Term
| Major Depressive Disorder (MDD) |
|
Definition
-One of the most common psychiatric disorders in the United States
• 12-month prevalence in the United States is ~7% • 16 million adults
• ~61% have a comorbid psychiatric diagnosis
Depression may occur in the context of several psychiatric disorders
• MDD
• Bipolar disorder
• Persistent depressive disorder (dysthymia)
• Substance/medication-induced depressive disorder
• Premenstrual dysmorphic disorder
• Post-partum depression |
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Term
|
Definition
| Pharmacotherapy, psychotherpay, somatic therapies- ECT, TMS, Light therapy |
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Term
|
Definition
Effectiveness generally comparable among antidepressant classes
• Treatment decisions guided by:
• Comorbid medical and psychiatric conditions
• Anticipated side effects
• Pharmacologic properties of the medications
• Half-life, CYP450 activity, drug interactions, metabolites
• Previous response to antidepressants
• Cost
• Patient preference
Maximum effect of any antidepressant will not be seen for 4-6 weeks! |
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Term
| Black Box Warning for antidepressants |
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Definition
• All antidepressants carry a black box warning for increased risk of suicidal thinking and behavior in children,
adolescents, and young adults (18–24)
with major depressive disorder and other psychiatric disorders in short-term studies.
• There is no increased risk for adults > 24 years of age. |
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Term
| First Generation antidepressant classes |
|
Definition
• Tricyclic antidepressants (TCAs)
• Monoamine oxidase inhibitors (MAOIs) |
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Term
| Second and Third Generation antidepressant classes |
|
Definition
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin norepinephrine
reuptake inhibitors (SNRIs)
• Mirtazapine
• Bupropion
• Trazodone |
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|
Term
|
Definition
| This graphic can be really helpful for helping to understand the different mechanisms of the different classes of antidepressants. And it may be more helpful for you to come back to this after we've gone through all the different families. I'll just point out briefly that the SSRIs really work by blocking the reuptake of serotonin. The SNRIs block the reuptake of serotonin and norepinephrine. And then the tricyclics also are blocking the uptake of serotonin and norepinephrine as well. |
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Term
| Tricyclic Antidepressants (TCAs) MOA |
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Definition
| Non-selective inhibitors of NE and 5-HT reuptake transporters |
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Term
|
Definition
Amitriptyline (am i right to pry a little)
Elavil
Imipramine (im a prime mime)
Tofranil
Clomipramine (claim a prime mine)
Anafranil
Doxepin (doxy pin)
Sinequan
Nortriptyline (notorize prime line)
Pamelor
Desipramine (despirate mime)
Norpramin
Trimipramine (try to prime mime)
Surmontil
Protriptyline (pro trip prime line)
Vivactil
Amoxapine (a moxy pine)
Asendin
Maprotiline (my prototype line)
Ludiomil |
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Term
|
Definition
a1- orthostatic hypotension
muscarinin- dry mouth, blurry vision, confusion ,constipation, urinary retention
H1 and 5HT2C- weight gain
H1- sedation |
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Term
• May be fatal in acute overdose
• Prolonged QTc, conduction disturbances • Seizures
• Anticholinergic toxicity |
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Definition
|
|
Term
| QTc prolongation meds from least to most (TCAs) |
|
Definition
| Doxepin, Amoxepine, Nortriptyline, Chlomipramine, Amitriptyline, Imipramine |
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Term
|
Definition
• Ex: imipramine, amitriptyline
• Significant side effect profile due to increased α1, H1, and M1 blockade |
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Term
|
Definition
• Ex: desipramine, nortriptyline
• Increased tolerability with minimal α1, H1, and M1 blockade |
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Term
| TCAs: Prescribing Considerations |
|
Definition
Consider unique features to narrow selection
• Tertiary vs. secondary amine
• Higher risk of CV and anticholinergic side effects
• Non-antidepressant effects may be evident within days of initiation
• Antidepressant effects superior to SSRIs in context of life-threatening illness with quicker onset
