Depression Flashcards
lifetime prevalence of depression?
- major depression - US 17%
- persistent depressive disorder 3% (no remission of depression)
Epidemiology of depression?
- gender: 10-25% in women 5-12% in men puberty to 50: women 2x rate of men after 50 - men = women - age: prevalence decreases with age becomes more common in odler adults with greater burden of medical illness assist. living, skilled nursing, acute/chronic medical conditions esp high risk
Pathogenesis of depression?
- group of heterogenous disorders that are phenotypically similar
- final common pathway of diff disease processes that occur across biopsychosocial continuum
- genetics
- early life adversity
- social factors
- psychological factors
- secondary depression (gen medical disorders/meds/substance abuse)
pathogenesis - genetics?
- genes+enviro+enviro altered gene expression
- no specific genes linked to risk - mult small genetic effects
- epigenetics: changes in expression of genes caused by early life experiences or chronic stress
- concordance rate for major depression in monozygotic twins: 37%
pathogenesis - early life adveristy?
- predisposes to major depression by alt sensitivity to stress and response to negative stimuli
- early life stress: hyperactive corticotropin releasing factor cells in hypothalamus - increased stress response (HPA axis)
- stress responses can be set for life and modify the activation of certain genes (epigenetic) and transmitted to offspring
pathogenesis - social factors?
- may lead to depression onset or lead to depressive episodes
- isolation
- poor social relationships
- criticism from family members (expressed emotion)
- depression in social networks
- influence sxs expressed and willingness/ability to access care
pathogenesis - psychological factors?
- cognitive/behavioral: negative/distorted patterns of thinking predispose to depression
these patterns worsen in depressed person - personality:
neuroticism - anxiety, moodiness, envy, frustration, loneliness - respond poorly to stressors, interpret ordinary situations as threatening, and minor frustrations as hopelessly difficult - psychodynamic: early losses, interpersonal relationships
Pathogenesis - secondary depression?
- general medical conditions
- meds
- drugs of abuse
Medical conditions that can lead to depression?
- sleep apnea
- hypothyroidism/vit D def/diabetes
- chronic pain and opioid use
- stroke
- heart disease - ischemic, HF, cardiomyopathy
- parkinsons
- MS
- epilepsy
- head injury
- cancer
- COPD
- dementia
- HIV/neurosyphilis
Meds that can cause depression?
- interferon
- corticosteroids - more likely to cause bipolar
- benzos/opioids
- varenicline (chantix)/BBlockers
Drugs of abuse that can cause depression?
as you are withdrawing: - PCP - amphetamines - cocaine - marijuana during intoxication: - sedative-hypnotics - alcohol - opiates - steroids
Neurobio of depression? - structure and fxn?
- altered brain structure and fxn: unknown if alterations represent cause or consequence of depression (mult episodes of depression causes structural changes in your hippocampus)
structure:
-increased ventricular - brain ratio - smaller frontal lobe volumes
- smaller hippocampal volumes
- number/density/size of neurons and glial cells are abnormal
fxn:
-NTs - abnorm fxning
monoamines (serotonin, NE, dopamine), GABA, glutamate
- HPA axis: excess excretion of glucocorticoids may lead to suppression of neurogenesis and hippocampal atrophy
- abnormal neuronal networks
- sleep/circadian rhythms: decreased REM latency and slow wave sleep inflammation - higher levels of inflammatory markers
3 diff manifestations of sxs of major depression?
- psychological
- neurovegetative
- psychomotor/physical
Psychological sxs of major depression?
- depressed mood (dyphoria)
- numbness
- anhedonia - inability to experience joy
- decreased interest
- irritability/anxiety
- guilt/worthlessness
- suicidal ideation
neurovegetative sxs of major depression?
- appetite - wt loss
- sleep - can’t sleep, wake up 3 am
- energy
- concentration
Pyschomotor/physical sxs of major depression?
- psychomotor: retardation agitation - physical: aches/pain weakness/malaise GI distress
Qualifers that rule in depression?
- sxs occur in same 2 weeks
- most of day nearly every day
- distress or impairment
- R/o substances/general med condition
- R/o bereavement
subtypes of depression?
- anxious
- atypical
- catatonic
- melancholic
- mixed features
- peripartum
- psychotic
- seasonal
Subcategories of depression?
- bipolar
- secondary:
medical illness
meds
drugs of abuse
comorbid psych conditions?
1. anxiety disorders: generalized anxiety panic disorder OCD PTSD 2. substance abuse
SIGECAPS?
S: sleep I: interest G: guilt/worthlessness E: energy C: concentration A: appetite P: psychomotor disturbance S: suicidal ideation
Depression eval?
- chronology of current sxs
- sxs occur in same 2 weeks
- most of day nearly q day
- distress or impairment
- prior hx of depressive episodes
- impact of episode on occupational and interpersonal fxning
- alleviating and aggravating factors (stressful life events)
- address comorbidity (substance, illness, meds, psych)
- eval for mania/hypomania
- distinguish major depression from persistent depressive disorder (dysthymia) - 2 yrs w/o s free interval of 2 months
- suicide risk
depression eval cont. - History component?
