Psychopharm Midterm Flashcards
Cost of bringing typical psychotropic drug to market
$1-2 billion
Time it takes a promising drug to be approved by the FDA
20 years
In order for a drug to be approved for a psychiatric condition, it must demonstrate safety and efficacy in ___ or more randomized placebo controlled trials regardless of the size of the study
2
- can have many failed trails and still get drug approved with 2 successful trials
- trials usually made up of young, healthy, etc. participants
FDA’s primary duty is to ______
Protect the public safety
Including: drug/food/cosmetic labels are accurate and drug is being used for/prescribed for given indication
Most commonly prescribed drug = ?
ADMs
The Split Model
Advantages:
Keeps psychotherapy focused on psychological issues.
Helps manage transference issues
Allows at least 2 observers to have input
May be superior to tx w/ different experts handling different aspects of care
May reduce cost
Disadvantages:
May undermine one modality of tx
May exacerbate splitting (e.g. w/ individual w/ BPD)
May retard integration through the dichotomy
May lead to a diffusion of responsibility (e.g. problematic if therapist thinks it’s prescribers job to handle meds only and don’t communicate when you see something that may be of concern and vice versa)
May be more expensive
Requires more work; communication
Possible patient responses to medication prescription/referral
Rejection
I’m too sick
This is a bio, not psych issue
I’m not in control
I’m cared for by powerful authority figures
It’s not my fault
I am one w/ my tx team as medication become a part of me
The medication = useful transitional object
Choosing a prescriber
Good working relationship (esp. regular communication)
Acceptance of role of psychotherapy
Clinically competent in psychopharm (won’t always be a psychiatrist, could be PCP or another med doctor)
Comfort w/ split tx
Personal style
How to:
Ask colleagues, university centers, ACNP/ACP, APA referral, phone book
At what points in time should you communicate with a psychopharmacologist?
At first consultation When pts condition changes acutely If the pt is significantly suicidal When a change in meds has occurred When there is a clinical question When there is significant splitting
Prescription privileges for psychologists offer what advantages (1) and what disadvantages (3)
Advantages:
Accessibility, esp. in rural areas
Disadvantages:
Can you feasibly train someone w/o medical background in 1-2 years?
Medicine is highly legislated
Malpractice issues
Define: Pharmacokinetics*
What the body does to the drug (to make use of it, then to eliminate it from the body). This includes the following processes: absorption, distribution, metabolism, and excretion.
Define: Absorption
the degree to which the drug is absorbed from the GI tract, affected by:
Solubility of the drug
Size of the drug
Presence of food in the GI tract
Will lessen presence of side effects such as nausea and vomiting
PH of the stomach
Blood flow in GI tract
Ex. taking antacids can impact absorption of drug
Define: Distribution
The degree to which a drug distributes itself throughout the body, affected by:
Membrane permeability
Plasma protein binding
Depot storage
Most drugs are lipophilic (love fat–chubby chasers)
Many drugs must be lipophilic to pass blood-brain barrier
Define: Metabolism*
Process by which the body transforms a drug to prepare it for removal. Process includes Phase I (liver oxidation) and Phase II (conjugation)
If there’s a liver issue, this can affect ability to break down drug → may need to avoid drugs, or reduce dose to accommodate
Define: Excretion
Removal of drug from the body, through urine (most commonly), as well as fecal and respiratory routes.
