Psychopharmacology

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Psychopharmacology

• Implications for the
• Mental Health Counselor
• By Rob Gerst, LPC, LMFT, CCMHC
• American Mental Health Counselors Association

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Biological Fundamentals
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The Fundamental Question

• Are emotions more mental or more physical?
• Yes, both are involved, but which is MORE
  involved in the experience of an emotion?
• No human being, in the history of the world, has
  EVER controlled having an emotion!

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The Role of the Nervous System

• The Sympathetic Nervous System
• Turns Things on
• Activates Emotional Responses
• Wakes one from sleep
• Activates Hunger

• The Parasympathetic Nervous System
• Turns Things off
• Differentiates Between Emotional Responses
• Calms
• Causes Sleep
• Quiets Hunger

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Typical Neuron
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A Neurons Communication Path
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Synapse
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Electron Microscope Scan of a Synapse
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Mood Disorders
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The Prevalence of Depression

• Lifetime prevalence of depression is as high as
  18 of the population.
• Each year 8 to 14 million Americans are diagnosed
  with clinical depression.
• About 4 of the population at any given time.
• The incidence increases with age.

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The Prevalence of Depression

• 1.5 to 3 times more common among relatives.
• Women seek treatment 2 times more often than men,
  (25 vs. 12).
• 50 to 85 relapse within 3 years.
• Less than one-third of people who have depressive
  symptoms seek treatment.

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The Impact of Depression

• Disability caused by depression is greater than
  that caused by common chronic physical
  conditions, such as back pain, arthritis,
  hypertension, and diabetes.
• Direct annual costs are estimated at 2.1
  billion.
• Indirect annual costs are estimated at 14.2
  billion.

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The Feelings of a Normal Person
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Comparing Normal Abnormal Mood
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Spec Scan Image of the Brain
Normal Brain Depressed Brain
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Causes of Depression

• Medication Side-Effects
• Substance Abuse
• Random Unknown Causes

• Genetic Predisposition
• Psycho-Social Stressors
• Medical Conditions

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Seasonal Affective Disorder
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Counseling Goals for Depression

• Correct Cognitive Errors
• Improve Coping Strategies
• Improve Support System
• Psycho-Education
• Disease Concept
• Improve Communication with Physician
• Medication Benefits to Risk
• Medication Compliance
• Post Depression Re-integration

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The Depression Cycle
Perceived Cause
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The Depression Cycle
Increased Depression
Perceived Cause
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The Depression Cycle
Increased Depression
Perceived Cause
Increased Anxiety
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The Depression Cycle
Increased Depression
Perceived Cause
Increased Anxiety
Increased Adrenaline
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The Depression Cycle
Increased Depression
Perceived Cause
Increased Anxiety
Decreased Endorphins
Increased Adrenaline
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Treating The Depression Cycle
Counseling Improved Cognition
Decreased Depression
Increased Anxiety
Decreased Endorphins
Increased Adrenaline
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Treating The Depression Cycle
Counseling Improved Cognition
Counseling Improved Coping
Decreased Depression
Decreased Anxiety
Decreased Endorphins
Increased Adrenaline
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Treating The Depression Cycle
Counseling Improved Cognition
Counseling Improved Coping
Decreased Depression
Decreased Anxiety
Decreased Endorphins
Anxiolytic Medication Education
Decreased Adrenaline
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Treating The Depression Cycle
Counseling Improved Cognition
Counseling Improved Coping
Decreased Depression
Decreased Anxiety
Increased Endorphins
Anti-depressant Medication Education
Anxiolytic Medication Education
Decreased Adrenaline
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Treating The Depression Cycle
Counseling Improved Cognition
Counseling Improved Coping
Decreased Depression
RELIEF
Decreased Anxiety
Increased Endorphins
Anti-depressant Medication Education
Anxiolytic Medication Education
Decreased Adrenaline
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Approved Uses for Anti-depressants

