Week 3: Bipolar, Anxiety Flashcards
What is Bipolar disorder
Cyclic mental illness with recurrent mood episodes that occur over a persons lifetime.
symptoms, course, severity and response to treatment
differ among individuals
Patho of bipolar disorder
caused by genetic factors, environmental triggers, and the dysregulation of neurotransmitters and second messenger systems in the brain
Etiology of bipolar disorder
caused by genetic factors, environmental triggers, and the dysregulation of neurotransmitters and second messenger systems in the brain
Key features of bipolar spectrum disorders
hx of mania or hypomania
dx includes dysthymia, persistent depressive disorder, cyclothymia, drugs induced hypomania and recurrent unipolar depression.
Bipolar 1 disorder
manic episode +/- major depressive or hypomanic episode (may be mixed)
MUST HAV A MANIC EPISODE
Bipolar 2 disorder
major depressive episode +hypomanic episode
common Characteristics of BD
<25 y.o
family hx of bipolar disorder
increased sleeping/ napping
increased appetite/ weight
psychomotor retardation
atypical depression (mood liability, irritability, agitation, racing thoughts, psychotic features, pathological guilt
co-occuring substance abuse
4A’S: ANXIOUS
ANGER
AGGITATION
lack of ATTENTION
Mania vs hypomanic
mania: >1 week of period of abnormal and persistent elevated mood, often leading to hospitalization
hypomania: at least 4 days of abnormal and persistent elevated mood, usually doesn’t lead to hospitalization
Challenges in dx
must rule out organic causes of mania or depression
accuracy in dx is key and requires excellent hx
mania may b confused with ADHD related dirosers
depression may appear to be unipolar
not the result of a substance (of abuse or prescribed)
execution if under antipdepressent trent: can be dx with mania or hypo
rapid cycling
> 4 episodes per year, often with key feature of frequent and severe episodes of depression
more freq. in women
poor prognosis, may require combo therapy
Goals of therapy for BD treatment
rapid control over behavioral sx, sleep restoration and mood stabilization
chance and maintain levels function
complete remission and prevent future episodes
optimize the chance for successful drug therapy such as increase adherence and reduce ADR and DI include pt therapy selection
General treatment approach for BD and non pharm
pharm:
must be individualized
must be specific to the episode patient is currently experiencing
should include for both PHARM AND NON pharm treatment
non pharm: address environmental factors
sleep
diet
exercise
psychoeducation, psychotherapy
List of FDA approved agents for BPD acute mani and mixed episode
lithium, valproate
carbamezapine ir+er
aripiprazole
asenapine
caripraszine
olanzipine
quetiapine
risperidone
ziprasidone
list of FDA approved agents for BPD maintenance
lithium
lamotrigine
aripiprazole
olanzipine
quetiapine
risperidone
ziprasidone (adjunct Li/VPA)
list of FDA approved medications for acute depression monotherapy
cariprazine
lurasidone
olanzipine (with fluoxetine)
quetiapine
General pharm BPD treatment guidelines
once dx with BPD, pt should remain on mood stabilizer(term used for some of meds to treat BPD) for their lifetime
augmentation meds should be added onto mood stabilizer during acute episodes, then withdrawn when clinically appropriate
LAI FDA approved for BPD
ARIPIPRAZOLE (ABILIFY MAINTENA) NOT aristatda: maintnace of BP1
RISPERIDONE (Risperdal Consta NOT perseris: monotherapy or adjunctive therapy to lithium or valproate for maintenance tretment of BP1
General treatment guidelines for acute manic and mixed episodes
General treatment to use Lithium, VPA, or SGA
