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Psychiatry Psychiatry The Study Aid Yet another

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					Psychiatry, The Study Aid
Yet another Chart by Ben

September 11, 2002, Psychiatry, Disorders of Cognition

Dementia and delirium
-Some of the most difficult disorders to diagnose
-Neuropsychological testing is expensive, mandates well trained experts
-1,000 unaware that they are cognitively impaired
-Conditions are often reversible
-Primary care clinicians do need to perform an MSE on all patients, follow mental decline, and justify drugs to prevent further damage
-Fulstein: 6-7 item test to evaluate depression
-MDQ: Mood disorder questionnaire . Checks for bipolar disorder. Reliable. This test will find almost all bipolar patients.
-Remember the manics that get anti-depressants: VROOM ZOOM ZOOM, off to the rubber motel room
-Behavior has an organic substrate
-Separate delirium vs. dementia

DELIRIUM                                                                               DEMENTIA
Acute disorder, rarely insidious                                                       Insidious and rarely acute
Fluctuating consciousness                                                              Stable LOC
Reduced attention, goal directed behavior                                              Multiple cognitive deficits in memory and aphasia, motor apraxias
Reversible                                                                             Generally not reversible
Hallucinations typical                                                                 No hallucinations
Impaired orientation                                                                   Impaired orientation
                                                                                       **In severe dementia, hallucinations can occur this event often results in
                                                                                       patient seeking attention from primary care providers
Incoherent speech                                                                      Paucity of speech
Disorganized thought                                                                   Poverty of thought

Dementia and its subtypes

Vascular                Multi-infarct type, small lesions with corticular damage. Motor function is good but cognition is impaired dramatically. MRI and CT shows
Dementia                evidence of damage. Problems with memory, aphasia, apraxia, agnosia, executive function. Step like decline in function. Decline from previous
                        level. Focal neurologic signs.
Alzheimer’s             Must r/o all other dementias to diagnose. Can occur with delirium, psychosis, and mood disorders. Gradual onset and continued mental decline.
Dementia                Memory, aphasia, apraxia, agnosia, executive function impairment. Prevent unnecessary mental decline using the Fulstein test to get an early ddx
                        of exclusion. Gradual onset and continue decline. R/O everything!
Dementia, other       Patients have memory, aphasia, apraxia, agnosia, similar signs. Decline from previous level of functioning. Clear evidence of etiology like:
causes                Vitamin B-12 decrease, r/o with Schilling’s Test
                      HIV in younger patients
Dementia, most        Alcohol related. Family will often relate finding. Dementia from primary or secondary brain neoplasms, trauma, post-anoxia., HIV, Parkinson’s,
common                multiple sclerosis.

DELIRIUM
-Several subtypes including: substance abuse, psychoactive agents, lyte abnormalities, medications, renal failure. Often clear etiologies.
-Most always associated with psychoactive medications
-Drugs include the 7A’s:
          1. Antibiotics
          2. Anticholinergics
          3. Anticonvulsants
          4. Anti-inflammatory
          5. Analgesics
          6. Antiparkinsonian agents
          7. Anti-arrhythmic drugs (cardiac drugs like Digoxin, Quinine)
-Sedative/hypnotics also implicated.
-DT also seen in alcohol withdrawal
-Lithium is a legendary cause of delirium
-Theophylline, cimetidine.

AMNESTIC DISORDERS
-Uncommon and unusual. Can’t lay down new short term memory
-Impaired functioning that is NOT due to delirium or dementia (talk about a diagnosis of double exclusion!)
-Most common is alcohol induced (generally younger people)
-TGA/Transient Global Amnesia is the transient inability to learn new information, vascular or drug etiology

MOOD DISORDERS DUE TO GENERAL MEDICAL CONDITION:
-Doctors need to warn patients of possible problems. (Depression with accutaine)
-Previously clear mental status
-Etiologies are vast, can include: CNS, SLE, meds, endocrinopathies
-Heavy metal toxicity

PERSONALITY CHANGE DUE TO GENERAL MEDICAL CONDITION
-Personality change due to medical/neuro entity
-Labile (cries easily), disinhibited, aggressive, apathetic, paranoid
-Etiologies are MS, SLE, cancer, hypothyroidism, metals, catatonic disorder
-Hoover-Busy Syndrome Amygdala change with inappropriate sexual behavior
-Catatonia attributed to a medical or neurological entity (negativism, mutism, withdrawal)
-CNS, neuroleptic induced

POSTCONCUSSIONAL SYNDROME
-Investigational diagnosis. Motorcyclistsorgan donors. Note personality changes
-Hx of head trauma with 2 symptoms
-LOC>5 minutes
-Onset of seizures within 6 months
-Posttraumatic amnesia>12 h
-Cognitive deficit, depression, lability, irritability, vertigo, impulsivity, anxiety

FOLSTEIN EXAM
-Note how often the family jumps in to assist the pt on completion of questions
-Brief but useful screening tool
-Assessment of cognitive changes
-Documentation of severity
-Tracks changes in cognition

WORKUP
-HP, MSE, Lytes, CBC, LFT, RPR (syphilis), EEG, CT, MRI, blah
-EEG sensitive for delirium but NOT dementia
-Depression and dementia may co exist
-28 is age of onset for major depression in the US
-Cereuloplasmin: test to rule out Wilson’s disease

Psychotherapy, September 18th, 2002, Dr. Dan Shaw’s Notes from Last Year

Know the tables in chapter 17
Psychotherapy defined:
-psychological methods for tx of mental disorders/psych problems
-Any acceleration in growth of a human being as a person
-Multidimensional interpersonal (needs>1 person) Process designed to influence change in a person or group
-Occurs when a clinician and pt meet in a professional setting to help pt with problem. Verbal/nonverbal communication
-Dr/Pt relationship powerfully affects pt’s ability to heal and cope with illness. Effective therapy is more than just learning a technique

