How clients conceptualize disorders

Medical Model accepted, “disease” is external

Symptoms more related to personal qualities and
behaviors (“it’s my fault”)
Symptoms response to crisis (“The stress got me”)
Symptoms signs of special powers (“God has chosen
me”)
Symptoms a punishment (“God hates me”)
Treatment is an attack (“Psychiatry is evil”)
Dealing with client understanings of
disorder (intrapsychic perspective)
Find out how your clients prefer to understand their
symptoms
Explore what the client gains from their preference
Explore how possible the client’s explanation is
Decide if you need to focus on their explanation (as an
intervention)
Irrational Beliefs & Common Compliance Problems
(based in antidepressants but applicable to other categories)
“The medication won’t work”
“I should feel better right away”
“My condition is incurable”
“Medication as evidence of defect”
Misinformation
Stopping for wrong reasons and not alerting the
prescribing professional
Supervision Issues
What do you want most out of supervision regarding
medication?
What do you need most?
Who is best situated to answer the latter?
Assessment, monitoring, and advocacy
DSM-5: Depressive Disorders
Disruptive Mood Dysregulation Disorder
Major Depressive Disorder, Single Episode
Major Depressive Disorder, Recurrent
Persistent Depressive Disorder (Dysthymic Disorder)
Premenstrual Dysphoric Disorder
Substance-Induced Depressive Disorder
Depressive Disorder Asso. w/ medical condition
Depressive Disorder NES
Vegetative Symptoms of Depression
Sleep disturbance (early morning waking, frequent
awakening, occasional hypersomnia)
Appetite disturbance (decreased or increased with
accompanying weight fluctuation)
Fatigue
Decreased sex drive
Restlessness, agitation, or psychomotor retardation
Diurnal variations in mood (usually feeling worse in the
morning)
Impaired concentration and forgetfulness
Pronounced anhedonia
The Double Blind, Placebo Controlled, multi-site litmus test
Categorical psychiatry
Linford Rees (1955)
Contergen (thalidomide, 1957)
Kefauver-Harris Drug amendments (1962)
Paul Leber (1980)
Dependent measures
Diagnosis, Drugs, & Dep. Measures
Diagnosis

Medication Symptoms

Measures
Categorical Psychiatry and Psychopharmacology:
Who’s on first?
Antidepressant Medications are used to tx:
Major Depressive Disorder
Obsessive Compulsive Disorder
Social Phobia
PTSD
PMDD
Other off-label uses
Other Problems
Other drugs used for depression
Opioids
Antipsychotics
Stimulants
The placebo response
The definition of disease
Evidence from studies of exercise and talk therapy
The Dalai Lama problem
History 101: Who discovered
Antidepressants?
1868 Graebe & Liebermann and Methylene Blue
1930s Daniel Bovet and antihistamines
1939 Benadryl, Malaria and Paul Charpentier
1942 WWII surgeons hypothesize link between
surgery & histamine release
1949 Henri Laborit and the pre-surgery cocktail
1950 Paul Charpentier and chlorpromazine
History 101 cont…
Jean Delay & Pierre Deniker
In 1952, published the first articles on
chlorpromazine/ Thorazine (antipsychotic)
During this period, mechanisms of action for
chlorpromazine were unknown
History 101 cont…
Nathan Kline
Popularized MAO inhibitors for their antidepressant
properties (Baumeister, Hawkins, & Uzelac, 2003)
Used an antitubercular drug, iproniazid/Marsilid, as an
antidepressant

Roland Kuhn
Began work with tricyclic antidepressants in Europe about
the same time MAO inhibitors were developing in United
States
Thought tricyclics worked similarly to MAO inhibitors
History 101 Continued
Delay, Lehmann and isoniazid
Nathan Kline and Iproniazid
Geigy, Kuhn and Imipramine
Lehmann and Kuhn

So who discovered antidepressants?