• Major Depression
• Depressive Episodes of Bipolar Disorder
• Seasonal Affective Disorder
• Panic Disorder / Other Anxiety Disorders
• Obsessive-Compulsive Disorder
• Enuresis in Children
• ADHD
• Chronic Pain Syndromes
• Post-Traumatic Stress Disorder

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Tricyclic Anti-depressants

• Generic Name Brand Name Dose Schedule
• Imipramine Tofranil 75-300 mg qd to tid
• Amitriptyline Elavil 75-300 mg
• Doxepin Sinequan 75-300 mg
• Desipramine Norpramin 75-300 mg
• Nortriptyline Pamelor 50-150 mg Aventyl
• Protrityline Vivactil 10-60 mg
• Trimipramine Surmontil 75-300 mg

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Tricyclic Anti-depressants

• Generic Name Brand Name Dose Schedule
• Clomipramine Anafranil 72-250 mg qd to tid

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Tricyclic Anti-depressants

• Strong Norepinephrine Effect
• Overdose Toxicity
• High

• Side Effects
• Sedation
• Anticholinergic Effects
• Orthostatic Hypotension
• Weight Gain

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2nd Generation Anti-depressants

• Generic Name Brand Name Dose Schedule
• Amoxapine Asendin 100-600 mg qhs
• Maprotilene Ludiomil 100-225 mg
• Trazodone Desyrel 100-600 mg
• Bupropion Wellbutrin 200-450 mg tid

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2nd Generation Anti-depressants

• Strong Norepinephrine Effect
• Overdose Toxicity
• High
• Wellbutrin is used also for nicotine addiction
• Trazodone is used as a sleep aid.

• Side Effects
• Sedation
• Anticholinergic Effects
• Orthostatic Hypotension
• Seizures

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Selective Serotonin Re-Uptake Inhibitors (SSRIs)

• Generic Name Brand Name Dose
• Fluoxetine Prozac 10-80 mg qam
• Fluvoxamine Luvox 100-300 mg/d bid/tid
• Paroxetine Paxil 20-50 mg qam
• Paroxetine Pexeva 10-50 mg qam
• Setraline Zoloft 25-200 mg qam
• Citalopram Celexa 20-40 mg qam
• Escitalopram Lexapro 10-40 mg qd

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Selective Serotonin Re-Uptake Inhibitors (SSRIs)

• Strong Serotonin effect
• Paxil Pexeva are used for Anxiety OCD
• Overdose Toxicity
• Low

• Side Effects
• Sexual Dysfunction
• Anxiety
• Insomnia
• Nausea
• Weight Loss
• Manic Symptoms

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New Heterocyclic Anti-depressants (SSNRI)

• Generic Name Brand Name Dose Schedule
• Venlafaxine Effexor 75-225 mg/d bid/tid
• Nefazodone Serzone 100-600 mg/d
• Duloxetine Cymbalta 40-60 mg/d
• bid/qd

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New Heterocyclic Anti-depressants (SSNRI)

• Dual-Action
• Strong Serotonin Norepinephrine effect
• Overdose Toxicity
• Low

• Side Effects
• Very Low
• Nausea
• Sedation
• Dizziness
• Sexual Side Effects

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MonoAmine Oxidase Inhibitors (MAOIs)

• Generic Name Brand Name Dose Schedule
• Isocarboxazid Marplan 10-50 mg qhs
• Phenelzine Nardil 15-90 mg
• Tranylcypromine Parnate 10-60 mg

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MonoAmine Oxidase Inhibitors (MAOIs)

• Reduces MonoAmine Oxidase
• Requires Restrictive Diet
• Works only in certain types of genetic depressions

• Overdose Toxicity
• Moderate
• Side Effects
• Very Low as long as the diet is followed
• Cardiovascular

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MonoAmine Oxidase Inhibitors (MAOIs)

