8005 final Flashcards
EPS cause
exposure to dopamine antagonist med
blocks D2 receptors means inhibiting dopamine and blocking ACH
this leads to more ACH release which turns into EPS
4 EPS symptoms
Dystonia
Akathesia
Parkinsonism
Tardive Dyskinesia
Dystonia sx
torticollis
sustained muscular contraction
oculogyric crisis
Dystonia tx
anticholinergic med
benztropine***
biperiden
diphenhydramine
Akathesia sx
restless
tapping
pacing
can’t sit still – psychomotor restlessness
Akathesia tx
Treatment (beta blocker) – propranolol***
mirtazapine
cyproheptadine
BZDs
i. Avoid polypharm or rapid dose increases to avoid akathisia
Parkinsonism sx
bradycardia
postural instability
tremor
rigidity
shuffling gait
Parkinsonism tx
Treatment (anticholinergic med) –
reduce dose or switch to lower risk med
***benzotropine (caution in elderly),
amantadine (good for elderly)
Tardive Dyskinesia sx, MOA
chronic manifestation
– involuntary movements of lower face, limbs, trunk –
reversibly inhibits VMAT2
Tardive dyskinesia risk factors
early presence of EPS
Tardive Dyskinesia tx
stop Rx
Valbenazine, deutetrabenazine, clozapine,
gingko biloba
serotonin syndrome vs NMS
onset
SS more rapid
serotonin syndrome vs NMS
which is deadly
NMS
serotonin syndrome vs NMS
3 similar sx
fever
Tachy
HTN
serotonin syndrome vs NMS
reflexes
SS: Clonus (hyperreflexia 4+)
NMS: rigidity
serotonin syndrome vs NMS
SS sx not in NMS
diarrhea
serotonin syndrome vs NMS
identifying labs
not SS
But NMS: inc CK, WBC, rhabdo
serotonin syndrome vs NMS
rx associations
SS: SSRI/SNRI, MAOI, linezolid, triptins, analgesics, cough med, St John wort, tryptophan
NMS: Antipsychotics though 1st gen more
serotonin syndrome TX
support flux BP and P,
avoid restraints
BZDs
cyproheptadine, olanzapine
DO NOT USE: propranolol, dantrolene, bromcriptine
NMS tx
DC med
Dantrolene, bromocriptine, amantadine
(too much DA is blocked, give some back)
Cooling measures (tyl & ibu ineffective)
SS to avoid
use wash out of 2 wk between SSRIs to TCAs unless it is fluoxetine, then it is 5 wks
NMS risk for recurrence
30% - start low and slow
SS acronym
Shits – diarrhea
Shivering
Hyperreflexia
Increased Temp
Vital signs instability Encephalopathy Restlessness
Sweating
Dopamine Pathways
Mesocortical
Mesolimbic
Nigrostriatal
Tuberinfundibular
mesocortical pathway
neg sx of schiz
dec d2 activity
impaired cognitions and flattening affect
mesolimbic pathway
pos sx of schiz
brain responds to dec D2 by inc activity in mesolimbic
Nigrostriatal pathway
regulates coordination and movement
major dec in parkinsons which is why antipsych can cause parkinsonism
tuberoinfundibular pathway
responsible for actions of pituitary (prolactin)
If Da is dec then inc prolactin
–causing galactorrhea, amenorrhea which means dec FSH
Dopamine made in the
VTA
5HT made in the
raphe nuclei
NE made in the
Locus Ceruleus
Ach regulated by the
parasympathetic nervous system
(side effect: dry mouth, itchy eyes, blurry vision, urinary retention,
memory impairment, elevated temp)
NT on and off switch
on is glutamate–excitatory
off is GABA–inhibitory
dopamine hypothesis
D2 receptor presynaptic autoreceptors (gatekeepers)
occupancy provides negative feedback.
Diseases or meds that ↑ DA will enhance or produce positive symptoms.
AntiΨ that ↓ DA activity will ↓ or stop psychoses.