Monotherapy and combo therapy are both first line treatments for acute mania. Choice depends on rapidity of response needed, hx of partial response to monotherapy, or severity of mania
D/C antidepressants of possible
treatment options for acute manic and mixed episodes
monotherapy:
LI, VPA or SGA (aripiprazole, asenapine, risperidone, , cariprazine)
General 1st line Treatment for acute major depressive episodes
Acute: BP1: LI, lamotrigine, quetiapine (IR&ER), lurasidone
acute BP-II: quetiapine (IR&ER)
agents NOT recommended for treatment of acute mania in BPD
gabapentin, topiramate, lamotrigine, verapamil, tigabine
combos: risperidone+carbamezapine, olanizpine +carbamezapine
agents NOT recommended for TREATMENT of acuteacutedepressive episode
gabapentin, aripiprazole, ziprazidone. A and z can worsen depression
combos: adjunctive ziprasidone, adjunctive levetiracetam (keppra)
agents NOT recommended for BPD maintenance
gabapentin, topiramate, or antidepressants
or adjunct fluphenthixol
Anticonvulsants approved for Bipolar
Valproate
indication:
MOA:
AE:
DDI:
CI:
Monitoring:
indication: first line treatment for both acute mania(fda approved) and ppx (non fda approved) for recurrent manic and depressive episodes
*also indicated for use in rapid cycling and mixed states
MOA:–
AE: dose related gi, TREMOR, AND SEDATION, PROLINGED BLEEDING, dose dependent Alopecia(reversible), weight gain,
DDI:
CI:
Monitoring:
BBW:panreatitis and/or liver toxicity, hepatotoxicity, urea disorders: educate pts to report flu like symptoms, gi pain, yellowing of skin, dark urine. intervene if LFTs 3x baseline.
Lithium use in bipolar disorder
indication:
MOA:
Adverse reactions:
DDI:
contraindicated
monitoring:
indication: euphoric mania (not for rapid cyclers or mixed states)
MOA:
Adverse reactions:
a: long term effects on kidneys polydipsia and polyuria w. or w.o nephrogenic diabetes insidious (NDI), AKI, CKD3 reported also
b. dose related CNS effects
c.muscle weakness
d.cardiac effects
e. decrease thyroid hormone synthesis
contraindications: severe cardiac or renal disease
DDI:NSAIDS, ace-I, arbs, diuretics, CCB, d/c lithium 2 days before and after electro convulsive therapy, caffeine
monitoring:
renal function (SCr, BUN)
baseline PE
CBC w. differential (reversible leukocytosis)
FG, lipids-weight, waist circumference
thyroid function test
serum electrolytes
dermatologic (acne)
lithium levels every 3 months
Considerations for Lithium in use for bipolar disorder
when can it be used?
what are the side/long term effects?
what do you have to monitor for?
what are interactions?
when can it be used?
First line for acute mania, acute bipolar depression and maintenance in BPI and BPII. NOT for rapid cycling or mixed states. decreases suicide significantly
how to be used?
900-2400mg/kg/day.
give with food
must maintain good hydration
onset for mania 6-10 days and full effect in 3 weeks, >4 weeks for depression
what are the side/long term effects?
*polydipsia nd polyuria w. or w.o NDI, AKI,or ckd
*GI or cns EFFECTS(dose related worst at peak
*muscle weekness and lethargy
*cardiac effects
*decreased thyroid hormone synthesis
Floppy baby syndrome
what do you have to monitor for?
*lithium levels: 0.6-1.2 mEq/L : 1.0-1.2 for acute mood episodes. >1.5mEq/L is toxic (if it is below range and drug still working, no need to increase dose). TDM 8-12 hrs after last dose, at Css.
*Renal function:containdicated in severe renal disease
*cardiac function: ci in severe cardiac disease
*thyroif function
*cbc w. differential
*FG, fasting glucose, waist circumference (metabolic)
*may unmask brigade syndrome(fast irrgefular heart beat)
what are interactions?
ACE-I, ARBs, NSAIDS, diuretics, blood dyscrasia w. clozapine d/c, ehanced neurotoxicity with electroconvulsive therapy, Methyl-xanthines like caffeine, etc.
