Defense Mechanisms

Jason Ryan, MD, MPH

Freudian Psychology
• Id - desire
• Superego – societal rules, morality
• Ego - mediator between id and superego

Wikipedia/Public Domain
Ego Defenses
• Unconscious adjustments in reality perception
• Resolve/manage conflict between id and superego
• Minimize anxiety
• Adaptation to stressful circumstances
Acting Out
• Avoiding emotions by bad behavior
• Attention seeking, socially inappropriate behavior
• Examples:
• Child with sick parents misbehaves at school
• Adolescent engages in promiscuous sex during parents’ divorce

PxFuel/Public Domain
Denial
• Refusing to accept unpleasant reality
• Examples:
• Patient thinks doctor is wrong about diagnosis
• Heavy drinker believes she drinks socially

Peter/Flikr
Projection
• Attributing feelings/emotions to others
• A cheater accuses a classmate of cheating off him

Clipart/Public Domain
Regression
• Reverting to behavior of younger person/child
• Stressed adult watches cartoons from childhood
• Sick adult wants parent to stay in hospital with them
• Hospitalized older child begins to wet his bed

Clipart/Public Domain
Displacement
• Directing emotions to another person
• Examples:
• Patient angry at doctor after injury
• Mother angry at husband yells at child
Reaction Formation
• Turning feelings into opposites
• Goes beyond denial
• Man who craves alcohol preaches abstinence
• Woman despises mother, throws birthday party
• Parent despises child shows extreme love/affection

Clipart/Public Domain
Intellectualization
• Avoiding emotions through reasoning
• Spouse going through divorce cites divorce statistics to friends to avoid admitting
sadness

Clipart/Public Domain
Rationalization
• Distorting events so outcome is positive
• “I’m glad I got fired, I needed a change.”

Clipart/Public Domain
Repression
• “Motivated forgetting”
• Usually forgetting one particular memory/fact
• Often something that happened long ago
• Example: difficult period of childhood
• First defense mechanism described by Freud
• Thoughts repressed to avoid guilt
Isolation of Affect
• Isolating a distressing memory/event
• Failing to experience emotions of event
• Person describes rape without expressing sadness

Clipart/Public Domain
Splitting
• Categorizing others at extremes
• “Wonderful” or “horrible” people
• Patient loves her doctor but hates nurse
• Common in borderline personality disorder

Clipart/Public Domain
Undoing
• Reaction to an unhealthy or destructive thoughts or acts
• Engaging in contrary behavior
• Trying to make things “unhappen”
• Example:
• Patient thinks about hurting someone
• Acts overly nice to person in response
Altruism
• Practice of concern for others
• Caring for others to reduce stress/anxiety
• Cancer survivors help others with same disease

Clipart/Public Domain
Humor
• Relief of anxiety with jokes/laughter
• Medical student jokes about board studying

Clipart/Public Domain
Sublimation
• Using negative emotions in a positive way
• Anxious person becomes a security guard
• Aggressive person becomes a boxer
Suppression
• Conscious defense mechanism
• Done intentionally to relieve stress/anxiety
• Ignoring stressful thoughts/feelings to cope
• “I’m not going to think about that now”
• Contrast with repression (unconscious)
Mature Defenses
• Sublimation
• Altruism
• Suppression
• Humor
Psychotic Disorders
Jason Ryan, MD, MPH
Psychosis
• Loss of perception of reality
• Occurs in medical and psychiatric disorders
• Delirium
• Schizophrenia
• Drug-induced (illicit and prescription)
• Three main manifestations
• Delusions
• Disorganized thought
• Hallucinations
Delusions
• Strongly held beliefs that conflict with reality

Delusion Example
Persecutory Someone is after me!
Grandiose I am a millionaire!
Erotomanic Brad Pitt is in love with me.
Somatic There are worms in my chest!
Delusions of Reference The television news caster is talking about me.
My body is controlled by aliens!
Delusions of control
I can control the sun!
Disorganized Thought
• Shown by patterns of speech
• Alogia (speech poverty)
• Thought blocking
• Sudden, abrupt stop while talking
• Loosening of association
• Ideas discussed that do not follow each other
• Tangentiality
• Diverging from topic under discussion to another

Nevit Dilmen/Wikipedia
Disorganized Thought
• Clanging
• Using words that rhyme but do not make sense
• “The cow said how he had to bow”
• Word salad: incoherent words that make no sense
• Perseveration: repeating words or ideas persistently

Clipart/Public Domain
Hallucinations
• Sensory perceptions without external stimuli
• Visual
• Seeing things that are not there
• Common in hospitalized patients with delirium
• Usually has an “organic” cause – drugs, disease
• Auditory
• Hearing voices or sounds
• Classic feature of schizophrenia
• Rarely olfactory (smell), gustatory (taste) or tactile (bugs crawling on skin)
Schizophrenia
• Chronic psychiatric syndrome
• Recurrent episodes of psychosis
• Cognitive dysfunction
• Negative symptoms
Schizophrenia
Pathology
• Excess central dopamine activity
• Dopamine antagonists used for therapy
• Also hypofunction of the NMDA glutamate receptor

Dopamine
Schizophrenia
Pathology
• MRI/CT:
• Lateral ventricular enlargement
• PET scan:
• Hypoactivity frontal lobe
• Hyperactivity basal ganglia

Wikipedia/Public Domain
Schizophrenia
Epidemiology
• Lifetime prevalence about 1% adults globally
• Slight male predominance
• Occurs in adolescence/young adulthood
• Men: 18 to 25
• Women: 25 to 35

Brenkee/pixabay
Schizophrenia
Risk Factors
• Living in urban areas (cities)
• Immigration
• UK study: immigrants ten times more risk

Pixabay/Public Domain
Schizophrenia
Risk Factors
• Obstetric complications
• Hemorrhage
• Preterm labor
• Blood-group mismatch
• Fetal hypoxia
• Maternal infection

Øyvind Holmstad/Wikipedia
Schizophrenia
Risk Factors
• Cannabis use
• Usually in adolescence
• Unclear if cause-effect
• Mild symptoms may lead to cannabis use

Chuck Grimmett/Wikipedia
Schizophrenia
Hallucinations and delusions
• Main manifestation: auditory hallucinations
• Hearing voices
• Strange sounds
• Delusions

Pixabay/Public Domain
Schizophrenia
Disorganized speech
• Most commonly tangential or circumstantial speech
• Tangential speech
• Changes topic frequently
• May not answer questions
• Circumstantial speech
• Long, round-about answers to questions
Schizophrenia
Cognitive impairment
• Difficulty processing information
• Poor attention
• Poor learning and memory

Onlineassignmenthelps/Wikipedia
Schizophrenia
Positive Symptoms
• Abnormal behaviors
• Hallucinations, delusions, disorganized thought
• Related to dopamine activity
• Respond to antipsychotics

Pixabay/Public Domain
Schizophrenia
Negative Symptoms
• Absence of normal behaviors
• Flat affect
• Poverty of speech (alogia)
• Cannot engage in social interactions (asociality)
• Lack of motivation/cannot complete tasks (avolition)
• Cannot feel pleasure (anhedonia)
• Often persist despite therapy

Pixabay/Public Domain
Schizophrenia
Complications
Le Suicidé
• High risk of suicide Édouard Manet, 1877
• 5% schizophrenics commit suicide
• 10% all suicides occur in schizophrenics
Schizophrenia
Diagnosis
• At least one month of two or more:
• Delusions
• Hallucinations
• Disorganized speech
• Disorganized or catatonic behavior
• Negative symptoms
• Must have either delusions, hallucinations or disorganized speech
• Continuous signs for at least six months
Schizophrenia
Treatment
• Antipsychotic drugs
• Psychotherapy

Wallpaper Flare.com/Public Domain

Schizophreniform Disorder
• Meets criteria for schizophrenia
• Duration one to six months
Brief Psychotic Disorder
• Psychotic symptoms
• Sudden onset
• Full remission within one month
• More common in women than men
• Commonly follows stressful life events
• Death in family
• Loss of job
Schizophrenia with Mania/Depression
• Schizoaffective Disorder
• Schizophrenia with mania or depression
• Must have some episodes psychosis alone
• Some psychosis in absence of mania/depression
• DSM-V: Two or more weeks with psychosis alone
• Mania or depression with psychotic features
• All psychotic episodes occur with mania/depression
Schizoaffective Disorder
Possible Course

Psychotic Symptoms
(Hallucinations, Delusions)

Mania/
Depression

1 2 3 4 5 6
Mood Disorder with Psychosis
Possible Course

Psychosis

Mania/ Mania/ Mania/

Depression Depression Depression

1 2 3 4 5 6
Delusional Disorder
• One or more delusions
• Lasts one month or longer
• Otherwise, no abnormal behavior
• Man believes he is being followed for past two months
• Frequently checks for someone behind him
• Cannot be persuaded he is safe
• No hallucinations, disorganized thought, negative symptoms
• Folie a deux (madness of two)
• Close friend shares delusions
 Psychotic Disorders

Disorder Features Time Frame

Schizophrenia Psychosis, Learning Disability, Negative Symptoms > 6 months
Schizophreniform Psychosis, Learning Disability, Negative Symptoms 1 to 6 months
Brief Psychotic Disorder Psychosis < 1 month
Delusional Disorder Delusions only > 1 month
Schizoaffective Psychosis Alone and Mood Symptoms --
Mood with Psychosis Mood Symptoms with Psychosis --
Mania
Jason Ryan, MD, MPH
Mood Disorders
• Abnormal emotional state
• Sadness (depression)
• Extreme happiness (mania)
Wikipedia/Public Domain

Depression Mania
Manic Episode
• Abnormally elevated mood and energy level
• Talking fast, pressured speech
• Decreased need for sleep
• But not tired
• Different from insomnia (tired but cannot sleep)
• Psychomotor agitation (pacing, fidgeting)
• Flight of ideas