Psychotherapy
-The talking cure; reduction vs. elimination of s/s
-The brain itself is the target of psychotherapy
-Behavior thoughts and emotions derive from brain activity and have a multidimensional, neurochemical, and neurophysiologic basis
-The psychotherapies aim to alter brain patterning and function

Art and Science
-Eclecticism: therapists use many different forms of therapies available and mix and match

Different Views
-No psychology; only biography and autobiography
-“The care of the id by the odd”
-Nature vs. nurture
-Biological vs. psychological
-Rigorous proof of psychotherapy’s effectiveness does not exist

Biomedical vs. Biopsychosocial Model
-Physiologic and social variables are of secondary importance in the treatment process and the physician’s major efforts should be primarily, if not exclusively, focused
on the biologic aspects

BIOPSYCHOSOCIAL MODEL
-Most illness, is a biologic, psychological, and social phenomenon
-Biologic, psychological, and social variables influence the predisposition, onset, course, and outcome of most illnesses
-Which gives do more things to look at in terms of how patient can be helped.
-To evaluate/manage the psychosocial aspects of patients medical problems adequately, physicians must be able to establish and maintain therapeutic doctor-pt
relationship with many different patient types.
ROLE OF PSYCHIATRIST:
Psychiatrist is trained to recognize and manage the:
-potential interaction of medication and psychotherapy
-medical status as a cause of or result of psychiatric illness=comorbidity=med illness can lead to psych illness
PHYSICIAN TASKS IN PROVIDING PERSONAL CARE
-Make your patient comfortable!
-Establish a helping relationship, a therapeutic alliance
-Elicit necessary information to diagnose and manage patients medical and psychosocial problems
-Inform patients about diagnosis, negotiating a plan, and advising on management
-Counsel on health concerns and prevention of disease and disability
THERAPEUTIC RELATIONSHIP
-Reciprocal quality is the given and take. Emotional exchanges take place involving several means of communication:
-Nuances
-Subtleties
-Unspoken
Non verbal communication via body language and facial expressions, good doc learns to see beyond
LEARN TO OBSERVE
-Slide blown off
LEVELS OF COMMUNICATION
-Linguistic, paralinguistic, non-verbal
ATTENDING
The act of truly focusing on the other person. Involves consciously making ourselves aware of what the other person is saying and of what they are tying to
communicate to us.
SOLER
=Sit Squarely in relation to the patient
=Open: maintain and open position
=Lean slightly towards the patient
=E:Maintain reasonable eye contact with the patient
=Relax
KEY CONCEPTS OF A HELPING RELATIONSHIP
=Empathy is the depth of understanding on an emotional level
=Respect is belief in the person as an individual
=Warmth is caring and positive regard
=Genuiness is honesty, realness (pt must feel like they are talking to a human being)
PSYCHOTHERAPEUTIC APPROACHES TO PSYCHOPATHOLOGY
-Psychoanalysis, intensive psychoanalytically directed psychotherapy, and brief psychodynamic psychotherapy
PSYCHOANALYSIS
-Sigmund Freud credited with its inception: devised the psyche as composed of three elements, the ID, the EGO, and the SUPEREGO
-GOAL: Understanding of childhood conflicts and the consequences in adult life, childhood experiences can have an impact
-Transference neurosis: Re-experiencing of the conflicts in the relation to the analyst
-Free association: Sit on couch and talk away
-Resistance: What doc tries to sense when they are on the couch, patient defense mechanisms
-Interpretation: linking past to present is the goal of the doctor
-Rule of neutrality: analyst favors neither ID or superego
-Doc shouldn’t prefer to hear talk about sexuality over guilt or anger, even though doc may be personally more interested in one topic over another
-Rule of abstinence: analyst avoids emotional gratification; doc doesn’t want patient to feel better and think its all because of doctor’s interventions
-Countertransferrence: Doc can’t help with all of the patient’s problems because the doc has his own neuroses and own resistance issues. Can’t help patient who chases
cars naked if doc happens to do this too.
TREATMENT INDICATIONS:
-Indicated: obsessional disorders, conversion disorders, anxiety disorders, dysthymic disorders, moderately severe personality disorders
-Contraindicated: Major depression, schizophrenia, borderline personality disorder
INTENSIVE PSYCHOANALYTICALLY ORIENTED PSYCHOTHERAPY:
-Uses perspectives and tools of psychoanalysis
-Moderate goals vs. reworking of personality
-greater focus on current conflicts.


Emergency Psychiatry/Sleep Disorders, Dissociative Disorders. Dr. Lewis, September 25, 2002