Valproate Considerations
indications: fda approved for acute manic and mixed episodes
BBW: pancreatitis and/or liver toxicity and urea disorders
formulations approved:
depakote , depakote ER,
Stavzor
dose related gi, tremor (can give bb to reduce)
sedation (give @hs)
dose related alopecia
weight gain
prolonged bleeding
Lamotrigine Considerations for use in bipolar disorder
anticonvulsant
FDA approved for maintenance therapy and acute depression
dose escalation must be low and slow to decrease risk of SJS
Cause less drowsiness than Other agents
When combined w. Valproate , lamotrigine dose must be halved
Carbamezapine considerations for use in BP
only FDA approved formulation is ER formulation (Equetro)
dose can be increased rapidly for inpt.
used for acute manic episodes: onset for mani is 7days. not used for maintenance. also sed after 1st line agents
CI: can cause neutropenia( bone marrow suppression) leukopenia, hematologist disease, agranulocytosis, patients with positive HLA
careful combo use with valproate because valproate can increase levels (also in lamotrigine
Considerations for antipsychotics as adjunctive therapy
SGA may be good for certain episodes, not all
FGA good for acute mania
use in combo w. lithium or valproate for acute or mixed
injectable APS good option for pts. with poor adherence
Considerations for antidepressants as adjunctive therapy
only used as add on therapy
do not use in bipolar disorder alone . may result in switch to mania if in depressed phase
Considerations for benzons as adjunctive therapy in BPD
high potency agents like clonazepam or lorazepam can be used during acute mania/ agitation or anxious features/ restore sleep
adjustt to response and adverse events
used short term
avoid in pts with substance use
bipolar treatment considerations in pregnancy
divalproex: can cause neural tube defects. avoid as 1st line in women who may become pregnant
carbamezapine: increased risk of spina bifida. avoid during pregnancy
lamotrigine: lower levels during pregnancy
lithium: increased doses during pregnancy, use care upon delivery. increased risk of abnormal tricuspid valve.
If psychosis is present during a bipolar episode, what agents to use
use an APS along with an agent to treat bipolar. an APS must be present
Lithium interactions effects
NSAIDS: increase Li lives
ACE/ARBs: increase Li levels
diuretics: increase Li levels
Methyl Xanthines(i.e caffeine): decrease Li levels
what is anxiety
an emotional state commonly caused by the perception of real or percieved danger
normal anxiety is an appropriate adaptive response
if excessive, can result in significant disability
treatment goal of generalized anxiety disorder
remission with minimal or anxiety symptoms and no functional impairment
what are the agents of choice for GAD managemeent?
antidepressants.
takes atleast 8-12 weeks to take effect. much slower response than when using these agents for depression
key features of GAD
excessive difficult to control anxiety and worry about multiple events or activities
SS of restlnessneds or feeling on the edge or tension
psychological SS: excessive anxiety
worries that arre out of control
feeling on edge
physical symptoms: restlness
fatigue
muscle tension
sleep disturbances
irritability
impairment:
socially
accupationally
poor coping skills
key features of panic disorder
recurrent expected panic attacks, in absense of triggers . persistent concerns about additinoal panic attacks and/or maladaptive change in behavior related to attacks
key features of agoraphobia
markes unreasonable fear or anxiety about a specific situation , which is activdely avoided due to thoughts that escape may be difficult and fear resulting in panic symptoms
key features ofspecific phobia
marked unreasonable fear or anxiety about a specific object or situation (flying spiders, recieving injection)
key features of social anxiety disorder
marked. excessive unreasonable fear of anxiety about social situations in which there may beb scrutiny by others, which is actively avoided
drugs that induce anxiety
anticonvulsants: carbamezapine, phenytoin