Clipart/Public Domain
Manic Episode
• Disinhibition and irresponsibility
• Waste money, wearing no clothes
• Grandiosity
• Increased self-esteem, confidence
• “I can do anything!”
• Typical case:
• Change in mood to elevated state
• Not sleeping
• Altered behavior
• Disruption of social functioning
Public Domain
Manic Episode
Diagnosis
• Symptoms for at least one week, most of the day
• Distractibility
• Irresponsibility
• Grandiosity
• Flight of ideas DIG FAST
• Agitation
• Less Sleep
• Talking too much, pressured speech
Hypomanic Episode
• Similar to those of mania but less severe
• Key feature: little/no impairment in functioning
• Inflated self-esteem but no delusions of grandeur
• More organized thought than mania
• More energy but leads to productive activity
• Contrast with mania: unproductive
• Milder risk-taking behavior
Hypomanic Episode
• Lasts at least 4 days
• No psychotic symptoms
• By definition psychotic symptoms = mania
• Typical case:
• Change in mood to elevated state
• Continued social functioning
• Resolves in few weeks
Bipolar Disorder
Manic Depression
• Symptoms of mania and depression
• Can present with mania, hypomania or depression
• Treatment with antidepressants may cause mania
• Bipolar I
• Manic episode +/- depression +/- hypomania
• Manic episodes = bipolar I
• Bipolar II
• Hypomania and depression
• No manic episodes

Clipart/Public Domain
Psychotic Features
• Often hallucinations or delusions
• Associated with severe forms of mood disorders
• May occur in bipolar disorder or depression
• Always occur together with mood symptoms
• Psychosis without mood symptoms: schizoaffective

Ingela Hjulfors Berg/Flikr

Cyclothymic Disorder
• Mild mania symptoms
• Mild depressive symptoms
• Do not meet criteria for hypomania or MDD
• Symptoms come/go over at least two years
• Come/go with ups and downs
• Occur at least half of the time
• Never absent for more than two consecutive months
Bipolar Disorder
Course
• Fluctuation: mania-hypomania-depression
• May have periods of euthymia (normal mood)
Bipolar Disorder
Treatment
• Mood stabilizers
• Lithium
• Valproic acid (anticonvulsant)
• Lamotrigine (antipsychotic)
• Carbamazepine (antipsychotic)
• Antipsychotics
• Electroconvulsive therapy (ECT)
• Antidepressants may cause mania
• Bipolar depression treated with mood stabilizers
Bipolar Disorder
Treatment
• Patients with new-onset acute mania:
• Lithium plus antipsychotic
• Alternative: Valproic acid plus antipsychotic
• Antipsychotics:
• Aripiprazole
• Haloperidol
• Olanzapine
• Quetiapine
• Risperidone
Lithium
• Chemical element/cation
• First medical therapy of bipolar disorder (1949)
• Mechanism poorly understood
• Many toxicities
• Narrow therapeutic index
• Serum level monitored to titrate dose
• Therapeutic range 0.8 to 1.2 mEq/L
Lithium
Elimination
• Primarily renal excretion
• Mostly reabsorbed in proximal tubule (like Na)
• Contraindicated with significant renal impairment
• Toxicity with acute renal failure
Lithium
Adverse Effects
• Acute effects
• Occur when starting drug
• Tremor
• Nausea
• Diarrhea
• Toxicity/poisoning
• Chronic effects

PublicDomainVectors.org
Lithium Toxicity
Lithium Poisoning
• Gastrointestinal: nausea, vomiting, and diarrhea
• Neurologic
• Confusion
• Tremors
• Seizures
• Treatment: stop drug +/- dialysis
• Dialysis for level > 5.0 mEq/L
• Or > 2.5 mEq/L with symptoms

FreeSVG/Public Domain
Lithium Tremor
• Occurs when drug is started or dose increased
• Symmetric
• Usually limited to hands or arms
• Often resolves over time
• Most common symptom of lithium toxicity
• Persistent tremor treatment: propranolol
Lithium Toxicity
Risk Factors
• Renal insufficiency
• Volume depletion
• Elderly patients (low glomerular filtration rate)
• Drug interaction

Image courtesy of BruceBlaus

Lithium Toxicity
Drug Interactions
• Increased lithium level (↓ renal excretion)
• Thiazide diuretics
• NSAIDS
• ACE inhibitors
• Metronidazole
• Tetracycline
• Decreased lithium level
• Potassium-sparing diuretics
• Varying effects: loop diuretics

Hydrochlorothiazide
Lithium
Adverse Long-term Effects
• Hypothyroidism
• Hyperparathyroidism
• Nephrogenic diabetes insipidus
• Cardiac
• Fetal effects
• Ebstein’s anomaly
• Mild leukocytosis
• Increased neutrophils
Thyroid Effects
Thyroid Gland
• Lithium: goitrogen
• Inhibits hormone release
• Commonly causes goiter (enlarged thyroid)
• 40-50% of patients on lithium
• May cause hypothyroidism

Wikipedia/Public Domain
Parathyroid Effects
Parathyroid Glands
• May elevate parathyroid hormone levels
• May cause mild hypercalcemia
• Usually asymptomatic

Busca tu equilibrio/Wikipedia
Diabetes Insipidus
• “Chronic tubulointerstitial nephropathy”
• Loss of tubule urine concentrating ability
• Tubules do not respond to ADH
• Dilute urine (low Uosm)
• Polyuria and polydipsia
• Serum sodium normal or increased
Diabetes Insipidus
Treatment
• Discontinue lithium (if possible)
• Amiloride
• Potassium-sparing diuretic
• Blocks lithium entry into renal cells
• Vasopressin: no response
• No change Uosm
• Nephrogenic DI
Amiloride
Amiloride

Lumen (Urine) Principal Cell Interstitium/Blood

Na+
Na+
Amiloride ATP
K+
K+

H2O
Cardiac Effects
• Suppression of sinus node
• Make cause sinus node dysfunction
• Bradycardia
• Pauses
• Syncope
Maternal Lithium
• Teratogen
• Completely equilibrates across the placenta
• Teratogenic effects primarily involve heart
• Ebstein’s anomaly most common
Lithium Management
• Prior to start:
• EKG (sinus rate)
• Chemistries (BUN, Cr, Ca)
• TSH
• Pregnancy test
• Urinalysis
• Blood levels
• At day 5, then every 2-3 days
• Once therapeutic every 6-12 months
• Check Cr and TSH q3-6 months
Shutterstock
Depression
Jason Ryan, MD, MPH
Mood Disorders
• Abnormal emotional state
• Sadness (depression)
• Extreme happiness (mania)
Wikipedia/Public Domain

Depression Mania
Major Depressive Disorder
• Depressed mood
• Loss of interest in activities (anhedonia)
• Appetite/weight changes
• Feeling worthless or guilty
• Inability to concentrate, make decisions
• Fatigue/loss of energy
• Psychomotor agitation/retardation
• Sleep disturbances
• Suicidal ideation/attempts

Public Domain
Major Depressive Disorder
Psychomotor agitation/retardation
• Psychomotor agitation
• Excessive motor activity
• Often repetitious
• Feeling of inner tension
• Fidgeting, pacing
• Psychomotor retardation
• Slowing of movements, thinking, or speech
• Slow to answer questions
• Low voice
• Few words

Pixabay/Public Domain
Major Depressive Disorder
Sleep Disturbances
• Difficulty getting to sleep (initial insomnia)
• Waking in the night (middle insomnia)
• Waking earlier than usual (terminal insomnia)
• Hypersomnia: excessive sleeping
• Altered sleep rhythms
• REM starts quicker after sleep onset (↓ REM latency)
• ↑ total REM sleep
• ↓ slow-wave sleep
• Sleep rhythms normalize on anti-depressant drugs
Pexels.com/Public Domain
Cortisol
• Severe depression: elevated serum cortisol
Depression-Related Cognitive Impairment
Pseudodementia
• DSM-V: Difficulty thinking and concentrating and/or making decisions

Dementia Pseudodementia
Mood Variable Depressed
Onset Slow Rapid
Progression Slow Rapid
Disability Diminished by patient Emphasized by patient
Answers to Questions Tries but unable “I don’t know”
Suicide Risk Low High
Major Depressive Disorder
Diagnosis
• At least 5 symptoms (of 9) for 2 weeks
• Depressed mood
• Sleep disturbance
• Lack of Interest
• Guilt SIG E CAPS
• Energy loss and fatigue
• Concentration problems
• Appetite/weight changes
• Psychomotor symptoms
• Suicidal ideation
• No evidence of mania
Psychotic Features
• Often hallucinations or delusions
• Associated with severe forms of mood disorders
• May occur in depression or bipolar disorder
• Always occur together with mood symptoms
• Psychosis without mood symptoms: schizoaffective
Persistent Depressive Disorder
Dysthymic Disorder
• Low grade form of depression
• Less severe but more chronic
• Depressed mood most of the time
• Lasts at least two years
• No symptom free periods lasting >2 months

Flikr/Public Domain
Persistent Depressive Disorder
Dysthymic Disorder
• At least two of the following:
• Hopelessness
• Decreased appetite
• Sleep problems
• Low energy
• Low concentration
• Low self-esteem

Flikr/Public Domain
Major Depressive Disorder
Subtypes
• Atypical
• Melancholic
• Catatonic
• Psychotic
• Mixed features
• Anxious
• Seasonal

Public Domain
Atypical Depression
• Mood reactivity (core unique feature)
• Able to react to pleasurable stimuli
• Feels better when good things happen
• Eating and sleeping all the time
• Increased appetite or weight gain
• Increased sleep (hypersomnia)
• Heavy or leaden feelings in limbs
• Sensitive to rejection
• History of interpersonal rejection sensitivity
Atypical Depression
• Most common subtype in some studies
• Older studies: increased response MAOi drugs
• SSRIs also effective
• Usually treated with SSRIs (fewer side effects)

Tom Varco/Wikipedia
Seasonal Depression
• Worsening depression in fall and winter
• Treatment: phototherapy
• In addition to other therapy

Wikipedia/Public domain
Major Depressive Disorder
Treatments
• Psychotherapy
• Cognitive behavioral
• Interpersonal
• Antidepressants
• Usually SSRIs and SNRIs
• Need 4 to 6 weeks to assess efficacy
• If still symptomatic, increase dose, add/switch drugs
• Few head-to-head trials or SSRI or SNRI
• Fluoxetine most widely studied in adolescents
• Electroconvulsive therapy (ECT)
• Hospitalization if high suicide risk

Shutterstock
ECT
Electroconvulsive Therapy
• Performed under general anesthesia
• Electricity administered → seizure
• Highly effective in treating depression
• Reserved for severe depression due to risks
• Can be used in pregnancy
• Persistent suicidal intent
• Depression with psychosis
• Catatonia
• Food refusal

