Inducible clonus + agitation or diaphoresis
- Ocular clonus + agitation or diaphoresis
- Tremor + hyperreflexia
- Hypertonia + temperature > 35 C + ocular clonus or inducible clonus
What are some drug interactions of antidepressants for Serotonin Syndrome?
- SSRIs
- TCAs
- SNRIs
- Mirtazapine
- MAO-Is
What is the drug interaction of Antibiotics for Serotonin Syndrome?
Linezolid
What are some drug interactions of appetite suppressants for Serotonin Syndrome?
Sibutramine
What are some drug interactions of opioids for Serotonin Syndrome?
- Dextromethorphan
- Meperidine
- Methadone
- Tramadol
- Fentanyl
What are the washout periods to prevent Serotonin Syndrome with MAOIs?
MAO-I–> non-MAO-I antidepressant
* Allow for 2-week washout period
Non-MAO-I antidepressant–> MAO-I
* Allow for 2-week washout period
* Allow for 5-week washout period after fluoxetine
MAO-I–> MAO-I
* Allow for 2-week washout period
What is the boxed warning on ALL antidepressants?
- Seen in children/adolescents up to 24 years old
- Notify family/caregiver to monitor
- Balance benefits vs risk
What is the symptoms of Discontinuation Syndrome?
- Flu-like, paresthesia
- Most severe: venlfaxine > SSRIs
What is the onset and duration of Discontinuation Syndrome?
- Onset: 1-2 days after discontinuation
- Duration: 1-2 weeks depending on medication half-life
What medication do you avoid in pregnant patients?
Paroxetine
What is the empiric therapy selection based on?
- History of antidepressant response
- Family history of antidepressant response
- Concurrent with diseaes states and drug therapy
- Drug interactions
- Adverse effect profile
- Cost