• Diet Avoid Foods High in Tyramine
• Aged Cheeses
• Aged Sausages
• Pickled Fish
• Beer or Red Wine
• Yeast or Protein Extracts
• Broad Bean Pods
• Liver

• Also Avoid
• Cold or Sinus Meds
• Herbal Sources of Ephedrine
• Stimulants
• Narcotics
• Asthma Inhalants
• Other Anti-depressants
• More

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Electroconvulsive Therapy

• Usually administered in 6 to 8 treatments over
  two weeks
• Often requires individual follow-up treatments
  over the next few months

• Dramatically quickly increases all
  neurotransmitter levels
• Side Effects
• Memory Loss
• Confusion Disorientation

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Symptom Domains of Bipolar Disorder
Dysphoric or Negative Mood and Behavior
Manic Mood and Behavior

• Euphoria
• Grandiosity
• Pressured speech
• Impulsivity
• Excessive libido
• Recklessness
• Social intrusiveness
• Diminished need for sleep

• Depression
• Anxiety
• Irritability
• Hostility
• Violence or suicide

Bipolar Disorder
Cognitive Symptoms

• Racing thoughts
• Distractibility
• Disorganization
• Inattentiveness

Psychotic Symptoms

• Delusions
• Hallucinations

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Bipolar Disorder
Bipolar-II
Bipolar-I
Cyclothymia
Mixed statenonpsychotic
Schizoaffective bipolar type
Potter WZ. J Clin Psychiatry. 199859(suppl
18)30-36.
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Bipolar I DisorderPrevalence and Course of
Illness

• Lifetime prevalence 0.81.6
• Gender influence men women
• Recurrent illness in 90 of patients
• episode frequency severity of
  residual symptoms between episodes
• Number of episodes may affect subsequent
  treatment response
• 25-50 of patients attempt suicide 1 time

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Genetic Risk Bipolar Disorder

• First-degree relative afflicted
• Bipolar disorder 10-15 (10-12 times risk)
• Monozygotic twin afflicted
• Bipolar disorder 60 (40 times risk)

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Bipolar I,Classic Mania
BorderlinePersonality Disorder
Bipolar I, Depressed
The Bipolar Spectrum
SchizoaffectiveDisorder,Bipolar Type
Bipolar I, Rapid Cycling and Mixed State
Bipolar II Disorder
Cyclothymic Disorder
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Bipolar Disorder Subtypes of Illness (proposed
for the DSM-V)

• Bipolar IV
• Anti-depressant-induced Hypomania
• Bipolar V
• Recurrent Major Depression with a Family History
  of Bipolar Disorder
• Bipolar VI
• Unipolar Mania

• Bipolar I
• Mania Major Depression
• Bipolar II
• Hypomania Major Depression
• Bipolar III
• Cyclothymia

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What is the Ideal Treatment ofBipolar Disorder?
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Mood-Stabilizing Agents

• Lithium
• Antiepileptic medications
• Valproate (Depakene?, Depakote?, Depakote ER?)
• Carbamazepine(Tegretol?)/Oxcarbazepine(Trileptal?
  )
• Gabapentin (Neurontin?)
• Topiramate (Topamax?)
• Lamotrigine (Lamictal?)
• Typical antipsychotics

• Novel antipsychotics
• Risperidone (Risperdal?)
• Ziprasidone (Geodon?)
• Olanzapine (Zyprexa?)
• Clozapine (Clozaril?)
• Quetiapine (Seroquel?)