Wikipedia/Public Domain
ECT
Electroconvulsive Therapy
• May cause amnesia
• Retrograde amnesia (memories before procedure)
• Anterograde amnesia (few weeks after)
• Often resolves over several months
• Lithium held before procedure
• Can worsen memory impairment
• Benzodiazepines avoided
• Anticonvulsant drugs
• Most other psychiatric drugs safe

Wikipedia/Public Domain
Suicide
• Seen in depression and bipolar disorder
• 95% successful attempts have psychiatric diagnosis
• Depression, bipolar, substance abuse, schizophrenia
• Women: more attempts, less successful
• Men: fewer attempts, more successful
• Most common method: firearms
• Increased risk with access to guns

Augustas Didžgalvis
Suicide
Risk Factors
• Sad person scale (0-10pts)
• Sex (male)
• Age (young adults or elderly)
• Depression
• Prior attempt (higher risk group) SAD PERSONS
• Ethanol or drugs
• Rational thinking loss (psychosis) 0-4: Low risk
•
•
Sickness (medical illness)
Organized plan 5-6: Medium risk
•
•
No spouse (or lack of social support)
Stated intent
7-10: High risk
Suicide
Risk Assessment
• Ideation (common – 60% depressed patients)
• Plan
• Intent
• High risk if all three present
• Hospitalization for highest risk patients

KOMUNews/Flikr
Suicide
Involuntary Hospitalization
• May be necessary if patient will not consent
• Absence of decision-making capacity due to mood disorder
• Imminent risk of harm must be present
Catatonia
• Behavioral syndrome
• Inability to move normally
• Occurs in patients with mental and medical illness
• Depression
• Bipolar
• Schizophrenia
• Treatment:
• Benzodiazepines (first-line)
• ECT
• Avoid antipsychotics

Pixabay/Public Domain
Catatonia
Clinical Features
• Immobility
• Stupor or mutism (decreased alertness of speech)
• Negativism (resistant to instructions)
• Catalepsy (remains in fixed position)
• Posturing (resistant to movement)
• Echolalia (meaningless repetition of another person's words)
• Echopraxia (meaningless imitation of movements of others)
Typical Acute Grief
• Normal response to loss of loved one
• Five stages (Kübler-Ross model)
• Denial (“He can’t be gone there must be a mistake”)
• Anger (“This is your fault!”)
• Bargaining (“I’ll do anything if she could be alive again”)
• Depression
• Acceptance
• Visions/voices of dead person may occur
• Usually resolves within 6 months

PickPic/Public Domain
Typical Acute Grief
• Depression can occur within 6 months of loss
• Symptoms more severe than grief
• Unable to be comforted by others
• Worthlessness
• Anhedonia
• Weight loss
• Suicidal ideation

PickPic/Public Domain
Complex Grief
• Lasts longer than 6 months
• Interferes with functioning
• May lead to major depressive disorder

Tim Green/Flikr
Anxiety Disorders
Jason Ryan, MD, MPH
Panic Attack
• Sudden onset of intense fear
• Often occur with no trigger
• Sometimes triggered by stressful event
• Brief: lasts for minutes to an hour

Nclm/Wikipedia/Public Domain
Panic Attack
• Physical symptoms caused by panic
• Palpitations, racing heart
• Sweating
• Trembling or shaking
• Chest pain or discomfort

Shutterstock
Panic Attack
Diagnosis
• Four or more of the following:
• Palpitations, pounding heart, or accelerated heart rate
• Sweating
• Trembling or shaking
• Sensations of shortness of breath or smothering
• Feelings of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, light-headed, or faint
• Chills or heat sensations
• Paresthesias (numbness or tingling sensations)
• Fear of losing control or "going crazy"
• Fear of dying
• Derealization
• Depersonalization
Panic Attack
Diagnosis
• Derealization
• Items in room look foggy, unreal
• Feel like in a foreign place despite being at home
• Often intensely scary
• Depersonalization
• “Out of body” experience
• Detached, looking at self from above

Shutterstock
Panic Disorder
Diagnosis
• Recurrent unexpected panic attacks
• No obvious trigger
• Not post-traumatic
• Not in response to phobia
• Attacks followed by 1 month or more:
• Persistent concern or worry about panic attacks
• Change in behavior to avoid attacks
Panic Disorder
• Median age: 24 years
• Twice as common in women vs. men
• Risk factors
• Genetic component
• 1st degree relative with PD increases risk
• History of physical or sexual abuse
• Life stress
• Treatments:
• Cognitive behavioral therapy
• Antidepressants (SSRIs)
• Benzodiazepines

Public Domain
Specific Phobias
• Fear of a specific object or situation
• Leads to avoidance behavior
• Persists for > 6 months
• Common: flying, dental procedures, blood draw

Flikr/Delmar Clemmons
Specific Phobias
• Social anxiety disorder
• Specific phobia of social settings
• Excessive fear of embarrassment in social settings
• Fear of being humiliated or judged
• Agoraphobia
• Agora = public space (Greek)
• Fear of leaving a safe place (home) for public setting
• Fear of needing to flee with no help available
• NOT fear of scrutiny and embarrassment
• Example: Fear of empty bus (no people)
• Often co-occurs with panic disorder
• Often patients fear panic attack in public setting
Specific Phobias
Treatments
• Medications
• Benzodiazepines for infrequent exposure
• Beta-blockers (blunt physical symptoms)
• SSRIs for frequent exposure

Tom Varco/Wikipedia
Specific Phobias
Treatments
• Often responds to behavioral therapy
• Systematic desensitization
• Imagining exposure to feared stimulus
• Relaxation
• Exposure therapy
• Confrontation of feared stimulus in safe/controlled manner
• Fear reduced over time (extinction learning)
Generalized Anxiety Disorder
• Chronic, persistent anxiety
• About many different events/activities
• Lasts > 6 months
• More days than not for at least six months

PicPedia
Generalized Anxiety Disorder
• Three or more of the following:
• Restlessness
• Fatigue
• Difficulty concentrating
• Irritability
• Muscle tension
• Sleep disturbance
• Treatment:
• Cognitive behavioral therapy + SSRIs
• Combination most effective
OCD
Obsessive-Compulsive Disorder
• Obsessions
• Recurrent, persistent thoughts, urges, or images
• Intrusive and unwanted
• Patient attempts to ignore or suppress
• Causes distress
• Compulsions
• Repetitive behaviors or mental acts
• Done to relieve obsessions
• Hand washing, checking stove
• Praying, counting, repeating words
• Patient feels driven to perform in response to obsessions
OCD
Obsessive-Compulsive Disorder
• Ego
• Mediates id (desire) and super-ego (rules, society)
• Egosyntonic
• Behaviors that achieve goals of the ego
• Obsessions/compulsions used to achieve goals
• Seen in obsessive-compulsive personality disorder
• Egodystonic
• Behaviors that conflict with goals of the ego
• Obsessions/compulsions are barriers to goals
• Seen in obsessive-compulsive disorder

Public Domain
OCD
Obsessive-Compulsive Disorder
• Commonly co-occurs with:
• Schizophrenia or schizoaffective disorder
• Bipolar disorder
• Eating disorders (anorexia/bulimia)
• Tourette’s disorder
• Treatment: cognitive behavioral therapy
• “Exposure and response” therapy
• Expose patient to obsessive thoughts/image
• Respond with non-compulsive behavior
• SSRIs
PTSD
Post Traumatic Stress Disorder
• Follows traumatic event
• Rape, physical assault, war
• Thoughts, nightmares, flashbacks
• Avoidance of reminders
• Hypervigilance
• Anxious, alert, scanning
• Sleep problems
• Restless, can’t fall or stay asleep
• Leads to social dysfunction

Public Domain
PTSD
Diagnosis
• Exposure to traumatic event
• Trauma persistently re-experienced
• Thoughts, nightmares, flashbacks
• Avoidance of trauma-related stimuli
• Negative thoughts or feelings after trauma
• Trauma-related arousal and reactivity
• Symptoms last for more than 1 month

Public Domain
PTSD
Treatments
• Cognitive behavioral therapy
• SSRIs or SNRIs
• Prazosin
• Alpha-1 blocker
• Reduces nightmares and improves sleep
• May cause orthostatic hypotension
• Avoid benzodiazepines or opioids
• Addiction potential

Tom Varco/Wikipedia
Acute Stress Disorder
• Exposure to threatened death, injury, sexual assault
• Recurrent, intrusive memories
• Recurrent distressing dreams
• Dissociative symptoms
• Altered sense of reality
• In a daze, time is slow
• Cannot remember aspects of trauma (dissociative amnesia)
• Lasts less than one month
• Treatment: CBT (no drugs)
Adjustment Disorder
• Behavioral or emotional symptoms
• Develop within 3 month of stressful life event
• Distress in excess of expected/usual
• Impairment of daily functioning
• Does not meet criteria for another disorder
• Usually resolves within 6 months
• Treatment: psychotherapy (various forms)

Piqsels
Body Dysmorphic Disorder
• Occurs in physically normal patients
• Preoccupation with physical appearance
• Focus on nonexistent or minor defects
• Patient believes they look abnormal, ugly, deformed
• Leads to repetitive behavior
• Checking mirror
• Combing hair
• Treatment: CBT plus SSRIs

Needpix.com
Personality Disorders
Jason Ryan, MD, MPH
Personality Traits
• Fixed patterns of behavior
• Way of interacting with environment
• No significant distress or impaired function
• Positive traits: kind, confident
• Negative traits: lazy, rude
• Person often aware of own traits
Personality Disorders
• Fixed patterns of behavior
• Way of interacting with environment
• Cause distress or impaired function
• Person often unaware
• All treated with psychotherapy
• Difficult to treat (“enduring”)
• Often strains doctor-patient relationship
Personality Disorders
• Cluster A (Weird)
• Paranoid, schizoid, schizotypal
• Odd and eccentric behavior
• Cluster B (Wild)
• Antisocial, borderline, histrionic, narcissistic
• Dramatic, erratic behavior
• Cluster C (Wacky)
• Avoidant, obsessive-compulsive, dependent
• Anxious, fearful behavior
Paranoid
Personality Disorder
• Distrust of others, even friends/family
• Guarded
• Suspicious
• Struggles to build close relationships
• Hallmark ego defense: projection
• Attributing unacceptable thoughts to others
• Often accuses others of being suspicious