• Monitor for response and titrate as tolerated |
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Term
May benefit in treatment of chronic pain, polyneuropathy, and migraines
Additional sedating properties |
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Definition
|
|
Term
| May benefit in treatment of myofascial pain and neuralgia |
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Definition
|
|
Term
| Additional benefit in treatment of neuropathic pain |
|
Definition
| Imipramine, Desipramine (TCA) |
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|
Term
| May be used as sleep aid at low doses |
|
Definition
|
|
Term
Monoamine Oxidase Inhibitors
• Mechanism of action |
|
Definition
Non-specific irreversible inhibition of monoamine
oxidase
• MAO is responsible for metabolism of 5HT, NE, and DA |
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Term
|
Definition
Phenelzine (Nardil) (fencing in line)
Diet restriction required
Tranylcypromine (Parnate) (trying to cycle promise)
Diet restriction required
Isocarboxazid (Marplan) (iso carbs and acid)
Diet restriction required
Selegiline patch (Emsam) (sell a guy's line)
Tyramine-diet restriction unnecessary unless daily
dose > 6 mg
Two active metabolites: amphetamine/
methamphetamineàurine tox may be (+) |
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Term
Has ADE:
• Sedation
• Insomnia
• Weight gain
• Changes in blood pressure |
|
Definition
|
|
Term
| MAOI Diet Recommendations |
|
Definition
• Foods to avoid
• Aged cheeses, dried meats, red wine, tap beers, sauerkraut, raw yeast, legumes
• Foods to limit
• Caffeinated beverages, chocolate, figs, meat tenderizers, raisins
• Very important to counsel patients
on how to successfully follow low tyramine diet! |
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Term
|
Definition
• Resulting from significant tyramine levels
• Usually develops 20–60 minutes after ingestion of the interacting food or drug
• Can lead to CVA or death
• Clinical presentation: nausea, vomiting, sweating, headache, stiff neck, chest pain, hypertension, palpitations |
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Term
|
Definition
• May result from over activation of central serotonin receptors
• Rare, but can occur with the combination of serotonergic medications
• May be life-threatening
So there can be really mild symptoms, GI distress, tremor, things like-- but it can continue on to become altered mental status, clonus, seizures, and can even be life-threatening. |
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Term
| Serotonin Syndrome presentation |
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Definition
| Abdominal pain, diarrhea, sweating, fever, tachycardia, delirium, hyperreflexia, clonus, irritability |
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Term
| Serotonin Syndrome treatment |
|
Definition
| Discontinue suspected causative agent(s), provide supportive therapy (symptoms often resolve within 24 hours of discontinuation) |
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Term
| Serotonin Syndrome prevention |
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Definition
• SSRIs (other than fluoxetine) Þ MAOIs: 2 week washout • Fluoxetine Þ MAOIs: 5 week washout
• MAOI Þ SSRI: 2 week washout |
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Term
| MAOIs: Prescribing Considerations |
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Definition
• Not commonly used as first-line agent for treatment of depression
• Many drug-drug interactions
• Many drug-food interactions |
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Term
|
Definition
Inhibit presynaptic serotonin reuptake by inhibition of the 5-HT
transporter
• Increased 5-HT in synaptic cleft |
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Term
| Has ADE GI, HE, Insomnia/Sedation, Anxiety, Sexual dysfuncion, SIADH, Discontinuation synderome |
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Definition
|
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Term
|
Definition
GI adverse effects
Take with small snack/meal
Headache
Adjust dose to evening
Insomnia/Sedation
Adjust dose to morning or evening as necessary
Anxiety
Slow dose titration to minimize exacerbation
Sexual dysfunction
Switch to different SSRI, SNRI or non- serotonergic agent (i.e., bupropion)
SIADH
Discontinue and switch to different antidepressant
Discontinuation syndrome
Slow taper if medication to be discontinued (exception: fluoxetine) |
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Term
|
Definition
Citalopram (Celexa®)
Dose-related risk of QT prolongation
Max doses for >65 y/o, hepatic impairment, or
