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Karboski's Pharmacology - UT AEMSN > Depression & Antipsychotics > Flashcards

Depression & Antipsychotics Flashcards

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1
Q

Define:

  1. Response
  2. Remission
  3. Recovery
  4. Relapse
  5. Recurrence
A
  1. Significant, not complete, ↓ in depressive Sx
  2. Complete resolution of depressive Sx
  3. Sustained remission for > 6 mo
  4. Return of depressive Sx w/in 6 mo of achieving remission
    • return of Sx w/in same MDD episode
  5. Successive episode of MDD after recovery from initial episode of MDD
    • return of Sx that may signal a new MDD episode
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2
Q
  1. What is Serotonin Synd?
  2. What is the classic Sx triad?
A
  1. Synd assoc w/ any antidepressant that ↑ [5HT]
  2. Triad:
    • mental status Δ
    • ANS instability
    • neuromuscl abnml
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3
Q

What is the paradoxical relationship between high, moderate, and low potency 1st gen antipsychotics?

A
  • As potency ↑ from low to high, D2 antagonism ↑
  • As potency ↓ from high to low, anti-Ach, α-antagonism, and sedation ↑
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4
Q

What is discontinuation syndrome?

A

Sx seen with abrupt D/C of serotonergic Rx

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5
Q
  1. What is brexanolone (Zulresso) indicated for?
  2. What is it?
  3. What is unique about its administration and cost?
A
  1. Postpartum depression
  2. Aqueous formulation of a metabolite or progesterone (allopregnanolone)
  3. Must be infused over 60 hrs w/ cont monitoring and costs $34k/infusion
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6
Q
  1. What is unique about levomilnacipran (Fetzima)?
  2. When would we use it?
A
  1. more NE reuptake blockade than 5HT reuptake blockade
    • more NE SE than 5HT
  2. reserved for situations where we want fewer 5HT SE and more NE effects
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7
Q
  1. What are the risk factors acute dystonia?
  2. How are acute dystonic rxn typically treated?
A
  1. risk factors:
    • male
    • young
    • high potency 1st gen
    • previous dystonic rxn
  2. treatment:
    • benztropine (1-6mg)
    • lorazepam (1-8mg)
    • diazepam (2-40mg)
    • diphenhydramine (50-300mg)
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8
Q

What are the guidelines for initiation and/or D/C r/t QTc and antipsychotic Rx’s?

A
  • QTc > 450 ms → avoid starting any QTc prolonging agent
  • QTc > 500 ms → D/C treatment

**In general normal QTc is btw 400 to 440 ms**

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9
Q

What are the risk factors for developing PseudoParkinsonism?

A
  • Female gender
  • High dose antipsychotics
  • High potency 1st gen antipsychotics
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10
Q

What are some other non-classic 5HT Synd Sx?

A
  • tremor + hyperreflexia
  • spont clonus
  • muscle rigidity + temp > 38 C° + ocular/inducible clonus
  • ocular/inducible clonus + agitation/diaphoresis
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11
Q
  1. What is the ratio of NE : 5HT blockade in duloxetine (Cymbalta)
  2. What is duloxetine FDA approved for?
  3. ADRs?
A
  1. Equal ratio of NE : 5HT blockade across dosage range
  2. neuropathic associated w/ DM
  3. ADRs:
    • similar to venlafaxine
    • significant rates of
      • nausea, dry mouth, constipatio, insomnia, and sweating
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12
Q

List the 6 SSRIs

A
  • citalopram (Celexa)
  • escitalopram (Lexapro)
  • fluoxetine (Prozac)
  • fluvoxamine (Luvox)
  • sertraline (Zoloft)
  • paroxetine (Paxil)
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13
Q

What are the hallmark Sx of depression?

A

depressed mood and/or anhedonia

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14
Q

What is pseudoparkinsonism and what types of Sx are observed?

