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124 Cards in this Set

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Clinicians diagnose depressive disorders according to the ____________________.
Diagnostic and Statistical Manual of Mental Disorders
What is the estimated prevalence of depression?
16%
What two trends are important regarding depression?
1. Increased rates of depression.
2. Decreased age of onset.
In what gender is depression more common?
Female
What is the typical onset of depression agewise?
25-30 yo
What typically precipitates the initial episode of depression?
Stressful life events.
Depressive symptoms appearing later in life (Late-onset syndrome) typically occurs in what patients?
Those with underlying neurological disorders.
Describe the genetic component of depression.
Depression and suicide tend to cluster in families.
What is the likelyhood of a person developing depression if a 1st degree relative becomes ill?
1.5-3x more likely to develop depression.
What are the risk factors for reocurring depression?
1. 1st degree relative with depression.
2. 1st episode before age 20
3. >2 prior episodes
4. H/O recurrence within 1 year after medication was discontinued
Describe the biogenic amine hypothesis for depression?
Depletion of NE, 5-HT and DA in the synapses. Not specific.
Expected 5-HT levels in a depressed individual
Decreased
Expected NE levels in a depressed individual
Decreased
Expected NE levels in a manic patient
Increased
Expected 5-HT levels in a manic patient
Decreased
Describe the dysregulation hypothesis of depression
Rather than focus on the activities of neurotransmitter systems, this theory focuses on the failure of homeostatic regulation.
A decreased in the receptor sensitivity is implicated.
THIS THEORY ADDRESSES WHY ANTI-DEPRESSANT EFFECTS ARE CHRONIC RATHER THAN ACUTE.
Describe the 5HT/NE hypothesis
Basically it states that both the serotenergic and noradrenergic systems must be functional for an antidepressant effect to be exerted.
Describe the biological markers that support a biological hypothesis
1. Neuroendocrine - many patients have neuroendocrine abnormality (Cortisol/TSH)
2. Sleep - REM earlier and have decreased slow-wave sleep, disruption of slep and early morning awakening.
Describe the Neurokinin theory
Suggests that Neurokinins have antidepressant properties, focus of research
Describe the structural abnormalities associated with depression
Decreased hippocampal volume after episode, deep white matter lesions
Name Endocrine disorders associated with depression
Hypothyroidism
Describe deficiency states associated with depression
Pernicious anemia, Wernicke's encephalopathy, severe anemia
Describe infections associated with depression
Influenza, TB, AIDs
Describe metabolic disorders associated with depression.
Hypokalemia
Hyponatremia
Describe cardiovascular events associated with depression
1. Post MI
2. Post CVA
3. CHF
Describe neurologic disorders associated with depression.
1.Alzheimers
2.Parkinsons
3.Post CVA
4.MS
Describe psychiatric disorders associated with depression.
1.Anxiety disorders
2.Eating disorders
3.Schizophrenia
4.Substance dependence
Describe some medications associated with depression
Alcohol Propranolol Diuretics Baclofen 5-FU Metoclopramide Ondansetron Reserpine Hydralazine OC's Brompheniramine INTERFERON-alpha Metronidazole Theophylline Methyldopa Clonidine Steroids Digoxin Isotretinoin NSAIDs
SIGECAPS
Signs of Depression
Sleep distrubance
Interest, loss of
Guilt
Energy, loss of
Concentration (Poor)
Appetite changes
Psychomotor changes
Suicidial Ideation
Suicide Risk factors (9)
Elderly
H/O prior attempts
Feelings of hopelessness
Living alone
Substance abuse
Anniversary of a loss
Unemployment
Family history
Lack of support system
Which gender attempts to commit suicide more often?
Female
Which gender SUCCEEDS in committing suicide more?
Men
Overall Tx Goals
1. Reduce depressive symptoms
2. Return patient to an optimal level of functioning
Nonpharmacologic Tx
1. Psychotherapy
2. Electric convulsive Tx
3. Light therapy
How long before antidepressant effects are typically seen?
2-4 weeks after initial dose
How long of a trial must be given to each agent?
4 weeks
Describe the improvement scheme for AD therapy(ie appetite, mood...)
First sleep, appetite and energy levels improve BEFORE the mood... Risk factor for suicide
What ADR's are associated with Dopamine reuptake inhibition?
Psychotic features, activation.
What ADR's are associated with serotonin reuptake inhibition?
N/V/D, Anxiety, Sexual dysfunction, insomnia
What ADR's are associated with Norepinephrine reuptake inhibition?