FDA approved for acute mania.
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APA Bipolar 2002 Treatment Guidelines

• Goals of Psychiatric Management
• Establishing and maintaining therapeutic alliance
• Monitoring the patients psychiatric status
• Providing education about Bipolar Disorder
• Enhancing treatment compliance
• Promoting regular patterns of activity and sleep
• Anticipating stressors
• Identifying new episodes early
• Minimizing functional impairments

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APA Bipolar 2002 Treatment Guidelines

• Pharmacologic management1
• Severe manic or mixed episodes lithium or
  valproate plus antipsychotic
• Less ill patients monotherapy with lithium, or
  valproate, or olanzapine
• Novel antipsychotics preferred over typical
  antipsychotics because of side-effect profile
  most data supporting olanzapine
• Clozapine may be particularly effective with
  refractory cases
• Maintenance treatment valproate, lithium, or
  olanzapine1,2

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An Ideal Primary Mood Stabilizer

• Any medication that stabilizes acute manic
  symptoms, does not induce depression, and
  prevents against future relapses into (mania or
  depression)

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Questions in Comparing Mood Stabilizers

• Efficacy for mania
• What are the comparative effects on treating
  mania?
• How many patients get better vs how many patients
  get well (response and remission rates)
• Are the medications effective for not only
  classic mania, but also for rapid cycling and
  mixed states?
• Efficacy for depression
• Does the medication worsen depressive symptoms?
• What are the comparative effects on improvement
  of depression?
• Tolerability and safety considerations
• Does mood stabilization come at the cost of
  cognitive dulling?
• How do the treatments differ in tolerability?
• What are the important serious safety
  considerations?
• Are they simple to prescribe and easy to use?

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Who Responds Best to Lithium?
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Factors Associated WithPositive Response to
Lithium

• Bipolar I (euphoric/elated mania)
• First episode manic
• Prior response to lithium
• Limitations
• No neurological impairment
• No substance abuse
• Relatively few illness episodes (i.e., no rapid
  cycling, mixed, other novel features)

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How are the Antiepileptic Medications Used in
Treating Bipolar Mania?
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Treatment of Bipolar ManiaDivalproex

• Efficacy comparable to lithium in classic mania
• Predictors of response
• Comparable efficacy in classic mania, mixed
  states, and rapid cycling

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Treatment of Bipolar ManiaLithium vs. Divalproex
Divalproex
Lithium

• Efficacy 49-70
• Onset of action 5-21 days
• Predictors of response
• Classic mania
• Few episodes
• Initial episode manic
• Tolerability cognitive dulling, tremor, renal
  insufficiency, polyuria, gastrointestinal,
• thyroid suppression, weight
• gain, sick sinus syndrome

• Efficacy 49-70
• Onset of action 3-10 days
• Predictors of response
• Comparable efficacy in classic,mixed, and rapid
  cycling
• Tolerability nausea, sedation, cognitive
  dulling, tremor, thrombocytopenia, weight gain,?
  insulin resistance

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Anxiety Disorders
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Normal Everyday Anxiety
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Generalized Anxiety Panic Attacks
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Anxiolytic Agents

• Benzodiazepines
• Short Acting
• Versed (Midazolam)
• Half-Life 20 hours
• Dose Range 1-5 mg IM
• Halcion (Triazolam)
• Half-Life 5 hours
• Dose Range 0.125-0.75 mg

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Anxiolytic Agents

• Benzodiazepines
• Intermediate Acting
• Xanax (Alprazolam)
• Half-Life 9 hours
• Dose Range 0.25-4 mg
• Ativan (Lorazepam)
• Half-Life 8 hours
• Dose Range 0.5-4 mg
• Restoril (Temazepam)
• Half-Life 3 hours
• Dose Range 7.5-30 mg

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Anxiolytic Agents

• Benzodiazepines
• Long Acting
• Klonopin (Clonazepam)
• Half-Life 19 hours
• Dose Range 0.25-3 mg
• Valium (Diazepam)
• Half-Life 14 hours
• Dose Range 2 mg-30mg
• Clorazepate
• Half-Life 1.3 hours
• Dose Range 3.75-22.5 mg

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Anxiolytic Agents

• Benzodiazepines
• Side Effects
• Moderate to high addiction potential
• Sedation, Dizziness, Drowsiness, Confusion,
  Fatigue
• Anticholinergic Effects
• Sexual Dysfunction