Aaron Tait/Flikr
Schizoid
Personality Disorder
• Chooses social isolation
• More comfortable alone
• Does not enjoy close relationships
• Little/no interest in sexual experiences
• Few/no pleasure activities (hobbies)
• Lacks close friends
• Detachment
• Flat affect

Public Domain
Schizotypal
Personality Disorder
• Fear of social interactions and few close friends
• Odd beliefs or magical thinking
• Superstitious
• Believes in telepathy, sixth sense
• Ideas of reference
• Believe events and happenings somehow related to them
• Key feature: open to challenges to beliefs
• May reconsider superstitions, etc.
• Contrast with delusions in schizophrenia
• Also no hallucinations, cognitive impairment Shutterstock
Antisocial
Personality Disorder
• More common in men
• Disregard for rights of others
• Often breaks the law
• Impulsive and lacks remorse
• Child (< 18) version: conduct disorder
• 25% girls and 40% boys with CD → ASPD
• Must be at least age 18 years old Public Domain

• Must have evidence of conduct disorder before 15

Borderline
Personality Disorder
• More common in women
• Unstable personal relationships
• All people are very good or very bad
• Stormy relationships
• “My boyfriend is the greatest guy in the world!”
• “My boyfriend is the devil!”
• Fear of abandonment
• May accuse others of abandoning them

Ingela Hjulfors Berg/Flikr

Borderline
Personality Disorder
• Impulsivity
• Spending sprees, sex with strangers, reckless driving
• Self mutilation
• Cutting, burning
• Suicide gestures or attempts
• Relates to fear of abandonment
• “You don’t care about me, so I’ll kill myself”
Splitting
• Major defense mechanism in borderline PD
• Black and white thinking (always-never)
• Cannot hold opposing views
• Patient's physician may be great or terrible
• All people/things/events wonderful or horrible

Pathfinder257/Pixabay
Dialectical Behavior Therapy
• Form of cognitive behavioral treatment
• Designed to treat chronic suicidality
• Gold standard for borderline personality disorder
• Weekly therapy for 1-2 years
• Mindfulness
• Distress tolerance
• Emotion regulation
Histrionic
Personality Disorder
• Wants to be the center of attention
• Talks loudly, tells wild stories, uses hand gestures
• Inappropriate sexually provocative behavior
• Often wears provocative clothing
• Touching others frequently
• Very concerned with physical appearance
• Exotic outfits, shoes, hats
Narcissistic
Personality Disorder
• Inflated sense of self
• Brags, thinks everything they do is great
• Lacks empathy for others
• Other people are competitors
• Wants to hear they are great
• Overreacts to criticism with anger/rage

Shutterstock
Avoidant
Personality Disorder
• Avoids social interactions
• “Social inhibition”
• Feels inadequate
• Afraid people won’t like them
• Afraid of embarrassment
• Struggles with intimate relationships
• “Maybe he/she doesn’t like me”
• Different from schizoid: wants to socialize but can’t
• Schizoid prefers to be alone (aloof)

Public Domain
Dependent
Personality Disorder
• Clingy
• Low self-confidence
• Struggle to care for themselves
• Depend on others excessively
• Rarely alone, always in a relationship
• Hard to make decisions on their own
• Want someone to tell them what to do
• Difficulty expressing an opinion
• May be involved in abusive relationships

Francisco Carbajal/Flikr
Obsessive-Compulsive
Personality Disorder
• Preoccupied with order and control
• Loves “To Do” lists
• Always needs a plan
• Inflexible at work or in relationships
• Behaviors help to achieve goals (contrast with OCD)

Pixabay/Public Domain
Obsessive-Compulsive
Personality Disorder
• Ego
• Mediates id (desire) and super-ego (rules, society)
• Egosyntonic
• Behaviors that achieve goals of the ego
• Obsessions/compulsions used to achieve goals
• Seen in obsessive-compulsive personality disorder
• Egodystonic
• Behaviors that conflict with goals of the ego
• Obsessions/compulsions are barriers to goals
• Seen in obsessive-compulsive disorder
Dissociative Disorders
Jason Ryan, MD, MPH
Dissociation
• Detachment from reality
• Feeling “like I was outside my own body”
• Extreme cases: becoming another person
• New name, age, job, etc.
• Often associated with psychological trauma
• May allow victim to cope with trauma

Shutterstock
Dissociative Amnesia
Psychogenic Amneisa
• Inability to recall autobiographical memories
• Past events
• Job
• Where they live
• Usually follows major trauma/stress
• Potentially reversible (memories may come back)
• Patient not bothered by lack of memory
• Amnesia not explained by another cause
Dissociative Amnesia
Psychogenic Amneisa
• Different from other forms of amnesia
• Large groups of memories: name, job, home
• Caused by overwhelming stress
• Different from repression
• Loss of autobiographical information: name, job, home

thebluediamondgallery.com
Dissociative Amnesia
Psychogenic Amneisa
• Example:
• Woman attacked in elevator
• Does not recall her job, where she lives, etc.
• Usually self-limited
• Treatment: psychotherapy

Picpedia.com
Dissociative Fugue
• Subtype of dissociative amnesia
• Fugue = Latin for flight or flee
• Sudden travel/wandering in dissociated state
• Example:
• Manager fired from work goes missing
• Found in another town
• No recollection of prior job

Wikipedia/Public Domain
DDD
Depersonalization/Derealization Disorder
• Depersonalization
• Feeling detached or estranged from one’s self
• “Like in a dream”
• “Like I am watching myself”
• Loss of control over thoughts, actions
• Derealization
• Detachment from surrounding world
• Objects seem unreal, foggy, visually distorted
DDD
Depersonalization/Derealization Disorder
• Often triggered by trauma
• Must cause significant distress/impairment
• Intact reality testing
• Differentiates from psychosis
• Patient aware that sensations are not real
• Treatment: psychotherapy

Public Domain
Dissociative Identity Disorder
• Multiple personality disorder
• More common in women
• Associated with childhood trauma/abuse
• Especially sexual abuse, often before age 6

Shutterstock
Dissociative Identity Disorder
• Two or more distinct identities
• “Personality states”
• Alterations in behavior, memory, thinking
• Observed by others or reported by patient
• Gaps in memory about events
• Symptoms cause distress or problems in functioning
• Treatment: psychotherapy

Alan Levine/Flikr
Dissociative Identity Disorder
Comorbidities
• High rate of occurrence with other disorders
• PTSD
• Depression and substance abuse
• Personality disorders: avoidant and borderline

Wikipedia
Dissociative Identity Disorder
Comorbidities
• Somatoform conditions
• Physical symptoms not explained by medical condition

Pixabay/Public Domain
Somatic Disorders
Jason Ryan, MD, MPH
Somatization
• Physical expression of stress or emotions
• Symptoms not explained by medical disease
• Not consciously created for gain (factitious)
• Associated with anxiety and depression
• Risk factors
• Female gender
• Less education
• Minority status
• Low socioeconomic status
Somatization
• Pain symptoms
• Headache, back pain, joint pain
• Gastrointestinal symptoms
• Nausea, abdominal pain, bloating, gas
• Cardiopulmonary symptoms
• Chest pain, dizziness, palpitations
• Neurologic symptoms
• Fainting, muscle weakness, blurred vision
• Dyspareunia, dysmenorrhea

Pixabay.com
Somatization
Management
• Avoid debating if symptoms are psychiatric or medical
• Do not challenge belief that symptoms are medical
• Regular visits with same physician
• Limit tests and referrals
• Reassure patient that serious diseases are ruled out
• Set goals of functional improvement
• Address psychiatric issues gently
• Psychotherapy

Wikipedia/Public Domain
Somatic Symptom Disorder
DSM-V Diagnosis
• Somatic symptoms that cause distress
• Persistent thoughts about seriousness of symptoms
• Anxiety about symptoms
• Excessive time and energy devoted to symptoms
• Persistent (usually more than six months)
Conversion Disorder
Functional neurologic symptom disorder
• Sudden onset usually following stressor
• Voluntary motor or sensory neurologic symptoms
• Inability to speak or move
• Blindness
• Seizures
• Neurologic work-up normal
• Positive findings incompatible with disease
• Example: absence plantar flexion but can stand on toes
• La belle indifference
• Patient shows lack of concern (indifference) about symptoms

Flikr/Public Domain
Illness Anxiety Disorder
DSM-V Diagnosis
• Preoccupation with having undiagnosed illness
• Mild or no somatic symptoms
• Anxiety about health
• Excessive health-related behaviors
• Repeatedly checking for signs of illness
• Present for at least six months
Factitious Disorder on Self
Munchausen syndrome
• Falsified medical or psychiatric symptoms
• Done consciously out of desire for attention
• Patient may feign illness
• May aggravate genuine illness
• Patient often willing to go for tests/surgeries
Factitious Disorder on Self
Munchausen syndrome
• Done for primary (internal) gain from illness
• Patient feels better in sick role
• Sick role solves internal conflict
• Example: patient is afraid of work or afraid to be alone
• Chronic, persistent
• Risk factors:
• Female gender
• Unmarried
• Prior or current healthcare worker

Pixabay/Public Domain
Factitious Disorder on Another
Munchausen by proxy
• Falsified medical symptoms by caregiver
• Often parent of child or caretaker of elderly

Public Domain
Malingering
• Consciously falsified medical symptoms
• Done for secondary (external) gain
• Allows patient to miss work but get paid
• Obtain workman’s compensation
• Self-limited
• Ends when secondary gain achieved
• Not a DSM-V psychiatric disorder
Eating Disorders
Jason Ryan, MD, MPH
Eating Disorders
• Abnormal eating patterns
• Disrupt health or psychosocial functioning
• More common in women
• Usually present in adolescence or young adulthood
• DSM-V Disorders
• Anorexia nervosa
• Bulimia nervosa
• Binge eating disorder
Anorexia Nervosa
• Diet and exercise that leads to low body weight
• World Health Organization: BMI < 18.5 kg/m2
• Intense fear of gaining weight
• Distorted perception of body weight
• Increased mortality from malnutrition
• Two subtypes:
• Restricting (low calorie intake/exercise)
• Binge-purging

