1. Psychotic disordersa. Defn: loss of contact w/ reality – can’t think, perceive, communicate behave correctlyb. Positive sx: delusion, hallucination, agitationc. Neg sx: dull affect, passive, anhedonia, amotivation

2. Disorders involving psychosis: a. Schizo (all 3 subtypes)b. Mood disorders w/ psychosis (bipolar, MDD)c. Delusional disorderd. Brief psychotic disordere. Psychosis from medical conditionf. d/t sub abuse

3. Chlorpromazine – initially surgical anesthetic, reduces psychotic sx4. Typical Antipsychotics – block D2 receptors in the mesolimbic sys to lower psychotic sx

a. GENERAL FACTS FOR Typical Antipsychotics: i. Good oral use

ii. Daily dosing works welliii. DON’T work well for negative symptoms

b. ALL Typical Antipsychotics CAUSE TARDIVE DYSKINESIA – abnormal involuntary movement, no tx

i. Who is at risk for TD? Old brain damaged female - length of tx is an absolute factor

Low potency: Medium potency High potency (MORE EPS)

Chlorpromazine Loxapine Fluphenazine (also come as depot injection)

Thioridazine Molindone Permitil

Mesoridazine Perphenazine Haloperidol (also come depot injection=long)

Thiothixene Pimozide

Trifluoperazine

c. High potency cause EPS: i. Parkinsonism

1. Pill-rolling tremor2. Cogwheeling/rigid3. Bradykinesia4. Posture imbalance5. Masked face6. Festinating gait7. Drooling

ii. Akathisia (can’t sit still)

iii. Dystonia (cramps)d. How to tx EPS?

i. Give anticholinergics (benztropine)i. Give antihistimines (diphenhydramine)

ii. B-blockers help w/ akathisiaiii. Benzos are good adjuncts too

e. LOW potency cause: i. Sedation

ii. Orthostatic hypotensioniii. Anticholinergic effects

5. Atypical Antipsychoticsa. Affect 5-HT and D2b. Fewer EPS or TD, but metabolic syndrome is more likelyc. Treat negative symptomsd. Aripiprazole

i. Oralii. 5-HT2A antag

iii. D2 partial agonistiv. NON sedatingv. NO WEIGHT GAIN

vi. Good for neg sxe. Asenapinef. Clozapine

i. “GOLD standard”ii. Treats:

1. REFRACTORY psychosis2. Neg sx3. No D2 effect4. No EPS, TD

iii. Sedatesiv. Orthostasisv. Weight gain

vi. Droolingvii. Constipation

viii. AGRANULOCYTOSIS1. CBC weekly to check status

g. Iloperidoneh. Lurasidonei. Olanzapine

i. Oral/IMii. Weight gain

iii. Dyslipidemia

iv. Metabolic syndromev. Sedation

vi. People stay on it bestj. Paliperidonek. Quetiapine

i. short actingii. low EPS

iii. long QT, sedationl. Risperidone

i. oral/IMii. EPS at high dose

iii. TDiv. weight gainv. sedation

vi. prolactin = galactorrheam. Ziprasidone

i. Oralii. low EPS

iii. NO WEIGHT GAINiv. long QT

DEPRESSION LECTURE

Major Depressive Disorder (MDD)

Need depressed mood and 4 of: anhedonia, weight change, sleep change, agitation, fatigue, guilt, focus change, thoughts of death/suicide (SIG:E:CAPS mnemonic)

Women, most have co-existing probs, many w/ recurring illness

HIGH SUICIDE RATE *** risk can INCREASE w/ treatment at first b/c they get energy with treatment to carry out their crazy self-terminating ideas. Mostly related to degree of hopelessness and not degree of depression

Dysthymia – depressed most of day or more often than not for 2 yrs, NO PSYCHOTIC SYMPTOMS

Need 2: lack of appetite, insomnia, fatigue, low self-esteem, can’t concentrate, hopelessness

Probs w/ tx? Only ¼ get tx, many don’t realize they are depressed, $$$, stigma

Why do people stop taking drugs for MDD? Side effects, “didn’t need it”, “feeling better”

Who will adhere? Well education on subject, people w/ fewer disabilities, fewer side effects c drug

Tx: Interpersonal therapy – relationship w/ therapist cures patient

CBT – helps them control pessimistic thinking

Psychodynamic tx – focus on developmental events and internal conflicts that stop them from success

