Lecture 11: Mood Disorders Part 1 Flashcards
Define mood.
Overall state of emotion at a given time.
Define mood disorder.
A condition affecting a person’s everyday emotional state/mood.
Sometimes known as affective disorders.
Comes as primary and secondary.
How common are mood disorders?
1 in 4 adults.
What are the 3 main NTs that regulate mood?
Serotonin
NE
Dopamine
What falls under depressive disorders?
MDD (Major Depressive Disorder)
Dysthymia/Persistent Depressive Disorder
SAD (Seasonal Affective Disorder)
PMDD (Premenstrual Dysphoric Disorder)
Disruptive Mood Dysregulation Disorder
What falls under bipolar disorders?
Bipolar I Disorder
Bipolar II Disorder (Cyclothymia)
What are the two main things we use to diagnose psychiatric conditions?
DSM (Diagnostic and Statistical Manual of Mental Disorders)
ICD (International Statistical Classifications of Diseases and Related Health Problems)
What is required to make a criteria-based decision according to the DSM?
Meeting all 3 of these conditions:
The condition is not caused by the direct effects of any drug or external exposure.
The disorder is not caused by effects of a medical condition.
There is SIGNIFICANT IMPAIRMENT of social functioning, occupational functioning, or both.
How common is MDD?
21% lifetime prevalence in the US.
At what age is MDD most common?
25-44, with an average onset age of 30.
Is MDD more common in men or women?
Women
What ethnicity is MDD most common and least common in?
MC in native americans
LC in asians/pacific islanders.
What are some genetic factors that may predispose someone to MDD?
FMHx of depression or alcoholism.
What medications fall under risk factors for MDD?
Glucocorticoids
Interferons
What is the diagnostic criteria for MDD according to the DSM 5?
Depressed mood or An-hedonia for >= 2 weeks
PLUS
at least 4 of the following:
Sleep Changes
Guilt
Fatigue
Decreased Concentration
Significant appetite/weight change
Activity changes
Recurrent thoughts of suicide/death
Note:
Symptoms must cause distress and cannot be due to other causes.
What is the MDD mnemonic?
SIG E CAPS
Sleep Disturbances
Interested Decreased (Anhedonia)
Guilt/Worthlessness
Energy Decreased
Concentration problems
Appetite/Weight change
Psychmotor agitation/retardation
Suicidal Ideation
What are the 8 subtypes of MDD episodes?
Anxiety
Atypical
Catatonic
Melancholic
Mixed
Peripartum
Psychotic
Seasonal
What is the minimum for someone to have MDD in terms of episodes?
1 major depressive episode at minimum
When is the highest risk for a recurrent major depressive episode?
Within the first few months following the resolution of the previous.
Is bereavement a differential for MDD?
No
What are some of the screening methods we use for MDD?
PHQ-2 (2 question screen asking for depressed mood and anhedonia)
PHQ-9 (9 question screen to follow up on the PHQ-2)
Zung Self-Rated Depression Scale (in-depth rating of current depressive symptoms)
What are the non-pharmacological options for treating MDD?
Psychotherapy
ECT
Vagal nerve stimulation
Transcranial magnetic stimulation (TMS)
What is the preferred approach to MDD treatment? What is the MC?
Most preferred is a combination.
MC is just pharmacotherapy
What are the goals of MDD treatment?
Provide education
Maintain patient safety
Achieve full remission of symptoms
Return patient to baseline function
How do we decide IP vs OP treatment of MDD?
Mild/Moderate can be treated OP, generally no SI/HI and still able to take care of themselves.
What is ECT?
Use of small electric current to induce cerebral seizure UNDER general anesthesia.
When is ECT indicated?
First-line therapy for any severe SI/psychosis/catatonia/malnutrition d/t food refusal 2/2 to depressive illness.
*More efficacious than any other treatment for severe MDD.
What are the CIs of ECT?