Wikipedia/Public Domain
Anorexia Nervosa
• Often co-exists with other disorders
• Depression
• Anxiety
• Obsessive-compulsive disorder
• Posttraumatic stress disorder
• Substance abuse
• Often secondary to eating disorder
• Improve with weight restoration
• Especially depression
Anorexia Nervosa
Endocrine Effects
• Reproductive hormones
• ↓ GnRH secretion
• ↓ LH/FSH
• Amenorrhea
• “Functional hypothalamic amenorrhea”
• Thyroid
• “Sick euthyroid” pattern of thyroid function tests
• Low T3
• High rT3
• Normal or low TSH/T4
Anorexia Nervosa
Electrolytes
• Hyponatremia
• Low solute intake
• Tea and toast diet
• Creatinine low (↓ muscle mass)
• If purging: hypokalemia

Wikipedia/Public Domain
Anorexia Nervosa
Bones
• ↓ bone density
• Low estrogen
• High cortisol
• Osteopenia
• Osteoporosis

Hellerhoff/Wikipedia
Anorexia Nervosa
Hematology
• Bone marrow suppression
• Anemia
• Leukopenia
• Thrombocytopenia

Keith Chambers/Wikipedia
Anorexia Nervosa
Cardiac
• Decreased cardiac mass
• May lead to cardiomyopathy
• May cause arrhythmias
Anorexia Nervosa
Physical Exam
• Low body mass index (< 18.5 kg/m2)
• Mild: 17 to 18.5
• Moderate: 16 to 16.99
• Severe: 15 to 15.99
• Extreme: < 15

Public Domain
Anorexia Nervosa
Physical Exam
• Bradycardia
• Hypotension
• ↓ bowel sounds
• Dry, scaly skin (xerosis)
• Hair loss
• Lanugo hair growth
• Soft, fine hair

Wikipedia/Public Domain
Anorexia Nervosa
Treatment
• Nutritional rehabilitation
• Structured meals with observation
• Calorie goals
• Psychotherapy
• Olanzapine (antipsychotic)
• Hospitalization indications
• Very low body weight
• Hemodynamic instability
• Volume depletion
• Refusal to eat

Shutterstock
Refeeding Syndrome
• Hallmark: hypophosphatemia
• Low PO4 from poor nutrition
• Glucose → ↑ insulin → ↑ metabolism
• Further ↓ PO4 from cellular uptake
• Loss of ATP → cardiac and respiratory failure
• Most fatalities: cardiac
• Poor contractility, low stroke volume
• Heart failure, arrhythmias
• Prevention: slow refeeding (gentle ↑ calorie intake) Phosphate
Bulimia Nervosa
• Binge eating
• Inappropriate compensation to avoid weight gain
• Vomiting (purging)
• Laxatives, diuretics, enemas
• Excessive exercise
• Fasting
• Severely restrictive diets
Bulimia Nervosa
• Occurs at least once a week for three months
• Weight usually normal (contrast with anorexia)
• Commonly coexists with other disorders
• Anxiety
• Depression
• Posttraumatic stress disorder
• Substance abuse
Bulimia Nervosa
Purging Complications
• Increased bicarbonate
• Vomiting
• Contraction alkalosis
• Hypokalemia
• Loss of potassium
• Hypochloremia
• Urinary chloride is low (<20)
Urinary Chloride
• Useful in metabolic alkalosis unknown cause
• Low (< 20) in vomiting
• Loss of Cl in gastric secretions
• High (> 20) in many other forms of alkalosis
• Classic scenario:
• Young woman with unexplained metabolic alkalosis
• Urinary chloride low

Wikipedia/Public Domain
Bulimia Nervosa
Purging Complications
• Parotid swelling
• “Parotid gland hypertrophy”
• Sialadenosis
• Erosion of dental enamel

BruceBlaus/Wikipedia
Russell’s Sign
• Scars on knuckles from induced-vomiting

Wikipedia/Public Domain
Bulimia Nervosa
Treatment
• Nutritional rehabilitation
• Psychotherapy
• SSRIs
Binge Eating Disorder
• Binge eating
• Compulsive overeating
• Excessively large amounts of food
• Often eaten quickly
• Patient feels they lack control
• Patient feels shame/embarrassment
• No inappropriate compensation
• Weight gain
• Occurs at least once a week for three months
Binge Eating Disorder
• Often occurs with other disorders
• Anxiety, depression
• Studies show high risk of type II diabetes
• First-line treatment: psychotherapy (CBT)
• Large clinical effect in trials
• Greater than medication effect
• SSRIs used but less effective
Binge Eating Disorder
• Lisdexamfetamine
• ADHD stimulant
• Topiramate
• Seizure medication
• Clinical trials: ↑ abstinence from binge episodes
• Both lead to reduced weight
Alcohol Use Disorder
Jason Ryan, MD, MPH
Substance Use Disorder
• DSM-V: Two or more during 12-month period
• Tolerance
• Withdrawal
• Taken in larger amounts or over a longer period
• Unsuccessful efforts to cut down or control use
• Lots of time spent to obtain, use, or recover from
• Craving or a strong desire or urge to use
• Failure to fulfill obligations at work, school, home
• Continued use despite social or interpersonal problems
• Social/occupational activities given up or reduced
• Use in situations in which it is physically hazardous
• Use despite knowledge of having a problem
Stages of Change

Toddatkins
Stages of Change
• Precontemplation
• No intention of behavior change
• May not recognize/acknowledge problem
• Contemplation
• Aware problem exists
• Not yet willing to change
• Preparation
• Intending to take action
• Action
• Maintenance
• Relapse
Alcohol
• “Alcohol” = ethyl alcohol = ethanol Ethanol
• Found in alcoholic beverages
• Commonly abused substance
• Metabolized by liver
• Activates GABA receptors
• Numerous biochemical effects

Wikipedia/Public Domain
Alcohol Intoxication
• CNS depressant
• Slurred speech
• Incoordination
• Unsteady gait
• Stupor
• Coma

Pixabay/Public Domain
Alcohol Intoxication
• Serum blood alcohol concentration (BAC)
• Most US states: legal limit 80 mg/dL
• “0.08 g/dL” or “0.08” or “8%”
• Number of drinks to reach limit varies with size

Jeffrey Smith/Flikr
Alcohol Biomarkers
• Markers of liver damage
• Used to screen for heavy, chronic use

Abstinence Time
Biomarker
for Return to Normal
Gamma–glutamyltransferase (GGT) 2-6 weeks
Aspartate aminotransferase (AST) 7 days

Also seen in chronic use: ↑ MCV and hypertension

Alcohol Poisoning
• Very high BAC → respiratory depression
• Can be fatal
• Treatment is mostly supportive
• May require ICU care

Pixabay/Public Domain
Alcohol Withdrawal
• Heavy drinkers after abrupt cessation
• 6 to 24 hours after last drink
• Tremors
• Anxiety
• GI upset
• Headache
• Sweating
• Palpitations
• Mental status intact
Alcohol Seizures
• 24 to 48 hours after last drink
• Generalized tonic-clonic seizures
• Single or in clusters of two to three

Public Domain
Alcohol Hallucinosis
• 24 to 48 hours after last drink
• Often visual hallucinations
• Seeing insects or animals
• Hearing voices
• Tactile sensations

Steve Jurvetson/Flikr
Delirium Tremens
• Between 48 and 96 hours after last drink
• Most severe withdrawal manifestation
• 20% mortality in some studies

Pixabay/Public Domain
Delirium Tremens
• Delirium
• Agitation
• Fever
• Drenching sweats
• Autonomic hyperactivity
• Tachycardia, hypertension
• Death from:
• Hyperthermia
• Cardiovascular collapse
• Arrhythmias
• Fluid/electrolyte abnormalities

Shutterstock
Alcohol Withdrawal
Treatment
• Benzodiazepines
• Functional liver: diazepam or chlordiazepoxide (long-acting)
• Cirrhosis or alcoholic hepatitis: lorazepam (short acting)
• Improve agitation and prevent progression
• CIWA scale
• Symptom-triggered therapy
• Clinical Institute Withdrawal Assessment for Alcohol
• Point system for assessing withdrawal symptoms
• Regular assessment of patient
• Benzodiazepine given if score is high
Alcohol Use Disorder
• Recurrent drinking causing impaired social functioning
• Many medical complications Chronic Pancreatitis
• Gastrointestinal
• Gastritis, hepatitis, cirrhosis, pancreatitis
• Cardiac
• Dilated cardiomyopathy, refractory hypertension
• Malignancy
• Esophageal and oropharyngeal cancers

Hellerhoff/Wikipedia
Alcohol Use Disorder
Wernicke-Korsakoff
• Wernicke: acute encephalopathy
• Korsakoff: chronic neurologic condition
• Usually a consequence of Wernicke
• Both associated with:
• Thiamine (B1) deficiency
• Alcohol use
• Atrophy of mammillary bodies common finding
• 80% for both conditions
• Associated with damage to thalamic nuclei
Alcohol Use Disorder
Wernicke-Korsakoff
• Wernicke Encephalopathy
• Visual disturbances/nystagmus
• Gait ataxia
• Confusion
• Often reversible with thiamine
• Korsakoff Amnesia
• Recent memory affected more than remote
• Can’t form new memories
• Confabulation: Can’t remember so makes things up
• Lack of interest or concern (apathy)
• Usually permanent

Shutterstock
Alcohol Use Disorder
Nutritional Deficiencies
• Thiamine (vitamin B1)
• Pyridoxine (vitamin B6)
• Folate (vitamin B9)
• Magnesium
• Calcium
• Phosphorus
Alcohol Use Disorder
Nutritional Deficiencies
• Banana bag
• IV infusion to alcohol users
• Thiamine, folate, and magnesium
• Wernicke precipitated by glucose without thiamine
• Thiamine co-factor glucose metabolism
• Glucose will worsen thiamine deficiency

Public Domain
Alcohol Use Disorder
Treatment
• Support groups (Alcoholics Anonymous)
• Three FDA-approved drugs
• Reduce risk of relapse
• Disulfiram (Antabuse)
• Naltrexone
• Acamprosate
Disulfiram
Antabuse
• Inhibits aldehyde dehydrogenase
• Acetaldehyde accumulates
• Triggers catecholamine release
• Sweating, flushing, palpitations, nausea, vomiting