antidepressants: buproprion, SSRI, TCA
anti-HTN: clonidine and felodipine
abx: quinolones, isoniazid
bronchodilators: albuterol, theophylline
corticosteroids: prednisone
dopamine agonists: amantadine, levedopa
herbal agents: ginseng, ephedra, ma huang
illicit substances: cocaine, ectasy, THC
stimulants: methylphenydate, caffeine, nicotine
toxicity: anticholinergics, digoxin
withdrawal: includes sedatives
dx for GAD
persistent symptoms for most days for at least 6 mo. and worry is unrealistic or excesive about a number of events or activities
gradual onset w. avergae onset @age21
women more likely than men
Goals of therpay for GAD
long term: remission, prevent occurance
acute: decrease severyity and duration of symptoms, increase function
at all times: decrease ADR, increace adherance
non pharm:
CMT, psychoeducation
avoid stimulants and alcohol
GAD pharm treatment
antidepressents: treatment of choice
APS and antihistimaines: high incidence of ADR and toxicity,
1st line GAD treatment
FDA approved
SSRI’s
*Escitalopram (Lexapro)
*Paroxetine (Paxil)
SNRI’s
*Duloxetine(Cymbalta)
*venlafaxine XR
NON FDA APPROVED:
SSRI:sertraline
AntiEpileptic: Pregablin
general Antidepressant treatment considerations for GAD
lag time of 2-4 weeks OR LONGER b4 any antianxiety effects
efficacy can take 8-12 weeks
start low and go slow, with gradual taper
response to treatnment described as improved, partial response after 4-6 weeks. if partial response, confirm adequacy of trial and consider augmentation, or switch AD
after adequate trial , continue for atleast 1 year
SSRI considerations
BBW: increased risk of suicide in ppl </=24 y.o
discontinuation syndrome
abnormal bleeding due to 5HT reuptake on patelets
hyponatremia
seretonin syndrome:SS: BASICALLY-HYPERACTIVITY
agitation
restlessness
confusion
diarrhea
sweating
tachycardia
HTN
dilated pupild
loss of muscle coordination
muscle rigidity
can occur if taking multiple agents with serotonin
such as…
triptan migraine agents
pain medication such as fentanyl and tramadol
nausea products such as zofran(ondansetron) and reglan(metoclopramide)
Busprione
Linezolid
Ritonavir
avoid drugs that impair the metabolism of serotonin
potential cognitive and motor impairment.
degrees of Qtc prolongation
require caution/ dose modifications with hepatic impairment
SNRI consideration
BBW: increased risk of suicide in ppl </=24 y.o
abnormal bleeding due to 5HT reuptake on platelets
potential for increased activation of mania
elevated BP
hyponatremia and seretonin syndrome
discontinuation syndrome
tend to be more energy boosting than any other AD
considerations for antihistamine use in GAD
hydroxyzine FDA approved
second line agent
beers list
considerations for APS use in GAD
BBW: increased risk of death in use in elderly w. dementia related psychosis: NOT for elderly pts who are being treated long term for another idnicatino like schizophrenia
quetiapine second line agent
ziprasidone not recommended
considerations fo rAED use in GAD
not a confirmed BBW, but increased risk of suicidal thoughts
conditions/comorbidities with anxieties and recommendations
sleep disturbance:
evaluate and mange causes
more sedating agants such as pregablin or hydroxyzine
elderly pts:
consider sertraline or escitalopram, beers list
neuropathic pain: consider pregablin
benzodiazepine considerations for use in GAD
provide rapid releif of symptoms 2-3 weeks. NOT EFFECTIVE for depression
long term use asocitaed w. phsyical and mental dependence
ci: allergy to bxd, hx of substance use, myasthenia gravis, severe hepatic disease, resp. disease, narrow angle glaucoma
BBW: ins=creased risk of death when used in combo with opiates. ALSO risk of abuse, misuse, and addiction
risk of rebond anxiety w. quick d/c
inceeased risk of seizures after d/c from high dose benzo and use of AED
d/c taper example:
25% [er week reduction until 50%, then decrease dose by 1/8 q4-7 days
fo rtherapy >8 weeks taper over 2-3 weeks
for therapy >6mo. taper over 4-8 weeks. if greater than 1 year, over 2-4 MONTHS
elderly ptsa increased risk of falls b/c of increased conc.
