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

Depression & Antipsychotics Flashcards

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
Q
  1. What is MoA for trazodone (Desyrel)?
  2. What is it typically used for?
A
  1. 5HT antagonist and reuptake inhibitor
    • Blocks 5HT reuptake and activity in synapse…weird
  2. Used a lot more for insomnia than depression
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26
Q

What are the clinical consequences of D2 blockade?

A
  • hyperprolactinemia
  • drug-induced movement disorders
    • EPS
      • dystonia, akathisia, pseudoparkinsonism
    • TD
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27
Q
  1. What makes the TCA SE profile unfavorable?
  2. What other ADRs do TCAs have?
A
  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
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28
Q

How do we manage Discontinuation Syndrome?

A

Taper off slowly

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29
Q

What assessment tool is used for Akathesia?

A

Barnes Akathesia Rating Scale

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30
Q
  1. What is vortioxetine (Trintellix)?
  2. What is it proposed to be particularly beneficial for?
A
  1. “multi-modal” 5HT Rx
  2. MDD + cognitive difficulties
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31
Q

What are the different stages of the time course to response to drug therapy for antipsychotics?

A
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32
Q

What is the onset profile for schizophrenia and who does it typically affect?

A
  • 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
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33
Q

What are the two main categories of 1st gen antipsychotics?

A
  • phenothiazines
    • ex. chlorpromazine (Thorazine), fluphenazine (Prolixin)
  • non-phenothiazines
    • ex. haloperidol (Haldol)
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34
Q

What are some risk factors for developing Tardive Dyskinesia?

A
  • taking antipsychotics
  • age (elderly), female, race (AA x2 risk)
  • long Tx duration
  • refractory psychosis, mood disorder
  • early EPS
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35
Q

How is desvenlafaxine (Pristiq) r/t venlafaxine (Effexor)?

A
  • desvenlafaxine is an active metabolite of venlafaxine
  • ADR profile similar
    • venlafaxine has Effexor + Pristiq SE
    • desvenlafaxine only has Pristiq SE
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36
Q

What are the treatment options for Akathesia?

A
  • ↓ 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
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37
Q

What are some medical conditions that are associated w/ depression?

A
  • HoTSH
  • Stroke, MI
  • Hep C
38
Q
  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?
A
  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
Q

What assessment tool is used for Pseudoparkinsonism?

A

Simpson Angus Rating Scale

40
Q

When is depression associated with increased mortality and worse outcomes?

A

Increased mortality in +50 y.o. and worse outcomes with chronic conditions

41
Q

What is the Biogenic Amine Theory?

A

States that low levels of 3 primary NTs (monoamines) highly correlate with occurance of depression

  • 5HT
  • NE
  • DA
42
Q

What are the 2 ways the Biogenic Amine Theory is applied to drug therapy?

A
  1. Monoamine reuptake inhibition
    • ↑ [NT] by blocking reuptake
  2. MAO inhibition
    • ↑ [NT] by blocking degredation
43
Q
  1. What is the MoA of TCAs?
  2. What is vitally important to know about TCA dosing?
A
  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
Q
  1. When is D/C of antidepressant therapy usually initiated?
  2. How is the duration of D/C decided?
A
  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
Q

What are some ways to manage insomnia ADRs for antidepressant Rx’s?

A
  • Regulate caffeine
  • AM dosing
  • ↓ dose
  • Δ antidepressant Rx
  • adjunct w/ sleeping Rx
46
Q

What is the difference btw Wellbutrin and Zyban?

A
  • Not a damn thing, they’re both bupropion
  • Only that Zyban is FDA approved for smoking cessation
47
Q

What are the newer Rx to manage TD?

  • MoA, outcome, SEs
A
  • valbenazine (Ingrezza) and deutetrabenazine (Austedi)
    • ↓ presynaptic DA
    • modest Sx improvement
    • sedation and dry mouth > 5%
48
Q
  1. What is psychosis?
  2. What does it lead to?
A
  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
Q

What are the desired treatment outcomes for schziophrenia?

A
  • alleviate target Sx
  • ↓/avoid SE
  • ↑ fxning and productivity
  • adhere to regimen
  • involve Pt in treatment planning
  • re-integration
50
Q
  1. What are the MAOI agents?
  2. When are they used?
  3. What unique interaction does this class have?
A
  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
Q

What are the typical/1st gen antipsychotic major SEs?