NAD+ NADH NAD+ NADH

Alcohol Aldehyde
Dehydrogenase Dehydrogenase

Ethanol Acetaldehyde Acetate

Naltrexone
• Long acting opioid antagonist
• Endogenous opioids reinforce alcohol effects
• Given orally to prevent relapse
• Also used in opioid abuse

Naltrexone
Acamprosate
• Mechanism incompletely understood
• Modulates NMDA receptors
• Alcohol disrupts CNS equilibrium
• Excitatory glutamate activity (NMDA receptor)
• Inhibitory GABA activity
• Common side effect (~15%): diarrhea

Acamprosate
Alcohol Use Disorder
Screening
• CAGE questionnaire
• Have you ever felt you should Cut down on your drinking?
• Have people Annoyed you by criticizing your drinking?
• Have you ever felt bad or Guilty about your drinking?
• Have you ever had a drink first thing in the morning as an Eye opener?
• Score of 2 or greater is clinically significant
• Other tools
• AUDIT (10 questions)
• MAST (25 questions)

Pixabay
Substance Abuse I
Jason Ryan, MD, MPH
Cocaine
• Two key physiologic effects
• #1: Local anesthetic (Na channel blocker)
• #2: Inhibits monoamine reuptake
• Monoamines: dopamine, serotonin, NE
• Sympathetic activation

Cocaine
 Norepinephrine

- α2
-
Cocaine Amphetamine
NE +
Amphetamines

NE
Receptor
Cocaine Intoxication
• Increased energy
• Decreased need for sleep
• Alertness
• Euphoria

Wikipedia/Public Domain
Cocaine Intoxication
• Hallucinations
• Classically tactile
• “Bugs crawling on my skin”
• Paranoia
• Fever
• Increased muscle activity
• Central dopamine release
• Anxiety
• May mimic psychosis
• Treatment: benzodiazepines
Michael "BuZZeR" Kadykov
Cocaine Intoxication
• Rhabdomyolysis
• Seizures
• Myocardial ischemia

Free SVG
Cocaine Intoxication
Signs
• Sympathetic nervous system activation
• Stimulation of alpha and beta receptors
• Dilated pupils
• Tachycardia
• Hypertension

OpenStax College/Wikipedia
Cocaine Intoxication
Myocardial Ischemia
• Angina common among cocaine users
• ↑ O2 demand (tachycardia, elevated BP)
• ↓ O2 supply (coronary vasoconstriction)
• O2 mismatch → angina
• May lead to thrombosis → myocardial infarction

Freestocks.org
Cocaine Intoxication
Myocardial Ischemia
• Treatment: benzodiazepines
• Sedating/calming
• Diminish cocaine-related stimulating effects
• Aspirin
• Catheterization in severe cases
• Avoid beta-blockers
• Increased alpha effects
• Worsening of hypertension and chest pain

Wikipedia/Public Domain
Cocaine Withdrawal
• Occurs with stopping after chronic, heavy use
• Usually not life-threatening
• Depression and anhedonia
• Anxiety
• Cravings
• Increased sleep
Amphetamines
• Modified phenethylamines
• Stimulants
• Indirect sympathomimetics
• Increase synaptic dopamine/NE levels

Phenethylamine Methamphetamine
Amphetamine Intoxication
• Similar to cocaine
• Euphoria/fever
• Sympathetic stimulation
• Tachycardia, hypertension
• Pupillary dilation
• Rhabdomyolysis/seizures/ischemia
• Treatment: benzodiazepines
• Withdrawal syndrome similar to cocaine

Wikipedia/Public Domain
Opioids
• Activate opioid receptors: mu, kappa and delta
• Prototype: morphine
• Also hydromorphone, meperidine, fentanyl, codeine
• Drug of abuse: heroin (diamorphine)

Morphine Heroin
Heroin
• Usually injected into vein
• Contaminated needle or drugs:
• Bacteremia → tricuspid endocarditis
• Hepatitis B & C
• HIV

Psychonaught/Wikipedia
Opioids
Central nervous system effects
• Pain relief (analgesia)
• Euphoria
• Sedation

Wikipedia/Public Domain
Opioids
Central nervous system effects
• Slurred speech
• Respiratory depression
• Cough suppression
• Miosis (small pupils)
• Exception: meperidine

Wikipedia/Public Domain
Opioids
Peripheral nervous system effects
• Constipation
• Nausea
• Vomiting
• Skin warmth and flushing

John Johnson/Pexels
Opioids
Clinical Uses
• Pain control
• Acute pulmonary edema (IV morphine)
• Cough suppression (codeine)
• Diarrhea (loperamide)
• Shivering: (meperidine/Demerol)
Opioids
Addiction & Tolerance
• Highly addictive
• Tolerance develops
• Less effect of drugs over time
• Higher dosages required to achieve effects
• No tolerance to miosis and constipation

Wikipedia/Public Domain John Johnson/Pexels

Opioids
Acute Intoxication
• Most common cause of drug overdose death
• Euphoria to depressed mental status
• Decreased respiratory rate
• Decreased bowel sounds
• Miotic (constricted) pupils
• Seizures
• Most common with tramadol or meperidine

Wikipedia/Public Domain
Opioid Intoxication
Treatment
• Naloxone
• Short-acting opioid antagonist
• May cause withdrawal if dose too high (“overshoot”)

Morphine Naloxone
Opioid Withdrawal
Causes
• Iatrogenic
• Caused by opioid antagonist
• Potentially life-threatening
• Surges in catecholamines
• Hemodynamic instability
• Naturally-occurring
• Usually not life-threatening
• Clinically Oriented Withdrawal Scale (COWS)
• 11-item scale
• Point system to assess symptoms
• Mild, moderate, severe withdrawal
Opioid Withdrawal
Naturally-Occurring
• Occurs in opioid-dependent individuals
• Usually starts 6-12 hours after last dose
• Reversal of CNS, eye, skin, GI effects
• Restlessness
• Yawning
• Rhinorrhea and lacrimation
• Piloerection
• Nausea, vomiting, abdominal cramps
• Diarrhea

FreeSVG
Opioid Withdrawal
Medical Therapy
• Minimizes withdrawal symptoms
• Clonidine
• Central alpha agonist
• Blunts sympathetic activation
• Sedating
• Opioid agonists
• Buprenorphine
• Methadone
Opioid Use Disorder
Treatment
• Buprenorphine
• Partial agonist (agonist and antagonist effects)
• Long duration of action
• Sublingual tablet
• DEA schedule III drug
• May cause withdrawal (like naloxone)
• Combined with naloxone
• Prevents abuse
• Naloxone not absorbed sublingually
• Crushed pill → IV injection → no effect
Buprenorphine
Opioid Use Disorder
Treatment
• Methadone
• Long-acting oral opiate
• Reduces cravings
• Maintenance
• Strictly regulated/controlled
• DEA schedule II

Methadone
Controlled Substances Act
• Places drugs in categories based on abuse potential

Schedule Meaning Examples

I No medical indication Heroin, LSD, ecstasy
II High abuse potential Cocaine, methadone, fentanyl, Ritalin
III Moderate abuse potential Buprenorphine, ketamine, anabolic steroids
IV Low abuse potential Benzodiazepines
V Very low abuse potential Cough medications with codeine
Opioid Use Disorder
Treatment
• Naltrexone
• Long-acting opioid antagonist
• Blocks effects of opioids if taken
• Administered to detoxified patients to prevent relapse
• Some data show prevention of relapse
• Also used in alcohol use disorder

Naltrexone
Substance Abuse II
Jason Ryan, MD, MPH
Barbiturates
Phenobarbital, pentobarbital
• Anti-seizure drugs
• GABA activators
• Used as sedatives in past
• Now largely replaced benzodiazepines
• Similar effects to alcohol (CNS depressants)
• Narrow therapeutic index
• Dangerous used together with alcohol

Wikipedia/Public Domain
Barbiturates
Phenobarbital, pentobarbital
• Overdose: respiratory depression
• No antidote
• Supportive care
• Heavy users must be weaned
• Abrupt withdrawal:
• Delirium
• Hallucinations
• Seizures
• Cardiovascular collapse → death

Wikipedia/Public Domain
Benzodiazepines
Diazepam, oxazepam, lorazepam
• Many medical uses (seizures, anxiety, alcohol withdrawal)
• Increase GABA activity
• Rarely cause respiratory depression (safer drugs)
• Classic overdose presentation:
• CNS depression with normal vitals
• Altered mental status
• Slurred speech
• Ataxia
Flumazenil
• Antagonist of benzodiazepine receptor
• Use to treat overdose controversial
• Overdose has low mortality rate
• Flumazenil may cause withdrawal seizures

Flumazenil
Benzodiazepine Withdrawal
• Occurs with abrupt cessation after chronic use
• Similar to alcohol withdrawal
• Tremors
• Anxiety
• Depressed mood (“dysphoria”)
• Hypersensitivity to sensations (noise, touch)
• Psychosis
• Seizures
• Can be life-threatening
• Treatment: benzodiazepines

Public Domain
Marijuana
• Derives from cannabis (plant)
• Psychiatric activity from tetrahydrocannabinol (THC)
• Also called dronabinol
• Stimulates cannabinoid receptors in CNS

Wikipedia/Public Domain
Marijuana
• Euphoria
• Anxiety
• Impaired coordination
• Conjunctival injection
• Dry mouth
• Increased appetite
• Tachycardia
• Blood pressure fluctuations
• Rarely causes hallucinations or psychosis
• Usually not life-threatening
Wikipedia/Public Domain
Synthetic Cannabinoids
• Pharmaceutical forms of dronabinol
• Available in capsule form
• Cannabis withdrawal
• Chemotherapy-induced nausea and vomiting
• Appetite stimulation in wasting illnesses
• Often end stage HIV/AIDS patients
Ecstasy
Methylenedioxymethamphetamine (MDMA)
• Major effect on serotonin
• Increased release of serotonin
• Inhibition of serotonin reuptake

Serotonin MDMA
Ecstasy
Methylenedioxymethamphetamine (MDMA)
• Euphoria
• Alertness
• Increased sociability
• Increased sexual desire
• Bruxism (grinding teeth)