Define: Agonist*
Drug which binds to a receptor and thus change cellular actions; stimulatory effect of receptor
If a drug (e.g. Trazedone) affects serotonin receptors → activates receptors, “turns on the switch”
Define: Antagonist*
Drugs that block receptor and prevent the actions of an agonist → “turns off the switch”
Define: Potency*
Amount of drug required to produce maximal effects (e.g. high potency drugs require smaller amount of drug to produce desired effects, such as Haldol, Klonopin); high potency drugs are not more efficacious, just require lower dose
Receptor targets for psychiatric drugs
Monoamines (most antipsychotics and antidepressants work via these transporters)
- 5HT (serotonin)
- NE (norepinephrine)
- DA (dopamine)
Other: histamine, steroid, glutamate, ACH, hypocretin, benzo, NA channel, Ca channel
FDA approval of a drug means…
An “approved” product
A package insert → guides safe use, promotes effective tx, sets the marketing parameters
Phases of Drug Development*
Phase I: First human safety studies
Phase II: First proof of concept studies
Phase III: Large efficacy studies leading to FDA approval
Phase IV: Post marketing studies for new indications
Phase I
Small, short studies, usually 10-20 pts, usually done in young, healthy males (done primarily at university medical centers)
First studies in humans, focus on safety, explore pharmacokinetics, explore dosing ranges
End of Phase 1 assessment: is it safe? How is it excreted/metabolized? Is the formulation suitable? Do we have enough drug and resources to go forward?
Phase II
Evaluate safety and efficacy in a selected patient population(e.g. those w/ PTSD, schizophrenia, etc.)
Does for longer period of time - weeks or 1-2 months
Refine the dose and dosing regimes
Usually RCTs
Control group
Placebo control (required in US, vs. active control aka comparator drug, dose comparison, historic controls)
Goals:
Establish “proof of concept” - does it work as expected?
Evaluate relationship of dose to effect (i.e. dose response)
Refine the dosing and formulation
Evaluate the risk-benefit profile of the drug (FDA)
End of Phase 2 Assessment: is it safe enough to go on? Does it work as expected? Do we know the right dose? Is the formulation okay? Do we know how to measure results? Do we have enough drug to proceed? Is it good enough to go on?
Phase III
“Pivotal studies” → basis for drug approval
Larger, longer studies to establish safety and efficacy → 100s or 1000s of pts for weeks or years
Study designs usually randomized, controlled; fewer protocol exclusions (“real world setting”), confirm safety and efficacy, show statistical significance
Many pts, many sites, may be multinational
Usually really expensive
Likely to be audited
Will examine raw data
Need financial disclosure statements
End of Phase 3 Assessment: is it safe and effective? Is it good enough to market? Is the data good enough to support an approval? Can we manufacture enough drug? Pricing/distribution?
Phase IV
post-approval/post-marketing
May be required under FDAMA
Evaluate new topics, e.g. decreasing side effects, compliance aids, testing same drug for new reason
Compare to competitors to support advertising claims
Disease management
Study designs = randomized, controlled; observational, epidemiologic, post-marketing surveillance may explore new indications
How long do antidepressants take to work?
3-8 weeks; side effects may occur from day one
Are antidepressants addictive?
No, not addictive in traditional sense
True or False: Any effective antidepressant can induce mania
True
All current antidepressants work on ___, ___, or ____
Serotonin, Norepinephrine, or Dopamine
True or false: It is not difficult to show that a given antidepressant is superior to another in most patients
False. It is difficult to show superiority
Antidepressants are chosen by ____ more than efficacy
side effect profile
Most antidepressants also help what disorder? (Except for Bupropion)
Anxiety disorders
Which types of depression show better responses to which classes of medication or ECT
Atypical:
MAOIs> TCAs, antidepressant > ECT
Melancholic:
TCAs > SSRIs, ECT> antidepressants
Psychotic:
ECT > antidepressant , antidepressant + antipsychotic
Selective Serotonin Re-uptake Inhibitors (SSRIs)
Mechanism: Inhibit serotonin reuptake which results in more serotonin in the synapse.
Prototype = Fluoxetine (Prozac)
Uses: MDD, OCD, Social Anxiety, Panic, Premenstrual Dysphoric Disorder, PTSD, Bulimia
Common side effects: acute GI issues, headache, and insomnia
Long term side effects: sexual (low libido, delayed orgasm)
Overdose: vomiting, seizure; rarely lethal
Discontinuation/Withdrawal: dizziness and unusual sensations (most common)