how AntiΨ = ↓ DA
= mesolimbic – improve + symptoms
= mesocortical – may worsen negative sympomts
= nigrostriatal – risk EPS inducing movement disorders
= tuberinfundibular – risk of galactorrhea, amenorrhea
defining characteristic of schiz
psychosis
psychosis associated with
schiz
mania
depression
cognitive disorders
psychosis definition
Set of symptoms which a person’s
mental capacity,
affective response
capacity to recognize reality
communicate,
relate to others
is impacted
Schizophrenia dx to know
Disorganized speech
Negative sx
PLUS
hallucinations
delusions
and/or
disorganized speech
6+ mo with at least 1 mo of :
- Delusions
- Hallucinations
- Disorganized speech or behavior
- Catatonic behavior
- Negative symptoms
target of most meds for schiz
positive sx
negative sx (5)
a. Alogia – reduced speech
b. Affective blunting - ↓emotional response
c. Asociality -↓social drive, limited eye contact
d. Anhedonia - ↓interest in pleasurable things
e. Avolution - ↓motivation, poor grooming
mesolimbic pos or neg
positive
mesocortical pos or neg
neg
antipsychotic neurotransmitters
DA
5HT
NE
His
Ach
Antipsych 1st vs 2nd NT focus
1st: D2 antagonist
2nd: D2/5HT2A antagonist
Antipsych 1st AE diff from 2nd
High EPS and NMS rates
2nd has lower affinity on D2 so lower risk of EPS
Antipsych 1st receptors and what they cause
D2
Alpha 1
(orthostasis, hypotension, priapism)
histamine 1
(wt gain, sedation),
muscarinic
(dry mouth, vision changes, constipation, difficulty urinating)
AIMS
used to assess for AE of antipsych
2 high potency 1st gen antipsych
Haloperidol
Fluphenazine
1 low potency 1st gen antipsych
Chlorpromazine
Haloperidol notes to know
highest rate of EPS
QT prolongation, torsades
less wt gain/metabolic
2nd gen antipsych AE
wt gain
so risk of:
inc cholesterol
DMII
Clozapine 4 points to know
REMS reporting
for tx resistant
frequent labs for agranulocytosis
watch for constipation
antipsych with highest rate of increased prolactin
risperidone
active metabolite of risperidone
paliperidone
2nd gen antipsych good for bipolar depression
lurasidone
common antipsych for peds
risperidone, aripiprazole
Antipsych rx SL
asenapine
Antipsych that cause sedation and which are less
PINES
less in pip, rip, done
Antipsych that cause wt gain and which are less
PINES
less in pip, rip, done
antipsych that cause anticholinergic
Pines
antipsych that cause EPS
DONES
less in pines
antipsych that cause hypotension
Pines and dones
antipsych that cause QTc
Pines and dones
less in pip, rip, zole
MDD patho
dysregulation of emotion in response to stress
dysregulation of 5HT, NE, DA
stress= release glucocorticoids, corticotropin, cytokines which all interfere with the NT more
MDD monoamine hypothesis
mood improved with adding MAOI and TCA
=deficiency 5HT, NE, and/or DA
MDD tx approach if partialk or no response
assess adherence
inc dose as tolerated
after 8 wks can inc dose, switch alternative, augment with antiD/atypical, psychotherapy
AE for MDD tx options
elderly: hyponatremia
SS
discontinuation syndrome: flu like
SI
Sex dys
dec Sz threshold: Buproprion
SSRI MOA
inhibition of presynaptic 5HT receptors by interfering with intracellular 5HT transporters
inhibits reuptake of 5HT which ↑ amount of 5HT active and available in synaptic cleft leading to increase 5HT in synaptic cleft
SSRI AE
HA, wt gain, GI upset, sexual dysfunction, agitation/anxiety when starting
SNRI MOA
inhibits presynaptic 5HT and NE transporters leading to ↑5HT and HE in synaptic cleft
SNRI AE
same as SSRIs plus HTN, nausea/diarrhea, sweating, dry mouth, dizziness, fatigue
TCA reserved for
Tx resistant depression
les tolerable and more deadly in OD due to cardiac
TCA MOA
inhibition of presynaptic 5HT and NE reuptake by inhibition of these transporters leading to ↑5HT and NE in synaptic cleft and antagonizes Ach and His,
also Na and Ca channel inhibitor (may result in some mood stabilization effects),
also binds to α and muscarinic receptors
TCA alt use
pain
TCA AE
more sedation,
anticholinergic effects of confusion, constipation, wt gain
Tertiary amines – more sedation and anticholinergic effects (amitriptyline, imipramine, clomipramine, doxepin)
Secondary amines – more cardiac effects (nortriptyline, desipramine, amoxapine)
TCA toxicity
Toxic levels reached at 7x/therapeutic dose. Monitor for QRD widening (tell tale sign of TCA OD)
TCA toxicity tc
Treatment is Sodium bicarb
MAOI MOA
irreversibly inhibits monoamine oxidase preventing metabolism of NE< 5HT, and DA which
Allows the levels to increase
MAOI AE
HTN crisis – avoid aged cheese, wine, soy, draft beer as well as amphetamines,
carbamazepine, decongestants, ephedrine, cough meds
MAOI use
tx resistant MDD
SSRI 1srt sx to improve
sleep problems
SSRI function of 5HT
Depression Obsession
Migraines
Anxiety
Intestines
Nausea
Sexual
SSRI longest half life
fluoxetine
good for if you forget meds
but careful with switch to another SSRI cuz of 5 wk washout need
Fluoxetine careful when switching to another SSRI due to
need of 5 wk washout
SSRI worst AE sex
paroxetine
due to rapid absorption
Paroxetine contraindication
pregnant
SSRI most GI AE
Sertraline
so take with food
SSRI safe from pregnancy
Sertraline
SSRI high tolerability and lack enzyme interactions
citalopram and escitalopram
citalopram and escitalopram AE
Qtc
EKG yearly
get genetic testing
citalopram interaction
omeprazole inhibits metabolism
SSRI approved for OCD
fluvoxamine
high number of interactions though
SNRI 2 common rx
venlafaxine and duloxetine
TCA rx for depression
Amitriptyline & Nortriptyline – Tertiary amine
TCA used for sleep
doxepin
Amitriptyline & Nortriptyline
which for elderly
Nortriptyline
less sedating so less fall risk and less hypotension
3 atypical antidepressants
Mirtazapine
Buproprion
Trazadone
Mirtazapine MOA
↑synaptic concentration of 5HT & NE through presynaptic α2 Antagonism – also 5HT2a and 5HT3 antagonists (better tolerability) and His antagonist.
