1. Psychopharmacology: An Update for Clinical Practice David B. Weiss, M
Psychopharmacology: An Update for Clinical Practice David B. Weiss, M.D. Denver, Colorado

2. Off-Label Uses Will Be Discussed
Disclosures
Speaker’s Bureau: Otsuka and Lundbeck
Off-Label Uses Will Be Discussed

3. Objectives
Review Common Psychiatric Diagnoses presenting in the primary care setting
Review available pharmacologic treatment options

4. 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

5. 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

6. 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%

7. 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

8. Epidemiology Sex Age Race Socioeconomic Marital Status Women > Men
Mean age of onset 40 years old
Race
Not differ from race to race
Socioeconomic
No correlation
Marital Status
Higher if no close relationships, divorced, separated

9. 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

10. Etiology Genetic Factors:
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

11. 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

12. 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

13. Differential Diagnosis
Bipolar Disorder
Premenstrual dysphoric Disorder
Dysthmia
PostPartum Depression
Cyclothymia
Depression 2nd to General Medical Condition
Schizoaffective Disorder
Schizophrenia
Infections
Anxiety Disorders
Endocrine Disorders
Personality Disorders
Neurological Disorders
Substance related Disorders
Neoplasms
Uncomplicated Bereavement
Inflammatory Disorders

14. Course and Prognosis Course Prognosis Chronic and Relapsing course
Untreated: 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

15. Treatment 1st Safety 2nd Safety 3rd Safety First Decision to make
Do you hospitalize the patient?
Voluntary vs. Involuntary

16. 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

17. Pharmacologic Options
Tricyclics
SSRIs
SNRIs
MAOIs
Other classes

18. Tricyclic Antidepressants
Common Uses:
Depression*
Neuropathic and Chronic Pain
Headache
Insomnia
Anxiety
OCD* (Clomipramine Anafranil)
Enuresis

19. Common Tricyclics Amitriptyline (Elavil) Nortriptyline (Pamelor)
Imipramine (Tofranil)
Despiramine (Norpramin)
Clomipramine (Anafranil)
Doxepin (Sinequan)
Trimipramine (Surmontil)
Protriptyline (Triptil)

20. 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

21. SSRIs Common Uses: Depression Panic Disorder Generalized Anxiety PTSD
OCD
Social Anxiety
PMDD

22. Common SSRIs Fluoxetine (Prozac) Paroxetine (Paxil)
Sertraline (Zoloft)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluvoxamine (Luvox)

23. SSRIs Mechanism of Action Common Side Effects
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

24. SNRIs Common Uses: Depression* Generalized Anxiety* Social Anxiety*
Panic Disorder*
PTSD
PMDD
Chronic Pain*
Fibromyalgia*

25. Common SNRIs Venlafaxine (Effexor) Duloxetine (Cymbalta)
Desvenlafaxine (Pristiq)

26. SNRIs Mechanism of Action Common Side Effects Drug Drug Interactions
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

27. MAOIs Common Uses: Depression* Social Anxiety Panic Disorder
Parkinson’s* (Selegiline)
Dementia

28. Common MAOIs Selegiline (EMSAM) Phenelzine (Nardil)
Tranylcypromine (Parnate)
Isocarboxazid (Marplan)

29. MAOIs Mechanism of Action Common Side Effects Drug Drug Interaction
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

30. “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

31. “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

32. “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)

33. “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
GI, sexual, sweating, palpitations, hypertension, bruising

34. “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

35. 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

36. Partial Responders/Augmentation
Dose?
Diagnosis?
Medical? Substance use?
Combination of Antidepressants
Lithium
Thyroid
Stimulants
Atypical Antipsychotics
Buspirone

37. Treatment Options Beyond Pharmacotherapy
Psychotherapy
ECT
PhotoTherapy
Magnetic Stimulation

38. 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

39. Anxiety Disorders
Anxiety disorders are the most common class of 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

40. Anxiety Excessive Worry Associated physical symptoms Avoidant Behavior
Unknown internal source vs. known external source
Sense of dread
Heightened apprehension

41. Causes of Anxiety Psychological Theories Behavioral 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

42. 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

43. Symptoms of Panic Attack
Palpitations
Sweating
Tremor
Shortness of Breath
Chest pain and discomfort
Nausea
Dizziness
Fear of losing control
Fear of dying