Group therapy – get support from group members

How to decide what drug to give? - check fam hx to a drug, suicide risk, age. i.e. fluoxetine works for kids w/ MDD and OCD, Sertraline (Zoloft) for kids w/ OCD

SSRI’s are better than TCA or MAOI

TRIcYCLIC antidepressants

Secondary Amines Tertiary Amines Tetracyclic amines

Desipramine Amitriptyline – pain, migraines, sleep Maprotiline

Nortriptyline Clomipramine – OCD Amaxapine

Doxepin -Dermatology

Imipramine – kids, bedwetting, d/t NE effect

Toxicities w/ TCAs? Anticholinergic and arrhythmias (esp amitriptyline)

SSRI’s

Fluoxetine

Fluvoxamine

Paroxetine

Citalopram

Escitalopram

Sertraline

Side effects? Insomnia, HX, GI, sex dysfxn, anxious, P450 inhibitor serotonin syndrome when too high

Serotonin synd: N/confusion, hyperthermia, tremor, rigid, seizures, death

DO NOT USE SSRI for 2 wks after stopping a MAOI, and don’t use MAOI for 5 wks after fluoxetine

Also don’t abruptly stop SSRI’s b/c you get SSRI d/c syndrome – dizzy, lethargic, N/Hx, diarrhea

Atypical agents

Nefazodone

Venlafaxine –MDD, anxiety

Desvenlafaxine

Bupropion – don’t give if they have seizures or ETOH withdrawal, no sexual dysfunction

Trazodone – good for insomnia, bad for your weiner

Duloxetine – MDD, anxiety

Remeron (mirtazapine) – sedates and lowers appetite the higher the dose

MAOI – used for DTN w/ atypical features like hunger hypersomnia, etc or anxiety; You MUST lower the tyramine in their diet to prevent crisis

Orthostatic hypotension, can’t use w/ SSRI

Phenelzine

Tranylcypromine

Selegiline – low dose – only works in brain, at 6mg no diet restriction, at 9mg, diet restriction

Tx options not previously mentioned:

ECT – for MDD, bipolar, catatonia, acute episodes of psychosis

Especially good for DTN in Parkinson’s pts. Also works for old, preg women

Contraindications (tested): intracranial mass, recent stroke or MI

Side effects: retrograde/anterograde amnesia – resolves w/ time

90% response rate, better than drugs, but high maintenance to do (appts 3/wk and need 6 tx)

Vagal nerve stimulation

Transcranial magnetic stimulation

BIPOLAR LECTURE

General bipolar features: men, native American, younger = more prevalent , frequently recurs, hard to stabilize if they have frequent episodes, higher risk for CVA, violence, Sub abuse = high mortality, ½ attempt suicide

Bipolar I – need a manic but NOT depressive episode

Bipolar II – need hypomanic and depressive episode

Rapid cycling – 4+ episodes over course of a year

Mixed Epixodes – full onset of mania and depression at exact same time for at least a week

Cyclothymia – dysthymia and hypomania, but never meets full manic / depressive state

Manic episode – elevated mood for at least a week and 3x DIGFASTsx (see below)

Hypomanic episode – elevated for 4 days, change in function, but doesn’t require hospitilization

Distractibility, Insomnia, Grandiosity (fly), Flight of ideas, Activities, Speech, Thoughtlessness

What makes you think bipolar? When antidepressants fail, antianxiety drugs fail, behavior disruption

It is a good idea to use screening tools in your waiting room (questionaires)

Picking a drug? Hard to do

Lithium *DOC for maintenece, takes 6 weeks to work, lowers relapse risk. Better at regulating manic than depressive sx. Better for classic bipolar I or II than a mixed. Helps w/ aggression, ONLY ONE TO PREVENT SUICIDE. Dose BID. Need to check THYROID b/c it competes and gives you hypothyroid. Not as good in kids, but dosing for adults and kids is =

Side effects: renal prob, polydipsia/uria, tremors, hypothyroid, acne, hair loss (kids), pretty much anything except pulmonary symptoms.