Mirtazapine AE
Sedation
wt gain
agranulocytosis
Bupropion MOA
boosts DA & NE but lacks 5HT involvement.
Inhibits DA & NE transporters = ↑DA and NE in synapse
Bupropion contraindication
bulimia
can cause sz
Trazadone MOA
5HT antagonist and reuptake inhibitor. Weak inhibition of 5HT and NE
reuptake, 5HT2a antagonist, weak α-1 antagonist and His antagonist
Trazadone AE
priapism
MAOI combo with SSRI/SNRI
can cause SS
needs 2 wk washout
5 wks for fluoxetine
5 Antidepressants with superior efficacy:
Escitalopram
Mirtazapine Sertraline Venlafaxine Citalopram
MDD tx avoid if worried about wt gain
avoid mirtazapine
MDD tx avoid if worried about sex AE
SSRI
when to augment MDD tx
after 2+ antidepressants
AE issues with effect that can be targeted
augmentation options for MDD
lithium
thyroid hormone
Antipsych: aripiprazole, quetiapine
stimulants: ritaline/adderall
ECT
MDD tx duration of therapy for 1st, 2nd, 3rd episode
6+ mo
12+ mo
lifetime
MDD tx with pain issue
SNRI
MDD tx with concentration issue
Bupropion
duloxetine
fluoxetine
Bipolar disorder etiology
Genetic
Neurological: NTs etc
Prenatal infxn
Bipolar DDX
SUD
rx induced
thyroid
other psych (schiz)
remember to r/o Bipolar in those with depression
Bipolar risk factors
abuse/neglect
psych stress
SUD
Bipolar patho (need to know?)
alterations in GABA, glutamate, and monoamines (NE, DA, 5ht) transmission
Ca dysregulation - ↑intracellular calcium signaling
DA hypothesis – intrinsic dysregulation in homeostatic regulation of dopaminergic functions
Hypothalmic-pituitary axis dysregulation - ↑glucocorticoids, ↓glucocorticoid receptor sensitivity
Autonomic dysregulation - ↑sympathetic activity, ↓parasympathetic activity
Monoamine hypothesis - ↓NE, DA, 5HT = depression
Monoamine receptor hypothesis - ↓NE, DA, 5HT = ↑receptors = depression
Glutamate –major excitatory neurotransmitter
GABA – major inhibitory neurotransmitter
5HT1A – agonism of receptor = ↑DA – antagonism of receptor = ↓DA
5HT2A – agonism of receptor = ↓DA – antagonism of receptor = ↑DA
↑amines = mania
Autoreceptors – regulate the release of the monoamine that acts on it – in the presence of the
monoamine, will turn off release of that monoamine NE: α2 receptor
DA: D2
5HT: 5HT1A, 5HT1B and D
Bipolar goals of tx
eliminate episode
prevent reoccurrence
minimize AE
pt compliance
BP1 DSM
mania+psychosis
elevated, expansive, or irritable mood most of the day
1+ wk with 3+ sx
w/wo psychotic episode
BP rapid cycling
rapid switch from mania to depression and back – mania recurs 4+/yr
BPII DSM
hypomania+ depression
elevated, expansive, or irritable mood most of the day
4+ days
3+ sx
at least 1+ hypomanic episode and 1+ major depressive episode
cyclothymia DSM
(hypomania + dysthymia) cyclic disorder
Brief episodes of hypomania and dysthymia
No full manic or major depressive episodes
chronic
cyclothymia sx
Distractibility
Irritability
Grandiosity
Flight of ideas
Activity increased
Sleep - ↓need Talkativeness
Bipolar tx options
1st: antipsychotics
Mood stabilizers
anti sz
BP tx options that need close monitoring
lithium
VPA
BP tx mania vs depression
All antipsychotics work for mania.