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Barbiturates

• Amytal (Amobarbital)
• Dose Range 60-200 mg
• Half-Life 14 hours
• Nembutral (Pentobarbital)
• Dose Range 50-200 mg
• Half-Life 21 hours

• Seconal (Secobarbital)
• Dose Range 50-200 mg
• Half-Life 2 hours
• Very Fast Acting
• Loses Effect With Time
• Very Addictive
• Very Sedating

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Anxiolytic Agents

• Non-Tranquilizers
• Paxil
• BuSpar
• Pexeva

• Addiction Potential Low
• Side effects similar to SSRIs

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ADD
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Stimulant Medications

• Ritalin (Methyiphenidate)
• Dose Range Child 5-40 mg 0.3-1.0 mg/KG body
  weight
• Dose Range Adult up to 120 mg
• Half-Life 3.5 hours
• Adderall (Dextromethanphetamine)
• Dose Range Child 5-40 mg 0.1-0.8 mg/KG
• Dose Range Adult up to 40 mg/day
• Half-Life 6.5 hours

• Concerta
• Cylert
• Dexedrine
• Focalin

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Stimulant Medications

• Side Effects
• Insomnia (up to 28)
• Irritability (up to 26)
• Headache (up to 10)
• Nervousness
• Upset Stomach (up to 23)
• Weight Loss
• Dry Mouth
• Blurred Vision
• Contra-indicated in Anorexia

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Before After Treatment with Ritalin
Before
After
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Before After Treatment with Adderall
After
Before
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Non-Stimulant Medications

• Strattera (Atomoxetine)
• Dose Range Child 5-100 mg
• Not more than 1.4 mg/KG body weight
• Dose Range Adult 40 mg to 100 mg
• Half life 36 hrs
• Onset of action 1-2 weeks allow 4-6 weeks
• Action is a norepinephrine reuptake inhibitor

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Non-Stimulant Medications

• Strattera (Atomoxetine)
• Side Effects (Similar to Tricyclic
  Anti-depressants)
• Aggression
• High BP
• Mood Swings
• Dry Month

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Psychotic Disorders
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Schizophrenia Socioeconomic Impact

• 1 of American population affected
• 25 of all hospital-bed days
• 40 of all long-term-care days
• 20 of all Social Security benefit days
• Total cost 33 billion/year

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Schizophrenia

• Neurodevelopmental disorder
• Multidimensional features
• Multifactorial causation
• Debilitating disability

Woods. Am J Psychiatry. 199815512. Buka S.
Psychiatric Ann. 1999293.
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Features of Schizophrenia
Positive SymptomsDelusionsHallucinationsDisorga
nized speechCatatonia
Negative SymptomsAffective flatteningAlogiaAvol
itionAnhedoniaSocial withdrawal
Social/Occupational Functioning WorkInterpersona
l relationshipsSelf-care
Mood SymptomsDepressionAnxietyAggression Hostil
ity Hopelessness Suicidality
Cognitive DeficitsAttentionMemoryExecutive
functions (e.g., abstraction)
Comorbid ConditionsMoodSubstance use
disorderAnxietyAggression
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The Continuum of Care
Efficacy
Positive symptom relief Hostility,
aggression Smooth IM to PO transition Alleviation
of comorbid depressive/manic symptoms
Negative symptom relief Improve mood and
depressive symptoms Cognitive improvement
Control Behavior (agitation)
Relapse Prevention
1-3 days
7-14 days
6 months
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History of Antipsychotics

• Typical Antipsychotics

• Novel Antipsychotics
• Clozapine 1989
• Risperidone 1993
• Olanzapine 1996
• Quetiapine 1997
• Ziprasidone 2001