Sexual dysfunction, insomnia, tachycardia, tremor
Describe Seratonin syndrome: What causes it and what are it's symptoms?
Associated with concurrent use of medications inhibiting the reuptake of serotonin.
Sx: Confusion, Seizures, Tachycardia, Agitation, Hyperthermia, Tremor, Coma, HTN and Ataxia
TCA's are typically classified as (sedating/activating) antidepressants?
Sedating
Amitriptyline - CLASS
TCA Tertiary Amine
Clomipramine - CLASS
TCA Tertiary Amine
Doxepin - CLASS
TCA Tertiary Amine
Impiramine - CLASS
TCA Tertiary Amine
Trimipramine - CLASS
TCA Tertiary Amine
Desipramine - CLASS
TCA - Secondary Amine
Nortriptyline - CLASS
TCA - Secondary Amine
Protriptyline - CLASS
TCA - Secondary Amine
Which TCA's are more efficacious per studies?
None, none are superior to others
What NT's do TCA's block the reuptake of?
5-HT, DA and NE
Besides the typicaly NT reuptake inhibition, what receptors are also blocked by TCA's?
Cholinergic, Histaminergic and Alpha-1
Are TCA's considered 1st line?
No
Off label uses of TCA's
Trigeminal and post-herpetic neuralgias, diabetic neuropathy, enuresis and migraine prophylaxis.
Which class of TCA's are preferred and why?
Secondary amines, they have LESS anticholinergic
Which class of antidepressants in particular is fatal in overdose?
TCA's
ADR's associated with TCA's
1.Anticholinergic
2.Antihistaminergic
3.Alpha-1 adrenergic blockade
4.Cardica conduction delays (heart block with those with preexisting conduction abnormalities.)
5.Drowsiness, weakness, lethargy, fatigue
6.Excessive perspiration
7.Sexual dysfunction
8.Seizures
9.Weight Gain
Advantages of TCA's
1.Well established efficacy
2.Generics available
3.Once daily dosing
4.Sedation
5.Effective for non-mood disorders
Disadvantages of TCA's
1.High rates of discontinuation
2.Dose titration normally required
3.Wide differences in metabolism among individuals
4.Overdose may be fatal
5.Weight gain
6.Sexual dysfunction
Relevant PK considerations as far as TCA's
1. Rapid absorption
2. First past metabolism
3. Food DOES NOT AFFECT ABSORPTION
4. Large Vd
5. Highly protein bound
6. Heavy hepatic metabolism
7. T1/2 is 24 hours, so qd
Which CYP isoenzymes metabolize TCA's
CYP1A2
CYP2D6 (Different in people)
CYP3A4
Two major drug interactions with TCA's
1.Alcohol - Increase risk of seizures
2.Buproprion - Increase risk of seizures
Venlafaxine - CLASS
SNRI
SNRI
Serotonin Noradrenergic Reuptake Inhibitors
Duloxetine - CLASS
SNRI
Which TCA is indicated for OCD?
Clomipramine
Which TCA is indicated for depression or anxiety associated with Alcoholism?
Doxepin
Which TCA is indicated for children experiencing enuresis?
Imipramine
Venlafaxine MOA
Inhibits reuptake of: 5-HT and NE and WEAKLY DA
Is venlafaxine a possible 1st line?
Yes
Venlafaxine is generally regarded as a (Activating/Sedating) antidepressant
Activating
ADR's associated with Venlafaxine
Nausea
Constipation
Dry mouth
Dizziness
Sweating
Sexual dysfunction
Agitation
HA
Insomnia
What DOSE related side effect may be observed with higher doses of Venlafaxine?
Increases in blood pressure
Is weight gain typically associated with Venlafaxine?
It is rare
PK considerations for Venlafaxine
1.Food has no effect on absorption
2.Not highly protein bound
3.Metabolized by 2D6
4.BID dosing normally used due to active metabolite (O-desmethylvenlafaxine)
Which Class/Drug is associated with the worst sexual dysfunction by far?
Venlafaxine
Significant drug interactions for Venlafaxine
MAO-Inhibitors, TCA's and other serotonergic meds
Describe dosing method for Venlafaxine
Must be titrated
FDA indications for Duloxetine
Depression, diabetic neuropathic pain
MOA of Duloxetine
5-HT, NE reuptake inhibition. Weak inhibitor of DA
ADR associated with Duloxetine
Insomnia, nausea, fatigue, diarrhea, dry mouth, dizziness, constipation, sexual dysfunction, MAY INCREASE LFTs
Which AD's can raise LFTs?
