questionnaires to evaluate depression
PHQ-2
PHQ-9
response to treatment is defined as
50% reduction in baseline score of PHQ-9
70-75% reach this
remission of depression defined as
-normal PHQ scores under 5
-symptom free for 2 months
(only 30% reach this)
SSRI drugs
fluoxetine sertraline paroxetine citalopram escitalopram fluvoxamine
SSRI with longest half life
fluoxetine
best tolerated SSRIs
sertraline and escitalopram
general SSRI side effects
- nausea
- GI irritation
- diarrhea (remits after 1 week)
- headache
- sexual dysfunction
side effects unique for fluoxetine
- anxiety/activation
- insomnia
side effects unique for sertraline
- anxiety/activation
- insomnia
side effects unique for paroxetine
- sedation
- weight gain
- anticholinergic effects
side effects unique for fluvoxamine
sedation
side effects unique for citalopram
QT prolongation
how to deal with GI side effects of SSRIs
- usually self limiting
- manage by slow titration and take with food
how to deal with activation/anxiety effects in SSRIs
- manage by titration
- take in morning
- bridge with benzo
how to deal with insomnia side effects from SSRIs
- take in morning
- add trazodone, mirtazapine, TCA at bedtime
how to deal with sedation effects from SSRIs
take at bedtime
how to deal with sexual dysfunction from SSRIs
- add/switch to bupropion
- add mirtazapine
- switch to nefazodone
- patients (may improve in 2-4 weeks)
- add PDE-5 inhibitors
how to deal with weight gain from SSRIs
-possibly switch to bupropion
SSRI with highest weight gain rate
paroxetine
time in SSRI therapy suicidal risk increases the most
weeks 1-3
unusual SSRI side effects
- hyponatremia
- EPS
- sweating
- bleeding
- triggering manic episodes
discontinuation syndrome symptoms
- Flu-like symptoms
- Insomnia
- Nausea
- Imbalance
- Sensory disturbances
- Hyperarousal
serotonergic medications that can cause serotonin syndrome when used with SSRIs/SNRIs
MAOI linezolid tramadol buspirone triptans dextromethorphan
treatment for serotonin syndrome
- go to ER
- discontinue offending agent
- supportive care
how long do you have to be off SSRI to have discontinuation syndrome
24-48 hours after
least common drug to have discontinuation syndrome
fluoxetine because of the long half life
advantages of venlafaxine/desvenlafaxine
also works well for anxiety disorders and neuropathic pain
adverse effects of venlafaxine/desvenlafaxine
- diarrhea
- N/V at low doses
- hypertension at high doses
advantages of duloxetine
works for neuropathic pain often used for diabetes
adverse effects of duloxetine
- diarrhea, nausea
- anticholinergic effects
- increased heart rate
- small changes in BP
bupropion MoA
NE/DA reuptake inhibitor
advantages of bupropion
- useful for add on for sexual dysfunction
- can be used in smoking cessation
bupropion adverse effects
- nausea
- dizziness
- tremor
- insomnia
- anxiety
- rarely increased seizures
trazodone MoA
5-HT2A antagonist
serotonin reuptake inhibitor
advantages of trazodone
can be added on to SSRIs for insomnia
adverse effects of trazodone
- orthostatic hypotension
- priapism
main adverse effect for nefazodone
liver toxicity
nefazodone use
for sexual dysfunction
mirtazapine advantages for its 2 serotonin activities
- from 5-HT2A, treats insomnia, sexual dysfunction
- from 5HT3 anti-emetic effect
adverse effect of mirtazapine
weight gain at lower doses
advantages of TCAs
-can be used to treat neuropathic pain and insomnia
adverse effects of TCAs
- anticholinergic
- neurologic
- cardiovascular
- weight gain
- sexual dysfunction
- cholinergic rebound if stopped abruptly
TCAs with tertiary amines
amitriptyline
imipramine
doxepin
clomipramine
TCAs with secondary amines
nortriptyline
desipramine
TCA group with worse side effects
tertiary amines
adverse effects of TCAs in high doses
cardiac
convulsions
coma
what happens if TCAs are abruptly stopped
cholinergic rebound
how to deal with anticholinergic side effects from TCAs
- artificial saliva or sugarless gum
- artificial tears
- decrease dose
how to deal with neurologic side effects from TCAs
- take at night
- change agent if seizure occurs
- titrate slowly for anxiety
- for tremor use beta blockers
how to deal with CV side effects from TCAs
- Pt education
- use nortriptyline
- baseline/serial EKG
antidepressants with GI side effects
fluoxetine
sertraline
venlafaxine
desvenlafaxine
antidepressants with insomnia side effects
fluoxetine
sertraline
bupropion
antidepressants with sedation side effects
paroxetine
fluvoxamine
miertazapine
TCAs
antidepressants with diarrhea side effect
sertraline
antidepressants with sexual dysfunction side effect
paroxetine
fluoxetine
TCAs
antidepressants with anticholinergic side effects
paroxetine
TCAs
antidepressants with weight gain side effect
paroxetine
TCAs
mirtazapine
when to use MAOI
- in atypical depression