with concomitant 2C19 inhibitors
Escitalopram (Lexapro®)
Dose-related risk of QT prolongation
S-enantiomer of citalopram
Fluoxetine (Prozac®)
↓ Dose by 50%
Activating 2D6 inhibitor
Active metabolite
(norfluoxetine) with long half-life (7–9
days), taper not required
Paroxetine (Paxil®)
Dry mouth, drowsiness, fatigue
More anti-cholinergic adverse effects
High risk of
discontinuation syndrome with abrupt d/c
due to short half-life 2D6 inhibitor
Sertraline (Zoloft®)
GI side effects (diarrhea, nausea, vomiting) common
->start with lower dose and titrate slowly
Active metabolite N- desmethylsertraline (half-
life 60–80 hours)
Fluvoxamine (Luvox®)
Potent 1A2 enzyme inhibitor
Generally only used in OCD |
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Term
| SSRIs: Prescribing Considerations |
|
Definition
•
SSRIs: Prescribing Considerations
Consider unique features to narrow selection
• Drug-drug interactions
• Renal adjustments are generally not necessary
Paroxetine
Strong anticholinergic effectsàmay benefit in appetite stimulation and weight gain
Sertraline
Most GI side effects
Fluoxetine
Longest half-life
Citalopram/Escitalopram
May prolong QTc
• • •
Monitor for response and titrate as tolerated
May require 4–6 weeks for full antidepressant effect |
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Term
|
Definition
All SSRIs are pregnancy category C
• Exception: Paroxetine (cardiac defects)->category D |
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Term
|
Definition
Inhibition of the 5HT and NE transporters ->
increased neurotransmitters in synaptic cleft |
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Term
|
Definition
• Venlafaxine (Effexor®) (venmo the fax machine)
• Desvenlafaxine (Pristiq®) (dat venmo the fax machine)
• Levomilnacipran (FetzimaTM) (levitate mili ants with pam)
• Duloxetine (Cymbalta®) (dull ox for time) |
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Term
|
Definition
• Venlafaxine
• Doses < 150 mg primarily inhibits 5HT-reuptake à higher doses provide dual NE and 5HT blockade
• Hypertension (dose-related) • <100 mg/day: 3%
• >300 mg/day: Up to 13%
• Desvenlafaxine
• Active metabolite of venlafaxine (CYP 2D6)
• Levomilnacipran
• NE > 5HT reuptake inhibition
• Duloxetine
• Equal affinity for 5HT and NE reuptake transporters |
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Term
|
Definition
Duloxetine- Monitor liver function
Venlafaxine IR and ER- Dose-related increase in blood pressure
Doses >150 mg required to get dual NE and 5HT transporter inhibition
Desvenlafaxine- Active metabolite of venlafaxine
Requires 2D6 for metabolism
$$$$
Levomilnacipran- BP and HR elevations can occur
NE > 5HT reuptake inhibitor |
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Term
| SNRIs: Prescribing Considerations |
|
Definition
• Consider unique features to narrow selection of SNRI
• All SNRIs are approved for treatment of depression
• Venlafaxine is also indicated for panic disorder/anxiety, neuropathic pain
• Dose-related increases in blood pressure
• Duloxetine has evidence in treatment of anxiety, fibromyalgia, and musculoskeletal pain
• Non-antidepressant properties may be evident within 1– 2 weeks of starting therapy
• Monitor for response and titrate as tolerated
• All SNRIs are pregnancy category C |
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Term
| Mirtazapine (Remeron®) MOA |
|
Definition
• Presynaptic α-2 antagonist
• Increases synaptic concentration of 5HT
and NE
• Antagonist at 5HT2 and 5HT3 |
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|
Term
Has ADE: • Increased appetite (17%)
• Weight gain (7.5%: >7% ↑ in BW)
• Constipation (13%) • Sedation (54%) |
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Definition
|
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Term
| Has unique features: Often scheduled at night for sedating and appetite-stimulating effects |
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Definition
|
|
Term
| Bupropion (Wellbutrin®) MOA |
|
Definition
| NE and DA reuptake blockade with no 5HT effects |
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Term
Has ADE: • Headache (25–34%) • Insomnia (11–20%)
• Dizziness (6–11%)
• Xerostomia (17–26%)
• Tachycardia (11%)
• Weight loss (14–23%)
• Agitation (2–9%) • Anxiety (5–7%)
• Seizures (0.1–0.4%) |
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Definition
|
|
Term
Has unique features: Activating (useful with fatigue, poor concentration) CYP 2B6 (major pathway), strong CYP2D6 inhibitor
No sexual dysfunction |
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Definition
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Term