A
  • Similar to idiopathic parkinsonism
    • akinesia, bradykinesia, slowed speech
    • cogwheel, rigidity, pill rolling tremor
    • gait abnormalities
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15
Q

What are the treatment approaches to depression?

A
  • drug em
    • pharmacotherapy
  • talk to em
    • Psychotherapy (CBT, intersocial)
  • shock em
    • ECT
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16
Q

What are the risk factors for QTc prolongation for antipsychotic Rx’s?

A
  • age
  • e-ltye imbalances
  • HF
  • bradycardia
  • female
  • eating disorders
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17
Q

What are some ways to manage the nausea ADRs with antidepressant Rx’s?

A
  • start low, titrate up
  • take w/ food
  • ↓ dose
  • Δ antidepressant
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18
Q

What does the black boxed warning for ALL antipsychotics say?

A
  • Elderly w/ dementia-related psychosis Tx w/ SGA are at ↑ risk of death vs placebo
    • 4.5% drug treated vs 2.6% in placebo
  • Cause of death varied, but most were related to either:
    • cardiovascular
    • infectious
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19
Q
  1. What type of antidepressive is bupropion (Wellbutrin)?
  2. What are the ADRs?
  3. What is one main drawback to bupropion?
  4. What is one main benefit when using bupropion?
A
  1. NDRI
  2. ADRs:
    • N/V, skin rxn, tremor, insomnia
  3. ↓ seizure threshold…debatable as to how much
  4. ↓ sexual SE
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20
Q

What are the five DSM - TR diagnostic criteria key points?

A
  1. persistant dysfxn ≥ 6 mo
  2. two or more* Sx for ≥ 1 mo
  3. significantly impaired fxning
  4. disturbance not d/t something else
  5. if h/o pervasive develop disorder exists, Dx of schizo made if:
    • delusions or hallucinations present for ≥ 1 mo
  • *Only 1 req’d if:
    • delusions are bizarre
    • hallucinations w/ commententary voices or 2 voices conversing
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21
Q

What are the general guidelines for choosing an antidepressant?

A
  • past hx of response
  • SE profile
  • co-occurring psychiatric/medical conditions
  • Rx interactions
  • cost
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22
Q

What are the different phases of antidepressant treatment and about how long are each?

A
  • Phases:
    • Acute - 6 to 12 wks
    • Continuation - 4 to 9 mo
    • Maintenance - 1 yr to permanent
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23
Q
  1. What can be the range of depression episodes?
  2. What % will episodes continue if left untreated
A
  1. 6 mo to 2 yrs
  2. 80%
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24
Q

In general what would the ideal antipsychotic be able to do?