For depression: quetiapine, lurasidone,
olanzapine-fluoxetine
BP tx for depression
quetiapine, lurasidone,
olanzapine-fluoxetine
BP med choices
- Lithium – effective for manic episodes and maintenance of reoccurrence
- Quetiapine
- Lamotrigine – preferred for bipolar depression
- Lurasidone
- Cariprazine
BP tx preferred for depression
lamotrigine
BP tx valproate vs lithium
Valproate better for rapid cycling
BP and carbamazepine
for acute mania and maintenance
BP mania tx
lithium,
valproic acid, carbamazepine
2nd line – quetiapine, risperidone, olanzapine, ziprasidone, aripiprazole, asenapine
BP tx maintenance
lithium
valproic acid
quetiapine
1st line tx for mania
lithium, quetiapine, valproate, asenapine, aripiprazole, paliperidone >6mg, risperidone,
Cariprazine
1st line x for acute mgmt of BP1 depression
quetiapine, lurasidone + lithium/valproate, lithium, lamotrigine, lurasidone, lamotrigine adjunct
1st line x for acute mgmt of BPII depression
quetiapine
1st line tx for maintenance for bipolar depression
lithium,
quetiapine,
valproate,
lamotrigine, quetiapine + lithium/valproate, asenapine,
aripiprazole (daily or monthly), aripiprazole + lithium/valproate
how to take lithium
with food
lithium AE
Lithium – monitor levels
Movement – toxicity = tremor
Nephrotoxicity – resolved with hydration and dialysis
hypOthyroidism – with long term use (6-18mo)– can be treatment with levothroid
Pregnancy – teratogen – can cause low implanted tricuspid valve
Lithium drug drug interactions
caffeine and theophylline = ↓levels
HCTZ, NSAIDs, ACE inhibitors = ↓renal
clearance = ↑effects of lithium
lithium monitoring
TSH, renal function, calcium, lithium levels, UA, CBC w/ diff, wt, pregnancy
lithium MOA
Inhibits GSK preventing cell death and creating neuroprotection
VPA MOA
Inhibits voltage-gated Na channels (anticonvulsant component)
↑amount of GABA (benzo like sedation)
VPA tx and prevents:
manic episodes
VPA AE
nausea, drowsiness, skin changes, wt gain, hair loss, dizziness
In women: PCOS, hyperandrogenism, menses changes
Teratogen in Pregnancy – neural tube defects (due to folate deficiency) – not recommended
In women of childbearing age
At high levels: vomiting, sedation, cognitive dulling
lithium and VPA clearance
renal
hepatic
VPA monitor
VPA level
LFT
CBC
pregnancy tests
Lamotrigine helps with
bipolar depression with little effect on mania
Lamotrigine MOA
blocking α unit of VSSC
Starting lamotrigine
slow and titrate over weeks to avoid SJS
lamotrigine AE
10% widespread itchy rash (1% turn into SJS)
sedation, HA, dizziness, ataxia, nausea
Lamotrigine drug drug
Valproate = ↑serum lamotrigine levels by double
Carbamazepine and phenytoin = ↓lamotrigine levels
OCPs and estrogens = ↓lamotrigine levels
Carbamazepine used for
tx and prevent manic episodes
also sz
Carbamazepine MOA
inhibits voltage-gated sodium channels and augments GABA transmission
Carbamazepine monitor
Agranulocytosis and SJS
genetic test asias for HLA
CBC, retic, Fe, fast cop
Carbamazepine AE
GI, rash, sedation, anticholinergic effects, dizziness, transient elevated LFTs
Serious side effects: diplopia, ↓Na, birth defects, SJS, aplastic anemia, agranulocytosis
Anxiety NT
5HT
Anxiety sx
1st symptom of anxiety is fear and 2nd is worry
↓concentration, sleep changes, fatigue, arousal, irritability, muscle tension, compulsions, phobic
avoidance, panic attacks
Anxiety patho
Amygdala (fear) – integrates sensory and cognitive information to determine fear response – emotions, motor response, endocrine response, autonomic responses, anxiety
CSTC Loops (worry) – cortico-striato-thalamo-cortical loops
–Regulates recurrent thoughts
–Involved 5HT, GABA, NE, DA, glutamate, voltage-gated ion channels
–↓COMT activity = ↑DA in circuits
–↑DA activity and ↓efficiency of info process under stress = worry and anxiety
–GABA – main inhibitory neurotransmitter
Main target for BZDs, barbiturates, sedative hypnotics, ETOH
–5HT and NE –
5HT regulates fear and worry
Excess NE creates nightmares, hyperarousal, flashbacks, panic attacks
Anxiety tx BZD MOA
enhance GABA actions to dec anxiety
Anxiety tx Buspirone MOA
– no withdrawal effects, no sedation
– can take weeks to level off
– not for PRN use
– can counteract sexual side effects from SSRI
Anxiety tx prazosin
most common a1 inhibitor
Anxiety tx propranolol
βblocker and low doses – crosses blood-brain barrier
Anxiety tx SSRI/SNRI to know
at start of SNRI, anxiety may worsen
– needs time for post synaptic receptors to down regulate and desensitize = ↓fear and worry in the long-term
Start low and slow
PTSD rx tx is based on
increasing GABA and decreasing Glutamate
acute stress disorder timing
sx <1 mo
Acute PTSD timing