Has ADE:• Dose-related seizure (0.1–0.4%)
• Maximum dose depends on formulation |
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Definition
|
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Term
| Bupropion (Wellbutrin®) contraindication |
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Definition
| history of seizures, history of anorexia/bulimia, abrupt disontinuation of EtOH, BDZ, barbituates antiepileptics, AVS malformation in CNS, severe head injurey stoke CNS tumor |
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Term
|
Definition
| Weak 5HT reuptake inhibitor Significantly blocks H1 and α1 receptors |
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Term
Has ADE: • Sedation (46%)
• Headache (33%)
• Dizziness (25%)
• Fatigue (15%)
• Dry mouth (25%)
• Nausea (21%)
• Constipation (8%) |
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Definition
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Term
| Used commonly as sleep aid, rarely as antidepressant |
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Definition
|
|
Term
| Nefazodone (Serzone®) MOA |
|
Definition
| 5HT2A antagonist with moderate inhibition of 5HT and NE reuptake |
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|
Term
Has ADE: • Dry mouth (25%)
• Sedation (25%)
• Nausea (22%)
• Dizziness (17%)
• Blurred vision (16%) |
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Definition
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|
Term
Not usually prescribed due to rare incidence of
hepatotoxicity |
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Definition
|
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Term
| Vilazodone (Viibryd®) MOA: |
|
Definition
• Inhibition of presynaptic 5HT transporter
• 5HT1A partial agonist |
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|
Term
Has ADE: • Diarrhea (28%)
• Nausea (23%)
• Vomiting (5%) |
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Definition
|
|
Term
| Pregnancy category C $$$$ |
|
Definition
|
|
Term
| Vortioxetine (Trintellix®) MOA |
|
Definition
• Inhibition of 5HT reuptake
• 5HT3 antagonist
• 5HT1A agonist |
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Term
HAs ADE: • Nausea (10–20%)
• Diarrhea (7–10%)
• Dry mouth (6–8%)
• Sexual dysfunction (males: 16–29%, females:
22–34%) |
|
Definition
| Vortioxetine (Trintellix®) |
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|
Term
| Pregnancy category C metabolized by CYP2D6 $$$$ |
|
Definition
| Vortioxetine (Trintellix®) |
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Term
| Sedation, increased appetite, weight gain |
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Definition
|
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Term
| 2nd and 3rd Generation SNRI Prescribing Considerations |
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Definition
• Consideruniquefeaturestonarrowselection
• Mirtazapinesupportsincreasedappetite,weight gain, and sedation with possible benefit as an antiemetic
• Trazodoneiscommonlyusedasasleepaidbuthas increased anticholinergic effects
• Newer atypical antidepressants have higher cost with no superior benefit over traditional agents
• Non-antidepressanteffectsmaybeevident within days of starting therapy
• Monitor for response and titrate as tolerated |
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Term
| Due to its 5HT3 receptor blockade, mirtazapine lacks which of the following adverse effects? |
|
Definition
| Nausea and vomiting (causes Weight gain Sedation Constipation) |
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Term
| For which of the following patients would bupropion be an acceptable option to treat MDD? |
|
Definition
| 36 y/o M with comorbid cocaine use disorder and borderline personality disorder |
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Term
| You decide to initiate Wellbutrin XL 150 mg daily for this patient. After reviewing this patient’s medication list, which of the following medications should be discontinued? |
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Definition
|
|
Term
| Which class of medications may cause or exacerbate anxiety symptoms? |
|
Definition
| Bronchodilators Steroids Anticonvulsants |
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Term
Generalized Anxiety
Disorder |
|
Definition
• Excessive anxiety, worry
• On edge
• Restlessness,
irritable
• Fatigue • Sleep
disturbance |
|
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Term
|
Definition
• Depersonalization
• Derealization
• Fear of going
crazy, dying, losing control
• Abdominal distress
• Chest pain • Dizziness
• Chills, hot flashes |
|
|
Term
