dep&anxiety gardner24winter-1hnid Flashcards

A. Emotional
B. Physical
C. Cognitive

– “Depressed”: sad, empty, hopeless
– Markedly diminished or lack of pleasure in usual activities
(anhedonia).
– No interest in the future.
– Restlessness, irritability, or crying spells.
– Feelings of guilt, worthlessness, helplessness, and hopelessness.

– Fatigue or loss of energy.
– Change in sleep patterns.
Too little
Too much
– Change in appetite and weight.
Decreased appetite with weight loss
Increased appetite with weight gain
– Unexplained physical problems.
Headaches, stomach problems, aches and pains, etc..(somatic complaints)

Depression can affect how one thinks
and what one thinks about.
– Lack of concentration and remembering.
– Difficulty in making decisions (ambivalence;
indecisiveness).
– Thoughts of death or suicide.
Suicide attempts

SIGECAPS

SADIFACES

Sleep
Interests
Guilt
Energy
Concentration
Appetite
Psychomotor agitation or
slowing
Suicidal ideation

Sleep – decrease or increase
Appetite – decrease or increase
Depressed mood
Interest (loss of)
Fatigue
Anxiety or agitation
Concentration (difficulty with)
Esteem (feelings of worthlessness)
Suicidal Thoughts or Ideations

Depression with …
– Psychotic features
– With seasonal pattern (seasonal affective disorder – SAD)
– With melancholic features
– With atypical features (reversed physical symptoms)
– With peripartum onset
– With anxious distress

Episode frequency,
duration, and
intensity vary among
individuals and can
change intra-
individually over
time.

-more in teens and 20s

-moderate freq in 40s

-less in 50s and 60s

A multifactorial, complex illness.
Optimal treatment ought to be
multifactorial also, addressing
biological, psychological, and
social factors.

The underlying required pathophysiology required for
depression is unknown. There may not be a single specific
required neuropathological abnormality.

How alteration of functional
BDNF result in depression. In
brief, BDNF is a molecule
involved in the control of
synapse formation and
regulation of activity-
dependent changes in
synapse structure and
function. BDNF stimulation
increases synaptic spine
density by a mechanism
dependent on the Ras/ERK
pathway. Dysfunction or
decreased BDNF leads to
malfunction of synaptic
plasticity, and decreased
excitatory neurons and
glutamate; and eventually
lead to depression.

decreased BDNF

decreased glutamate which leads to :

-decrease in synaptic transmission

-increase in neuronal degeneration

both leading to depression

stress can be a factor

10-15 bullet points that help you develop an appreciation of and understanding of the complex neurobiology of depression
• Involves and goes beyond
monoamines
• Synaptic plasticity & BDNF
• Multiple factors lead to neurotrophic
dysregulation
• Stress and glucocorticoid release
impact sensitive brain region volume
and functioning
• Neuroinflammation and depression
• Circadian rhythm disruption and
depression

Selected anxiety disorders:
• Panic Disorder
• Social Anxiety Disorder (Social Phobia )
• Generalized Anxiety Disorder

• Obsessive-Compulsive Disorder
• Post-Traumatic Stress Disorder

• Psychotherapy
– First-line for mild-moderate presentations
• CBT (most common … multiple formats

“Third wave” CBT approaches:
Acceptance and commitment therapy (ACT)
Mindfulness-based cognitive therapy
Dialectical behaviour therapy
Psychodynamic therapy
Interpersonal therapy (IPT)

– For moderate-severe anxiety, combine with psychotherapy (ideal) or use alone:
• Antidepressants (acute & maintenance)
• Benzodiazepines (short-term/acute)

Drug therapy should be reserved for anxiety that interferes with daily functioning for which non-
drug interventions have failed or are not available, or at the outset when anxiety is severe.

First-line for depressive and anxiety disorders

Enhance intrasynaptic catecholamine (5-HT, NA, DA) availability:

serotonin and noradrenaline reuptake inhibition

They are a good choice for those whose depression is resistant to other drugs, but some may find their side effects unpleasant

-cause GI sx-bcus we have 5ht receptors in gut

-sexual dysfunction

-sx go away in a couple of days

actions of this drugs include :

-irritation, agitation, hair at the back of neck erection, alert, tremors, jump out your skin.