A
  • ↓ DA in one pathway → treats positive Sx
  • ↑ DA in another pathway → treats negative Sx
  • DA levels maintained in other pathways → SE minmized
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25
1. What is MoA for trazodone (Desyrel)? 2. What is it typically used for?
1. 5HT antagonist and reuptake inhibitor * Blocks 5HT reuptake and activity in synapse...weird 2. Used a lot more for insomnia than depression
26
What are the clinical consequences of D2 blockade?
* hyperprolactinemia * drug-induced movement disorders * EPS * dystonia, akathisia, pseudoparkinsonism * TD
27
1. What makes the TCA SE profile unfavorable? 2. What other ADRs do TCAs have?
1. Effects on other receptor systems * anti-Ach - can't see/shit/spit/pee * α-adrenergic - orthostasis * very sedating 2. Weight ↑, glucose dysreg, cardiac conduction effects
28
How do we manage Discontinuation Syndrome?
Taper off slowly
29
What assessment tool is used for Akathesia?
Barnes Akathesia Rating Scale
30
1. What is vortioxetine (Trintellix)? 2. What is it proposed to be particularly beneficial for?
1. "multi-modal" 5HT Rx 2. MDD + cognitive difficulties
31
What are the different stages of the time course to response to drug therapy for antipsychotics?
32
What is the onset profile for schizophrenia and who does it typically affect?
* late adolescence or early adulthood * rarely before adolescence or after 40 yo * earlier in males * males 20s, females 20s to 30s * affects genders and ethnicities equally
33
What are the two main categories of 1st gen antipsychotics?
* phenothiazines * ex. chlorpromazine (Thorazine), fluphenazine (Prolixin) * non-phenothiazines * ex. haloperidol (Haldol)
34
What are some risk factors for developing Tardive Dyskinesia?
* taking antipsychotics * age (elderly), female, race (AA x2 risk) * long Tx duration * refractory psychosis, mood disorder * early EPS
35
How is desvenlafaxine (Pristiq) r/t venlafaxine (Effexor)?
* desvenlafaxine is an active metabolite of venlafaxine * ADR profile similar * venlafaxine has Effexor + Pristiq SE * desvenlafaxine only has Pristiq SE
36
What are the treatment options for Akathesia?
* ↓ dose of antispsychotic * use 2nd gen antipsychotic * treat with: * β -blocker (Rx of choice) * propranolol 20-160 mg qday * metoprolol 200-300 mg qday * benztropine → alternative * anti-Ach → Ø very effective
37
What are some medical conditions that are associated w/ depression?
* HoTSH * Stroke, MI * Hep C
38
1. What is the class-wide pregnancy warning for all antipsychotics? 2. What are some of the Sx of EPS and withdrawal? 3. What Tx is recommended?
1. ↑ risk of EPS/withdrawal in newborns if mother treated during 3rd trimester 2. Agitation, abnml ↑ or ↓ muscle tone, tremor, sleepiness, severe difficult breathing, and difficult in feeding\* * Lasts hours to days 3. No specific treatment recommended \*Δ in feeding is a key sign like AMS is for elderly
39
What assessment tool is used for Pseudoparkinsonism?
Simpson Angus Rating Scale
40
When is depression associated with increased mortality and worse outcomes?
Increased mortality in +50 y.o. and worse outcomes with chronic conditions
41
What is the Biogenic Amine Theory?
States that low levels of 3 primary NTs (monoamines) highly correlate with occurance of depression * 5HT * NE * DA
42
What are the 2 ways the Biogenic Amine Theory is applied to drug therapy?
1. Monoamine reuptake inhibition * ↑ [NT] by blocking reuptake 2. MAO inhibition * ↑ [NT] by blocking degredation
43
1. What is the MoA of TCAs? 2. What is vitally important to know about TCA dosing?
1. Inhibit NE and 5HT reuptake * TCA = SNRIs that are a unique chemical class * potency and selectivity vary among agents 2. Lethal if OD (≤ 3x daily dose) * Never say "take 3 and call me in the morning"
44
1. When is D/C of antidepressant therapy usually initiated? 2. How is the duration of D/C decided?