Wikipedia/Public Domain
Ecstasy
Methylenedioxymethamphetamine (MDMA)
• Tachycardia and hypertension
• Hyperthermia
• Hyponatremia
• Increased fluid intake
• Secretion of antidiuretic hormone
• Reports of seizures and death
• Hepatotoxicity
• RUQ pain
• Increased AST/ALT
• Can cause serotonin syndrome
Ecstasy Withdrawal
• “Crash” after using MDMA
• Depression and anxiety
• Fatigue and lethargy
• Difficulty concentrating
• Loss of appetite
• Jaw soreness (from grinding teeth while high)

Public Domain
LSD
Lysergic acid diethylamide
• Hallucinogen
• Exact mechanism unknown
• Binds serotonin 5-HT2A receptors

LSD
LSD
Lysergic acid diethylamide
• Causes LSD “trip”
• Feeling of expanded consciousness
• Can sense things beyond usual reality
• Synesthesia (a blending of the senses)
• “Hearing" colors or "seeing" sounds
• Depersonalization
• Feeling disconnected or detached from body
• “Bad trip”
• Paranoia, anxiety
Shutterstock
LSD
Lysergic acid diethylamide
• May causes “flashbacks”
• Return of hallucinogen effects after stopping drug
• May occur days, weeks, even months later
• Intoxication management: supportive

Pariroxy/Wikipedia
PCP
Phencyclidine
• “Angel dust”
• Antagonist of NMDA receptor in CNS
• N-methyl-D-aspartate
• Glutamate receptor
• Blockade: hallucinations and psychosis
• Inhibits reuptake of dopamine, NE, 5HT
• Increases sympathetic activity

Phencyclidine
PCP
Phencyclidine
• Stimulant
• Altered mental status
• Psychosis (with hallucinations)
• “Psychomotor agitation”
• Classically agitated, violent behavior
• Tachycardia, hypertension
• Nystagmus (repetitive involuntary eye movements)
• Rarely coma and seizures with overdose

Pxhere/public domain
PCP
Phencyclidine
• Fatalities most commonly from trauma
• Psychosis plus loss of pain/sensation
• Patients may dissociate
• Walk into traffic
• Jump from buildings
• Treatment:
• Benzodiazepines
• Haloperidol (rapid-acting anti-psychotic)

Alisha Vargas/Flikr
Caffeine
• Methylxanthine
• Antagonist of adenosine receptors
• Leads to release of dopamine/NE
• Renal adenosine blockade → diuresis

Caffeine
Adenosine
Chemical Stress Tests
• Intravenous adenosine used as a vasodilator
• Induces coronary steal for chemical stress testing
• Effects blocked by caffeine
• Also blocked by theophylline (COPD drug)

Adenosine Caffeine Theophylline

Antidepressants
Jason Ryan, MD, MPH
Antidepressants
• Tricyclics
• MAO inhibitors
• SSRIs
• SNRIs
• Atypical antidepressants
Depression
• Associated with CNS neurotransmitter changes:
• ↓ serotonin
• ↓ norepinephrine
• ↓ dopamine
• Improved symptoms with increased CNS levels Norepinephrine

• Most antidepressant drugs increase synaptic levels

• Block re-uptake
• Inhibit breakdown

Serotonin
Dopamine 5-HT
 Pre-synaptic
Neuron

NT

Reuptake Breakdown
NT

Post-synaptic
Neuron
Monoamines
• Serotonin, norepinephrine, histamine, dopamine
• Most drugs affect more than one monoamine Dopamine
• Anti-histamine: sedation, dry mouth
• NE blockade: hypotension (alpha-1)
• Muscarinic blockade: tachycardia, urinary retention

Histamine

Serotonin
5-HT
Acetylcholine
Norepinephrine
Tricyclic Antidepressants
• Old antidepressants (1970s)
• Block re-uptake of 5-HT and norepinephrine
• “Broad spectrum”
• Anti-histamine
• Anti-muscarinic Amitriptyline
• Block alpha-1 receptors
• Many side effects

Imipramine

Nortriptyline
Tricyclic Antidepressants
• Anti-histamine
• Sedation, weight gain, confusion (especially elderly)
• Anti-cholinergic (muscarinic)
• Blurry vision, constipation, dry mouth, urinary retention, sexual dysfunction
• Alpha-1 block
• Orthostatic hypotension

Shutterstock
Tricyclic Antidepressants
• Tertiary amines (3 nitrogen attachments)
• Amitriptyline, imipramine, clomipramine, doxepin
• More sedating (anti-histamine effects)
• Secondary amines (2 nitrogen attachments) Imipramine
• Desipramine, nortriptyline
• More activating (norepinephrine effects)

Nortriptyline
Tricyclic Antidepressants
Overdose
• Potentially fatal
• Seizures and coma
• TCAs antagonize GABA receptors
• Anticholinergic toxicity
• Hyperthermia (loss of sweating)
• Skin flushing, dilated pupils
• Ileus, urinary retention
• Hypotension (alpha blockade)
• Major cause of death
• Prolongation of QT interval → arrhythmias

Pixabay.com
Tricyclic Antidepressants
Overdose
• Monitor ECG for increased QRS interval
• Most prominent manifestation of toxicity
• TCAs block cardiac sodium channels
• Treatment: sodium bicarbonate
• Extra sodium overcomes TCA Na-channel blockade
• Also ↑ pH favors inactive form of drug
Tricyclic Antidepressants
Non-depression uses
• Obsessive-compulsive disorder (clomipramine)
• Diabetic peripheral neuropathy
• Amitriptyline, desipramine
• Chronic pain
• Amitriptyline, doxepin, imipramine, nortriptyline, desipramine
• Prevention of migraine headaches
• Amitriptyline
• Bedwetting (enuresis)
• Not first-line therapy (desmopressin)
• Imipramine, amitriptyline, and desipramine
• Insomnia (doxepin)
MAO Inhibitors
Monoamine Oxidase Inhibitors
• Inhibits monoamine oxidase
• ↓ breakdown of monoamines
• Serotonin, norepinephrine, dopamine
• MAO-A Norepinephrine
• Dopamine, serotonin, norepinephrine
• MAO-B
• Dopamine

Serotonin
Dopamine 5-HT
MAO Inhibitors
Monoamine Oxidase Inhibitors
• Non-selective MAO inhibitors
• Tranylcypromine, phenelzine, isocarboxazid
• MAO-B selective: selegiline
• Used in Parkinson’s
• Rarely used as antidepressants in modern era
• Refractory depression
• Anxiety
Serotonin Syndrome
• Classic triad: Three As
• #1: Mental status changes
• Agitation, restlessness, and disorientation
• #2: Autonomic hyperactivity
• Diaphoresis, tachycardia, hyperthermia
• #3: Neuromuscular hyperactivity
• Tremor, clonus, hyperreflexia, bilateral Babinski sign
• Treatment: cyproheptadine Cyproheptadine
• 5 –HT antagonist
Serotonin Syndrome
• Often caused by MAOI plus another serotonin drug
• Any drug that that ↑ serotonin activity
• SSRIs, SNRIs, TCAs
• MDMA (ecstasy)
• Ondansetron (nausea; 5-HT3 antagonist)
• Tramadol (weak opioid; inhibits 5-HT reuptake)
• Meperidine (opioid; inhibits 5-HT reuptake)
• Triptans (migraines; 5-HT agonists)
• Linezolid (antibiotic; weak MAO inhibitor)
• Dextromethorphan (cough suppressant; weak SSRI)
• St. John’s wort (herbal supplement; increase 5-HT activity)
Serotonin Syndrome
• When switching from MAOI to SSRI:
• Two-week washout
• When switching from SSRI to MAOI:
• Usually two-week washout
• Fluoxetine: five weeks (long half life)
Tyramine
• Naturally occurring monoamine
Tyramine
• Sympathomimetic
• Causes sympathetic activation
• Normally metabolized GI tract
• Patients on MAOI → tyramine in blood
• Hypertensive crisis
• “Cheese effect”
• Cheese, red wine, some meats

Pixabay/Public Domain
SSRIs
Selective serotonin reuptake inhibitors
• Inhibit 5-HT reuptake by neurons
• Lead to ↑ 5-HT levels in synaptic cleft Fluoxetine
• Take 4-8 weeks to have effects Sertraline
• Used in many psychiatric disorders Paroxetine
• Depression Citalopram
• Generalized anxiety disorder Escitalopram
• Panic disorder
• Obsessive-compulsive disorder
Fluvoxamine
• PTSD
• Bulimia
• Social anxiety disorder
SSRIs
Selective serotonin reuptake inhibitors
• Non-specific side effects that often subside with use
• Headache
• Insomnia
• GI upset (nausea, diarrhea)
• Drowsiness
• Rare, dangerous effects
• SIADH and hyponatremia
• QT prolongation
• Serotonin syndrome
• Sexual dysfunction
SSRIs
Selective serotonin reuptake inhibitors
• Common side effect: sexual dysfunction
• Increased serotonin effects in spinal cord
• Decreased libido (54 percent)
• Anorgasmia: difficulty achieving orgasm (36 percent)
• Erectile dysfunction in males (37 percent)
• Usually does not subside over time
• SSRIs can treat premature ejaculation

Wikipedia/Public Domain
Discontinuation Syndrome
• Abrupt discontinuation of antidepressant
• Can occur with any antidepressant
• Most common with SSRIs
• Exception: fluoxetine (long half life)
• Dizziness
• Fatigue
• Headache
• Nausea
• Avoid by slowly tapering off drug

Shutterstock
SNRIs
Serotonin-norepinephrine reuptake inhibitors
• Inhibit 5-HT and NE reuptake by neurons
• Take 4-8 weeks to have effects
• Used in many psychiatric disorders Venlafaxine
• Depression Desvenlafaxine
• Generalized anxiety disorder
• Social anxiety disorder
Duloxetine
• Panic disorder Milnacipran
• PTSD Levomilnacipran
• Obsessive-compulsive disorder
• Fibromyalgia (duloxetine)
• Diabetic neuropathy (venlafaxine)
SNRIs
Serotonin-norepinephrine reuptake inhibitors
• Similar side effects to SSRIs
• May increase blood pressure
• Norepinephrine effects
• Sexual dysfunction
• Highest rate: venlafaxine

Public Domain
Bupropion
• Blocks reuptake of NE and dopamine
• Increases presynaptic release of catecholamines
• No effects on serotonin
• Used in depression and smoking cessation
• May improve sexual dysfunction of SSRIs
• Toxicity related to stimulant effects
• Anxiety
• Insomnia
• Lowers seizure threshold