- general medical illness
- family hx: depression, suicide, psychosis, bipolar
- social hx: interpersonal, occupational, financial stressors - sources of support, assessment of family/relationship dynamics
depression eval cont. - exam and labs?
- complete physical and neuro exam
- MMSE
- toxicological screen
- lab screen: CBC, TSH, LFTs, Chem7, Ca, B12, folate, HIV
- brain imaging (psychosis or neuro findings)
- +/- EEG, LP (psychosis or neuro findings)
Psychotic features of depression?
What ?s should you ask pt?
- delusions
- hallucinations
- disordered thought
- up to 20% of pts
- markedly higher suicide risk
?s:
does your mind ever play tricks on you?
do you ever hear things/see things?
do you ever feel like people are out to get you?
Suicide RFs?
- S: sex (male)
- A: age- elderly or adolescent
- D: depression
- P: prev. suicide attempts
- E: ethanol abuse
- R: rational thinking loss
- S: social supports lacking
- O: organized plan - suicide
- N: no spouse-div, wid, single
- S: sickness (physical illness)
How to ask about suicide attempts?
- organized plan?
- access to lethal means?
- previous attempts?
- family hx?
- non-suicidal self injury
- previous attempts: who, what, when, where, why, how? - what exactly did you do? - was it planned? - did you tell anyone? - risk/rescue
suicidal ideation - assessment?
- do you feel hopeless?
- do you feel like life isn’t worth living?
- do you think about suicide?
- Have you ever…..?
How to ask about suicide intent, plan and means?
- what specific thoughts have you had?
- do you have access to guns?
- have you been stock piling meds? Can you bring them in?
When should you hospitalize a potential suicidal pt?
- plan, intent, means = hospitalization
- less acute - safety plan
- crisis center, stay with family, more freq visits (even daily)
What is a part of the safety tx plan?
- crisis numbers - written and programemd in phone (family, friends, suicide hotline, ER, clinic)
- ROI for family in chart
- commitment to adhere to emds, appts, contact office with concerns
- agree to remove lethal means - have someone take guns, bring in extra meds
Alcohol questionnaire?
C: have you ever felt you should Cut down on your drinking?
A: have people Annoyed you by criticizing your drinking?
G: have you ever felt Guilty about your drinking?
E: have you ever had an Eye opener?
2 or more= clinically significant
Scales to use for depression screening?
- Beck depression inventory: self admin, for screening and tx response
- quick inventory of depressive symptomatology
- mood disorder questionnaire
- hamilton anxiety rating scale: over 20 indicates sig anxiety, pts with depression tend to score higher
MSE: observation?
presence of depressive signs:
- affect
- cognition (attention/concentration, memory)
- psychomotor activity
- ruminative thought process
- speech
- psychosis
- suicidal thoughts
SSRI MOA?
- block reuptake of serotonin
- downregulates receptors because there is so much serotonin in synaptic cleft
SSRIs indications?
Common SSRIs?
- 1st line tx of depressive disorders
- no real diff in efficacy
- diff in SEs and half lives
- paxil
- zoloft
- celexa
- prozac
- lexapro
Common side effects of SSRIs?
- GI disturbance: nausea, diarrhea, appetite
- sexual dysfxn: SSRI/SNRI - 50-70%
- anxiety
- insomnia or sedation
- sweating
- dizziness
SNRIs? Use?
- effexor
- cymbalta
- 2nd line of depressive disorders, more SEs
- acts on both serotonin and NE
- not clearly more efficacious
- when effexor is less than 225 mg = SSRI
SEs: HTN, tachycardia - cymbalta: good for diabetic neuropathy
Why aren’t TCAs widely used? Examples?
- amitriptyline
- clomipramine
- doxepin
- imipramine
- More side effects: anticholinergic (constipation), antihistamine
orthostatic hypotension
cardiac arrythmia - lethal in overdose
- more drug-drug interactions
Use of MAOi’s? Why aren’t these widely used?
- Nardil
- pamate
- more efficacious but..
- poorly tolerated - wt gain and sedation
- drug-drug interactions: serotonin syndrome, hypertensive crisis
- dietary restrictions - can’t eat tyramine containing foods
Indications for trazodone? What to watch for?
- good for sleep at low doses
- if tolerated - fxns as AD at higher doses
- watch for sedation, orthostasis, priapism - use lowest dose possible
When should you avoid buproprion? What happens with excess dopamine?
- avoid in seizure disorders
- avoid in bulimia
- enhances dopamine = caution:
anxiety
psychosis
dopaminergic agents
Pros of bupropion?
- no sexual side effects
- smoking cessation
- comorbid ADHD
- often used with SSRIs: augment antidepressant, reverse sexual side effects
- consider with sleepy, slowed down pts
- safe in pregnancy (B)
Pros and cons of mirtazapine?
- good for pts with nausea
- less sexual side effects
- causes sedation
- wt gain: use in elderly
Is it better to augment or switch classes of antidepressants?