A
  • sedation
  • orthostasis
  • anti-Ach
  • EPS
  • NMS
  • Prolonged OTc
52
Q

In which patients should we be concerned about Discontinuation Syndrome?

A
  • Pts on high dose SSRIs to achieve effects
  • Pts that don’t like SEs → abrupt d/c
53
Q
  1. What is schizophrenia and what are its main components?
  2. What primarily causes it?
A
  1. thought disorder composed of positive, negative, and cognitive Sx
  2. imbalance of brain chemicals
    • dopamine
54
Q
  1. What is the pregnancy category for ALL antipsychotics?
    • What is the one exception?
  2. When is the greatest risk during pregnancy?
A
  1. Category C
    • clozapine = category B
  2. During 1st trimester
55
Q
  1. What type of antidepressant is mirtazapine (Remeron)
  2. What are the ADRs?
  3. What activity occurs at lower doses? Higher doses?
A
  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
Q
  • Remission is the goal of treatment for MDD.
    • What are the benefits to treating to remission?
A
  • Improve overall function
  • ↓ risk of another episode
  • ↑ amount of time until another episode
    • for those who experience recurrence
57
Q

Why has nefazodone (Serzone) fallen out of use?

A

Black box warning for hepatic toxicity including liver failure

58
Q
  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?
A
  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
Q
  1. What is vilazodone (Viibryd)?
  2. What is it proposed to be particularly beneficial for?
A
  1. SSRI + 5HT receptor partial agonist
  2. MDD + anxiety
60
Q
  1. List the Mixed Serotonergic Effect drugs
  2. When are they used?
A
  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
Q

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

A
  • wait it out
    • may be transient d/t Rx Δ
  • minimize or avoid caffeine
  • ↓ dose and titrate gradually
  • β-blocker or benzodiazepine
62
Q
  1. How do all antipsychotics affect seizures?
  2. How is mgmt approached r/t seizures?
A
  1. All lower seizure thresholds
  2. Mgmt:
    • ↓ starting dose and/or titration
    • add antiepileptic
    • Δ antipsychotic agent
63
Q
  1. When should mirtazapine typically be taken?
    • When is this useful?
  2. What is one SE that occurs at a very low rate?
A
  1. At bedtime d/t very sedating effects
    • when insomnia part of presentation
  2. Low rate of sexual dysfxn
64
Q
  1. What is Tardive Dyskinesia (TD)?
    • body parts affected?
    • what can severe Sx impair?
  2. What is the onset?
A
  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
Q

What are the benefits of atypical antipsychotics vs 1st gen?

A
  • 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
Q

What are the differences between the prodromal phase and acute episodes of schizophrenia?

A
  • prodromal
    • withdrawn
    • odd beliefs
    • peculiar behaviors
  • acute episode
    • lose touch
    • hallucinations/delusions
    • flat or inapp affect
    • difficult w/ self-care
67
Q
  1. What is the rate of occurrance of PseudoParkinsonism?
    • aka Drug-Induced Parkinson’s
  2. What is the onset?
A
  1. Occurs 10-40% in Pts w/ 1st gen antipsychotics
  2. 1-3 months after antipsychotic initiation
68
Q

What are some drugs associated with depression?

A
  • α -interferon
  • Resperpine (vesicular monoamine transport 1 & 2 inhibitor)
  • Periph α-blockers/Central α-agonists
  • substance abuse (MDMA, cocaine)
69
Q
  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?
A
  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
Q

What are the SSRI ADRs?

A
  1. R/t ↑ 5HT stimulation
  2. 5HT side effects
    • N/V
    • sleep Δ
    • sexual dysfxn
    • weight ↑
71
Q

What are the metabolic SE of atypical antipsychotics?

A
  • 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
Q
  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
A
  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
Q

What are some treatment options for PseudoParkinsonism?

A
  • lower dose of antipsychtic
  • Δ to 2nd gen antipsychotic
  • add antiparkinsonian agent
    • preferred anti-Ach: benztropine
    • amantadine 100-400 mg/day
74
Q
  1. What is acute dystonia?
  2. When does it typically occur?
A
  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
Q

What DSM-5 criteria must be met for a MDD Dx?