1. Treat ≥ 4 to 9 months before tapering 2. Duration of taper based on # of MDD episodes 1. single ep → \> 6 mo of remission before taper 2. two ep → \> 1 yr of remission before taper 3. multiple ep → consider indefinite treatment
45
What are some ways to manage insomnia ADRs for antidepressant Rx's?
* Regulate caffeine * AM dosing * ↓ dose * Δ antidepressant Rx * adjunct w/ sleeping Rx
46
What is the difference btw Wellbutrin and Zyban?
* Not a damn thing, they're both bupropion * Only that Zyban is FDA approved for smoking cessation
47
What are the newer Rx to manage TD? * MoA, outcome, SEs
* valbenazine (Ingrezza) and deutetrabenazine (Austedi) * ↓ presynaptic DA * modest Sx improvement * sedation and dry mouth \> 5%
48
1. What is psychosis? 2. What does it lead to?
1. A severe mental disturbance that involves a profound misinterpretation of perceptions or loss of contact w/ reality 2. inappropriate ability to interact w/ others or with the enviroment
49
What are the desired treatment outcomes for schziophrenia?
* alleviate target Sx * ↓/avoid SE * ↑ fxning and productivity * adhere to regimen * involve Pt in treatment planning * re-integration
50
1. What are the MAOI agents? 2. When are they used? 3. What unique interaction does this class have?
1. MAOIs: * phenelzine (Nardil) * tranylcypromine (Parnate) * selegiline (Eldepryl) 2. Reserved for treatment of resistant depression 3. Interaction with food w/ ↑ [tyramine] * MAOI → ↑ [NT] already
51
What are the typical/1st gen antipsychotic major SEs?
* sedation * orthostasis * anti-Ach * EPS * NMS * Prolonged OTc
52
In which patients should we be concerned about Discontinuation Syndrome?
* Pts on high dose SSRIs to achieve effects * Pts that don't like SEs → abrupt d/c
53
1. What is schizophrenia and what are its main components? 2. What primarily causes it?
1. thought disorder composed of positive, negative, and cognitive Sx 2. imbalance of brain chemicals * dopamine
54
1. What is the pregnancy category for ALL antipsychotics? * What is the one exception? 2. When is the greatest risk during pregnancy?
1. Category C * clozapine = category B 2. During 1st trimester
55
1. What type of antidepressant is mirtazapine (Remeron) 2. What are the ADRs? 3. What activity occurs at lower doses? Higher doses?
1. 5HT + α2 receptor antagonist 2. _ADRs_: * sedating anti-hist effects * significant weight ↑ 3. Sedation at lower doses and ↑ NE activity at higher doses
56
* Remission is the goal of treatment for MDD. * What are the benefits to treating to remission?
* Improve overall function * ↓ risk of another episode * ↑ amount of time until another episode * for those who experience recurrence
57
Why has nefazodone (Serzone) fallen out of use?
Black box warning for hepatic toxicity including liver failure
58
1. What are some **general** monitoring parameters for 2nd gen antipsychotics? * What are some of the ongoing parameters? 2. What are the **drug-specific** monitor parameters for 2nd gen antipsychotics?
1. General: * BMI * ongoing = q mo x 6 mo, then quarterly) * FBG or HbA1c * ongoing = q yr unless risk of DM or Wt ↑ → q 4 mo * FLP w/in 30 day of start * q 2 yr if @ goal * EPS * Pregnancy test (if indicated) 2. Drug-Specific: * AIMS → TD * CBC → clozapine * EKG → clozapine and ziprasidone
59
1. What is vilazodone (Viibryd)? 2. What is it proposed to be particularly beneficial for?
1. SSRI + 5HT receptor partial agonist 2. MDD + anxiety
60
1. List the Mixed Serotonergic Effect drugs 2. When are they used?
1. Drugs: 1. Trazadone (Desyrel) - usually used 1st 2. Nefazodone (Serzone) 3. Vilazodone (Viibryd) 4. Vortioxetine (Trintillex) 2. Reserved for if either: * Pts don't tolerate SSRIs/SNRIs * Don't see efficacy in using SSRIs/SNRIs
61
What are some ways to manage the anxiety ADRs with antidepressant Rx's?