44. 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

45. 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

46. 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

47. 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

48. Phobias
Phobia: irrational fear resulting in a conscious 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

49. Phobias
Social: Fear of humiliation or embarrassment in either general or specific social situations
Commonly involving public speaking, urinating in public restrooms, stage fright

50. Treatment Phobias Specific Phobias Social Phobias
Exposure therapy (behavioral therapy)
Insight oriented psychotherapy
Pharmacotherapy (Benzodiazepines, SSRIs)
Social Phobias
Psychotherapy (behavioral, cognitive, insight oriented)
Pharmacotherapy (Beta Blockers, SSRIs, Benzodiazepines, Buspirone)

51. 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)

52. Diagnosis
Obsession: A recurrent and intrusive thought, feeling, 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

53. Treatment OCD Pharmacotherapy Psychotherapy Other Clomipramine SSRIs
Lithium
Benzodiazepines
Psychotherapy
Behavioral therapy (exposure, response and flooding)
Other
ECT
Psychosurgery (cingulotomy)

54. Post Traumatic Stress Disorder
Experience an emotional stress of potentially life 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

55. 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

56. Treatment PTSD Pharmacotherapy Psychotherapy SSRIs Mood Stabilizers
Hypnotics
Anxiolytics
Antipsychotics
Psychotherapy
Supportive
Cognitive
Group
Family

57. 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

58. Treatment GAD Pharmacotherapy Psychotherapy Benzodiazepines Buspirone
Mood Stabilizers
Antipsychotics
SSRIs
SNRIs
TCA
Psychotherapy
Cognitive Behavioral
Insight Oriented
Supportive

59. 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

60. Psychotic Disorders Schizophrenia Schizoaffective Disorder
Among top 10 leading cause of disability worldwide in people 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

61. Psychotic Disorders Clinical Features
Delusions
Hallucinations
Disorganized Speech
Disorganized Behavior
Negative Symptoms
Affect blunting
Alogia
Avolition

62. Differential Diagnosis Psychosis
Bipolar Disorder
Depression
Personality Disorder
Temporal lobe epilepsy
Tumor, Stroke
Infectious Disease
Autoimmune Disorder
Toxic illness
Drug Intoxications
Alcohol withdrawal

63. Clinical Management Safety Pharmacotherapy Family Therapy
Social Skills Training
Cognitive Rehabilitation

64. Pharmacotherapy Psychosis
First Generation, Traditional, Neuroleptics, Typical Antipsychotics
Main Therapeutic Effect by Blocking D2 Receptors
Second Generation, Atypical Antipsychotics
Blocks D1 , D2, 5HT2

65. Dopamine Pathways Four Well Defined Dopamine Pathways Mesolimbic
Mesocortical
Nigrostriatal
DA and Acetylcholine have a reciprocal relationship
Tuberoinfundibular
DA and Prolactin have a reciprocal relationship

66. Common Typical Antipsychotics
Chlorpromazine (Thorazine)
Haloperidol (Haldol)
Fluphenazine (Prolixin)
Perphenazine (Trilafon)
Thiothixene (Navane)
Trifluoperazine (Stelazine)

67. Common Atypical Antipsychotics
Aripiprazole (Abilify)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Paliperidone (Invega)
Clozapine (Clozaril)
Asenapine (Sapharis)
Lurasidone (Latuda)

68. Side Effects with AntiPsychotics
Typicals
Neurologic
EPS, Dystonia, Pseudoparkinsonism, akathesia,
Atypicals
Metabolic
Weight gain, Glucose, Lipids,
Tardive Dyskinesia, NMS, Q-T prolongation, Hyperprolactinemia

69. Treating EPS Anticholinergics Antihistaminics Dopaminergics
Benztropine
Trihexyphenidyl
Antihistaminics
Diphenhydramine
Dopaminergics
Amantadine
Beta-Blockers
Benzodiazepines

70. Treating EPS Use lowest possible dose
Move toward a lower potency antipsychotic
Use anticholinergic therapy
Use Amantadine, Benzodiazepine, Beta-Blocker
Consider Atypical

71. Long Acting Injectable AntiPsychotics
Typicals
Haloperidol
Fluphenazine
Atypicals
Risperidone
Paliperidone
Olanzapine
Aripiprazole

72. Thank you ! ?’s