-Differentiate between medical and functional illness
-4-20% patients referred inappropriately
-Reasons for premature referral:
         -Bias, disordered perception
         -Violence and self induced illness (of the patient)
-        -Frank ageism
ER Psych Interview:
-A misnomer. In an emergency, you probably shouldn’t be referring to a psychiatrist.
-Demonstrate control and stay focused
-Establish rapport and offer food and drink
-Laying on of the hands.
-Allow for appropriate cooling off time
-Medication is an option, but be careful probably better to make patient seem like they have control of the situation
-Don’t just push drugs into them
-Offer meds and ask their opinion
-Mutism: when patient refuses to talk; actually, this is generally a good reason for a psych referral. Condition is usually 100% psych based
KEYS TO MANAGEMENT OF VIOLENT PATIENT:
-Get patient to vent feelings
-Don’t reason with them
-Stay near door
-Offer foods, meds
-Admit feelings, always be within earshot of help
RAPID TRANQ:
-Historically, these pts were controlled by extreme measures
-Combination of powerful drugs and ECT
-Tranquilizers are used for the stabilization of aggression, agitation, restlessness, and psychomotor excitement
-Very safe for all diagnosis
-IV Haldol is a common ICU drug
NRT, NOVEL RAPID TRANQUILIZERS
-Olanazapine: ZYPREXA: Used as an initial oral loading dose
-Post initial dose, it is tapered for desired effect
-Risks and side effects include EPS signs/spontaneous motor activity initiated in the basal ganglia
-Zydis: New drug given in a rapid melt form. Patients cant hide the pill in their Cheek\
SIDE EFFECTS OF RT’s:
-Acute dystonic reactions
-Opisthonotos: acute/arching back spasm
-Torticollis: Contracted state of the neck muscles that causes sideways rotation, called wryneck
-Retrocollis: Spasm that affects the posterior neck muscles
-Laryngospasm
-Akathisia: Condition of motor restlessness in which there is a feeling of muscular quivering, an urge to constantly move about. Inability to sit still. Sometimes called
the thorazine shuffle.
-NMS: Neuroleptic Malignant Syndrome: A condition associated with RT’s characterized by fever, BP, tachypnea, altered LOC, diaphoresis and leukocytosis.
PHYSICAL RESTRAINT:
Safe and extremely effective, but frowned upon by the general public
Never threaten patient with restraint
-Contrary to popular belief, it does not destroy the therapeutic alliance
-Patients are usually grateful, since it is a way to treat psychosis without medications.
SUICIDAL PATIENT:
-Tough to identify
-Older patients more likely to attempt, females more likely to attempt, males more likely to succeed.
-Indicators of a dangerous and potentially successful plan include:
 Decreased likelihood of rescue
Lethality
Substance abuse
Prior family history
Prior hx of attempt
SUBSTANCE INTOXICATION:
Abuse of many substances can be associated with acute psychosis
-Alcohol, barbiturates, cocaine, amphetamines, phencyclidine, opiates
NOW ONTO SLEEP
-Disorders are a very common problem, very poorly understood
-Not merely a state of consciousness
ARCHITECTURE:
-Awake: On an EEG, characterized by random, fast, low voltage
-Non REM sleep: 75% is non REM, goes through stages
-Stage 1: Theta waves
-Stage 2: Characterized by sleep spindles, K complexes
-Stage ¾: Deep sleep, characterized by delta waves. You get less Stage ¾ sleep as you age many older patients may feel tired
-REM 25% is deep sleep
-REM latency is 90 minutes; usually takes 90 minutes from when you fall asleep to enter REM
EVALUATION:
Generally 3 chief complaints associated with sleep disorders
-Insomnia, Excessive Daytime Somnolence, Parasomnias
-Parasomnias include the weird disorders of: sleep apnea, sleep walking, etc
SLEEP HYGEINE HISTORY
-Circumstances associated with falling asleep, such as meals, exercise, noise, light, temp, drugs and medications
 -MSE: Conduct on all patients when diagnosing a sleep disorder
-PMH: another major factor
-Polysomnography: A sleep test lasting 3-4 hours

Inadequate sleep hygiene                                                               Circumstances not conductive to falling asleep
Insufficient sleep syndrome
Sleep apnea syndromes
Narcolepsy                                                                             Rare, genetic disorder when you fall asleep very quickly and enter REM in less
                                                                                       than 5-10 minutes. When this happens, you essentially get paralyzed. Not too
                                                                                       much of a problem when you’re not engaged in activities like driving, etc.
Nocturnal Myoclonus                                                                    Restless leg syndrome: Sudden twitching of muscles or parts of muscles, without
                                                                                       rhythm or pattern. Diagnosed by interviewing the patients bed partner

Genetic Disorder of REM latency                                                        Some people are prone to having prolonged/shortened REM latency
EDS naps                                                                               May be an indicator of a sleep disorder
Sleep paralysis (Cataplexy)                                                            Like narcolepsy
Hypnagogic and Hypnopomic Hallucinations                                               Usually auditory hallucinations heard immediately before falling asleep,
                                                                                       immediately before being fully awake.
Management of sleep disorders:                                                         Psychostimulants and anti-depressants

Nocturnal Myoclonus vs. Restless Leg Syndrome:
-In Restless leg, the patient is aware of the strange sensations
-In nocturnal myoclonus, the patient is not aware of his/her condition
-Medication can reduce rate of tremor and disruption

The Dissociative Disorders
-Disorders of consciousness, memory, identity, not related to an organic phenomenon
Dissociative amnesia           Inability to recall personal info; beyond normal forgetfulness. It is not a neurological disorder.
                               Localized: Cant remember something about a specific event or time
                               Generalized type: when you forget everything about an event
                               Continuous type: Forgetting things after an event
                               Mgmt: Benzo, SSRI, psychotherapy
Dissociative fugue             Person unexpectedly confused about their past, person may travel somewhere and assume a new identity. May last hours to days. Often
                               associated with severe stressor. Treat with hypnosis, psychotherapy, sedatives
Dissociative identity          Formerly known as MPD: 2 or more identities or personalities with distinct patterns of perception or thought. Patient is unaware of
disorder                       other personalities. Associated with abuse hx and comorbidities
Dossociative disorder          Trance disorder: Sudden alteration in consciousness, not accompanied by distinct alternative identities
NOS                            Possession Trance: Possession trance involves assumption of a distinct, alternative identity, usually that of a deity, ancestor, or spirit
                               Ganser’s Syndrome: Approximation syndrome. The giving of approximate answers to questions. 2+2=5, when not associated with
                               amnesia or fugue.
                               Recovered Memory Syndrome: Essentially discredited, this is when you magically remember some traumatic event from the past.
Depersonalization              Patient has an altered experience, feels detached, outside observer of body or mental processes.
disorder                       Comorbid with anxiety disorder
                               Often accompanied by derealization.
                               Things may seem strange, two dimensional, etc
                               Management: Often just resolves, psychotherapy / treat for anxiety.