Medical Model Theories of Depression &
Antidepressants
Amine Theory
Permissive Theory
Downregulation
Imidazoline Receptor Theory
Neuroendocrine Theory
Substance “P”
Molecular and Cellular Theory
Duman, Heninger, & Nestler, 1997
Increased NT leads to downregulation
Increased NT causes increased cAMP
Increased cAMP leads to more neurotrophic factors
Although receptors downregulate, levels of cAMP and
neurotrophins remain elevated
Recent Theories
The idea that different subtypes of depression may be
better treated with different antidepressants has yet to
be supported (Stein, Lerer, Stahl, Evidence-based
psychpharmacology)
“No antidepressant agent of any class has
demonstrated clear superiority in the tx of this illness”
(Stein, Lerer, Stahl op cit)
Recent Theories
There is a chance that antidepressants can trigger
changes that lead to epigenetic adjustments (e.g.
changes in gene expression within the potential of the
genome in question).
This theory remains on the table until we more clearly
understand the genetic components of MDD.
Latest Studies
34,549 patients had their DNA analyzed by 86
researchers (and loads of computers) to pinpoint
anomalies related to depression
In 17 studies the results failed to show genetic factors
associated with specific symptoms.
MAO Inhibitors
More History
Disable MAO
Irreversible Binding
Side Effects
Tyramine Intolerance
Response Rates
Reversible Inhibitors of MAO
MAOIs: Side Effects
Orthostatic Hypotension
Nightime insomnia
Headache
Muscle Cramps
Weight Gain
Difficulty Urinating
Tyramine Intolerance
Contraindications
History of liver disease
History of heart disease
Other drug use/abuse
Hypertension
Tyramine consumption
Clinical Uses
Depression
Social Phobia
Migraines
Dermatitis
Agoraphobia
Borderline Personality Disorder
Panic Disorder
New Material
Marplan (iscarboxazid) reformulated but no more
effective than Parnate or Nardil (generic now)
Tricyclic Antidepressants
Response Rates
Acetylcholinesterase Theory
Julius Axelrod
Downregulation Theory
Side Effects
Drug/Drug Interactions
Mechanisms of Action
Block reuptake transporter
molecule (mostly NE)
Downregulation
Ripple effects on other NT systems
Also block DA, Histamine, and
Ach reuptake
Drawbacks of TCAs
onset of action may be slower for
sumbunall clients
difficult side effects for some clients
overdose potential (cardiotoxicity)
unreliable effectiveness from client to
client
Not effective in children (and can be
dangerous)
Advantages to TCAs
No documented withdrawal
Well documented medication
re: interactions, mechanisms,
and metabolism
Contraindications
Cardiac Abnormalities
MAOI Therapy
Metabolic problems related
to illness or age
Alcohol Use
Specific NE reuptake inhibitors
Reboxetine (Vestra, Edronax)
By Upjohn
Blocks transporter responsible for reuptake
Fewer side effects (cleaner) than TCAs
Does not seem to be cardiotoxic
As effective as Prozac generally, more effective in
patients with severe depression
New Material
Silenor (doxepin)
Used for sleep (http://www.silenor.com/)
Sometimes for depression but no better than generic
version
1 month supply of Silenor $214
1 month supply of generic $4
 Derivative TCA Antidepressants
usually made from metabolites
fewer side effects
May have better efficacy and
faster onset
Examples of TCA Derivatives
Desipramine (from
Imipramine)
Nortriptyline (from
Amitriptyline)
Amoxapine (from
protriptyline)
Examples of Medications Increasing TCA
Plasma Levels
SSRIs
Ritalin
Antabuse
Examples of Medications Decreasing TCA
Plasma Levels
Nicotine
Tegretol
Barbiturates
FDA Approved Uses for TCAs
Major Depressive Disorder
Anxiety
Childhood Enuresis
Off-Label Uses for TCAs
Insomnia
Panic Disorder
OCD
PTSD
Fibromyalgia
GAD
Chronic Pain
Bulimia
SSRIs: Selective Serotonin Reuptake
Inhibitors
Available since the mid 1980s
Mechanism of action is blocking presynaptic
transporter for serotonin reuptake.
Available in multiple fomulations and brands
Have documented withdrawal associated with them
SSRI Withdrawal
Serotonin Reuptake Inhibitor Discontinuation
Syndrome (Schatzberg, et al., 1997)
Dizziness
GI upset
Lethargy
Fatigue
Chills
Parasthesia (prickling or burning sensation)
Insomnia
SSRI Brand Names (from most to least toxic in overdose)