Pixabay/Public Domain
Mirtazapine
• Blocks presynaptic alpha-2 receptors
• More norepinephrine and serotonin release
• Blocks postsynaptic serotonin 5-HT2 and 5-HT3
• More 5-HT1 activity
• Anti-histamine side effects
• Sedation
• Dry mouth
• Increased appetite
• Weight gain

Pexels
Alpha 2 Receptors
α2 receptors in CNS
Presynaptic receptor Pre-
Feedback to nerve when NE released synaptic
Activation leads to ↓NE release
Neuron

α2
Norepinephrine
NE
Serotonin

Post-synaptic
Neuron
Trazadone and Nefazodone
• Weak serotonin reuptake inhibitors
• Affects serotonin 5-HT2A and 5-HT2C receptors
• Low doses: serotonin antagonist
• High doses: serotonin agonist
• Trazadone
• Main clinic use is insomnia (sedating)
• Nefazodone
• May cause liver failure
• Must monitor AST/ALT

Public Domain
Priapism Priapus
Greek Fertility God

• Persistent erection
• Causes compartment syndrome
• Hypoxia and acidosis in cavernous tissue
• Rare, dangerous adverse effect of trazadone
• Usually within 1 month of starting treatment
• Urgent urology evaluation
• Treatment: intracavernosal vasoconstrictor injection
• Contracts cavernous smooth muscle allowing venous outflow
• Epinephrine
• Phenylephrine

Public Domain
Antipsychotics
Jason Ryan, MD, MPH
Dopamine
• 1950s: chlorpromazine found to improve psychosis
• Also found to block CNS dopamine receptors
• Dopamine hypothesis

Dopamine
Antipsychotics
First Generation or Typical
• Haloperidol
• Chlorpromazine
• Trifluoperazine
• Fluphenazine
• Thioridazine
• Pimozide
• Primary antipsychotic effect: D2 receptor blockade
Parkinson’s Disease
• Motor dysfunction
• Tremors, rigidity
• Associated with ↓ CNS dopamine activity

Wikipedia/Public Domain
Neurotransmitters

Histamine Serotonin
5-HT

Dopamine

Acetylcholine
Epinephrine
(Muscarinic)
Antipsychotics
First Generation or Typical
• Dopamine blockade
• Serotonin blockade
• Histamine blockade
• Acetylcholine (muscarinic) blockade
• Epinephrine (alpha-1) blockade

Chlorpromazine: α1=5HT> D2
Haloperidol: D2 > α1 > 5HT > H1
Antipsychotics
First Generation or Typical
• Dopamine blockade
• Parkinsonian effects (extrapyramidal)
• Hyperprolactinemia
• Gynecomastia
• Galactorrhea
• Amenorrhea
• Anti-emetic (Prochlorperazine/Chlorpromazine)
Antipsychotics Xerostomia
First Generation or Typical (Dry Mouth)
• ACh muscarinic receptor blockade
• Dry mouth
• Constipation
• Urinary retention
• Tachycardia
• Sexual dysfunction
• α1 receptor blockade
• Hypotension
• Histamine receptor blockade
• Sedation
• Weight gain Wikipedia/Public Domain
Pyramidal vs. Extrapyramidal
• Pyramidal system
• Corticospinal tract
• Run in pyramids of medulla
• Damage → weakness
• Extrapyramidal system
• Basal ganglia nuclei and associated tracts
• Modulation of movement
• Damage → movement disorders

Wikipedia/Public Domain
EPS
Extrapyramidal Symptoms
• Response to dopamine receptor blockade
• Movement side effects
• Dystonia
• Akathisia
• Bradykinesia
• Tardive dyskinesia
Dystonia
Extrapyramidal Symptoms
• Acute side effect
• Occurs within hours/days Writer’s Cramp

• Involuntary contraction of muscles

• Spasms, stiffness
• Treatments:
• Benztropine (anticholinergic)
• Diphenhydramine (antihistamine)
• Improves dystonia
Akathisia
Extrapyramidal Symptoms
• Occurs within days
• Most common EPS adverse effect
• Restlessness, urge to move
• Sometimes misdiagnosed as worsening agitation
• Treatments:
• Lower dose
• Benzodiazepines
• Propranolol
Bradykinesia
Extrapyramidal Symptoms
• Occurs weeks after starting drug
• “Drug-induced Parkinsonism”
• Slow movements (Parkinson-like)
• Treatment: benztropine
• Second line: amantadine
Tardive Dyskinesia
Extrapyramidal Symptoms
• Occurs months or years after starting drug
• Choreoathetosis
• Chorea: irregular migrating contractions
• Athetosis: twisting and writhing
• Mouth, tongue, face, limbs
• Smacking lips, grimacing
• Often irreversible
• Stopping drug doesn’t help
• One FDA-approved drug: valbenazine
• Inhibits VMAT2
• Depletes dopamine storage in presynaptic vesicles
Antipsychotics
First Generation or Typical
• High potency agents
• Haloperidol, fluphenazine, pimozide
• Lower dose required to achieve effect
• Example: haloperidol 1mg
• Little effect on histamine and muscarinic receptors
• Less sedation (histamine) or dry mouth (muscarinic)
• Extrapyramidal side effects

Chlorpromazine: α1=5HT> D2
Haloperidol: D2 > α1 > 5HT > H1
Antipsychotics
First Generation or Typical
• Low potency agents
• Thioridazine, chlorpromazine
• Example: Thioridazine 50-100mg
• Less extrapyramidal side effects
• More non-neurologic side effects
• Sedating (“sedatives”)
• Dry mouth

Chlorpromazine: α1=5HT> D2
Haloperidol: D2 > α1 > 5HT > H1
Antipsychotics
First Generation or Typical

High Potency
Low Potency
Haloperidol
Thioridazine
Trifluoperazine
Chlorpromazine
Fluphenazine

Non-EPS Effects EPS Effects

Sedation Movement symptoms
Dry mouth
NMS
Neuroleptic Malignant Syndrome
• Rare, dangerous reaction to neuroleptics
• Usually high-potency first-generation drugs
• Haloperidol, fluphenazine
• Usually 7-10 days after treatment started
• Fever and rigid muscles
• Mental status changes (encephalopathy)
• Elevated creatine kinase (muscle damage)
• Myoglobinuria → acute renal failure (rhabdomyolysis)
NMS
Treatment
• Dantrolene (muscle relaxant)
• Bromocriptine (dopamine agonist)
• Similar to malignant hyperthermia
• Reaction to halothane, succinylcholine
• Same treatment: dantrolene (muscle relaxant)
QT interval
• May block cardiac potassium channels
• Prolongs QT interval
• Strongest association with IV haloperidol

Torsade de Pointes
Thioridazine and Chlorpromazine
• Retinal deposits
• Advanced cases resemble retinitis pigmentosa
• May cause “browning” of vision
• Uses lower doses to avoid this complication
• More common with thioridazine (higher doses)
• Corneal deposits Christian Hamel

• May accelerate aging of lens

• Possibly associated with cataracts

Sushil et a.. Ophth Res 4(4) 108-111

Chlorpromazine
• Skin effects
• Occurs in sun-exposed areas
• Photosensitivity
• Skin pigmentation (blue-gray)
• Cholestatic jaundice
• Occurs in 1 to 2 percent of patients

International journal of dermatology 2016

Chlorpromazine-induced severe skin pigmentation and corneal opacities in a patient with schizophrenia.
Ana María Molina-Ruiz, Águeda Pulpillo, R. M. Molina-Ruíz, Teresa Sagrario, Luis Requena
Antipsychotics
First Generation or Typical
• Common modern uses
• Acute agitation/confusion: haloperidol
• Nausea/vomiting: prochlorperazine, chlorpromazine
• Adverse effects
• Dystonic reactions
• Qt prolongation
Antipsychotics
Second Generation or Atypical
• Clozapine
• Olanzapine
Pines
• Quetiapine Lowest EPS risk
• Asenapine Quetiapine is quiet
• Iloperidone
• Paliperidone
Dones
• Risperidone Highest EPS risk
• Lurasidone Especially high doses
Risperidone = highest risk
• Ziprasidone
• Defining feature: Less EPS adverse effects
Serotonin
5-hydroxytryptamine (5 HT)
• LSD (lysergic acid diethylamide)
• 5-HT agonist
• Produces hallucinations via 5-HT2A activity
• ↓ 5-HT2A activity seen with many atypicals
• As or more effective 5-HT blockade versus dopamine

Serotonin

Clozapine: α1 > 5HT > D2

Olanzapine: 5HT > H1 > D2 > α1
Metabolic Syndrome
• May occur with any antipsychotic
• Common with “pines” – especially clozapine and olanzapine
• Weight gain
• Hyperglycemia
• Hyperlipidemia

Tibor Végh
QT interval
• Prolongation also can occur with atypical drugs
• More risk with “dones”
• Highest risk: ziprasidone

Torsade de Pointes
Clozapine
• Highly effective but not first line due to adverse effects
• Used in refractory cases
• May cause agranulocytosis (1-2% of patients)
• Must monitor WBCs during therapy
• Weekly at start
• Every few weeks to monthly thereafter
• Stop if neutrophil counts < 1500
• Reversible when drug stopped
• May also cause seizures (2-5% of patients)
• Dose related
• Rarely associated with myocarditis
Dr Graham Beards
Hyperprolactinemia
• Antipsychotics: most common drug-induced cause
• Dopamine blockade → ↑ prolactin
• Gynecomastia in men
• Galactorrhea
• Amenorrhea in women
• Highest rates:
• Haloperidol
• Fluphenazine
• Risperidone
• Paliperidone

Pituitary Gland
Aripiprazole
• D2 partial agonist
• Some blockade, some agonist effects
• Hyperprolactinemia very rare
• Less weight gain, sedation
• Most common side effect: akathisia
• Associated with loss of impulse control
• Pathologic gambling
• Binge eating
• Shopping sprees

Flikr/Public Domain
Atypical Antipsychotics

Drug Key Adverse Effects

Olanzapine and “pines” Metabolic syndrome
Ziprasidone and “dones” Highest risk of QT prolongation
Risperidone and “dones” Highest risk of EPS
Clozapine Agranulocytosis
Lowest risk of EPS (Quetiapine is quiet)
Quetiapine
Use in patients with movement disorders (Parkinson’s)
Aripiprazole Loss of impulse control