1mo to 40+ yrs
Chronic PTSD timing
6 mo to 40+ yrs
Broad DSM def of PTSD
must have traumatic event with psych distress sx
exposure
presence of 1+ intrusion sx assoc with event
persistent avoidance
negative alteration in cognition or mood
marked alteration in arousal and reactivity
1+ mo sx
PTSD tx 1st line generally
SSRI/SNRI
PTSD tx for combat
fluoxetine better than sertraline
PTSD SSRI?SNRI options for tx
fluoxetine, paroxetine, sertraline, venlafaxine
PTSD alt tx for chronic nightmares
prazosin
PTSD tx for psychosis
antipsychotics
augment with olanzapine, quetiapine, or risperidone
why no BZD for PTSD
potentiate effect of GABA – AVOID – may worsen outcomes
catatonia s/sx
catalepsy (gesture held against gravity)
agitation
posturing
grimacing
resistance to
movement
stupor
mutism
mannerisms,
negativism
mimicking speech, mimicking movements, repetitive movements
catatonia as comorbidity
30% w/ schiz
43% with bipolar
may also be seen in autism, OCD, PTSD, withdrawal from ETOH, BZD
catatonia patho
dysfunction or interference in frontal cortex-basal ganglia circuitry
↓in GABA and DA activity
Localized seizures in frontal lobe and anterior limbic system
catatonia test
Bush-Francis Catatonia Rating Scale – score of 2+ = positive finding
catatonia tx 1st line
BZD- Ativan trial
Other catatonia tx
ECT
Antipsychotics – depends on pt
Zolpidem (GABA agonist) – alternative to lorazepam challenge
Dopamine Agonist – Amantadine, memantine
Supportive Care
Wake promoters r/t sleep
Ach, corticotropin factors, DA, His, NE, Orexin, Substance P
Sleep promoters
Adenosine, GABA, melatonin
Insomnia criteria
difficulty falling asleep, staying asleep, waking early
3+ nights for 3+ months
Not explained by another medical condition or SUD
Needs to cause clinical distress
Insomnia 1st line tx
CBT-I and sleep hygiene – try before meds
Insomnia rx tx options
Melatonin and valerian
Diphenhydramine, unisom, hydroxyzine
BZDs
NonBZDs – z-meds
Belsomra, Dayvigo (orexin receptor antagonist) – avoid ETOH and CNS depressant (opioid)
Antidepressants: Elavil, doxepin, mirtazapine, trazodone – good for BZD avoidance
Gabapentin, tiagabine
Antipsychotics – quetiapine (insomnia assoc w/ schiz, bipolar, depression), olanzapine
ADHD 1st line tx
4-5
6-12
12-18yo
4-5 yo – PTBM, classroom interventions (these are for all ages)
6-12 yo – Methylphenidate, amphetamines
12-18 yo – FDA approved meds w/ collaborative agreement with pt
methylphenidate MOA
selectively blocks/inhibits presynaptic reuptake of DA and NE (more NE & DA Available in synapse = ↑action)
psych rx in pregnancy and lactation needs dose adjustment because (4)
bodily changes
inc in free drug levels
serum concentrations can drop up to 50%
some liver enzymes can go up or downn or not change
body changes in pregnancy mostly occur ___ and reverse ___
2nd and 3rd tri
1-2 wks post partum
major congenital malformations happen when
1st tri up to 14 wks
most fetal anomaly deaths come from
structural anomalies
VPA and pregnancy
Neural tube defect
functional defect
definition
altered function with no change in structure
when do learning problems and functional deficits and hearing loss issues occur during pregnancy
2nd and 3rd tri
risk of untreated mental illness to pregnancy
poor compliance with tx which risks later fetal/baby issues
SUD and misuse
impaired bonding
suicide and infanticide
psychiatric relapse (BP, MDD, Schiz, Anx etc)
risk of relapse with d/c of antidepressant
75%
risk of mood episodes with d/c of mood stabilizer
85%
risk of relapse with d/c of schiz rx tx
50%
The body’s response to untreated anxiety in pregnancy
vasoconstrictive stress hormone
reduced placenta blood flow
=
problems with nutrient and o2 delivery
% chance of major congenital malformation in gen pop
3%
if on psychotropic rx when initially pregnant, avoid___ and consider
abrupt d/c
past responses, exposures, med risk/benefit
if poss change in meds should be done ___ pregnancy
before
ideally wait for stabilization ___ months before trying to conceive
3
FDA pregnancy categories
Pregnancy, Lactation, and Females and Males of reproductive potential
RID and definition
relative infant dose
Quantifies risk of Rx use in breastfeeding
relative infant dose equation
drug ingested by infant during exclusive breastfeeding/kg
RID % probably safe
<10%
2 antidepressants not ideal in pregnancy and why
fluvoxamine and paroxetine
high number of drug interactions
preferred SSRI in pregnancy
sertraline and paroxetine
probably safe rx in pregnancy
nortriptyline, imipramine, escitalopram, duloxetine, doxepin, amitriptyline
bupropion and pregnancy
low in breast milk but potential for sz
Characteristics that change rx placental transfer and transfer into breastmilk