* wait it out * may be transient d/t Rx Δ * minimize or avoid caffeine * ↓ dose and titrate gradually * β-blocker or benzodiazepine
62
1. How do all antipsychotics affect seizures? 2. How is mgmt approached r/t seizures?
1. All lower seizure thresholds 2. _Mgmt_: * ↓ starting dose and/or titration * add antiepileptic * Δ antipsychotic agent
63
1. When should mirtazapine typically be taken? * When is this useful? 2. What is one SE that occurs at a very low rate?
1. At bedtime d/t very sedating effects * when insomnia part of presentation 2. Low rate of sexual dysfxn
64
1. What is Tardive Dyskinesia (TD)? * body parts affected? * what can severe Sx impair? 2. What is the onset?
1. Abnormal, involuntary movements → potentially irreversible * face, tongue, lips, limbs * can impair speaking, chewing, swallowing 2. Can occur w/in 3 mo to many yrs s/p antipsychotic Tx
65
What are the benefits of atypical antipsychotics vs 1st gen?
* positive sx efficacy * clozapine for mgmt of resistant positve Sx * possible enhanced efficacy for neg/cog Sx * ↓ movement disorder incidence * minimal or no effect on prolactin at nml doses * risperidone and paliperidone are exceptions
66
What are the differences between the prodromal phase and acute episodes of schizophrenia?
* prodromal * withdrawn * odd beliefs * peculiar behaviors * acute episode * lose touch * hallucinations/delusions * flat or inapp affect * difficult w/ self-care
67
1. What is the rate of occurrance of PseudoParkinsonism? * aka Drug-Induced Parkinson's 2. What is the onset?
1. Occurs 10-40% in Pts w/ 1st gen antipsychotics 2. 1-3 months after antipsychotic initiation
68
What are some drugs associated with depression?
* α -interferon * Resperpine (vesicular monoamine transport 1 & 2 inhibitor) * Periph α-blockers/Central α-agonists * substance abuse (MDMA, cocaine)
69
1. What is unique about venlafaxine 5HT & NE reuptake inhibition * What dose related SE dose it cause? 2. What are the two formulations? 3. What are the ADRs?
1. Always blocks 5HT reuptake but only blocks NE reuptake \> 200 mg/day * Dose related ↑ in BP 2. _Formulations_: * XR → Q day * IR → BID or TID 3. _ADRs_: 1. Serotonergic (N/V, GI, sleep Δ, sexual SE) 2. NE-related (↑ BP, sweating, agitation)
70
What are the SSRI ADRs?
1. R/t ↑ 5HT stimulation 2. 5HT side effects * N/V * sleep Δ * sexual dysfxn * weight ↑
71
What are the metabolic SE of atypical antipsychotics?
* weight ↑ * new onset DM or glucose dysregulation * ↑ BGL can be w/out ↑ weight * new DM typically w/in 6 mo of starting * worsening lipid profile
72
1. What is esketamine (Spravato) used for and what is its MoA? 2. Admin route? 3. Unique about administration? 4. What is black box warning and how is it addressed
1. Treatment resistant depression; MoA unknown 2. Nasal spray 3. Only admin at treatment center w/ 2 hr monitoring * Use associated w/ sedation, dissociation, and abuse/misuse 4. ↑ risk of suicidality in ≤ 24 y.o. * addressed w/ regular monitoring and limited Rx prescribed
73
What are some treatment options for PseudoParkinsonism?
* lower dose of antipsychtic * Δ to 2nd gen antipsychotic * add antiparkinsonian agent * preferred anti-Ach: benztropine * amantadine 100-400 mg/day
74
1. What is acute dystonia? 2. When does it typically occur?
1. abnormal muscle spasms and posturing of eyes, face, neck, throat, abdomen, and extremities 2. 90% start w/in 3 days of starting antipsychotic Rx
75
What DSM-5 criteria must be met for a MDD Dx?
* 5 listed criteria w/ 1 being depressed mood or anhedonia * significant distress or impairment of fxn * Sx \> 2 wks
76
What some key differences between continuation phase and maintenance phase of MDD treatment?
* Continuation phase: * occurs for every Pt during an episode of treatment * bridges remission to recovery * Rx may be d/c after the conclusion of this phase * Maintenance phase: * Not for all Pts * For Pts w/ ↑ risk of recurrance and/or risk factors for recurrance * Rx for extended time, perhaps indefinitely
