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Psychopharmacology: An Update for Clinical Practice David B. Weiss, M

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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

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