high protein bound= less transfer to milk
Increased lipophilicity - <800 Dalton crosses into milk
Low molecular weight - <500 Dalton=readily diffuse across the placenta
Decreased protein binding - Rx protein bound do not cross placenta or epithelia – only free
unbound drug is able to cross cell membranes
longer half lives
Poorly ionized drugs diffuse readily across placenta – a degree of ionization depends on PK and pH of maternal blood
Weak acids are ionized and held in maternal plasma – since fetal plasma and amniotic fluid are more acidic than maternal pH, weak bases, free drug becomes ionized. and trapped in fetal circulation and amniotic fluid
most common psych rx that affect pregnancy and lactation are those that
affect the CNS as they can inc the free rx concentration
Also those that cause sedation, lethergy, apnea, seizures, tremors, irritability, resp depression, hypotonia
—Caused by opioids, BZDs, antiepileptics, antipsychotics
Antidepressants and pregnancy
no confirmed birth defect but 1st tri paroxetine did should poss cardiac
modest risk of miscarriage early
slight inc risk of persistent pulm HTN in newborn
poor neonatal adaptation syndrome 3rd tri
BZD and pregnancy
highly lipid soluable and unionized – causes rapid and complete diffusion across placenta
but no teratogenesis - possible cleft palate during 1st trimester (avoid during 1st trimester)
Not CI but can cause sedation, poor wt gain, apnea, irritability in infants
short acting preferred: lorazepam, oxezapam
maternal sedation does not equal
infant sedation
gabapentin and pregnancy
poss preterm birth
in breastmilk
z meds and pregnancy
no major malformations, preterm delivery possible
– zolpidem & zalepion have low
milk levels and short halflife (likely OK)
trazadone and pregnancy
major malformations unlikely – limited data
insomnia in pregnancy recommendations
sleep hygiene and CBT are 1st line prior to any meds
antipsychotics and pregnacy
no major congenital
some risk with risperidone
potential floppy baby with clozapine
Risk of GDM and increased wt in mom and baby with clozapine and olanzapine
placental pressure highest to lowest (4)
- Olanzapine,
- haloperidol,
- risperidone,
4 (lowest) quetiapine
SGA with most reproductive safety data
Quetiapine, olanzapine, and risperidone
hyperprolactinemia and pregnancy
can impair fertility in males and females – consider switching to lower risk agent PRECONCEPTION
highest to lowest risk of hyperprolactinemia and pregnancy
risperidone & paliperidone -> FGAs -> olanzapine ->ziprasidone -> quetiapine -> clozapine -> aripiprazole
clozapine and pregnancy
appropriate tx should be continued (benefits outweigh risks) with weekly
monitoring for severe neutropenia in mom and baby x6 mo post partum
Long acting injections and pregnancy
continue if benefits outweigh risks
antipsychotics and lactation
generally compatible with lactation EXCEPT clozapine (neutropenia, seizures) women should continue to breast feed unless on clozapine
Monitor infant for sedation, poor feeding, motor abnormalities, neurodevelopmental abnormalities – especially premies who are at greater risk
low RID antipsych rx
olanzapine and quetiapine
moderate RID antipsych
risperidone and aripiprazole
Bipolar in pregnancy rx tx pref
antipsych preferred to mood stabilizers
carbamazepine and pregnancy
give high dose folate before and during prengnacy
potential for neural tube defects, hypospadias, diaphragmic hernia, skelatal/facial abnormalities, neonatal hemorrhage
lower risk than valproic acid
carbamazepine and lactation
safe but monitor for sedation and poor sucking
lamotrigine and pregnancy
likely no risk of major malformation, poss cleft palate
serum concentrations dec significantly in pregnancy so have to monitor monthly and divide dose to reduce peak exposure
lamotrigine and lactation
consider alternative
D/c if skin rash in baby
lithium and pregnancy
rate but poss ebstein anomaly
avoid in 1st tri with 4 wk taper before conception
when resume divide doses to limit peak exposure
montly monitor x3-6 wks then weekly until delivery
reduce/hold 24-48 hrs before labor
prepregnancy dose should be resumed post partum
lithium and lactation
not preferred but monitor levels in mom
VPA and pregnancy
neural tube and cardiac defects, cleft palate, craniofacial anomalies, cognition/brain volume, hypospadias
—also poss association with autism
should NOT be prescribed to women of child-bearing potential or pregnant women unless viable alternatives to not exist
taper over 4 wks in planning pregnancy
if you have to cont rx, use as monotherapy with lowest effective dose. If combo or higher doses= inc malformation rate