If Li<2 – D/Vomit/drowsy, weak

If Li<3 – ataxia, large output of dilute urine

Li >3 – arrhythmia, siezures, come

Depakote(valproic acid) – DOC for mixed episodes and rapid cycling, kids start at lower dose HEPATOTOXIC, teratogen – neural tube, pancreatitis, rash, weight gain, CLOUDY thoughts

Carbamazepine –mixed episode and rapid cycling – induces self-metabolism (as dose inc, levels in blood drop)

***Stevens Johnson Syndrome – screen for HLA-B 1502, esp in asians

Oxcarbazepine – same but hyponatremia, don’t monitor blood levels, NO WEIGHT GAIN

Lamictal(lamotrigine) –MAINTENANCE for Bipolar, Acute bipolar DTN, don’t monitor blood levels, can add to Li, STEVEN jOHNSON syndrome, high risk for ASEPTIC MENINGITIS

Topiramate – blocks GABA reuptake, WEIGHT LOSS, add to bipolar tx

Atypical Antipsychotics – work for acute bipolar attacks and maintenece of DTN

Risperidone– bipolar acute mania

Zyprexa (olanzapine)– weight gain

Geodon(ziprasidone) – monitor QT, no weight gain, for bipolar manic

Seroquel (quetiapine)– depression assoc w/ bipolar, maintenance added to Li, sedation, low EPS

Aripiprazole – bipolar mania

Fluoxetine/olanzapine (symbyax) – for treatment resistant DTN

Addiction LECTURE

Defn: primary chronic dx of brain reward, motivation, mem. Pathologically pursuing reward/relief

Can’t abstain

Impaired behavior control

Don’t recognize signifigant probs

Dysfunctional emotional response

Addiction is progressive and can lead to death (Michael Jackson)

Unique features: personal responsibility involved in recovery. Pts need 3 things to recover. Self-management, mutual support, professional care.

Effective AA dose? 300 meetings. Detox doesn’t work (3% of time)

What to look for during treatment

- Compulsory external supervision – accountability- New friends- New love or habit- Deepening spirituality or group membership

AA does all 4 requirements

Spirituality is? Personal value system, your connection w/ yourself and others, your search for meaning

DEFN of ABUSE (not the same as addiction)

- NOT fulfilling role at work, school, etc- Physically hazardous situations- Legal probs

- Social/interpersonal probs

When a diagnosis of substance ABUSE is made, the treatment is EDUCATIONAL

- Pt is vulnerable to loss of control- Other substances may be used- Other behavior may emerge

When a diagnosis of ADDICTION has been made? Assess 6 dimensions using ASAM

- Put them inpt/outpt- Make treatment plan (for rest of their LIFE) (alcoholism not alcoholWASISM) - 6 dimensions: intox potential, medical condition, emotional /behavior condition, readiness to

change, relapse potential, recovery environment

3 causes of relapse: Drug exposure (even to other drug), stress exposure, cue-re-exposure

Trigger #1: Free drug – nucleus accumbens activated even if drug is not the one they are addicted to

REWARD_REINFORCEMENT CIRCUIT

Stage 1: stim from AntBedN-MedForeBundle to VTA Stage 2:DA stim from VTA to NA Stage 3 NA inhibits DA from VTA and enkephalinergic to VP and VTA

Addictive dopaminergic spike at the NA. from any of 8 addictive drugs. Naloxone blocks it

Ben, Barb, and Nick got Drunk(ETOH) by some poppies

Case: young laborer did cannabis when young. Got off it. Got hurt at work and rx was opioid. He got ENERGIZED FROM OPIOIDS (not normal, usually cause lethargy) and he got addicted to opioids.

PTS w/ addiction need a good H and P, a MULTI-AXIAL ASSESSMENT, then a ASAM tx (see above): addiction potential, medical cond, emotional/behav cond, readiness to change, relapse pot, recovery env

Naltrexone is a full opiate blocker

Suboxone – can use if they have pain (FYI partial Mu agonist, full kapp antagonist)

Nicotine detox: note that dopamine levels from taking nicotine spike like crazy. See below

TRIGGER #2

Stress exposure (via NE neurons from lateral tegmental area (LTA) to extended amygdala)

There is only 1 stressor that makes us want BOTH alcohol and opiates----------SOCIAL ISOLATION

TRIGGER #3

Cue-induced exposure: mediated by glutamatergic projections involving:

- Basolateral Amygdala to mPFC- mPFC to NA CORE***- Ventral subiculum of hippocampus to NA and mPFC (amplifies response)

-- You can give naltrexone for gambling. Remember casino and sex are cue-induced relapses- Blocks reward craving- Acamprosate is also for cue-induced relapse, GABAergic, blocks glutamate at NMDA – see below

-

-- Mu-opioid receptor activation inhibits: CRF production (stress NT) and ACTH production

Mechanism of action of Naltrexone follows:

- Blocks opiate receptors that modulate DA release in Nucleus accumbens- Promotes abstinence, and blocks cue-induced relapse, but not stress-induced relapse

- note purple “C”’s

Human Glucocorticoid Receptor (hGR)

hGRa: is the cortisol receptor

hGRb: inhibits action of hGRa

therefore, when hGRB’s effects are dominant, you get glucocorticoid resistance

CRF receptors do the same thing

CRF-1 is assoc w/ the behavior response to stress – and gives a drug reward = high stress

CRF-2 revereses increased anxiety-like behavior (good for stress control) note the purple blocks (naltrexone)

ANXIETY DISORDERS and EATING DISORDERS – not much, just look at slides? He had hardly any info

Social anxiety disorder – fear of being judged in public. They blush, tremble, palpations, hx,etc. they are afraid of being the unwated center of focus.

Often comorbid with MDD, bipolar, ETOH abuse, schizo, etc. often put on backburner b/c Dr.’s often treat the comorbid condition first.

Treatment: mainstay is SSRI, also CBT. Combined most effective

- High rate of relapse when drugs are d/c, best to combine drugs w/ therapy- MAOI, - side effects/food- Benzodiazepines - clonazepam- Propranolol- CBT- Individual psychotherapy

Specific Phobia – fear of any one thing (snakes, heights, school)

Treatment: behavioral therapy w/ exposure to feared stimulus + relaxation technique

- Flooding/implosion (flooding: put them into anxiety situation, throw them in the pool when they are afraid of swimming). Implosion is when you have them IMAGINE they are in a situation.)

- B-blockers- Benzos

Generalized anxiety disorder – worry about anything/everything. See muscle tension, irritable, must have sx for at least 6 months!

¼ develop panic disorder, ½ get depression

Treatment: stress management ****key

- Relaxation tx- CBT- Buspirone- Antidepressants (TCA, SSRI, SNRI)- Benzos (help w/ all anxiety disorders. Good for acute, but don’t do long term)

NON – Drug therapies

- Stop caffeine- Avoid ETOH- Exercise- Adequate sleep

Panic Disorder – discrete periods of intense terror 10-15 min w/o warning or precipitation

“panic attack”, they think they are dying

- Strong Fam history relation

- Female, early adult- Suicide risk- Often abuse alcohol to avoid having a panic attack

3 C’s

Chest pain Chills choking

Treatment – CBT, behavior tx

- SSRI often first line- TCA- SNRI- Benzos

OCD -------obsessions (recurrent, persistant things in the mind, person recognizes they produce them)

-------------compulsions (counting, checking,etc that is excessive or unreasonable)

- Often have DEPRESSION- Avoid situations that will “show off” their sx in public - like won’t

Treatment:

- CBT (best for long term response)- Clomipramine (TCA) (drugs are best for short term response)- Sertraline (SSRI)- Paroxetine- Fluvoxamine- Fluoxetine

PTSD – have traumatic event outside normal human experience, they re-experience it via flashbacks/nightmares or distress w/ something reminds them of their experience

- Often are avoidant- Can have amnesia, or act detached- Hyperarousal – cant concentrate, sleep, irritable, startle easy- Need symptoms for at least ONE MONTH (differentiates from acute stress disorder)

Treatment: Psychotherapy (CBT, exposure, EMDR – eye movement desensitization and reprocessing)

- Family support is key- Benzos for hyperarousal- TCA/SSRI

- B-blockers- Valproic acid – mood stabilizer & works great

Acute stress disorder- PTSD but sx are under a month. Lasts between 2 days – 4 wks

- Treatment- Same, but can add a sleep agent (zolpidem, etc)

Eating disorders – no gold standard, multidisciplinary treatment

Anorexia

First step w/ treating anorexia is return to target weight

May need to admit

Treatment: individual therapy – often very difficult to change, very long term

- Family therapy is very helpful- Group therapy – creative arts are very useful (horses, art, movement)- CBT – need to learn how to maintain a healthy body weight- May need antipsychotic low dose- Important to communicate w/ other providers is key

Few studies for med use – vitamins/hormones/ECT not been proved beneficial yet

Can try: SSRI – bupropion – lower seizure threshold, be careful w/ eating disorder

- Anxiolytic – not good long term- 10% can die from this disorder

Bulemia

- Multidisciplinary approach- Family is key- Fluoxetine is approved by FDA

Treatment – behavioral therapy

- Group therapy- Nutritional counseling- Imipramine

desipramine – reduces bulimic symptoms12 step programs are benificial