- significant anxiety
- phobias
MAOI drugs
phenelzine
tranylcypromine
adverse effects of MAOIs
- orthostasis
- weight gain
- sedation or activation
- hypertensive crisis (cheese effect)
drug interactions with MAOIs
- cold/sinus medications
- amphetamines
- pressors
- meperidine (certain death)
- SSRIs/SNRIs
paroxetine inhibits what CYPs
2D6
fluoxetine inhibits what CYPs
2D6
2C9
2C19
duloxetine inhibits what CYPs
2D6
bupropion inhibits what CYPs
2D6
fluvoxamine inhibits what CYPs
3A4
1A2
2C9
2C19
nefazodone inhibits what CYPs
3A4
TCAs inhibit what CYPs
3A4
if pt. has comorbid smoking or parkinsons what drug do we use
bupropion
if Pt. has comorbid anxiety what drugs do we use
SSRIs first
venlafaxine
TCA
if Pt. has comorbid weight gain, sedation, nausea what drug do we use
mirtazapine
if Pt. has comorbid alzheimers what drug do we use
SSRIs
bupropion
if Pt. has comorbid alzheimers what drug do we avoid
TCAs
if Pt. has comorbid DM what drugs do we use
- TCAs for neuropathy
- SSRIs may help BG
- duloxetine for neuropathy
if Pt. has comorbid insomnia what drugs do we use
trazodone
mirtazapine
TCAs
drug of choice for pregnancy
- SSRI - consider sertraline
- baby may have withdrawal symptoms for a few days
paroxetine use in pregnancy
- if they are already on it and doing well don’t D/C
- do not start it though
antidepressants in pregnancy
- if mom is already on one and it is working don’t stop it
- consider tapering before due to do reduce withdrawal in baby
antidepressant of choice in breast feeding
sertraline
first line in elderly w/ depression
SSRIs
AVOID TCAs
considerations for children w/ depression
- high suicidality concern
- monitor for impulsivity
drug of choice in children w/ MDD
fluoxetine
time course of response in week 1
- anxiety/agitation
- GI upset
- after few days anxiety decreases and sleep improves
time course of response in weeks 1-3
- cognitive symptoms improve
- increased activity and energy (suicide risk)
- improved concentration
- increased libido
- sleep/appetite normalize
time course of response in weeks 4-6
- depressed mood subsides
- re-experience pleasure
- less suicidal thoughts
length of treatment with antidepressants
-6-12 months for initial treatment, after symptoms remit
who do we consider lifetime treatment w/ antidepressants
- elderly
- 3rd episode
what to do for pts. refractory to treatment
- ensure adherence/dose optimization
- switch to another agent w/ different MoA
- combine SSRIs w/ bupropion, trazodone, mirtazapine, or TCA
- use atypical antipsychotics or lithium
drugs for severe acute manic symptoms in ER
- 1-3 mg IV lorazepam
- IM antipsychotic (ziprasidone, aripiprazole, haloperidol)
- start lithium 300 mg tid, increase 300 mg q 3 days to reach therapeutic dose
metabolism/elimination of lithium
- not metabolized; renally eliminated
- T1/2 is 20 hours
- therapeutic levels reached in 5-7 days
lithium therapeutic serum drug concentrations
acute: 0.8-1.2 mEq/L
maintenance: 0.4-0.7 mEq/L
early adverse effects of lithium
- GI upset
- fine hand tremor
- sedation
- ataxia
- diabetes insipidus
- edema
long term adverse effect sof lithium
- hypothyroidism
- acne
- leukocytosis
- renal toxicity
- bradycardia
- memory impairment
lithium in breastfeeding
don’t do it
baseline tests when starting lithium
- Thyroid
- Blood work (CBC)
- Electrolytes (Na, K)
- Electrocardiogram
- Renal function tests
- pregnancy test
lithium drug interactions that increase serum drug levels
- NSAIDs
- ACEI
- thiazides
- dehydration
lithium drug interactions that decrease serum drug levels
caffeine
salt
lithium drug interactions that cause serotonin syndrome
SSRIs
tramadol
lithium drug interactions that cause neurotoxicity
antipsychotics
atypical antipsychotic drugs
aripiprazole lurasidone olanzapine quetiapine risperidone ziprasidone
antipsychotic use in bipolar
acute mania
adverse effects of atypical antipsychotics
- increased weight, glucose, lipids
- sedation
- EPS
valproate in bipolar
often used first line in rapid cyclers
adverse effects of valproate
nasuea
sedation
hepatotoxicity
valproate and carbamazepine in pregnancy
don’t do it due to neural tube defects
valproate baseline tests at initiation
- CBC
- LFTs
- weight
- serum HCG (pregnancy)
carbamazepine use in bipolar
useful for rapid cyclers
adverse effects of carbamazepine
- blood dyscrasias (bone marrow suppression)
- sedation
carbamazepine baseline tests
- CBC
- LFTs
- ECG if >40
- serum HCG
- asians may get genetic testing to test for HLA-B and SJS susceptibility
lamotrigine use in bipolar
useful for rapid cyclers who have more than 4 cycles in a year
lamotrigine adverse effects
stevens johnson syndrome
drugs that may be used in bipolar depression
- quetiapine
- olanzapine+fluoxetine
- lurasidone
- lamotrigine
- NOT TRADITIONAL ANTIDEPRESSANTS AS MONOTHERAPY*