No absolute CI.
Caution in cardio, neuro, or AC use.
What are the MC adverse effects from ECT?
Cardiopulmonary, HA, Nausea, transient cognitive impairment, and muscle aches.
What is vagal nerve stimulation?
Usually a device implanted in chest wall, connected to a vagus nerve. (usually left).
When is vagal nerve stimulation mainly used?
Refractory epilepsy.
Can be helpful for refractory depression.
What is TMS?
Metal coil with magnetic field placed against scalp.
Induces depolarization of neurons in a focal area WITHOUT any sedation or anesthesia.
When is TMS indicated?
Refractory depression.
What are the CIs of TMS?
High seizure risk, incompatible implants
*Less efficacious than ECT.
What supplements can one take for MDD?
S-Adenosylmethionine (SAMe)
5-Hydroxytryptophan (5-HTP)
Omega-3 FAs
What is SAMe?
Naturally occurring substance in the body that may raise dopamine levels.
Used as an adjunctive option for mild to moderate depression in pregnant patients.
*May trigger manic episodes
What is 5-HTP?
Natural precursor to serotonin, but risk of GI upset, serotonin syndrome, and eosinophilic myalgia syndrome.
When are omega-3 FAs best used for MDD? What are they cautionary in?
Work better with antidepressants.
Caution in anyone on AC, bc increases bleed risk.
What herbals are often used for MDD?
St. John’s Wort
Saffron
Gingko biloba
What does St. John’s Wort do?
Increases serotonin, and possibly NE and Dopamine levels as well.
Risk of GI upset, serotonin syndrome, and photosensitivity.
Many drug drug interactions (DDIs, such as warfarin)
What does saffron do?
Could help with depression.
Risk of GI upset, mania, bleeding, and is fatal at high doses.
What does gingko biloba do?
Improved mood in pts being treated for memory loss; may increase sensitivity to serotonin
May increase risk of bleeding.
*Commonly used by older people for memory loss.
What are some general guidelines for antidepressant use?
Start low and go slow, titrating over 7-10 days.
Trial for at least FOUR WEEKS MINIMUM!!!!!!!!!!!!
Rx should be continued for SIX MONTHS IF IMPROVING.
GRADUAL DOWN TITRATION if you want to dc the antidepressant.
What SSRIs have slightly increased efficacy according to some studies?
Paroxetine, escitalopram.
What SNRI has slightly increased efficacy according to some studies?
Venlafaxine
What serotonin modulators have slightly increased efficacy according to some studies?
Mirtazapine
Vortioxetine
What TCA has slightly increased efficacy according to some studies?
Amitriptyline
What are the big SEs of SSRIs?
Weight gain and sexual dysfunction.
What drug classes comprise first gen antidepressants?
MAOIs
TCA
TeCAs
What drug classes compromise 2nd gen antidepressants?
SSRIs
SNRIs
Atypical antidepressants
Serotonin modulators
Ketamine/esketamine
What are SSRIs? When are they indicated?
1st line treatment for MDD.
Selectively decreases the action of 5-HT reuptake pump, leading to increased serotonin levels in the synapse.
What drugs fall under SSRIs?
Sertraline/Zoloft
Citalopram/Celexa
Escitalopram/Lexapro
Fluoxetine/Prozac
Paroxetine/Paxil
Fluvoxamine/Luvox
Which SSRI is known for a very long half life?
Prozac/Fluoxetine.
Often used to titrate down people.
How are SSRIs typically dosed? How are they excreted?
QAM.
Hepatic metabolism, caution in hepatic impairment.
What are the CIs of SSRIs?
Allergy
MAOI within 2 weeks.
If using fluoxetine/prozac, must wait for 5 weeks before starting an MAOI.
What are the main SE of SSRIs? When do they usually occur?
Weight gain
Sexual dysfunction
Increased SI
Serotonin syndrome
QT prolongation.
