Transcript David Weiss, M.D.

Disclosures
 Speaker’s Bureau: Otsuka and Lundbeck
Off-Label Uses Will Be Discussed
Objectives
 Review Common Psychiatric Diagnoses
presenting in the primary care setting
 Review available pharmacologic
treatment options
Depressive Disorders
 History
 Prevalence: 15% total, 25% woman
 Cost: estimate $45-55 Billion annually in U.S.
 Treatment: 2/3 of people with depression do not
realize they have it (Andrew, 3/2012) and only 20% of
those diagnosed received appropriate treatment
Depressive Disorders
 Depressed patients lose on average 5-6 hours of
productive work every week
 Depressed patients are more than 2 times likely to take
sick days
 Depressed patients are 7 times more likely to be
unemployed
Depressive Disorders
 Depressed patients have an 11% decrease in the
probability of getting married
 Patients have a 35% decrease in lifetime income due to
depression
 Rates of undetected depression among drug and
alcohol users are estimated to be at least 30%
Depressive Disorders
 According to WHO, depression was the 3rd most
important cause of disease burden worldwide in 2004
 A Toronto study showed workers who were treated for
severe depression were 7 times more likely to be high
performing than those who were not
Epidemiology
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Sex
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Age
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Not differ from race to race
Socioeconomic
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Mean age of onset 40 years old
Race
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Women > Men
No correlation
Marital Status
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Higher if no close relationships, divorced, separated
Etiology
 Cause Unknown
 Causative factors divided into biological factors,
genetic factors, and psychosocial factors
 Biological Factors
 Mood disorders associated with dysregulations of biogenic
amines norepinephrine, serotonin, dopamine
 Adrenal Axis: Hypersecretion of cortisol
 Thyroid Axis: Abnormal regulation, autoimmune disorder
(10% have antithyroid antibodies)
 Growth hormone: Blunted sleep induced stimulation of
growth hormone release
Etiology
 Genetic Factors:
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Data strongly suggestive of genetic component
Pattern unknown
Family studies
 1st degree relatives 2 to 10 times more likely
Adoption studies
 Biological children reared in non affected adoptive family
Twin studies
 50% in monozygotic twins
Diagnosis
 DSM IV-R specific diagnostic criteria
 Qualifiers: Severity, Psychotic, Recurrent, Single,
Remission
 Significant distress, functional impairment
 Not due to direct physiological effects of a substance
 Not better accounted for by bereavement
 Symptoms not persist > 2 months after loss
 Not suicidal, no significant functional impairment
Clinical Features
 Depressed Mood: Subjective or observation
 Marked decrease interest
 Decrease/Increase appetite, weight change
 Sleep disturbance
 Psychomotor agitation/retardation
 Loss of energy
 Guilt, worthlessness
 Poor concentration, indecisiveness
 Recurrent thoughts of death, suicidal thoughts
Differential Diagnosis
 Bipolar Disorder
 Premenstrual dysphoric
 Dysthmia
Disorder
 PostPartum Depression
 Depression 2nd to General
Medical Condition
 Cyclothymia
 Schizoaffective Disorder
 Schizophrenia
 Anxiety Disorders
 Personality Disorders
 Substance related Disorders
 Uncomplicated
Bereavement
 Infections
 Endocrine Disorders
 Neurological Disorders
 Neoplasms
 Inflammatory Disorders
Course and Prognosis
 Course
 Chronic and Relapsing course
 Untreated: 6-13 months
 Treated: 8 weeks – 3 months
 20 year period: mean number 5-6 episodes
 If hospitalized, 75% recur within 5 years
 Prognosis
 Poor if: coexisting dysthymic disorder, alcohol abuse,
anxiety disorders, multiple episodes, hospitalization,
men, poor support, personality disorder, late age initial
onset, psychotic component
Treatment
 1st Safety
 2nd Safety
 3rd Safety
 First Decision to make
 Do you hospitalize the patient?