From Psychology: psychopharmacology, October 23, 2002

A lengthy SSRI discussion

1) Getting better with SSRI?
-Measured in response and remission
-Response is a 50% reduction in Hamilton/Montgomery depression rating score
-Remission is a score on Hamilton of 7 or less
-SSRI does not push depression into remission very well
-We have given up some efficacy with SSRI, but we have gained a broad spectrum effect on anxiety, some activity on mood, and a lot of safety/ease of use
-SSRI good first line drugs
-#1 problem: sexual dysfunction up to 10% of patients. Delayed ejaculation and hindrance of female orgasm. Actual numbers may be higher.
-Insomnia, weight gain (Paxil is worst), GI distress (early on and time limited because there are lots of 5-HT receptors in gut), anxiety, agitation, prolactinemia,
cognition and apathy
-Poop out syndrome: efficacy failure over time; patient becomes resistant to the SSRI; may start to make him sick
-Short half life agents have bad withdrawal symptoms that go away after a few days- taper patients off of drugs.
-Paxil has an extremely short half life; Prozac takes weeks to remove from system
2) Apathetic recovery
-Mildly, chemically lobotomize patients on SSRI
-Physicians fail to see this: pt comes in depressed, SSRI therapy started, patient gets better. Pt returns in 3 months and cannot cry anymore, is not depressed anymore,
doesn’t cry at son’s own funeral, nothing is fun. Patient is NUMBED
-Many mistake the apathetic recovery for return of depression and the SSRI dose is increased patient gets worse
-How to distinguish between re-emergence of depression vs. apathetic recovery? Look at original notes and complaints
-Reduce dose of SSRI in apathetic patients

3) Dirty and Clean drugs
-An SNRI is dirtier than SSRI because it has more mechanisms of action
-TCAs have 14 mechanisms and are thus dirtier drugs
-SSRIs are clean due to single mechanism
-Dirtier drugs work better but with more side effects
-Cymbalta: new drug out in 6 to 8 months; tolerability better than SSRI. Dirtiness has been retained without problems of sexual dysfunction and weight gain and
discontinuation response.

DRUG/CLASS            MECH                                                                                           CLINICAL
SSRI                  Prevent reuptake of serotonin. Put a “chock in the wheel”of the reuptake transporter. Do       Major depression- 2 to 4 weeks
                      it through negative allosteric modulation- occurs at a site AWAY from actual transporter.      OCD: takes 10 to 12 weeks for down regulation,
                      Net effect is to shut the transporter off. Levels of serotonin rise dramatically. 30-60 mins   large doses required
                      for levels to rise. Latency of response with SRI; people take approx 2 to 4 weeks to down      PTSD: respond nicely to SSRI; work much better in
                      regulate. People don’t, “get happy fast”                                                       women
                                                                                                                     SAD: high predictive value. Must screen these
                                                                                                                     patients for bipolar disorder. Paxil or other
                                                                                                                     SSRI/anti depressant will make patient worse
                                                                                                                     PD: Respond nicely to SSRI; start patients at low
                                                                                                                     dose. Extreme sensitivity to serotonin levels. Sudden
                                                                                                                     rise may initially precipitate more panic.
                                                                                                                     Binging/purging: eating disorders probably related
                                                                                                                     to OCD; purging portion of behavior responses
                                                                                                                     very well to high dose SSRI therapy.
                                                                                                                     Agents work better for anxiety than depression.
                                                                                                                     Patients with depression do not get better as much
                                                                                                                     as those with anxiety
TCA’s                 Very dirty drug- effects NE, serotonin, dopamine. Nasty side effects, particularly             OCD patients: Anafranil
                      muscarinic. Patients fall down and have postural hypotension. Useless in psychosis,            PD
                      profound effects in mood.                                                                      ADVERSE/SE: May include weight gain, dizziness,
                      Number one drug found in blood of suicide victims                                              drowsiness, dry mouth, night sweats, body
                     Patients get better on TCA and SNRI probably because of NE uptake effects                  temperature.
                     Mild to moderately ill people would rather live with the disease                           If side effects aren’t occurring, then blood levels of
                                                                                                                drug are probably not high enough

Trazodone and        Newer, popular in the eighties because it had less side effects than the TCA.              Nefazodone: Improvement in mood, no sexual
Nefazodone           Mechanism of action was inhibition of serotonin II receptors; but does have some           dysfunction. Protecting the IIA receptor; may,
                     serotonin uptake effects.                                                                  however, cause hepatic failure. Dizziness and lots of
                     Companion drugs, developed at the same time>                                               sedation may occur. Tolerable and safe in case of
                                                                                                                overdose.
Venlafaxine          Yields excellent results. Drug is a selective neuroepinepherine reuptake inhibitor         Better results than older SSRIs
SNRI                 Drug is dirty at highest doses.                                                            Elevation of HR/BP at higher doses
                     Efficacy superior to SSRI and comparable to TCA                                            Dose escalation required to effect catecholamine
                                                                                                                release
                                                                                                                Drug is dirty at high doses and may cause nausea,
                                                                                                                sexual dysfunction and discontinuation syndrome.

NDRI                 Dopamine reuptake effects                                                                  Depression
Buproprion           Work in the frontal lobe                                                                   ADHD
                     Well tolerated but not as efficacious                                                      Cravings
                                                                                                                ADVERSE/SE: Agitation, GI distress, risk of
                                                                                                                seizures are 3-4 in 1000.
                                                                                                                Useless in anxiety
                                                                                                                Marginal in depression
Mirtasapine          Works only on receptors, serotonin II, III, and alpha II. Serotonin II activity helps      Improves mood
(Remeron)            irritable bowel syndrome, causes reduction of nausea.                                      No sexual dysfunction
                     Main mechanism for depression is its alpha II receptor antagonism- the alpha II receptor   Reliable sedation effect
                     is a brake receptor. Shutting it off INCREASES adrenergic flow.                            Lots of H1 activity, lots of weight gain and sedation,
                                                                                                                actually very helpful in kids with ADHD and
                                                                                                                geriatric depression.
                                                                                                                Safety is excellent, no one is able to kill themselves,
                                                                                                                but Histamine side effects mentioned are very bad
                                                                                                                and may be intolerable.