Usually occurs when starting and when increasing dose.
What is serotonin syndrome?
Increased serotonergic activity that commonly occurs within 24 hours (usually 6) of starting/changing a med or ODing.
Most commonly associated with SSRIs.
How does serotonin syndrome present?
Diarrhea
Increased bowel sounds
Agitation
HYPERREFLEXIA
Dry mucous membranes
AUTONOMIC INSTABILITY (AKA fluctuating vitals)
Hyperthermia
HTN
Tremor
Clonus
Seizure
DEATH
How is serotonin syndrome diagnosed?
Clinical.
5-HT levels DO NOT CORRESPOND.
How is serotonin syndrome treated?
Supportive care
D/C serotonin meds
Sedate with Benzos
Normalize vitals and hydration.
What are the pros and cons of sertraline/zoloft?
Pros:
Less likely to cause QT prolongation or drowsiness.
Cons:
Higher likelihood of insomnia
More GI upset, esp diarrhea.
Overall: Ideal for pts with heart conditions.
What are the pros and cons of escitalopram/lexapro?
Pros:
Minimal SE.
Least inhibition of hepatic CYP.
Cons:
Most associated with QT prolongation.
Overall: Ideal for pts WITHOUT heart conditions.
What are the pros and cons of fluvoxamine/luvox?
Pros:
Short half life
Cons:
Multiple DDIs due to cytochrome inhibition.
Causes somnolence.
What are the pros and cons of fluoxetine/prozac?
Pros:
Long half life
1st SSRI ever on the market.
Cons:
Insomnia
Anxiety
Cannot be used with tamoxifen (breast cancer drug)
Overall: usually used to titrate someone’s effexor down.
What are the pros and cons of paroxetine/paxil?
Pros:
Good for insomnia?
Cons:
Anticholinergic SE
DDIs
Cannot be used with tamoxifen
When are SNRIs indicated?
First-line, or second-line if failed SSRI.
Often used in other disorders, such as anxiety, fibromyalgia, neuropathy, and menopausal s/s.
What is the MOA of a SNRI?
Blocks reuptake of 5-HT and NE, increasing levels in the synapse.
Which SNRI has a greater effect on NE than all others?
Savella and Fetzima
What drugs fall under SNRIs?
Venlafaxine/Effexor
Desvenlafaxine/Pristiq
Duloxetine/Cymbalta
Milnacipran/Savella
Levomilnacipran/Fetzima
AKA two variations of venlafaxine, two variations of milnacipran, and duloxetine.
What kind of patients are a good fit for duloxetine?
Diabetics with nerve pain and depression, since all of these can be treated by duloxetine.
How are SNRIs dosed and cleared?
QD
Kidney and liver
What are the CIs of SNRIs?
MAOI use within 2 weeks.
Allergy
use of other serotonergic drugs
Angle closure glaucoma
What are the main SE of SNRIs?
Minor weight gain (less than SSRIs)
Sexual dysfunction (less than SSRIs)
Increased SI
Serotonin syndrome
What are the cons of venlafaxine?
Higher risk of SE than its other SNRIs.
Most associated with ELEVATED BP.
What are the pros of desvenlafaxine?
Less risk of HTN and general SE than venlafaxine.
It is just the synthetic form of venlafaxine’s major metabolite.
What are the pros and cons of duloxetine/cymbalta?
Pros:
Least associated with elevated BP.
Indicated for chronic pain relief as well.
Cons:
Most likely to have DDIs among the SNRIs.
Only cytochrome inhibitor in the SNRIs.
Overall: Good SNRI for pts with HTN or chronic pain
What are the pros and cons of milnacipran and levomilnacipran?
Pros:
Pain relief
Fibromyalgia (main indication)
Cons:
Pseudo-anticholinergic SE
Not really marketed for depression (Savella)
When are atypical antidepressants indicated?
Second-line therapy.
Only first-line in special cases.