-do not take HS

DAT=dopamine transporter

NET=norepinephrine transporter

NA and 5-HT release + serotonin antagonist

inhibit metabolism (deamination) of catecholamines

Dry mouth. Nausea, diarrhea or constipation. Headache. Drowsiness. Insomnia. Dizziness or lightheadedness. Skin reaction at the patch site.

dopamine and adrenaline, are hormones that the brain, nerve tissues, and adrenal glands produce. They are responsible for the body’s “fight-or-flight” response.

Dopamine, adrenaline, and noradrenaline are all catecholamines. The body releases catecholamines in response to emotional or physical stress.

CATECHOLAMINES

balance

Focused
Alert/vigilant
Hyperarousal
Tense

Increasingly Serotonergic
Reduced emotional response
Apathy
Nausea
Sexual dysfunction

most serotonergic effect

§ The hippocampus & PFC exhibits stress-sensitive structural plasticity
§ Stress reduces hippocampal and prefrontal cortex neuronal volume
§ Animal studies have shown that stress decreases neurogenesis
§ Antidepressants reverse the effects of stress; neuroprotective action
§ It is not clear that low hippocampal/prefrontal volume is associated with depression,
but BDNF-produced neuronal volume regeneration (growth) seems to be a
requirement for an antidepressant response
§ The role BDNF in antidepressant response has been observed with standard
antidepressants (gradual onset) and ketamine (fast onset)

involved in the pathogenesis of depression and antidepressant response

§ Antidepressants

BDNF-produced neuronal volume

standard antidepressants (gradual onset) and ketamine (fast onset)

long t1/2

a PD interaction

Antagonist action

TCAs WITH ki value <1 to 100 (high and moderate to high) will cause more:

delirium

memory impairment

blurred vision

dry mouth

reduced GI motility

desipramine,
nortriptyline,
paroxetine

antidepressants will cause moderate side effects at muscarinic receptors of individuals taking these.

bupropion, SSRIs,
SNRIs

-would cause low adverse effects (Delirium, memory
impairment, blurred
vision, dry mouth,
reduced GI motility)

high and moderate to (hi ki<1-100=mirtazapine) would cause sedation and weight gain

its ki value is 100-200

these tcas would cause low side effects because because their ki value is high >200

TCAs with hi and mod to high ki value(<1-100) e.g trazodone

Dizziness

orthostatic hypotension

reflex tachycardia

moderate Dizziness, orthostatic
hypotension, reflex
tachycardia

low Dizziness, orthostatic
hypotension, reflex
tachycardia.

because of their high ki values >200

VFX (SNRIs) > Fluoxetine > other SSRIs

these s/e diminish over time

Sertraline > others

Paroxetine > SSRIs (25-50%) (citalopram25%) > SNRIs 25% >> BPR, MTZ, MLB[<10%]

Paroxetine > SSRIs (25-50%) (citalopram25%) > SNRIs 25% >> BPR, MTZ, MLB[<10%]

no diminution over time

Mirtazapine > Paroxetine > others

possible diminution overtime

Mirtazapine > Paroxetine > others

maybe possible diminution overtime

NRIs (VFX, DLX, BPR)

-NRIs not good for people with high BP

no diminution over time

Paroxetine, venlafaxine > SSRIs >> fluoxetine

-taper always

SIADH of concern with all ADs

BPR > others

Common, safer combinations:
Mirtazapine + SSRI/SNRI
SSRI/SNRI + trazodone
Mirtazapine + bupropion
SSRI/SNRI + bupropion

MAOI + other AD (antidepressants) (avoid)
RIMA + other AD (avoid)
TCA low dose +
SSRI/SNRI/bupropion/trazodone
/mirtazapine (check PK interactions)

Nomenclature:
• MAOI: phenelzine, tranylcypromine
– Non-selective (A&B), irreversible
• MAO-A inhibitor: moclobemide (RIMA)
– Selective, reversible, competitive inhibitor
• MAO-B inhibitor: selegiline, Rasagiline
– Selective, irreversible

A: Yes. This is commonplace.
Usually safe, with dangerous, possibly deadly exceptions

Anti-depressant---(5t1/2) b4 starting MAOI (tranylcypromine(Parnate)
Phenelzine (Nardil)---(wait 2 weeks b4 switching to another Anti-depressant)

-also wait 5t1/2 b4 switching to-RIMA(Moclobemide (Manerix)) follow with another 5 t1/2 if switching to another.