- switching classes doesn’t improve remission
- tolerability similar b/t classes
- augmentation may be better than switching
- remission rate decreases with each failed med trial
Positive predictors of remission?
- caucasian
- female
- employed
- educated
Negative predictors of remission?
- longer index episodes
- drug abuse
- anxiety disorders
- medical disorders
- lower fxning
Why is Remission such a great thing in depression?
- return of normal fxning
- lower rates of relapse
- lower risk of suicide
- less alcohol and drug abuse
acute tx of depression (1st 12 weeks)?
- mild: consider psychotherapy alone
- mod-severe: med +/- therapy
- bipolar: mood stabilizer +/- antidepressant
- psychotic: antipsychotic + antidepressant
continuation phase of depression tx?
- 4-6 months following remission
- high risk of relapse
- use full therapeutic dosage
lifetime recurrence rate (off meds)?
- one episode: 50%
- 2 episodes: 70%
- 3 episodes: 90% (lifelong depression)
Med adherence factors, tolerability of meds?
- 40% are non-adherent first month socioeconomic factors tolerability - SSRI, SNRI more tolerable than TCA pyschiatric = nonpsychiatric psychotherapy education
Med education for pt?
- min of 2-4 weeks needed for meds to be effective
- take q day even if feeling better
- will need to take 4-6 months
- SEs often time dependent
General principles of pharmacotherapy in depression tx?
- titrate to target dose w/in 1st couple of weeks
- monitor for side effects:
agitation
suicidal ideation
insomnia
sexual - monitor adherence
- no improvenment in 4-6 wks - consider switch
- limited response: consider increase or augmentation
- side effects: switch or augment
factors to be considered when choosing an antidepressant?
- personal hx
- pharmacogenics
- family hx
- cost
- overdose/safety
- side effects/unique benefits
- drug-drug interactions
- comorbid conditions
- depression subtypes
What is pharmacogenetics?
- study of the role of genetic variation on drug response
- the ID of genetic factors that influence drug absorption, metabolism, and action at receptor level
- allow for individualized therapy - this could optimize drug effficacy and minimize toxicity. The potential for cost savings and for decreased morbidity and mortality and fewer adverse drug rxns
Overdose of drug classes?
- TCAs: highly lethal
- SSRIs: much safer
- lithium - lethal, shown to decrease suicidal ideation and impulsivity though
BBW for antidepressants? Importance of antidepressants?
- increased risk of SI with antidepressants up to 24 yrs
- tx depression beneficial
- there is also risk of suicide with untx depression
- suicide attempt rates highest month b/f tx
- decline after AD or psychotherapy begins
- monitor pt at regular intervals - SI, substance abuse, hopelessness, impulsivity
- refer for psychotherapy
- avoid giving refills to encourage f/u
- start low and go slow in 18-24 year olds
What should you do if a pt encounters SEs?
- wait!!!
- lower dose, slow titration
- change dosing schedule
- augment
Wht should you recommend if pt encounters sexual side effects?
- drug holiday - watch for withdrawal
- augment:
bupropion
trazodone - rare risk of priapism
ED meds
buspirone - lower dose
- wait or switch meds
What are good drugs for anxiety?
- benzos
- gabapentin
- lyrica
- buspirone
- therapy/medication/exercise
- if prominent agitation consider BIPOLAR!!
What are good drugs for insomnia?
- benzos
- sleepers: zolpidem
- trazodone
- therapy/meds/exercise
benzos - use?
- goal of short term use
- scheduled over prn
- longer acting with lower abuse potential: clonazepam, lorazepam over alprazolam, diazepam
- caution in comorbid substance abuse
D/c of drugs - withdrawal adverse effects?
- nausea, HA, irritability, vivid dreams, vertigo
- slow taper +/- short term bentos
- worst - paroxetine, venlafaxine
- fluoxetine - self tapering
SSRIs - drug interactions?
- 2D6 inhibition
- fluoxetine (prozac), paroxetine (paxil), fluvoxamine - have most drug interactions
- escitalopram (lexapro) - has least amt
Pt is on risperidone, trazodone and hydrocodone, and he is now started on paroxetine for depression, he calls a week later complaining of stiffness, anxiety and pain. Why is this and why is he having these sxs?
- 2d6 inhibition from paroxetine
- so there is increased risperdone - EPS
- increased metabolite of trazodone - leading to anxiety
- decreased conversion of codeine to morphine - leading to pain
Depression subtypes?
- psychotic depression: higher remission with combo of AD and antipsychotic
- bipolar depression: 30-50% risk of cycling into mania on AD w/o mood stabilizer
Psychotherapy options?
- cognitive behavior psychotherapy: understand distortions in thinking
learn new ways of coping - interpersonal thinking: grief, role transition/role dispute, interpersonal deficits
- both are evidenced based with well documented efficacy
Augmentation strategies?
- bibliotherapy - self help books
- relaxation techniques - visualization/muscle relaxation
- meditation
- exercise - aerobic 3-5x/wk for 45-60 min
- apps/support groups/telepsychology for rural areas
