Psychobiology of depressive disorders Flashcards
What five regions are consistently dysfunctional in most patients with depression?
dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, anterior cingulate cortex, and hippocampus
Patients with depression have an excessive activity of BLANK and increased BLANK.
Patients with depression have an excessive activity of the Hypothalamic-pituitary-adrenal axis (HPA axis) and increased plasma cortisol levels.
Those with anhedonia or inability to feel pleasure suffer from impairment of
the reward system
Postmortem microscopic examinations have shown what happens to the brain in those with depressive disorders?
decreased cortical thickness as well as diminished neural size
What is BDNF
brain-derived neurotrophic factor a brain growth factor
Increased BDNF leads to
increased neurogenesis
What five things have been shown to have increases in BDNF and neurogenesis that treat depression?
antidepressants, lithium, stimulation treatments, estrogen, and exercise
A single IV administration of this drug can have a robust response in less than 2 hours in upward of 75% of the subjects-lasting several days to 2 weeks in relieving depression.
Ketamine
Diathesis
what you are born with, genetically determinants
Stress
What happens later, environmental determinants
When is a depressive improvement called a remission?
removal of essentially all symptoms. it is called remission for the first several months and then recovery if it is sustained for longer than 6 months.
When are depressive symptoms referred to as a relapse?
When depression returns before there is a full remission of symptoms or within the first several months following remission of symptoms
When are depressive symptoms referred to as a recurrence?
When depression returns after a patient has recovered
How many of depressed patients will remit during treatment with any antidepressant initially?
One third
What are the most common residual symptoms in patients who do not achieve remission?
insomnia, fatigue, painful physical complaints, problems concentrating, and lack of interest
What age group is the risk benefit ratio for antidepressants the most favorable?
adults 25-64
What age group is the risk benefit ratio for antidepressants the worst?
Ages 6-12
What age group has the an increased risk of suicide when on antidepressants?
19-24 and possibly children and adolescents
What age group may not respond as well to antidepressants and may experience more side effects?
65 and older
What hypothesis explains the delayed clinical affect of antidepressants as well as possibly anxiolytics (and additionally the development of tolerance to the acute side effects of antidepressant drugs)?
Changes in neurotransmitter receptor sensitivity may mediate the clinical effects of antidepressant drugs
What hypothesis explains the delayed clinical affect of antidepressants as well as possibly anxiolytics (and additionally the development of tolerance to the acute side effects of antidepressant drugs)?
Changes in neurotransmitter receptor sensitivity may mediate the clinical effects of antidepressant drugs
Name the six SSRIs?
Fluoxetine (Prozac), Sertraline (zoloft), Paroxetine (paxil), Fluvoxamine (Luvox), Citalopram (Celexa)/Escitalopram (Lexapro)
All six SSRIs have what same major pharmacologic feature in common?
Selective and potent inhibition of serotonin reuptake, also known as inhibition of serotonin transporter or SERT
The action of SSRIs occurs at
both the presynaptic axon terminal and at the somatodendritic end of the serotonin neuron
Which new medication is a “SPARI” (Serotonin partial agonist/reuptake inhibitor)?
Vilazodone
Why would the predominance of 5HT1A be potentially significant in Vilazodone?
It may mitigate the sexual dysfunction
Prozac (Fluoxetine)
Mechanism of Action:
Prozac (Fluoxetine)
Mechanism of Action: SSRI (selectively blocks neuronal reuptake of serotonin which increases the concentration of 5HT
Prozac (Fluoxetine)
Approved Therapeutic use:
Approved Therapeutic use: Depression, bipolar, OCD, panic disorder, bulimia nervosa, and premenstrual dysphoric disorder
Prozac (Fluoxetine)
Off label therapeutic use:
Off label therapeutic use: social phobia, generalized anxiety disorder, PTSD
Prozac (Fluoxetine)
pharmacokinetics:
pharmacokinetics: hepatic metabolism by CYP2D6, half life of 2 days
Prozac (Fluoxetine)
Adverse Effects:
Adverse Effects: Sexual dysfunction, weight gain, serotonin syndrome, during pregnancy causes NAS and PPHN, overall low risk for teratogenicity
Prozac (Fluoxetine)
Important Drug reactions:
Important Drug reactions: MAOIs, tricyclic antidepressants, lithium, antiplatelet drugs, and anticoagulants.