Psychopharmacology of select anti-depressants, depression overview


October 2, 2002, 1-3 pm, Frederick Lewis, DO
Depression overview
-10-25% of adults will suffer depression
-Rates are increasing
-Suicide is a major risk

Risk of recurrence
-Most depressed patients will have another episode
-50% after one, 70% after two, almost 90% after 3 episodes

Maintenance Treatment Considerations
-Very strongly recommended for 3 episodes of MDD
-Strongly recommended for 2 episodes of MDD
         1. + FMHX of bipolar disorder
         2. Hx of recurrence within 1 year after previously effective medication is discontinued
         3. Early onset of first depressive episode (before age 20)
         4. Both episodes severe, sudden, or life threatening in the past 3 years
-Symptomatic:                Isolated symptom
-Syndrome:                   Multiple S/S
-Pathophysiologic: Structural and chemical change
-Etiologic:                  Known causative factor

Several principles
#1:                  Pharmacology alone don’t cut it. Need case management, social services, vocational rehab, psychotherapy
#2:                  Phase of an illness is important in terms of the direction of tx. Phases are acute, relapse, recurrence
#3:                  Risk to benefit ratio must always be considered when developing a treatment strategy. Factors include comorbidities, medical status, age, economics
#4:                  Poor personal and family HX of tx response dictates tx of choice in subsequent episodes.
#5:                  Don’t reinvent the wheel . Monitor specific symptoms that serve as markers for underlying illness. Target their presence or absence during tx.
#6                   Observe for adverse effects throughout tx. Do mental status checks, PE, lab, therapeutic drug monitoring

SNRD vs. Depression
-Specific neurotransmitter regulation dysfunction:

Review of select drugs:
A-antagonistMirtazapine
Mechanism of action of all SSRI’s:
Blockade of serotonin transporter (receptor pump)
Down regulates 5HT-1a by increasing serotonin level in postsynaptic area and down regulates 5HT-1a at presynaptic area
Disinhibition of serotonin release
Secondary mechanisms of the SSRI’s:
Zoloft: Has dopamine reuptake inhibition activity, also a sigma-1 antagonist
Prozac: Has serotonin 5HT-2c receptor activity resulting in early weight loss
Luvox: Sigma 1 antagonist, least known about this drug, patients violent when rapidly withdrawn
Celexa: Unknown, but 5HT-2c receptor activity may be present. Perhaps responsible for weight gain, craving, sleeping
Paxil: muscarinic-cholinergic receptor activity. Nitric Oxide Synthetase (NOS) inhibition. Causes more weight gain and cognition impairments and basal ganglion
problems.


DRUG/CLASS         MECH                                                                EXAMPLE
SARI               Serotonin antagonist reuptake inhibitor                             Nefadozone, serzone
NDRI               Noradrenergic dopamine reuptake inhibitors                          Buproprion (wellbutrin)
                                                                                       -used for smoking cessation
                                                                                       -increases dopamine levels so you feel pleasurable, improvement in mood
SNRI               Serotonin norepinepherine reuptake inhibitors                       Venlafaxine (Effexor)
                                                                                       Sibutramine (meridian)
                                                                                       -used for weight loss by stimulating post synaptic 5HT-2c receptor
                                                                                       Duloxetine (cymbalta)
NASA               Noradrenergic antagonists, specific serotonin antagonists           Remeron, mirtazapine
NRI                Norepinepherine reuptake inhibitors                                 Atomoxetine (stritena)
                                                                                       -potent NRI
                                                                                       -failed for clinical use of depression
                                                                                       -approved for ADD
                                                                                       Reboxetine (vestra)
MAOI               Monoamine oxidase inhibitor                                         Nardil-causes hypotension
                                                                                       Parnate-tranylcypromine
                                                                                       Eldepryl (selegilene)
TCA                Tricyclic Antidepressant                                            TCA reflects on structure, not mechanism of action.
                                                                                       Tofranil (imipramine)
                                                                                       -tertiary amine
                                                                                       -many side effects, so secondary amines were developed
                                                                                       Norpramin (desipramine)
                                                                                       -less side effects
                                                                                       -weaker serotenergic effect
                                                                                       -more dopaminergic and noradrenergic effect
                                                                                       Surmontril (trimipramine)
SSRI               The mainstay. Reviewed many times, in many different lectures.      Prozac/Serafem (fluoxetine)
                    These prevent the reuptake of serotonin, thus making more of the   -Vitamin P
                    chemical available for the brain’s use. Used for PD, OCD,          -First antidepressant in the USA
                    depression, panic.                                                 -Effective for depression/anxiety
                                                                                       -effective for PMDD
                                                                                       Zoloft (sertraline)
                                                                                       -Already in active form, no S or R chirality
                                                                                       Paxil (Paroxetine)
                                                                                       -also already in active form- no need to choose between R and S forms.
                                                                                       -Most potent in shutting off the SS reuptake pump
                                                                                       -associated with weight gain
                                                                                       Luvox (Fluvoamine)
                                                                                       -Taken by and discontinued by the Columbine shooter
                                                                                       -pts become violent, hostile if discontinued
                                                                                       -approved for OCD
                                                                                       Celexa (citalopram)
                                                                                       -Only S form active at uptake site
                                                                                       -R form is worthless
                                                                                       -20 mg of lexapro=40 mg citalopram?

Many different serotonin receptors;
5-HT
1a       Depression, anxiety, panic, OCD
1b       Food intake, temp, erection
1c       Anxiety, depression, pain
1d       Migraine
2        Depression, psychosis, sleep
2c       Appetite, psychosis, lose cognition but you lose weight, anxiety and pain, LSD specific for 5HT-2c
3        Anxiety, psychosis, emesis, Lotronex works here. This receptor also found in the good and contributes to pathology of irritable bowel syndrome
4        contraction of small bowel muscle

Side effects and receptorology
M1:       Anticholinergic effects
H1:       Sedation, weight gain, hypotension
alpha1:   Orthostasis, dizziness, tachycardia
alpha2:   priapism
5HT:      anxiety, headache, GI, insomnia, sex
DA:       endocrine and movement effects
Some brain/psych anatomy/function:
Basal ganglion implicated in OCD
Hippocampus implicated in panic disorder
Hypothalamus implicated in eating, binging, purging problems
Brain stem implicated in sexual dysfunction.