What drugs are atypical antidepressants?
Bupropion/wellbutrin/zyban
Mirtazapine/Remeron
What is the MOA of bupropion?
Dopamine-NE reuptake inhibitor.
Antagonizes NICOTINIC RECEPTORS
Used also for smoking cessation.
What is the MOA of mirtazapine/Remeron?
Antagonizes alpha2 adrenergics and 5-HT2 and 5-HT3 receptors.
Causes increased release of serotonin and NE.
When would we use bupropion? What SE should we warn about?
Useful if depressive symptoms + need help with tobacco cessation.
SE: DDIs, dry mouth, insomnia, seizure risk, risk of SI.
When is bupropion CId?
Allergy
Seizure disorder
High seizure risk pts
Anorexic/bulimic Hx
Use within 2 weeks of an MAOI.
Why are anorexia and bulimia CIs for bupropion?
They can lead to electrolyte abnormalities, which predisposes someone to seizures.
When would we use mirtazapine/remeron? What SE should we warn about?
Useful with patients who have depressive symptoms + insomnia. Lower risk of orthostatic hypotension. Less sexual dysfunction than SSRIs.
Few DDIs.
SE: Dry mouth, DROWSINESS, sedation, increased appetite, WEIGHT GAIN (more than SSRIs and SNRIs), sexual dysfunction.
When is mirtazapine/remeron CId?
Allergy
Use of MAOI within 2 weeks.
When are serotonin modulators indicated?
Second-line therapy.
May be first-line in special cases.
What is the main MOA of serotonin modulators?
Blocking reuptake of 5-HT.
What drugs fall under serotonin modulators?
Nefazodone/Serzone
Trazodone/Desyrel
Vilazodone/Viibryd
Vortioxetine/Brintellix/Trintellix
What is the additional MOA of nefazodone and trazodone?
Also antagonizes 5-HT receptors, causing increased release of serotonin.
What is the additional MOA of vilazodone and vortioxetine?
Also partial agonist of 5-HT receptors, mimicking serotonergic effects.
What kind of pts typically end up on serotonin modulators?
Pts that are strictly depressed and unable to tolerate any other medications.
How are serotonin modulators dosed and cleared?
QD-BID
Hepatic clearing
What are the CIs of serotonin modulators?
Allergy
Use within 2 weeks of a MAOI.
Caution if using other serotonergic drugs.
What are the primary SE of serotonin modulators?
HA
Diarrha
Nausea
Increased SI
Serotonin syndrome risk
What are the pros and cons of nefazodone?
Pros:
No sexual SE
Minor GI upset/weight gain.
Cons:
Most DDI risk in its class.
BBW for hepatotoxicity.
Xerostomia
Hypotension
What are the pros and cons of trazodone?
Pros:
Sedation
Less sexual dysfunction
No weight change
Cons:
Cardiac arrhythmias
Priapism
Often used at night for insomnia.
What are the Pros of vilazodone and vortioxetine?
Faster onset and less sexual dysfunction than SSRIs and SNRIs.
What is ketamine usually used for?
Severe, refractory depression w/o psychosis.
Given IV.
Esketamine given IN.
What is ketamine/esketamine indicated for in terms of duration? Why?
SHORT TERM ONLY.
HIGH ABUSE POTENTIAL
NEUROTOXICITY
PSYCHOMIMETIC EFFECTS
What is the MOA of ketamine/esketamine?
Opioid and AMPA (glutamtate) agonist, NMDA antagonist.
What are the main SE of ketamine/esketamine?
Psychomimetic
HTN
Tachycardia
Anxiety
Dizziness
HA
N/V
Longterm: abuse, nephrotoxicity, hepatoxicity
What are the CIs of ketamine/esketamine?
Allergy
Aneurysmal disease or AV malformation
Hx of ICH
Inability to tolerate an increase in BP.
When are MAOIs used and what is their MOA?