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Voluntary vs. Involuntary
Suicide
 15% of depressed people take their own lives
 Risk Factors
 Male
 Elderly
 Caucasian
 History of previous suicide attepts
 Co-Morbid medical illness
 Drug/Alcohol use
 Co-Morbid psychiatric illness
 Social isolation, poor social support
 Low job satisfaction, financial stress
Pharmacologic Options
Tricyclics
SSRIs
SNRIs
MAOIs
Other classes
Tricyclic Antidepressants
 Common Uses:
 Depression*
 Neuropathic and Chronic Pain
 Headache
 Insomnia
 Anxiety
 OCD* (Clomipramine Anafranil)
 Enuresis
Common Tricyclics
 Amitriptyline (Elavil)
 Nortriptyline (Pamelor)
 Imipramine (Tofranil)
 Despiramine (Norpramin)
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Clomipramine (Anafranil)
Doxepin (Sinequan)
Trimipramine (Surmontil)
Protriptyline (Triptil)
Tricyclic Antidepressants
 Mechanism of Action
 Block reuptake of norepinephrine
 Common Side Effects
 Anticholinergic
Dry mouth, constipation, urinary hesitancy
 Cardiovascular
 Hypotension, palpitations, conduction slowing
 CNS
 Tremor, sedation, stimulation
 Other
 Weight gain, sexual, perspiration
 Common Drug Drug Interactions
 CNS depressants: Sedation
 SSRIs: Increase TCA levels
 MAOIs: Serotonin Syndrome
 Tramadol: Increase Seizure Risk
 Antihypertensive drugs: May alter affect
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SSRIs
 Common Uses:
 Depression
 Panic Disorder
 Generalized Anxiety
 PTSD
 OCD
 Social Anxiety
 PMDD
Common SSRIs
 Fluoxetine (Prozac)
 Paroxetine (Paxil)
 Sertraline (Zoloft)
 Citalopram (Celexa)
 Escitalopram (Lexapro)
 Fluvoxamine (Luvox)
SSRIs
 Mechanism of Action
 Block “Selectively” Serotonin Reuptake
 Common Side Effects
 GI, CNS activation, sedation, sexual, weight gain, HAs
 Common Drug Drug Interaction
 TCAs
 MAOIs: Serotonin Syndrome
 Warfarin, NSAIDs: potential increase risk of bleeding
 Tramadol: Increase seizure risk
SNRIs
 Common Uses:
 Depression*
 Generalized Anxiety*
 Social Anxiety*
 Panic Disorder*
 PTSD
 PMDD
 Chronic Pain*
 Fibromyalgia*
Common SNRIs
 Venlafaxine (Effexor)
 Duloxetine (Cymbalta)
 Desvenlafaxine (Pristiq)
SNRIs
 Mechanism of Action
 Blocks Serotonin and Norepinephrine Reuptake
 Common Side Effects
 Similar to SSRIs
 HTN
 Drug Drug Interactions
 MAOIs: Serotonin Syndrome
 Tramadol: Increase seizure risk
 Warfarin, NSAIDs: Potential increase risk of bleeding
MAOIs
 Common Uses:
 Depression*
 Social Anxiety
 Panic Disorder
 Parkinson’s* (Selegiline)
 Dementia
Common MAOIs
 Selegiline (EMSAM)
 Phenelzine (Nardil)
 Tranylcypromine (Parnate)
 Isocarboxazid (Marplan)
MAOIs
 Mechanism of Action
 Blocks MAO from breaking down norepinephrine, serotonin, dopamine
 Common Side Effects
 Orthostatic hypotension, hypertensive crisis, sexual, sedation, insomnia
 Drug Drug Interaction
 High Tyramine Foods
 SSRIs
 SNRIs
 TCA
 Meperidine
 Dextromethorphan
 Carbamazepine
 Bupropion
 Beta-Blockers
 Sympathomimetics
“Other”classes and Newer Agents
 Bupropion
 Mechanism of Action: NDRI
 Common Side Effects: headache, insomnia, tremor,
anorexia, seizures (rare)
 Drug Drug Interaction: TCA (increase), MAOIs,
Tramadol
“Other” Classes and Newer Agents
 Mirtazapine (Remeron)
 Mechanism of Action: alpha 2 antagonist, dual serotonin
and norepinephrine agent
 Common Side Effects: appetite increase, sedation,
weight gain, dry mouth, hypotension
 Drug Drug Interaction: MAOIs, Tramadol
“Other” Classes and Newer Agents
 Vilazodone (Viibryd)
 Mechanism of Action: Serotonin partial agonist
reuptake inhibitor
 Common Side Effects: Nausea, diarrhea, vomiting,
sexual (? Less), brusing
 Drug Drug Interactions: MAOIs, Tramadol, SSRIs