| Post Traumatic Stress Disorder |
|
Definition
• Recurrent intrusive
memories, dreams
• Hypervigilance
• Irritability/anger
• Sleep disturbance |
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Term
| Treatment of Anxiety Ingeneral |
|
Definition
• Firstline:CBT+SSRIorSNRI
• Secondline:Switchantidepressant
• Thirdline:Augmentà
• Second generation antipsychotic • Benzodiazepine
• Antihistamine
• Buspirone • Pregabalin |
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|
Term
| major inhibitory neurotransmitters in CNS |
|
Definition
• GABA (Present throughout CNS)
• Glycine (Present in spinal cord and brainstem) |
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Term
|
Definition
• Used historically to treat anxiety
• Phenobarbital, secobarbital, primidone
• Current use: sedative-hypnotic, anticonvulsant
• Rarely used due to toxicity, dependence, development of tolerance
• Over sedation
• Impaired cognitive function
• High doses: anesthesia, coma, death
• First benzodiazepine available in 1950s |
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|
Term
Benzodiazepines (BZPs)
• MOA |
|
Definition
| Bind to the gamma subunit of the GABAA receptor -> allosteric modification of receptor -> GABA binds -> increased frequency of channel opening -> increase in chloride ion conductance and inhibition of the action potential |
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Term
|
Definition
• Categories based on elimination half-life
• Most hepatically metabolized via CYP system
Ultra-short acting (Midazolam, clorazepate)- middle of the lamb, chlorine pete, Short acting (Triazolam)- try a lamb, Intermediate-acting agents (Alprazolam, estazolam, temazepam, oxazepam, lorazepam)- alpine lamb, esta lamb, team lamb, ox lamb, lauel lamb, Long-acting agents (Flurazepam, diazepam, quazepam, clonazepam)- fluffy lamb, die a lamb, quazi lamb, clone lamb |
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Term
| Alprazolam (Xanax) indications |
|
Definition
|
|
Term
| chlordiazepoxide (Librium) indication |
|
Definition
| anxiety, pre-op anx, alcohol withdrawal |
|
|
Term
| clonazepam (Klonopin) indications |
|
Definition
|
|
Term
| diazepam (valium) indications |
|
Definition
| anxiety, pre-op anx, panic, alcohol withdrawal, seizure |
|
|
Term
| lorazepam (ativan) indications |
|
Definition
| anxiety, seizure, insomnia |
|
|
Term
| oxazepam (serax) indications |
|
Definition
| anxiety, alcohol withdrawl, insomnia |
|
|
Term
| estazolam (prosom) indications |
|
Definition
|
|
Term
| flurazepam (dalmane) indicaxitons |
|
Definition
|
|
Term
| temazepam (restoril) indications |
|
Definition
|
|
Term
Has ADE: • Impaired psychomotor performance
• Amnesia
• Sedation, somnolence, fatigue
• Dependence, withdrawal- More likely when treated with BZDs with shorter half-lives
• Rebound anxiety
• Cognitive dysfunction, confusion |
|
Definition
|
|
Term
|
Definition
• Most intentional ingestions involve coingestant (ex: alcohol)
• Slurred speech
• Ataxia
• Altered mental status
• Respiratory compromise->much more likely with concomitant ingestion of sedatives |
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Term
| BZDs: Prescribing Considerations |
|
Definition
• Elimination half-life
• Slow taper to avoid potential for seizures
• Generally safe when used alone - Present a fall risk for elderly patients!
• Potential for physiological and psychological dependence
• Reserve for short-term therapy
• Preferred agents in elderly or with poor hepatic
function: lorazepam, oxazepam, temazepam |
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Term
|
Definition
| Hydroxyzine (atarax), gabapentin (neurotin), pregabalin (lyrica), buspirone (buspar) |
|
|
Term
|
Definition
| Binds to H1 receptors for skeletal muscle relaxing, antihistamine, antiemetic effects |
|
|
Term
| has ADE: Xerostomia, somnolence |
|
Definition
|
|
Term
| gabapentin (neurotonin) MOA |
|
Definition
| Structurally related to GABA, does not bind to GABAA or GABAB receptors |
|
|
Term
| has ADE: Sleepiness (25%), dizziness (23%), ataxia (20%), nystagmus, headache, fatigue, peripheral edema |
|
Definition
|
|
Term
|
Definition
Not completely understood
GABA analog à binds to alpha2-delta site |
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|
Term
| Has ADE: Weight gain, peripheral edema, constipation, xerostomia, ataxia, dizziness, headache, fatigue, disturbance in thinking/SI |
|
Definition
|
|
Term
|
Definition
| Unknown, high affinity for 5-HT1A receptors and moderate affinity for D2 receptors |
|
|
Term
| Has ADE: Nausea, dizziness, somnolence, headache |
|
Definition
|
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