Celexa (citralopram) possible lengthening of QTc

interval
Luvox (fluvoxamine)
Celexa
Lexapro (escitalopram - metabolite of Celexa)
Paxil (paroxetine)
Zoloft (sertraline)
Prozac/Serafem (fluoxetine)
SSRI Indications: FDA Approved
Major Depressive Disorder
Obsessive Compulsive Disorders
Dysthymia
Bulimia
Panic Disorder
Social Phobia
Post Traumatic Stress Disorder
SSRI Uses” Off-label
Autism
ADHD
Borderline Personality Disorder
Premature ejaculation
Bulimia
Chronic Pain
Others
AISD Side Effects
Anorgasmia
Delayed Ejaculation
Decreased Libido
Impotence
Tx of AISD Side Effects
Bupropion Augmentation
Switch to Bupropion
BuSpar Augmentation
Trazodone Augmentation
Amantadine Augmentation (for EPS side effects from
Neuroleptics
Augmentation strategies mixed in literature
Sildenefil
New Material
Viibyrd (vilazodone)
https://www.viibryd.com/?guid=PPC|G|1&mkwid=srf
YJv9BR|pcrid|31745878287|pkw|viibryd|pmt|e|pdv|c|3
38p3k11877
|
SSRI plus 5-HT-1a partial agonist (partial efficacy at
receptor)
As good as SSRI’s
New Material
Oleptro (Trazodone extended release)
http://www.oleptro.com/
Trazodone generic used as sleep aid (non-addictive)
and this new formulation causes sleepiness, nausea
and dizziness as side effect.
Selling of Depression: Part II
Targeting Females
“Yes Virginia, you can have it all.”
http://www.wnd.com/2013/01/top-psychiatrist-meds-b
ehind-school-massacres/
(Mozilla)

http://www.youtube.com/watch?v=m7rbUdp_XIE

http://www.youtube.com/watch?v=5bu1uApqIr4 (640)
http://www.youtube.com/watch?v=nNBvL920Zaw
(minds or manuals?)
Scientology doc http://
www.youtube.com/watch?v=II96QkZaz1E
Dual-Acting & Other Antidepressants
Bupropion
NE and DA reuptake inhibitor
(NDRI)
Exerts cocaine-like action without
inducing dependency
Wellbutrin & Zyban
Acts as a “prodrug” or “precursor
Bupropion
Anabolic process
Active metabolite
hydroxybupropion
Metabolite mediates
antidepressant effect
Bupropion Contraindications
Seizure Disorder
Head Injury
Anorexia
Bulimia
Bupropion Side Effect Profile
Slight risk of seizure
No AISD
No cholinergic side effects
No orthostatic hypotension
Serotonin Norepinephrine Reuptake
Inhibitors
Effexor
Good in melancholic patients
effective w/ chronic pain
effective with ADD
Effexor Side Effects
May cause more nausea
Some treatment emergent
hypertension
monitor blood pressure first 2
months of tx
Desvenlafaxine/Prestiq
Metabolite of Venlafaxine (Effexor)
Produced in Wyeth’s Puerto Rico facility (?)
Very similar to Effexor but has on-label approval for
menopause symptoms
Serotonin Norepinephrine Reuptake
Inhibitors (SNRI)
Cymbalta (duloxetine)
Marketing for chronic pain (Depression Hurts)
 Many cases of depression may have been caused by fibromyalgia
Also on-label for generalized anxiety
Side Effects:
 Nausea
 Drowsiness, dizziness, headache

 Weight gain

 Anxiety, increased sweating

 Sore throat

 AISD
 5-HT2 Antagonist/Reuptake Inhibitors
(SARIs): Anxiety & Depression
Trazodone
5-HT2 antagonist
5-HT reuptake inhibitor
blocks adrenergic receptors
blocks histaminic receptors
5-HT2 Antagonist/Reuptake Inhibitors
(SARIs)
Nefazodone: designed to improve the
side effect profile of Trazodone
Associated with liver failure (1 in 250,000)
and taken off Canadian market in 2003
and U.S. in 2004.
Bristol-Myers-Squibb insists the
medication was pulled due to declining
sales, not lethal side-effects.
Oddly generic formulations can still be
found.
Mirtazapine (Remeron)
Introduced in 1997
NE and 5-HT receptor antagonist
Blocks autoreceptors
Also blocks postsynaptic 5-HT receptors
Also blocks histamine receptors
Causes more 5-HT and NE to be available at the
synapse.
Ketamine
Used as anesthesia for about 40 years
 N-methyl-D-aspartate (NMDA/Glutamate) receptor
antagonist
NMDA receptors affect memory and cellular plasticity
Seems like a promising tx but irrational stigma
(Calvinistic Pharmacology) holding back the research.
Right now IV infusion leads to improvement in hours
that lasts for days. Problem is making an extended
release version and decreasing abuse potential.
Antidepressants: Updates
SSRIs and breastfeeding
Paxil and Tourette’s
Sertraline for OCD in children
The mysterious “substance p”
Antidepressants and Children
MAOIs: Little efficacy
TCAs: Little efficacy
SSRIs: Questionable efficacy
Guidelines for use of ADs in children
• Counseling
• Education model
• Parents
• Rating Scales
• Timelines
Antidepressants and the Elderly
Poor epidemiologic data
Risk factors for depression
Problems with current studies
Age
Health
Level of Depression
Therapeutic Response