(increase levels), Carbamazapine (decrease levels)
“Other” Classes and Newer Agents
 Levomilnacipran (Fetzima)
 Milnacipran (Savella) FDA approved only for
fibromyalgia
 Levomilnacipran is a left isomer of milnacipran
 Not approved for treatment of fibromyalgia
 Indication: Major Depression
 Mechanism of Action: SNRI
 Common Side Effects
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GI, sexual, sweating, palpitations, hypertension, bruising
“Other Classes and Newer Agents”
 Vortioxetine (Brintellix)
 Mechanism of Action: SRI (?)
 Indication: Major Depression
 Common Side Effects: GI, dizziness, sexual, bruising,
 Drug Drug Interactions: MAOIs, SSRIs, SNRIs,
Warfarin, NSAIDs
Treatment Strategies Depression
 Where to begin?
 If it works, what next?
 Length
 Monitoring
 If it doesn’t work, what next?
 Dosing
 Augment
 Switch
 Diagnosis
 Therapy
Partial Responders/Augmentation
 Dose?
 Diagnosis?
 Medical?
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Substance use?
Combination of Antidepressants
Lithium
Thyroid
Stimulants
Atypical Antipsychotics
Buspirone
Treatment Options Beyond
Pharmacotherapy
 Psychotherapy
 ECT
 PhotoTherapy
 Magnetic Stimulation
The Good News
 Treatment Responsive
 Satisfying to Treat
 Major Impact on Quality of Patient’s lives, family and
society
 Improved Response to Medical Treatment and
Prognosis
 Cost Effective Treatment
Anxiety Disorders
 Anxiety disorders are the most common class of
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mental disorders present in the general population
Affecting 40 million adults in the US in a given year
Only 1/3 suffering receive treatment
Cost $42 billion a year direct/indirect costs
Patients with anxiety disorder 5 times more likely to
access medical care
Anxiety
 Excessive Worry
 Associated physical symptoms
 Avoidant Behavior
 Unknown internal source vs. known external source
 Sense of dread
 Heightened apprehension
Causes of Anxiety
 Psychological Theories
 Freud: anxiety is a signal to the ego that an unacceptable
drive is pressing for conscious representation
 Behavioral Theories
 Anxiety is a conditioned response to a specific
environmental stimuli
 Biological Theories
 Neurotransmitter dysregulation
Anxiety Disorder Sub-Types
 Panic Disorder
 Generalized Anxiety
 Post Traumatic Stress Disorder
 Specific Phobias
 Social Anxiety Disorder (Social Phobia)
 Obsessive Compulsive Disorder
 Anxiety Disorder Due to a General Medical Condition
 Substance Induced Anxiety Disorder
 Anxiety Disorder NOS
Symptoms of Panic Attack
 Palpitations
 Sweating
 Tremor
 Shortness of Breath
 Chest pain and discomfort
 Nausea
 Dizziness
 Fear of losing control
 Fear of dying
Panic Disorder
 Recurrent, unexpected panic attacks
 Followed by at least one month of:
 Persistent concern about having more attacks
 Worry about the implications of the attacks
 A significant change in behavior related to the attacks
 Panic Attack
 A discrete period of intense fear or discomfort
associated with multiple physical manifestations
developing abruptly and reaching a peak within 10 min
Panic Disorder
 Prevalence: 2% of the population
 Sex: 1:2 Male to Female Ratio
 Usual onset early adulthood
 Attacks usually last a few minutes
 Associated symptoms of agoraphobia, depression,
substance abuse
 Higher rate of suicide
 Marital tension, conflict at work, financial difficulties,
higher rate of accessing medical care
Differential Diagnosis for Panic
Disorder
 Medical Disorders
 Cardiovascular diseases
 Pulmonary diseases
 Neurological diseases
 Endocrine diseases
 Drug intoxications
 Drug withdrawal
 Mental Disorders
 Malingering
 Hypochondriasis
 Phobias
 Post traumatic Stress Disorder