Prozac (Fluoxetine)
Availability:
Availability: 20/5mL liquid, 10, 20, 60 mg tablets, 90 mg delayed release, 10, 20, 40 mg capsules
Prozac (Fluoxetine)
Initial dose:
Initial dose: 20 mg
Prozac (Fluoxetine)
Maintenance dose:
Maintenance dose: 20-80
Prozac (Fluoxetine)
Approach to discontinuing:
Approach to discontinuing: taper over 1-3 weeks
Prozac (Fluoxetine)
Approach to switching meds:
Approach to switching meds: takes 4 weeks to get out of system
Venlafaxine (Effexor)
Mechanism of action
Inhibits the reuptake of both serotonin and norepinephrine
Venlafaxine (Effexor)
Approved therapeutic use:
major depression, generalized anxiety disorder, social anxiety disorder, and panic disorder
Venlafaxine (Effexor)
Off label use:
ADHD, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prevention, PTSD< OCD, premenstrual dysphoric disorder
Venlafaxine (Effexor)
pharmacokinetics
Processed through the liver with a half life of 5 hours for the drug and 11 hours for the metabolite
Venlafaxine (Effexor)
Adverse effects:
Nausea, headache, anorexia, nervousness, sweating, somnolence, and insomnia, dose related sustained diastolic hypertension, and sexual dysfunction. Neonatal withdrawal syndrome
Venlafaxine (Effexor)
Important drug reactions
hyponatremia with diuretics, MAOI contraindicated
Venlafaxine (Effexor)
Availability
25, 37,.5, 50, 75, 100 mg tablets
- 5, 75, 150, 225 mg extended release tablets
- 5, 75, 150 mg extended release capsules
Venlafaxine (Effexor)
Initial dosing
37.5 mg-75 mg
Venlafaxine (Effexor)
Maintenance dosing
75 mg-375 mg
Venlafaxine (Effexor)
Discontinuing:
Taper over 2-4 weeks
Venlafaxine (Effexor)
Switching
MAOI should be discontinued at least 14 days prior to starting Venlafaxine. Venlafaxine should be discontinued 7 days prior before starting the MAOI
What are the four SNRIs?
Venlafaxine (effexor), Desvenlafxine (Pristiq), Duloxetine (cymbalta), Milnacipran (Savella)
What are the signs and symptoms of serotonin syndrome?
It begins 2-72 hours after treatment onset and include altered mental status (agitation, confusion, disorientation, anxiety, hallucinations, poor concentration), incoordination, myoclonus, hyperreflexia, excessive sweating, tremor and fever.