Treatment-resistant or atypical depression.
MAOa = breaks down serotonin and NE.
MAOb = breaks down dopamine.
What drugs are MAOIs?
Tranylcypromine (parnate)
Phenelzine (Nardil)
Isocaboxazid (Marplan)
Selegiline (eldepryl) - used in low doses for parkinson’s
What are the CIs and DDIs and SEs of MAOIs?
CI:
Allergy
CVD
Pheo
Hepatic or renal impairment
Use of other serotonergic drugs in past 2 weeks.
DDI: many
SE:
Hypotension, GI upset, urinary hesistancy, HA, myoclonic jerks, edema, SI, HTN crisis
Note:
Selegiline has less CIs than other MAOIs.
When does a HTN crisis due to MAOIs usually occur?
Tyramine consumption, which is found in aged cheese, soy sauce, cured meats, tap beer, tofu, and sauerkraut.
Not as common with transdermal selegiline.
When are TCAs indicated? What is the MOA?
Second-line treatment.
Treats anxiety and neuropathy and HAs.
MOA: inhibits reuptake of 5-HT and NE.
What are the two types of TCAs?
Tertiary amines, better at 5-HT reuptake.
Secondary amines, better at NE reuptake.
What drugs fall under tertiary amines for TCAs?
Amitriptyline/elavil
Doxepin/Silenor
Imipramine/tofranil
Clomipramine/anafranil
Trimipramine/surmontil
What drugs fall under secondary amines for TCAs?
Nortriptyline/Pamelor (metabolite of amitriptyline)
Despipramine/Norpramin (metabolite of imipramine)
Protriptyline/Vivactil
What is the danger of TCA dosing?
You need very low doses, so an OD on a TCA is very high mortality.
What are the CIs for TCAs?
Allergy
Use within 2 weeks of an MAOI
use in the acute recovery phase of an MI
What are the SEs of TCAs? Which ones have the least SE profile?
Anticholinergic SE
Drowsiness
Sexual dysfunction
Diaphoresis
Tremor
Weight gain
Increased appetite
Risk of SI
Risk of cardiotoxicity (QT Prolongation)
High potential for fatality in OD.
Nortriptyline and desipramine have the highest tolerability (Both secondary amines)
What is the difference between a TCA and TeCA?
TeCAs have an extra cyclic ring, indicated more for refractory or atypical depression.
What drugs are TeCAs?
Maprotiline/Ludiomil: blocks reuptake of NE and 5-HT (Mainly 5-HT)
Amoxapine/Asendin: blocks reuptake of NE. Blocks dopamine receptors (antipsychotic)
Sometimes classified as a secondary amine TCA.
What are the pros and cons of a TeCA vs a TCA?
TeCAs have less anticholinergic SEs but more anti-histamine SE.
What is lithium mainly used in? Why?
Bipolar, but can be used in unipolar depression.
It has many SE, toxicity, and not as efficacious.
What are antipsychotics used for in depression?
ADDON therapy.
Includes Aririprazole/abilify, brexpiprazole/Rexulti, quetiapine/seroquel, symbyax/fluoxetine+olanzapine.
Many SE.
What is persistent depressive disorder/dysthymia?
A patient with ongoing depressive symptoms lasting for 2+ years.
You do NOT need to have full major depressive episode for 2 years.
What is MDD sometimes known as?
Unipolar depression.
What is the criteria for PDD/Dysthymia?
2+ years of depressed mood MOST of the time.
Cannot have more than 2 months asymptomatic.
2+ of the following:
Appetite changes
Sleep changes
Fatigue
Diminished ability to think
Low self-esteem
Feelings of hopelessness
NO MANIC SYMPTOMS OR SECONDARY CAUSE
What is the best treatment option for PDD/Dysthymia?
Combined pharmacotherapy and psychotherapy.
First-line pharmacotherapy: SSRIs
Second-line: TCAs and MAOIs