need folic acid supp before and during
VPA and lactation
safe but caution with high doses
stimulants and pregnancy
not recc due to inc risk for spontaneous abortion/miscarriage/neonatal withdrawal syndrome
no major congenital
stimulants and lactation
not recc, monitor for infant wt gain and AE
Methylphenidate/amphetamines may impair milk production via reductions in prolactin levels
smoking tx and pregnancy
non pharm is 1st line
NRT preferred to smoking
Bupropion and varenciline not recc
smoking tx and lactation
NRT pref, may consider bupropion but consider Sz risk
no varenciline due to psych AE
alcohol dependence and pregnancy tx
send for inpatient withdrawals
once inpatient: Chlordiazepoxide and diazepam preferred
insufficient data on acamprosate, naltrexone, disulfiram
alcohol dependence and lactation
pharmacotherapy not recommended due to limited data
BZD dependance and pregnancy
need inpatient withdrawal
consider taper with long acting BZD but may inc fetal exposure
taper 20-30% per day as tolerated until d/c
opioid dependence and pregnancy
1st line: opioid agonist
neonatal adaptation syndrome seen w/ buprenorphine and methadone
Buprenorphine – no major congenital malformations – inpt detox typically required for exposed infants
shorter neonatal abstinence syndrome vs methadone
Limited data for buprenorphine/naloxone (switch to buprenorphine)
Methadone – historically drug of choice – no major congenital malformation Inpt detox
Naltrexone – no major congenital malformations – risk of spontaneous abortion, premature labor, fetal distress
may hinder use of pain rx in delivery
NOT preferred due to opioid withdrawal and fetal complications at initiation may occur
opioid dependence and lactation
Breastfeeding encouraged w/ MAT – small amounts of buprenorphine and methadone pass into milk
Discourage breastfeeding in women on illicit substances
BPD etiology
inheritable
mixed gene and environment
BPD sx
affective instability/negative
poor coping
rumination/anger
impulsivity
instability in personal relationships
sustained behavior and dependent on environmental triggers (unlike bipolar/depression)
1st line tx for all personality disorders
psychotherapy
Rx tx options and personality disorder
no rx is FDA approved and should be adjunct and not the sole tx
lack of consensus but generally based on domains:
Affective instability: SSRI/SNRI
Impulsive/self injury: SSRI or mood (lithium/VPA/CBZ)
Cognitive/perception disturb: low dose antipsych: FGA (halo), olanzapine, risperidone, clozapine
emotional dysregulation: SSRI/mood
Impulsivity/aggression: Antipsych (olanzapine), mood
personality disorders and adherence and comorbidity
adherence is poor
comorbid guidelines underdeveloped and many likely face social adversity make response/drop out worse
anxiety/SUD, depression more common
Antisocial personality disorder rx tc
only Rx antipsychotics or sedatives for short-term crisis management
Schizotypal rx tx
some evidence for SGA (risperidone, olanzapine) and low dose FGA (haloperisol, thiothixene) - no reliable evidence for antidepressants
avoidant personality disorder rx tx
may consider SSRI, SNRI (venlafaxine), MAOI, gabapentin, pregabalin NO BZDs
restricted diet and neurotransmitter
less tryptophan so less 5HT
anorexia nervosa patient presentation
perfectionist
obsessed with food
ritualized
Bulimia severity
Mild – 1-3/wk
Mod – 4-7/wk
Severe – 8-13/wk
Extreme – 14+/wk
Bulimia tx 1st line
CBT
Bulimia and rx tx
rx shows poor efficacy
maybe low dose olanzapine or SSRI with comorbid anx/dep
Bulimia and rx wt gain
Dronabinol
DHEA
D-Cycloserine
Bulimia and rx for binging/purging
high dose fluoxetine is FDA approved with goal to dec # of occurences
Bulimia patient presentation
driven to restrain food intake
loss of control with overeating occurs intermittently
extreme fear of wt gain
high impulsivity/impulse dysregulation as compared to anorexia
– novelty seeking – more likely to have substance abuse issues than anorexia
Binge eating tx
same as bulimia but may also use amphetamine
antiD and topamaz may enhance CBT effective
OCD assessment
Yale-Brown Obsessive-Compulsive Scale –
Gold standard but needs training to perform
2 others reliable
OCD patho
dysregulate DA, 5HT, Glutamate
OCD tx mild, mod, severe
Mild – CBT including exposure therapy
Mod – SSRI or intensive CBT
Severe – SSRI + CBT
OCD 1st line rx and for how long
SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline)
high dose associated with better outcomes
max tolerated for 8-12 wks as trial
note w/d associate with major relapse risk
Cont Rx for 1-2 yrs before tapering with periodic CBT booster sessions for 3-6 mo after acute tx or 12 months after remission