FDA approved BZds for anxiety and considerations
CLAD
Clorazepate: needs acid
Lorazepam: Over the liver (OTL), less lipophilic, longer duration of action
Alprazolam (Xanax):HIGH POTENCY. available as ODT
Diazepam: euphoria, misuse, more lipophilic, faster rate of absorption and short duration of action
Panic disorder
a series of unexpected, spontaneous attacks of intense terifying fear
attack is followed by at least 1 month of having persistent fear
attack last 20-30 min but highest intensity in first 10 min
nic disorder symptoms
psycho:
fear of losing control
fear of going crazy
fear of dying
depersonalization
de-realization
phsyical: gi distress
chestpain/ disocmforrt
chills/hot flashes
dizziness
palpitations
sob
trembling
shaking
sweating
panic disorder (agoraphobia)
being in atleats 2 situations or places where escape is difficult
cause pts. to avoid situations
pharm treatment for PD
treatment of choice: antidepressants
PD ctreatment considerations
start low and go slow with dosing
(up to 1/2 of doses used for depression, esp, with SSR and SNRI
antidepresssant therapy may take 8-12 weeks to see full efficacy
1st lines PD agents
FDA APPROVED
SSRI
fluoxetine
paroxetine
sertraline
SNRI:
venlafaxineXR
NON FDA approved
citalopram
escitalopram
fluvoxamine
not recommended agents in PD
buspirone (due to slow onset of action)
propanolol
tiagbine
trazadone
goals of therapy of PD
same as GAD
long term: remission, prevent occurance
acute: decrease severyity and duration of symptoms, increase function
at all times: decrease ADR, increace adherance
non pharm:
CMT, psychoeducation
avoid stimulants and alcohol
considerations for benzos in panic disorders
can be used as a first step if there is an urgency and no delay in relief is possible
high potency bzd are preffered such as alprazolam and clonazepam, but lorazepam and diazepam can also be used
alterniative drug therapies fo r PD
buspirone, trazadone, buprorpion, , APS, beta blockers and antihistamines shown to be INEFFECTIVE
buspirone has NO antidepressant effects
treatment fo PD in special populations
edlerdy: less and fewer intense attacks
children: tend to have fear of dying and agoraphobia
in general SSRI best choice
PD: Specific phobia
persistent fear of object or situation
treatment of PD: specific phobia
unresponsive to drug therapy
highlighy response to CBT
PD: social anxiety disorder
intense fear by intense, irrational and persistent fear of being scrutinized or judged in social settings or performance situations
etiology of SAD
mean age is mid teend
SAD higher in women
mean age 20 year course
dx of PD:SAD
ADULTS <18 Y.O. SS for atleast 6 mo to meet dx criteria
feers: judged by others
embarassed
humiliated
addressing group of ppl
eating or writing infront of tohers
interacting with authority
speaking in public
talking to strangers
use of public facilities
goals of therapy PD:SAD
long term: remission, prevent occurance
acute: decrease severyity and duration of symptoms, increase function
at all times: decrease ADR, increace adherance
non pharm:
CMT, psychoeducation
avoid stimulants and alcohol
first line options for SAD treatment
antidepressants
1st line SAD options
FDA approved:
SSRI:
*paroxetine
Sertraline
SNRI
Venlafaxine
non FDA approved
escitalopram
fluvoaxamine
not recommended in PD-SAD
busprinone, atenelol, levetiracetam, quetiapine, propanalol (only if symptoms are present)
considerations for special population for SAD treatment:
elderly: pk/pd changes, organ function, increased risk of falls and sensitivity etc.
children: cbt is a good treatment option..
pregnancy: do not use paroxetine:
PTSD treatment considerations
non pharm theapy options are best… such as cbt and eye movement desensitization
SSRI’s and venlafaxine first line pharm treatment options
BENZOS are not recommended
prazosin and clonidine for PTSD related nightmares
PTSD first line treatments
FDA Approved
ssri: paroxetine
serttraline
WSNRI:
venlafaxine
non fda approved:
fluoxetine
PTSD epidemiology
exposure to a traumatic event
response to event must incude intense horror, fear, or feelings of helplessness
pt must have one intrusion symptom, 1 avoidance, and 2 symptoms of negartive alterations in cognition
must cause significant distress or impairment of dysfunction
benzo diazepine treatment in PTSD
DO NOT GIVE BENZOS
can impair cbt effectiveness
augmentation therapy for ptsd
for pts with persistant symptoms
OCD tratment
SSRI treatment of choice alone or with CBT
augmentation of ssri w. low dose APS may be helpful
non pharm:
cbt
exposure
first line agents for OCD
fluoxetine (prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline(Zoloft)
