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

Psychopharmacology: An Update for Clinical Practice David B. Weiss, M.D. Denver, Colorado. Disclosures. Speaker’s Bureau: Otsuka and Lundbeck Off-Label Uses Will Be Discussed. Objectives. Review Common Psychiatric Diagnoses presenting in the primary care setting

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

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

  2. 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 • Women > Men • Age • 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 • Dysthmia • Cyclothymia • Schizoaffective Disorder • Schizophrenia • Anxiety Disorders • Personality Disorders • Substance related Disorders • Uncomplicated Bereavement • Premenstrual dysphoric Disorder • PostPartum Depression • Depression 2nd to General Medical Condition • Infections • Endocrine Disorders • Neurological Disorders • Neoplasms • Inflammatory Disorders

  14. 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

  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* (ClomipramineAnafranil) • 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 • 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 • 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 • 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 • 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 • Exposure therapy (behavioral therapy) • Insight oriented psychotherapy • Pharmacotherapy (Benzodiazepines, SSRIs) • Social Phobias • Psychotherapy (behavioral, cognitive, insight oriented) • Pharmacotherapy (Beta Blockers, SSRIs, Benzodiazepines, Buspirone)

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