• Chlorpromazine 1953
• Trifluoperazine 1958
• Perphenazine 1958
• Fluphenazine 1959
• Thioridazine 1959
• Thiothixene 1967
• Haloperidol 1967
• Mesoridazine 1970
• Loxapine 1975
• Molindone 1977
• Pimozide 1984

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Antipsychotic Agents
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Defining Treatment Effectiveness

• Acute symptom control
• Broad spectrum of efficacy
• Response ratelikelihood of getting better
• Participation of special populations in efficacy
• Clear benefit for continuing treatment
• Benchmarks for long-term treatment
• Delivering improved quality of life
• Reintegrationachieving personal goals

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Goals of Antipsychotic Treatment

• Comfortable tolerability
• Broad range of efficacy
• Willingness to comply with treatment
• Ability to reintegrate

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Receptor Binding Profiles

Clozapine
Olanzapine
Haloperidol
Musc
a 2
a 1
a 2
5-HT2C
H1
D4
H1
5-HT2A
a 1
a 1
D1
a 2
D1
D2
D2
D1
D4
5-HT2A
D2
Musc
5-HT2C
5-HT2A
D4
Risperidone
Quetiapine
Ziprasidone
5-HT2C
a 2
a 1
5-HT2C
H1
a 1
a 2
H1
D1
D1
D1
5-HT2A
5-HT2A
D2
D2
D2
D4
5-HT2A
a 1
5-HT2C
D4



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Relative Binding of Antipsychotics to D2 Receptors
100
Quetiapine Clozapine
Loose
Olanzapine Sertindole
10
Intermediate
K at D2 (nM)
Dopamine K (1.5nM)
1
Ziprasidone Chlorpromazine Haloperidol Fluphenazin
e Risperidone
Tightly
0.1
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Implications of D2 Receptor Binding Differences
High Binding Affinity Tight
DA
DA
Tight binding May lead to DA receptor
upregulation - relapse
DA Postsynaptic Neuron
DA
DA Postsynaptic Neuron
DA
DA
DA
DA
DA
DA
Intermediate or Low Affinity Loose
DA
Loose binding has less chance of
upregulation and D2 receptors more
responsive to endogenous DA which decrease
EPS and elevated prolactin
DA
DA Postsynaptic Neuron
DA Postsynaptic Neuron
DA
DA
DA
DA
DA
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Schizophrenia and Agitation

• Agitation is a common component of schizophrenia
  that may present as a psychiatric emergency
  requiring rapid resolution
• Rapid control of agitation protects both the
  patientand caregiver from potential injury
• Oral medications are often not a treatment option
  due to lack of patient cooperation and relatively
  slow onset of action
• Currently available parenteral medications are
  associated with significant side effects, such as
  EPS, QTc prolongation, and excessive sedation

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Alzheimers
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Memory Enhancing Medication

• Aricept (Donepezil)
• Dose Range 5-10 mg
• Half-Life 70-80 hours
• Cognex (Tacrine)
• Dose Range 40-160 mg
• Half-Life 70-80 hours

• Side Effects
• -GI Upset
• -Headache
• -Irritability
• -Dizziness
• DO NOT STOP ABRUPTLY!!!

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Substance Abuse
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Substance Abuse

• Vivitrol
• For Alcohol Opiate Addiction.
• Blocks the m-opioid receptor interfering with the
  brains reward system and thus stopping the
  craving for alcohol or opiates.
• Is administered IM once a month for 12 months.

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SPEC Scan of the Brain

• Comparing the Effects of Long Term Substance
  Abuse

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Spec Scan of a Normal Brain
99
Brain After 2 Yrs of Cocaine Use
100
Brain After 20 Yrs of Heroin Use
101
Brain After 25 Yrs of Alcohol Use
102
Brain After 12 Yrs of Marijuana
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The American Mental Health Counseling Association

• Serving Your Interest For 28 Years.
• Thank You For Your Participation

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For Handouts

• You may download a copy of the outline of this
  presentation at
• www.the-care-center.org