Duloxetine and Trazodone
Describe relevant PK information for Duloxetine
1.Well absorbed
2.Food WILL delay extent and rate of absorption
3.Heavy hepatic metabolism
Significant Duloxetine ADR's
Nausea
LFTs
Sexual Dysfunction
Describe dosing method for Duloxetine
Must titrate
Advantages of Venlafaxine
ER formulation available
Relatively safe in overdose
Minimal Drug interactions
Disadvantages of Venlafaxine
1.High rates of Sexual dysfunction
2.Cost
3.Potential for increased blood pressure
4.Dose titration required
SSRI's are typically considered which line of therapy?
1st
ADR's common to all SSRI's
Nausea, HA, sleep disturbances, anxiety, sexual dysfunction, tremor
Fluoxetine has been associated with the most __________________.
Agitation (Activating)
Paroxetine has been associated with the most ____________________.
Sedation, weight gain
Sertaline has been associated with the most ______________.
Diarrhea
CYP450 considerations as far as SSRI's
Fluoxetine and Paroxetine are potent 2D6 inhibitors
Describe the PK of Fluoxetine
2-3 day half life of active and 7-9 days of active metabolite, so qd or qW weekly dosing used. CAN SELF TAPER
Drug interactions are most likely with which SSRI's
Fluoxetine, paroxetine
Drug interactions are least likely with which SSRI's?
Citalopram, escitalopram
Major interaction associated with SSRI's
Warfarin! May increase INR
Effect of 5-HT2 antagonism?
Reduced Anxiety, Insomnia, Sexual dysfunction
Trazodone - MOA
5-HT2 antagonist, 5-HT reuptake inhibitor
Nefazodone - MOA
5-HT2 antagonist and 5-HT reuptake inhibitor
Main use of Trazodone in the market?
Sedative-hypnotic
ADR's associated with Trazodone/Nefadazone
SEDATION, ORTHOSTATIC HYPOTENSION, somnolence, dry mouth, nausea, ha, constipation
PRIAPISM
BLACK BOX ON NEFADAZONE: HEPATOTOXICITY!
PK considerations for Nefazodone
Food decreses extent of absorption and bioavailability of nefazodone
Half life - 2-4 hours, therefore BID dosing
Drug interactions for Nefazodone
CYP3A4 POTENT INHIBITOR
Alprazolam, Carbamazepine, Digoxin, Statins (Rhabdo), MAOIs, PI's, Buspirone
Drug interactions for Trazodone
Antipsychotics, Alcohol, MAOI, Digoxin, phenytoin, Warfarin, Carbamazepine
How would you dose Trazodone?
QHS! Major sedation
Buproprion- CLASS
Mixed DA/NE Reuptake inhibitor
Buproprion Indications
Depression, Seasonal affective disorder and SMOKING CESSATION
ADR for Buproprion
Dry mouth, insomnia, HA, N/V, agitation, anxiety, dizziness, tremor, constipation.
Buproprion is contraindicated in which group?
Those having seizures
MAJOR Drug interactions for buproprion
Antipsychotics, AD's (Esp TCAs) and Alcohol DUE TO SEIZURE THRESHOLD LOWERING!
Maximum daily dose of Buproprion
450mg/day
Mirtazapine MOA
Enhances central NE and 5-HT activity through antagonism of central presynaptic alpha 2 adrenergic autoreceptors and heteroreceptors.
Also blocks 5-HT types 2 and 3, cholinergic and histamine receptors
Mirtazapine blocks 5-HT2 receptors which reduces _____________.
Anxiety, insomnia and sexual dysfunction
Mirtazapine blocks 5-HT3 receptors which reduces _________________.
Nausea
Common ADR associated with Mirtazapine
Sedation, increased appetite, weight gain, constipation, dry mouth
Does food affec the rate or extent of absorption of Mirtazpine?
Nope
Normal dosing frequency for Mirtazapine
QD
What do you do if Mirtazapine dosing results in activaiton rather than sedation?
Adjust administration time
Phenelzine - Class
Non-selective MAOI
Tranylcypromine- Class
Non-selective MAOI
MOA of non-selective MAOI's
Increases concentrations of NE, 5-HT and DA within the neuronal synapse due to inhibition of MAO enzyme
Selegiline - CLASS
MAO-I type B selective