Steps in selection of antidepressant:
SAFETY
TOLERABILITY
EFFICACY
PAMENT
SIMPLICITY
The key is SSRI therapy as a first line choice

Final thoughts:
Genetic polymorphism, beware of CYP450 interactions
Grapefruit juice will inhibit some CYP450 pathways
Nonlinear kinetics and dosing
Many psychiatric drugs have CYP450 minutes:
CYP1a2:            Luvox
CYP2c19:                      Prozac, Luvox
CYP2d6:            SSRI
CYP3a4:            Prozac, Luvox, serzone

Recall that SSRIs are psychiatric broad spectrum drugs, treat: MD, PD, ED, OCD, PTSD, PMDD
SSRIs also have secondary mechanisms
Zoloft may work on some dopamine receptors
Prozac has 5ht2c activity
Paxil has activity at M-Ach receptor / NOS inhibition resulting in weight gain and problems with cognition
Luvox has sigma 1 antagonism




October 9th, 2002, Somatoform Disorders, Factitious Disorders, Malingering, Dr. Ethan Kass Presiding

-Dr. Kass basically went through slides that summarized a wide range of pathology.
DISORDER              DESCRIPTION                                                                    TX
Hypochondriasis       Disease fear, concern ,worry. Present in males and females. Not feigned, no    Tx is supportive, psychotherapy (PTX)
                      goal. Prognosis is fair and episodic. People come to the PMDs office with
                      major medical complaints, yet physicians cannot find a physiological reason
                      for illness
                            1. Preoccupation with idea that one has serious illness
                            2. Misinterprets bodily symptoms
                            3. Persists despite medical attention
                            4. Not of delusional intensity
                            5. Social and occupational impairment
Body Dysmorphic       Subjective feelings of being ugly or defective, AKA: Michael Jackson           Tx is therapy, medications
Disorder              syndrome. Young females. Comorbidity of OCD, personality disorder, and         Criteria:
                      eating disorders is not uncommon. Prognosis is fair to good. Not feigned, no   -Preoccupation with imagined defect in appearance
                      goal, unconscious                                                              -Distress in social and occupational finding

Factitious            Factitious with physical symptoms
Disorders             Factitious without physical symptoms
                      Munchausen’s syndrome
                      Munchausen’s by proxy
Factitious Disorder   Feigned illness                                                                Tx: Confront, psychiatric management
With Physical         Goal is “sick role” with no clear gain
Symptoms              Unconscious
                      Females or males in medical fields
                      Comorbid with depression, personality disorder
Factitious Disorder   Feigned psychiatric illness. Females/males in the medical fields. Comorbid     Tx: Confront, psychiatric management
With Psychological    with personality disorder and depression. Feigned, no goal, unconscious.
Symptoms
Munchausen’s          Triad of:                                                                      Tx: Confront
Syndrome              Feigned illness
                      Pathological liar                                                              Munchausen’s By Proxy:
                      Wanderlust                                                                     Parent makes child sick and repeatedly takes them to
                      Young males, comorbid with antisocial, substance abuse. Poor prognosis.        doctors. 7 cases of SIDS in one family, or parent states that
                      Feigned, no goal, unconscious                                                  child stops breathing in the middle of the night / parent
                                                                                                     might actually be smothering the child.
Malingering           Feigned physical or psychiatric illness                                        Tx: Confront, consider social problems
                      Males > Females
                      Clear goal, unconscious, feigned
                         EX: Pt thinks he has Crohn’s disease because their favorite celebrity has it.
                         The patient wants a lot of tests, procedures, and attention.


October 30, 2002 Psychiatry, Fred Lewis, DO

Neuroleptic patients: Risk of tardive dyskinesia increases for patients with chronic antipsychotic pathway
Post synaptic upregulation may result in tardive dyskinesia
Side effects: osteoporosis, other effects.
Mesolimbic overactivity= positive psychotic symptoms.

Lets run the gamut of the anti-psychotics:

DRUG            MECHANISM                                                                                                CLINICAL/SIDE EFFECTS
Clozapine       Atypical antipsychotic, will impact mood. Expensive, selective for mesolimbic pathway. Beat lithium in   Bipolar disorder monotherapy
                terms of efficacy and keeping patients well.                                                             Antipsychotic
                High 5HT2 to D2 ratio                                                                                    No tardive dyskinesia
                                                                                                                         Expensive
Risperdone      Tight binding to the D2 receptor, lacks the broad spectrum effect of clozapine. Hybrid drug.             Does not require blood monitoring
                                                                                                                         Some tardive dyskinesia
                                                                                                                         Less expensive
                                                                                                                         EPS effects
                                                                                                                         Prolactinemia
                                                                                                                         No anti-depressant effect
Olanzapine      Moderate 5ht2c to D2 ratio. Lilly’s entry has a tremendous database. Broad spectrum antipsychotic,       Weight gain
                has been used for its mood stabilizing effects. High efficacy.                                           Risk of type II diabetes
                                                                                                                         Lower risk of TD, EPS, prolactinemia
Quetiapine      -Low 5htd2 ratio                                                                                         No withdrawal
                Affinity for d1, 5ht1a receptor                                                                          Approx 15-20 refractory patients respond
                -Patients with comorbid neurological disorder                                                            Extremely well tolerated
                -Affinity for alpha and muscarinic receptors.                                                            Used for patients with co-morbid mood
                -Approx 15-20% refractory patients respond                                                               disorder
                -Clozapine best, Olanzapine next…
Ziprasidone    -Has not done very well on the market                                                                      Significant QT/QTc prolongation
               -Very high 5HT2c ratio, has not done well in efficacy battle                                               Cardiac dysrhythmias
               -Similar to risperidone                                                                                    Does not cause weight gain
               -Does not perform wall as the…..pine drugs                                                                 Preferred over Haldol
               -Significant direct serotonin receptor activities                                                          Good strategy for the violent patient in need
               -Messes around with catecholamine release. Built in anti-depressant effect with this agent directly. Bi-   of a neuroleptic,.
               directional effect on mood possible?                                                                       Only antipsychotic that comes in IM form
               -Minimal H1 effects, does not cause weight gain