Treatment Panic Disorder
 Pharmacotherapy
 Tricyclics
 SSRIs
 Benzodiazepines
 Cognitive Behavioral Therapy
 Address patient’s false beliefs about panic attack
 Relaxation techniques, gaining sense of control
 Family Therapy
 Insight oriented psychodynamic psychotherapy
 Help patient understand the unconscious meaning of the
anxiety
Phobias
 Phobia: irrational fear resulting in a conscious
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avoidance of the feared object, activity or situation
The single most common mental disorders in the US
10-25% of population are afflicted
Increased risk for other psychiatric complications
including depression and substance abuse
Specific: Fear or avoidance of objects or situations
other than agoraphobia or social phobia
 Commonly involves animals, insects, injury or
procedures, heights, darkness
Phobias
 Social: Fear of humiliation or embarrassment in either
general or specific social situations
Commonly involving public speaking, urinating in
public restrooms, stage fright
Treatment Phobias
 Specific Phobias
 Exposure therapy (behavioral therapy)
 Insight oriented psychotherapy
 Pharmacotherapy (Benzodiazepines, SSRIs)
 Social Phobias
 Psychotherapy (behavioral, cognitive, insight oriented)
 Pharmacotherapy (Beta Blockers, SSRIs,
Benzodiazepines, Buspirone)
Obsessive Compulsive Disorder
 Lifetime prevalence: 2-3% of population
 4th most common psychiatric disorder
 Men = Women
 Mean age of onset 20 years old
 2/3 of cases onset before age of 25 years old
 Can occur in childhood; has been seen in 2 year olds
 Single more affected than married
 Caucasian > African American (access to healthcare)
Diagnosis
 Obsession: A recurrent and intrusive thought, feeling,
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idea, or sensation
Compulsion: A conscious, standardized, recurrent
thought or behavior, such as counting, checking, or
avoiding
Obsessions increase a patient’s anxiety
Compulsions decrease a patient’s anxiety
If resist compulsion, anxiety increases
A patient realizes the irrationality of the obsessions
Either obsession or compulsion. Over 75% have both
Treatment OCD
 Pharmacotherapy
 Clomipramine
 SSRIs
 Lithium
 Benzodiazepines
 Psychotherapy
 Behavioral therapy (exposure, response and flooding)
 Other
 ECT
 Psychosurgery (cingulotomy)
Post Traumatic Stress Disorder
 Experience an emotional stress of potentially life
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threatening magnitude that would be traumatic for
almost anyone
Re-experiencing of the trauma through dreams and
waking thoughts
Persistent avoidance of reminders of the trauma
Numbing of responsiveness to such reminders
Persistent hyperarousal
Symptoms greater than a month
Etiololgy
 The stressor is the prime causative factor
 Predisposing vulnerability include presence of
childhood trauma, personality disorders, poor social
support, genetic vulnerability to psychiatric illness,
recent stressful life change, recent excessive alcohol
use
Treatment PTSD
 Pharmacotherapy
 SSRIs
 Mood Stabilizers
 Hypnotics
 Anxiolytics
 Antipsychotics
 Psychotherapy
 Supportive
 Cognitive
 Group
 Family
Generalized Anxiety Disorder
 An excessive and pervasive worry accompanied by a
variety of somatic symptoms, that cause significant
impairment in social or occupational functioning or
marked distress
 A person finds it difficult to control the anxiety
 Not due tot eh direct physiological affects of a
substance
Treatment GAD
 Pharmacotherapy
 Benzodiazepines
 Buspirone
 Mood Stabilizers
 Antipsychotics
 SSRIs
 SNRIs
 TCA
 Psychotherapy
 Cognitive Behavioral
 Insight Oriented
 Supportive
Treatment Strategies Anxiety
 Where to begin?