77
1. What are other terms for 1st gen antipsychotics * examples? 2. What are other terms for 2nd gen antipsychotics * examples?
1. 1st gen = conventional = typical * haloperidol, fluphenazine, chlorpromazine 2. 2nd gen = atypical * olanzaine, clozapine, aripiprazole, etc
78
1. What is Akathisia? 2. What is an objective finding?
1. Inner feeling of restlessness, anxiety * Constant need to move in order to feel better 2. Motor hyperactivity → pacing, rocking
79
\*\*Don't need to know secondary vs tertiary\*\* 1. What are the secondary amine TCAs? 2. What are the tertiary amine TCAs?
1. _Secondary Amines_ "ADNP" * **_A_**moxapine * **_D_**esipramine * **_N_**ortriptyline * **_P_**rotriptyline 2. _Tertiary Amines_ "ACID" * **_A_**mitriptyline * **_C_**lomipramine * **_I_**mipramine * **_D_**oxepin
80
1. What unique monitoring takes place when Pts are on clozapine? 2. What specific steps must occur during 3. What specific steps if D/C'd?
1. monitoring for agranulocytosis * possibly d/t toxic myeloid precursors (N-desmethyl clozapine) 2. CBC w/ diff at base * then Q wk x 6 mo * then Q 2 wks x 6 mo * then monthly 3. CBC w/ diff for ≥ 4 weeks
81
What is the assessment tool used for Tardive Dyskinesia?
Abnormal Involuntary Movement Scale (AIMS)
82
1. What is the MoA for SSRIs? 2. Typical admin? 3. What dictates timing of dosing?
1. Inhibits 5HT transporter --\> ↑ [5HT] in synapse 2. Q day 3. Effect on sleep cycle * insomnia vs sedation as SE
83
What are the 3 types of Sx associated with D/C Syndrome?
* Somatic (ex. GI) * Neurologic (ex. "shock-like" sensation) * Psychological (ex. anxiety)
84
1. What is the MoA of SNRIs 2. List the SNRIs
1. Inhibit neuronal reuptake of 5HT and NE 2. SNRI List: * Desvenlafaxine (Pristiq) * Venlafaxine (Effexor) * Duloxetine (Cymbalta) * Levomilnacipran (Fetzima) * Milnacipran (Savella)\* ## Footnote \*only approved for fibromyalgia in USA
85
What are some ways to manage the sexual ADRs with antidepressant medications?
* wait it out for tolerance * ↓ antidepressant dose * Δ antidepressants * bupropion * mirtazipine * adjuncts * sildenafil, etc...
86
How is Tardive Dysinkesia managed?
* Prevention = key * D/C or Δ antipsychotics if possible * If Ø d/c → Δ from FGA to SGA * Clozapine = Rx of choice if TD severe * Vit E, melatonin, Ach, BC amino acids → poor outcomes * newer Rx * Sx ↓ but Ø cure
87
What is clinically significant QTc prolongation for: * ≤ 5ms * 5-10ms * 10-20ms * ≥ 20ms
* not associated w/ ↑ risk * Pt at low risk * Pt at moderate risk * High risk of inducing proarrhythmias
88
* What are the differences between positive, negative, and cognitive Sx of schizophrenia? * What are examples of each?
* positive adds Sx to normal presentation * hallucinations, delusions * negative takes away something from normal presentation * anhedonia, poor abstract thinking * cognitive are ↓ in cognitive fxning * poor coordination, impaired executive fxning
89
1. What is unique about the dosing and effects of trazadone (Desyrel)? 2. What are the ADRs?
1. _Dosing Effects_: * Doses \< 300 mg used for insomnia * Antidepressant at higher doses 2. _ADRs_: * sedation * nausea, GI upset * priapism
90
1. What is the average age of onset for depression? 2. What % typically has their 1st episode by what age?
1. mid-20s 2. \>50% by 40 y.o.
91
1. What are the risk factors for developing Akathesia? 2. What is a typical onset of Sx?
1. Risk Factors: * high dose * rapid dose ↑ * high potency 1st gen antipsychotic 2. Appears w/in days to wks of Tx
92
* Atypical antipsychotic potential therapeutic effects: 1. for 5HT2a antagonism 2. for 5HT1a partial agonism
1. Treats other schizo Sx, ↓ EPS, improved slow-wave sleep 2. Anxiolytic effects

Karboski's Pharmacology - UT AEMSN (11 decks)

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