Clozapine
-Summary on antipsychotic:
        -traditional
        -high and low potency
        -limited efficacy to positive symptoms
        -may exacerbate other things
        -patients may feel worse, but not experience the hallucinations
        -TD is the number two reason psychiatrists are sued you motherfucking bastard. Comb your sideburns.
        -Atypicals are safer, better, etc.
        -Community mental health centers run on tight budgets, grants, may use low cost antipsychotics.
        -Atypicals are the only ones working for schizoaffective disorders
        -Bipolar disorder monotherapy
        -Onset of schizophrenia after age 45 is rare
        -Best management is the combination of the neuroleptics and psychosocial interventions

October 30, 2002, Frederick Lewis, DO, Anxiolytics and mood stabilizers

-Much use in the primary care arena
-SSRIs and atypicals have opened the door for primary care physicians
-Broad spectrum efficacy has made MDs/Dos more comfortable.

Review of anxiety
-Stem from GAD, generalized anxiety disorder
-Strange and slippery disease state. High placebo response rate.
-Phobic disorders, social phobia, panic disorder are more clear cut than GAD
-Drugs have approval for specific indications like PD, social phobia, etc.
-Phobic disorders don’t respond too much with psychopharmacotherapy
-OCD responds well
-Pts presenting in primary care settings are more somatically occupied
-Risk of abuse and dependence is of prime importance in anxiolytics.
-Screen patients for drug abuse
-Ask family members about drug use.




DRUG                   MECH                                                                                                                  CLASS
Benzodiazepines        Act on GABA receptor, potentiate GABA                                                                                 Tachyphylaxis may occur
Xanax                  ½ life, potency differ                                                                                                No tachyphylaxis from
Clonazepam             Patients can become dependent on benzodiazepenes                                                                      anxiolytic effect
Diazepam               Indications                                                                                                           See patients frequently
Ativan                 Work rapidly                                                                                                          Sedation, tolerance,
Lorazepam                                                                                                                                    dependence, addition
                                                                                                                                             Relive worry
                                                                                                                                             Good for physical symptom
                                                                                                                                             Autonomic hyperactivity
                                                                                                                                             Panic

Barbituates            Freddy doesn’t like these drugs
Anticholinergic        Not good anxiolytics                                                                                                  Sedating effect
agents
Benadryl
Azipirones             5ht1a partial agonist receptor. Evidently, this is an axiolytic. Works on pre and post synaptic receptors. Increase   Anxiolytic agents
(Buspar)               or decrease serotinergic tone. Should treat depression or anxiety, but………….                                           Not a bad try in
                                                                                                                                             pharmacologically naieve
                                                                                                                                             patents
                                                                                                                                             Latency of response
                                                                                                                                             Doesn’t work in panic
                                                                                                                                             Few SE
                                                                                                                                             No abuse potential
SSRIs                  These things prevent the reuptake of serotonin. Work in depressed and panicked patients. First line approach      Broad spectrum anxioltyics
Sertaline              recommended.                                                                                                      PMDD
Celexa                                                                                                                                   GAD
Paroxetine                                                                                                                               Panic disorder
Fluvoxamine                                                                                                                              OCD
                                                                                                                                         No abuse potential
                                                                                                                                         Will treat smouldering co-
                                                                                                                                         morbid spectrum
Mood stabilizers       Mood stabilizers. Remember to not treat bipolar disorder with anti-depressants. Lithium is a pain to use;         Hypothyroidism
Lithium                required blood level monitoring. Narrow therapeutic index. Blood levels may be good but almost toxic.             Kidney disease
Carbamazepine          Lithium: Serotinergic, receptor downregulations. Discovered once guinea pigs allowed people to rub their          Heart problems with
Valproic acid          bellies. Indications for: mania, psychosis. SE’s are toxicity, renal function, thyroid                            Lithium
Lamotragine            Carbamazepine: MOA is limbic kindling. Has mood stabilizing effects. Narrow therapeutic index. Indications:       Doesn’t work so well
Gabapentin (Don’t      convulsions, seizures, mood stabilizing. SE include stevens-johnson syndrome. Drug also increases its own         Works horribly in SUBTLE
work)                  metabolism. CYP450 upregulation. Increases metabolism of birth control pills.                                     bipolar d/o
Topiramate (Don’t      Valproic acid: Depakote, unknown MOA? Wider therapeutic index. Good in bipolar and mania. Can use high            Works great in Type I
work)                  doses.                                                                                                            bipolar
                                                                                                                                         Depakote: not a great anti-
                                                                                                                                         depressant

ECT                    Lots of indications, no absolute contraindications. NO ABSOLUTE may be a question on exam. Indicated for medication failure. Extremely
                       safe treatment. Failure of two doses with augmentation for an adequate time period.. Also indicated for psychotic depression. Failure of
                       medication and an atypical? You get BuZzEd. Might be indicated for violent and suicidal patients. Hx of response to ECT is important; may be
                       on the examination. Mood stablizier, has a bi-directional effect on mood.