OCD if SSRI inadequate
switch or augment with SGA
OCD tx monitoring
suicide
ECG with high dose citalopram
clomipramine: anticholinergic/arrythmia/Sz
Body dysmorphic disorder clinical appearance
appearance preoccupations
delusionality and referential thinking (poor insight, worse
than OCD pts, 50% are deluded)
compulsive and safety behaviors (time consuming behaviors to
diminish distress)
effects males and females equally
Body dysmorphic disorder tx 1st line
CBT
Rx SSRI (fluoxetine, fluvoxamine for 6-9 wks, citalopram and
escitalopram for 5 wks), clomipramine
12-16 wks then switch to another SSRI if no response
Trichotillomania & Excoriation
onset
onset is early puberty
then relapsing/remitting
Trichotillomania & Excoriation tx
CBT
poor evidence for SSRI/ other rx
CBT much superior
Hoarding disorder tx
CBT (group and indiv)
rx: venlafaxine/paroxetine
Addiction patho
impulsivity and compulsivity dysregulation
PFC inhibits activity of ventral striatum
drugs cause mesolimbic to release DA to inc pleasure
DA stop responding to drug and instead to conditioned stimulus associated with drug causing cravings and compulsive use
AUD patho
short term ETOH inc GABA and dec Glut
long term: brain tries to restore equilibrium by doing opposite
ETOH w/d has no compensation and shift is toward hyperexcitation
AUD DSM w/d dx
need cessation or dec ETOH and have distress
Sx 2+
-insomnia
-increased hand tremor
-anxiety
-seizures
-autonomic symptoms (sweating, tachycardia) -nausea/vomiting
-psychomotor agitation (tapping, pacing, rapid talking)
-hallucinations/perceptual disturbances (auditory, tactile, visual)
AUD w/d stages
1st stage – fairly mild - within 8 hrs– N/V, stomach pain, tiredness, depression
2nd stage – begins 24 hrs after last drink – HTN, anxiety, irritability, mood swings
3rd stage – severe – can last about 72 hrs – symptoms include stages 1 & 2
assess acute w/d AUD
CIWA
Mild = <10
Mod = 10-18
Severe = >19
Complicated = >19 – includes hallucinations, seizures, delirium
AUD w/d tx 1st line
BZD- dec w/d including Sz/delirium and agonist at GABA
front load with long acting- diazepam
- pref for severe CIWA <19
AUD tx options
Naltrexone
acamprosate
disulfiram
AUD and naltrexone
patho
versions
black box
monitor
antagonist and multiple receptors
dec mesolimbic reward = dec consumption
ok if cont to drink
LA inject: vivitrol
black box for hepatotoxicity
monitor LFT before and every 6 mo
avoid opioids
many stop due to AE N/D
acamprosate and AUD
MOA
indication
contra
AE
MOA: blocks NMDA and inc GABA and dec Glut to restore balance
indication for maint of abstinence, ok if hepatic disease or on opioid tx
contra: kidney
AE: D/anxiety/insomnia but usually well tolerated
Disulfiram and AUD
MOA
reaction time
AE
CI
population
MOA: inhibit aldehyde enzyme leading to rapid accumulation and toxic reaction
drinks ETOH and gets sick
reaction 10-30 min and can last for hours
AE: flushing, nausea, thirst, palpitations, CP, hypotension somnolence, metallic after-taste and peripheral neuropathy
CI: severe cardiac, severe hepatic, psychotic
population: support other rx, mod-sev AUD
non FDA AUD rx tx
topiramate
gabapentin
baclofen
zofran
nicotine 5As
ask, advise, assess, assist (create tx plan), arrange (for f/u)
nicotine behavioral tx model
transtheoretical model
nicotine 1st line tx
NRT monotherapy consistently (not PRN)
Bupropion/chantix
can use in combo with NRT
nicotine tx rx CI
pregnant, smokeless tobacco, light smokers, adolescents MI in last 2 wks, serious arrhythmia, worsening angina
bupropion for nicotine
MOA
start
Dose
CI
MOA: blocks NE/DA reuptake to mimic nicotine
Start 7 days prior to quit
Dose AM and early PM to avoid insomnia
CI: Sz, head injury, eating disorder
Varenicline for nicotine
MOA
Start
precaution
MOA: nAChR partial agonist/antagonist. Basically some relief while blocking nicotine effect
Start 1 wk before quit date
precaution: poss inc agitation, SI, mood swings
Dose change in renal
why abuse gabapentin/pregabalin
MOA
tx
pregabalin 6x more potent and faster peak
self tx pain, euphoria
can boost cocaine, BZD< opioid, caffeine, ETOH
MOA: inc GABA
w/d poss, more craving with pregabalin and similar to opioid
Tx: taper slow. No BZD. Poss efficacy with haloperidol/benadryl
types of pain
Nociceptive pain – somatic: well localized, aching, throbbing – bone, skin, soft tissue
Visceral – poorly localized, deep aching, cramping, pressure – hollow and solid organs
Neuropathic pain – tingling, numbness, radiating pain – due to pathologic damage to nervous system - occurs after disease or traums – fibromyalgia
Chronic pain syndrome – Pain for 3+ months and has a psychological impact