A
  • 5 listed criteria w/ 1 being depressed mood or anhedonia
  • significant distress or impairment of fxn
  • Sx > 2 wks
76
Q

What some key differences between continuation phase and maintenance phase of MDD treatment?

A
  • 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
Q
  1. What are other terms for 1st gen antipsychotics
    • examples?
  2. What are other terms for 2nd gen antipsychotics
    • examples?
A
  1. 1st gen = conventional = typical
    • haloperidol, fluphenazine, chlorpromazine
  2. 2nd gen = atypical
    • olanzaine, clozapine, aripiprazole, etc
78
Q
  1. What is Akathisia?
  2. What is an objective finding?
A
  1. Inner feeling of restlessness, anxiety
    • Constant need to move in order to feel better
  2. Motor hyperactivity → pacing, rocking
79
Q

**Don’t need to know secondary vs tertiary**

  1. What are the secondary amine TCAs?
  2. What are the tertiary amine TCAs?
A
  1. Secondary Amines “ADNP”
    • Amoxapine
    • Desipramine
    • Nortriptyline
    • Protriptyline
  2. Tertiary Amines “ACID”
    • Amitriptyline
    • Clomipramine
    • Imipramine
    • Doxepin
80
Q
  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?
A
  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
Q

What is the assessment tool used for Tardive Dyskinesia?

A

Abnormal Involuntary Movement Scale (AIMS)

82
Q
  1. What is the MoA for SSRIs?
  2. Typical admin?
  3. What dictates timing of dosing?
A
  1. Inhibits 5HT transporter –> ↑ [5HT] in synapse
  2. Q day
  3. Effect on sleep cycle
    • insomnia vs sedation as SE
83
Q

What are the 3 types of Sx associated with D/C Syndrome?

A
  • Somatic (ex. GI)
  • Neurologic (ex. “shock-like” sensation)
  • Psychological (ex. anxiety)
84
Q
  1. What is the MoA of SNRIs
  2. List the SNRIs
A
  1. Inhibit neuronal reuptake of 5HT and NE
  2. SNRI List:
    • Desvenlafaxine (Pristiq)
    • Venlafaxine (Effexor)
    • Duloxetine (Cymbalta)
    • Levomilnacipran (Fetzima)
    • Milnacipran (Savella)*

*only approved for fibromyalgia in USA

85
Q

What are some ways to manage the sexual ADRs with antidepressant medications?

A
  • wait it out for tolerance
  • ↓ antidepressant dose
  • Δ antidepressants
    • bupropion
    • mirtazipine
  • adjuncts
    • sildenafil, etc…
86
Q

How is Tardive Dysinkesia managed?

A
  • 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
Q

What is clinically significant QTc prolongation for:

  • ≤ 5ms
  • 5-10ms
  • 10-20ms
  • ≥ 20ms
A
  • not associated w/ ↑ risk
  • Pt at low risk
  • Pt at moderate risk
  • High risk of inducing proarrhythmias
88
Q
  • What are the differences between positive, negative, and cognitive Sx of schizophrenia?
    • What are examples of each?
A
  • 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
Q
  1. What is unique about the dosing and effects of trazadone (Desyrel)?
  2. What are the ADRs?
A
  1. Dosing Effects:
    • Doses < 300 mg used for insomnia
    • Antidepressant at higher doses
  2. ADRs:
    • sedation
    • nausea, GI upset
    • priapism
90
Q
  1. What is the average age of onset for depression?
  2. What % typically has their 1st episode by what age?
A
  1. mid-20s
  2. >50% by 40 y.o.
91
Q
  1. What are the risk factors for developing Akathesia?
  2. What is a typical onset of Sx?
A
  1. Risk Factors:
    • high dose
    • rapid dose ↑
    • high potency 1st gen antipsychotic
  2. Appears w/in days to wks of Tx
92
Q
  • Atypical antipsychotic potential therapeutic effects:
    1. for 5HT2a antagonism
    2. for 5HT1a partial agonism
A
  1. Treats other schizo Sx, ↓ EPS, improved slow-wave sleep
  2. Anxiolytic effects

Karboski's Pharmacology - UT AEMSN (11 decks)

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