Garbage system malfunctioning
MAOIs substantially reduce the
metabolism (clearance) of neuronal
serotonin.
Supply system hyperactive
Drugs (and substances) that enhance
neuronal concentration of serotonin
(e.g., SRI

Garbage system malfunctioning
MAOIs substantially reduce the
metabolism (clearance) of neuronal
noradrenaline.
Supply system hyperactive
Substances (and drugs) that enhance
neuronal concentration of
noradrenaline (e.g., tyramine in
cheese)

autonomic instability -hypertensive

tachycardia

mydriasis

agitation

tremor

diaphoresis

increased bowel sounds

hyperflexia-greater in lower extremities

Autonomic dysfunction: fever, tachycardia, diarrhea, hyperactive
bowel sounds, diaphoresis, pupil dilation
– Neuromuscular: hyperreflexia (especially in lower extremities),
shivering, clonus (inducible, spontaneous, ocular), myoclonus,
tremors, muscular rigidity
– Cognitive: anxiety, agitation, restlessness, hypervigilance, pressured
speech, agitated delirium

fever,

tachycardia,

diarrhea,

hyperactive bowel sounds,

diaphoresis,

pupil dilation

hyperreflexia (especially in lower extremities),
shivering,

clonus (inducible, spontaneous, ocular),

myoclonus,
tremors,

muscular rigidity

anxiety,

agitation,

restlessness,

hypervigilance,

pressured speech,

agitated delirium

life threatening toxicity

met acidosis
rhabdomyolysis
seizures
renal failure
DIC

akathisia

hyperthermia

hypertension

muscular hypertonicity

tremors

altered mental state

clonus induced

-Phenelzine (Nardil®)
-Tranylcypromine (Parnate®)
-Isocarboxazid (Marplan U.S.A only)
-Moclobemide (Manerix®) – less risky due to MOA

Effective for depression, especially treatment refractory depression and atypicaldepressive episodes

Dizziness and lightheadedness
– Weight gain and fluid retention
– Sexual dysfunction
– Insomnia

– drug and food interactions!!!!!!

Substances (and drugs) that enhance
neuronal concentration of
noradrenaline (e.g., tyramine in
cheese)

Food (apply to tranylcypromine and
phenelzine only)
Absolute
• aged cheeses
• cured meats
• tap beer
• sauerkraut
• Marmite/Vegemite
• fava & broad beans
• Conc. soy products
Moderation
• bottled beer and wine (2 glasses)

Drug (apply to tranylcypromine, phenelzine, and
moclobemide)
Prescription
• SSRIs/TCAs/Venlafaxine
• meperidine (Demerol)
• L-tryptophan
• L-dopa
• epinephrine/norepinephrine
• stimulants: methylphenidate, amphetamine,
phentermine
• hypoglycemic agents
Non-prescription
• decongestants (pseudoephedrine, etc)
• dextromethorphan (DM)
Street: cocaine

–Patient preference
–Past response
–Subtype of depression
–Symptoms
–Suicide risk
–Toxicity in overdose
–Medical history
–Drug interactions
–Adverse effect profile
–Fertility status
–Convenience
–Cost

What is mostly the same?•

Overall benefits
• Time to see benefits
• Chance of benefiting
- Somewhat: 80%
- Significantly: 60-70%
- Completely: 50%

Chance of stopping Rx prematurely
->50% within 3 months
• Duration of treatment
-1st or 2nd episode: 6-12 months
->2 episodes close together: >1
year to indefinitely

Individual response
• Side effects
• Drug interactions
• Precautions
• Cost
• Dosing
• Chance for side effects when
stopping treatment
• Drug-drug, drug-disease, drug-food
interactions
• Specific pharmacological actions
• Patient preferences

multiple
antidepressant
trials

Short-term (8-12 weeks):
Reduction in symptoms to full remission
An improvement in quality of life
Return of normal level of functioning
Long-term (>3 months):
Prevention of a return of depressive or anxious symptoms
Maintenance of a stable mood
End of treatment:
Reduce or eliminate risk for discontinuation symptoms

improved
sleep, appetite,
energy

depressed mood, loss of
pleasure, pessimism, irritability
significantly improve

slow return
of functioning

response/remission

6-12 weeks

4-9 months

1 or mo yrs

NNT: 3-6
For every 3-6 people in which
treatment is extended for 1-2
years, an additional person
avoids relapsing.