 If it works, what next?
 Length
 Monitoring
 Therapy
 If it doesn’t work, what next?
 Dosing
 ETOH
 Switch
 Diagnosis
 Therapy
Psychotic Disorders
 Schizophrenia
 Among top 10 leading cause of disability worldwide in people
15-44 age range WHO
 Peak onset young adulthood
 All cultures, all ethnic groups, M = W
 High Risk of suicide 1/3 attempt
 Schizoaffective Disorder
 Brief Psychotic Disorder
 Schizophreniform Disorder
 Delusional Disorder
 Shared Psychotic Disorder
Psychotic Disorders Clinical
Features
 Delusions
 Hallucinations
 Disorganized Speech
 Disorganized Behavior
 Negative Symptoms
 Affect blunting
 Alogia
 Avolition
Differential Diagnosis Psychosis
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Bipolar Disorder
Depression
Personality Disorder
Temporal lobe epilepsy
Tumor, Stroke
Infectious Disease
Autoimmune Disorder
Toxic illness
Drug Intoxications
Alcohol withdrawal
Clinical Management
 Safety
 Pharmacotherapy
 Family Therapy
 Social Skills Training
 Cognitive Rehabilitation
Pharmacotherapy Psychosis
 First Generation, Traditional, Neuroleptics, Typical
Antipsychotics
 Main Therapeutic Effect by Blocking D2 Receptors
 Second Generation, Atypical Antipsychotics
 Blocks D1 , D2, 5HT2
Dopamine Pathways
 Four Well Defined Dopamine Pathways
 Mesolimbic
 Mesocortical
 Nigrostriatal
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DA and Acetylcholine have a reciprocal relationship
 Tuberoinfundibular
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DA and Prolactin have a reciprocal relationship
Common Typical Antipsychotics
 Chlorpromazine (Thorazine)
 Haloperidol (Haldol)
 Fluphenazine (Prolixin)
 Perphenazine (Trilafon)
 Thiothixene (Navane)
 Trifluoperazine (Stelazine)
Common Atypical Antipsychotics
 Aripiprazole (Abilify)
 Olanzapine (Zyprexa)
 Quetiapine (Seroquel)
 Risperidone (Risperdal)
 Ziprasidone (Geodon)
 Paliperidone (Invega)
 Clozapine (Clozaril)
 Asenapine (Sapharis)
 Lurasidone (Latuda)
Side Effects with AntiPsychotics
 Typicals
 Neurologic
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EPS, Dystonia, Pseudoparkinsonism, akathesia,
 Atypicals
 Metabolic
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Weight gain, Glucose, Lipids,
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Tardive Dyskinesia, NMS, Q-T prolongation,
Hyperprolactinemia
Treating EPS
 Anticholinergics
 Benztropine
 Trihexyphenidyl
 Antihistaminics
 Diphenhydramine
 Dopaminergics
 Amantadine
 Beta-Blockers
 Benzodiazepines
Treating EPS
 Use lowest possible dose
 Move toward a lower potency antipsychotic
 Use anticholinergic therapy
 Use Amantadine, Benzodiazepine, Beta-Blocker
 Consider Atypical
Long Acting Injectable
AntiPsychotics
 Typicals
 Haloperidol
 Fluphenazine
 Atypicals
 Risperidone
 Paliperidone
 Olanzapine
 Aripiprazole
Thank you !
?’s