Bupropion (Wellbutrin, Zyban)
Mechanism of action
inhibits the reuptake of both dopamine and norepinephrine
Bupropion (Wellbutrin, Zyban)
Approved therapeutic use:
Major depression, seasonal affect disorder, and smoking cessation
Bupropion (Wellbutrin, Zyban)
Off label use:
neuropathic pain, depressive episodes in bipolar, management of ADHD
Bupropion (Wellbutrin, Zyban)
Pharmacokinetics:
hepatic metabolism primarily by CYP2B6 and half life 8-24 hours
Bupropion (Wellbutrin, Zyban)
Adverse Reactions:
agitation, headache, dry mouth, constipation, weight loss, GI upset, dizziness, tremor, insomnia, blurred vision, and tachycardia. SEIZURES, do not use in patients with psychotic disorders
Bupropion (Wellbutrin, Zyban)
Important drug reactions:
Do not combine with sertraline, fluoxetine, paroxetine or MAOIs
Bupropion (Wellbutrin, Zyban)
Initial dosing
200 mg
Bupropion (Wellbutrin, Zyban)
Maintenance dosing
300-450 mg
Bupropion (Wellbutrin, Zyban)
Discontinuing:
Taper over 1-2 weeks
Bupropion (Wellbutrin, Zyban)
Switching
Stop MAOIs at least 2 weeks prior to starting bupropion
Bupropion (Wellbutrin, Zyban)
Switching
Stop MAOIs at least 2 weeks prior to starting bupropion
Trazadone
Mechanism of action
At moderate to high doses it is a 5HT2A/5HT2C antagonism with SERT and at low doses it is a 5HT2A antagonist, H1 histaminic and alpha 1 adrenergic receptors
Trazadone
Approved therapeutic actions
at moderate to high doses it is an antidepressant. At low doses it is for insomnia
Trazadone
Availability
50, 100, 150, 300 mg tablets
150 and 300 mg XR
Trazadone
initial dosing
200 OR 150 XR
Trazadone maintenance dosing
150-600 OR 150-375 XR
Trazadone
Adverse Effects
daytime grogginess and postural hypotension
Phenelzine (Nardil)
Mechanism of Action
Irreversible enzyme inhibitors of Monoamine Oxidase (Increasing 5HT, NE, and DA)
Phenelzine (Nardil)
Approved therapeutic use:
Depression
Phenelzine (Nardil)
Off label uses
treatment-resistant depression, panic disorder, obsessive-compulsive disorder, and social anxiety disorder
Phenelzine (Nardil)
Adverse Reactions
Central nervous system stimulation (anxiety, insomnia, agitation, hypomania, mania), Orthostatic hypotension, hypertensive crisis from dietary tyramine
Phenelzine (Nardil)
Important drug reactions
Indirect-acting sympathomimetic agents, epinephrine, NE, and dopamine, tricyclic antidepressants, SSRIs, antihypertensives
What types of food have tyramine?
avocados, anything fermented or over ripe, figs, bananas, aged, smoked meats, liver, spoiled meats, dried, cured fish, all cheeses, yeast, beers, wine, shrimp paste, soy sauce
Phenelzine (Nardil)
Availability
15 mg tablets
Phenelzine (Nardil)
Initial dosing
45 mg
Phenelzine (Nardil)
Maintenance dosing
60-90 mg
Phenelzine (Nardil)
Discontinuing
taper
Phenelzine (Nardil)
Switching
at least 14 days before switching to a different medication
Imipramine (Tofranil)
Mechanism of Action
Block both serotonin and norepinephrine reuptake and have antagonist actions at 5HT2A and 5HT2C
Imipramine (Tofranil)
Adverse reaction
Agitation, insomnia, diaphroesisanticholinergic, sedation, hypotension, seizure toxicity, CARDIAC toxicity, weight gain and sexual dysfunction
Imipramine (Tofranil)
Availability
10, 25, 50 mg tablets
75, 100, 125, 150 mg tablets
Imipramine (Tofranil)
Initial dose:
25-50 mg
Imipramine (Tofranil)
Maintenance dose
100-200 mgs
Imipramine (Tofranil)
Approved therapeutic uses:
Depression
Imipramine (Tofranil)
Off label uses
neuropathic pain, chronic insomnia, ADHD, panic disorder, OCD
Imipramine (Tofranil)
Important drug reactions
MAOI, direct acting sympathomimetic drugs (epinephrine, dopamine), indirect acting sympathomimetic drugs (ephedrine and amphetamine), anticholinergic agents, CNS system depressants (alcohol, antihistamines, opioids, and barbiturates)
Imipramine (Tofranil)
discontinuing
taper
Imipramine (Tofranil) switching
half life is 19 hours (out of system in 3-5 days)