Final Final Review
From Lectures on October 23rd and October 30th

Pathways and Antipsychotics

I. CONVENTIONAL ANTIPSYCHOTICS:
-Patients develop tardive dyskinesia
-Newer generation drugs attempt to limit the negative symptoms
II. THE NIGROSTRIATAL PATHWAY
-Interfering/tampering with this p[athway causes EPS; the extrapyramidal signs are a prognostic indicator for the development of tardive dyskinesia
-Patients who develop significant EPS are 2.5x more likely to develop the dreaded TD
-What is desired is potent and tight binding to postsynaptic D2 receptors.
-Dopaminergic tone should theoretically be reduced
-Presynaptic terminals may downregulate; this may lead to the reduction of dopaminergic transmission in general
-Unfortunately, postsynaptic regulators get UPREGULATED and allow for the development of tardive dyskinesia
-MAIN POINTS:
          -Tight/potent binding to D2 postsynaptic receptorsreduction in dopaminergic tone
          -Downregulation of presynaptic terminalsreduced dopaminergic transmission
          -Post synaptic receptors eventually get upregulatedlikely mechanism for development of TD
III. THE MESOCORTICAL PATHWAY
-Increase in negative s/s
-Most common reason for noncompliance with antipsychotics
-No one refills Haldol
-Mesocortical pathway actions cause a chemical lobotomy of the cortex
-Newer antipsychotics do not cause more negative symptoms, nor do they exacerbate pre-existing negative s/s
-Newer antipsychotics are superior just because they don’t make negative symptoms worse
IV. THE TUBEROINFUNDIBULAR PATHWAY
-Prolactin elvations as a result of conventional antipsychotics
-Chronic prolactinemia that leads to osteoporosis and more depression
-Non compliance, etc.
-Atypical antipsychotics have a lighter affinity and weaker binding for post synaptic receptors
-Agonist, like DA, is allowed to knock the antagonist (evil drug) out of the binding site.
V. REVIEW OF ATYPICALS
-Only drugs that work for the schizo-affective patients
-Atypicals have effects on mood
-Bipolar treated with Quetiapine and Olanzapine
-Borderline patients derserve a trial with the above drugs

DRUG                                                   MOA                                                   CLINICAL
Clozapine                                              Dramatic effect on positive symptoms in psychotic     No EPS/prolactinemia
(Novartis pharm)                                       patients. Chips away at negative s/s. Pts less        30% refractory patients will respond
Broad-spectrum antipsychotic                           apathetic.                                            1% risk of fatal agranulocytosis
                                                       First antipsychotic with an atypical profile          Atypical antipsychotic
                                                       Selective for MESOLIMBIC pathway                      Affinity for alpha receptors causes tachycardia
                                                       High 5HT/D2 ratio, drives up serotinergic tone        H1 receptor affinity causes weight gain, dry mouth,
                                                       and suppresses dopaminergic tone.                     sedation
                                                       Other drugs, like Serzone, Desaril, and Remeron       Drink high caffeine diet cola or coffee to increase
                                                       antagonize the D2 receptor and help maintain the      alertness
                                                       balance between SE and DA.                            Many anticholinergic effects
                                                       Maintenance of balance is extremely beneficial;       Patients are less apathetic and withdrawn
                                 avoids sexual dysfunction as a side effect.        Blood monitoring required

Risperdone                       High 5HT/D2 ratio                                  Minimal H1 as compared to Clozapine
(Janseen)                        Dose related occupancy of D2 receptors             Risk of TD, prolactinemia
                                 Affinity for A1 and S2                             Not as specific as Clozapine
                                 Does NOT assist with mood stabilization            Hybrid agent; acts a little like clozapine and Haldol
                                                                                    No blood monitoring
                                                                                    14% of refractory patients will respond
Olazapine (Lilly)                Moderate 5H2/D2 ratio                              No agranulocytosis
(Broad-spectrum antipsychotic)   Similar to Clozapine                               Affinity to A1, H1, and M1 receptors makes SE
                                 Affinity for D1,D3,D4 receptors                    profile similar to Clozapine (Watch for obesity, DM)
                                 Does assist with mood stablization                 Low risk of TD and prolactinemia
                                                                                    Once daily dosing
                                                                                    Approx 20% refractory patients respond
                                                                                    Watch for discontinuation and rebound psychosis
Quetiapine                       Low 5HT/D2 receptor affinity                       No EPS
                                 affinity for D1, 5HT1a, and alpha receptors        No TD
                                                                                    No prolactinemia
                                                                                    Well tolerated
                                                                                    Approx 15-20% refractory patients respond
                                                                                    Patients with co-morbid disorders
Ziprasidone                      Extremely high 5HT/D2 ratio. Affinity for D3,      QT/QTc interval problems
                                 5HT1a, 5HT2c, 5HT6 and 7 receptors                 Minimal weight gain
                                 Similar to antidepressant drugs due to Se and DA   Low EPS
                                 reuptake inhibition                                Low TD
                                                                                    Low prolactinemia
                                                                                    Short acting IM form
                                                                                    Better than Haldol for short term management




Here’s another comparison:
                             5HT/2D ratio                EPS/Prolactinemia/TD            Weight gain        Mood stabliziation           Caution
Clozapine                    High                        None                            Yes                Yes                          Agranulocytosis
                                                                                                                                         Monitor blood levels
                                                                                                                                         Muscarinic side effects
                                                                                                                                         Consider serzone or
                                                                                                                                         remeron to balance
                                                                                                                                         D2 mediated effects
Risperidone                  High                        Minimal                         Minimal, low H1    No
Olanzapine                   Moderate                    Minimal (Low)                   Yes                Yes                          DM
                                                                                                                                         Discontinuation and
                                                                                                                                         rebound psychosis
                                                                                                                                         possible
Quetiapine                   Low                         None                            Yes                Yes                          Risk of weight gain,
                                                                                                                                         type II DM
Ziprasidone                  High                        Low                             Minimal            Yes- 5HT and DA              Comes in short acting
                                                                                                            reuptake inhibition,         form, has muscarinic
                                                                                                            similar to antidepressants   Side effects like
                                                                                                                                         Clozapine
                                                                                                                                         QT/QTc interval
                                                                                                                                         problems
Consider the atypicals as an adjuvant to refractory depression. Increase effectiveness of anti-depressant
Tx bipolar with Quetiapine and Olanzapine
Personality disorders can be treated with atypicals ie: borderline personalities
Conduct disorders may be an early sign of bipolar disorders

				
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