Common with abrupt cessation of SSRI or SNRI

1-2 weeks of feeling “off” or “flu’ish”, occ. protracted course

Common: dizziness, anxiety, nausea, sweating, coryza, headache, insomnia
Occasionally: shock-like sensations, parasthesias, visual disturbances, myalgias, chills, confusion

Prevent by advising patient not to stop SSRI/SNRI cold turkey (exception fluoxetine)
Taper SSRI/SNRI over 1-4 weeks
If mild symptoms: encourage them to try to let it pass over 1-2 weeks
If moderate to severe or symptom > 2 weeks REINTRODUCE SSRI and taper more slowly or switch to fluoxetine (long t1/2) then taper

venlafaxine RR =8.84(1.12, 69.51)

paroxetine =2.15 (0.71, 6.52)

For every 100 pediatric patients treated, 2 to 3 patients have
some increase in suicidality during short-term treatment, (i.e.,
beyond the risk with the disease being treated)

Design:
– MC, RCT, 12 weeks
Patients:
– moderate to severe depression
– included comorbid illnesses
– N=439, 12-17 years
Interventions:
– Fluoxetine 10-40 mg/day
– CBT + fluoxetine
– CBT alone
– Placebo
Outcomes
– Children’s depression scale, Clinical Global Impression for
Improvement (CGI-I)
– Suicidal Ideation Questionnaire (29% suicidal at baseline)
– Prospectively assessed ‘suicide-related’ and ‘harm-related’ events

Combo FLU + CBT was superior to PLA (p = .001),

FLU alone(p= .02), and CBT alone (p = .01)
FLU alone was superior to CBT alone (p = .01

• Fluoxetine to be more effective than placebo and CBT alone
• Reduced suicidality across treatments (including placebo) but level of reduction varied (smallest mean reduction with fluoxetine alone)
• Fluoxetine associated with more self-harm vs. CBT or placebo

• 20-100 attempts for every successful suicide
• Women: more attempts than men
• Men: more suicides than women
• Most common methods:
– Attempts: overdose
– Death from suicide: hanging (men); overdose (women)

Risk factors for suicide attempts

1 in 6 repeat overdose

With a median 5.3 year follow-up:
6.3% die (all cause)
1.5% die from suicide(42-fold higher risk of suicide Median time to
suicide: 1.6 years)
0.6% die from intentional overdose
highest risk: seniors

Inquire,
acknowledge & communicate Plan & follow- up Document Limit access to
means Find other supports

Most commonly used antidepressants are not “ sedatives” and do not substantially add to the impairing effects of alcohol … when consumed responsibly
– SSRIs, venlafaxine, bupropion, desipramine
Most people with mood disorders (e.g., depression) are vulnerable to alcohol’s effect on mood stability. All patients taking antidepressants should be encouraged to limit their alcohol intake to a minimum to allow for improvement and stabilization of mood

antidepressant.

anxiety disorders than for depression.

< 50%

getting them well.

....is much more about the process and less about the decision.

non-adherence

NDRI: Bupropion

Advice: Have you ever had a seizure or epilepsy?
This medication can make you feel quite restless in the beginning …

Amitriptyline,

clomipramine,

desipramine,

doxepin,

imipramine,

nortriptyline,
trimipramine

– Remains in common use
– Sedative, neuropathic pain, depression,
anxiety

– SSRI-like mechanism
– Obsessive-compulsive disorder

– Noradrenergic
– Reasonably tolerated
– Not sedating

– TCA of choice for depression
– Blood levels useful

• Multiple pharmacological effects –
desired and undesired
• Serotonin and noradrenaline
reuptake blockers
• Block histaminic, alpha adrenergic,
and muscarinic receptors causing …
– Sedation, appetite stimulation
– Dizziness (upon standing) – risk for falls
– Anticholinergic side effects (dry mouth …confusion)
• Cardiovascular toxicity
• Dangerous in overdose
• Safe and effective when used in
appropriate patients

SSRI+

aka trintlex used to treat major depressive disorder

Vortioxetine works by increasing the activity of a chemical called serotonin in the brain.

Indicated in combination with a SSRI or SNRI, for the treatment of major depressive disorder in adults who have not responded adequately to at least two separate courses of treatment with different antidepressants, each of adequate dose and duration, in the current moderate to severe depressive episode.

1. Ketamine infusion: none for mental illness
2. Esketamine: treatment-refractory depression when combined with SSRI or SNRI (Spravato®, Health Canada)

2. Specialized infusion/administration clinic
Post-admin observation: ≥ 2 hr
Post-admin precaution: no driving, etc. till next day

2. Induction phase (4 weeks): twice weekly
2. Maintenance phase (5-? weeks): q1w x 4, q1w or q2w x ? weeks

NMDA receptor antagonist