The Basics of Clinical Psychopharmacology: Therapeutic Alliance and Adherence

1. The Basics of Clinical Psychopharmacology: Therapeutic Alliance and Adherence

2. Author

3. Slide Reviewers

4. Objectivesfrom ADMSEP Psychiatry Learning Objectives Taskforce, 2007 By completion of the clerkship/medical school, the student will be able to: Slide 2Slide 2

5. ADMSEP Objectives�con�t 1. Discuss the common, currently available psychotropic medications with regard to clinical indications and contraindications, presumed mechanism of action and relevant pharmacodynamics, common and serious adverse effects, pharmacokinetics, evidence for efficacy, cost, risk of drug-drug interactions and drug-disease interactions, and issues relevant to use in special populations (e.g., pregnancy and lactation, childhood and adolescence, the elderly, persons using herbal and over-the-counter treatments). 2. Propose selected psychotropic pharmacotherapy for designated patients and provide clinical reasoning that includes discussion of factors influencing treatment selection (e.g.,patient-specific and drug-specific variables, scientific evidence). Slide 2Slide 2

6. ADMSEP Objectives�con�t 3. Discuss the factors relevant to implementing, monitoring and discontinuing psychotropic pharmacotherapy including drug dosing, treatment duration, and adherence, and make management recommendations for dealing with an unsuccessful treatment trial (e.g., lack of efficacy, intolerability). 4. Counsel patients about psychotropic pharmacotherapy including risks and benefits of recommended treatment, treatment alternatives, and no treatment 5. Identify and discuss resources to maintain an up-to-date knowledge of psychotropic pharmacotherapy Slide 2Slide 2

7. ADMSEP Objectives�con�t 6. Discuss special issues and concerns related to specific psychotropic drug classes including metabolic, hematologic, hepatic, etc. For Anxiolytics and Sedative-Hypnotic Agents: Be able to discuss the risks, early detection, relevance and interventions for drug toxicity, dependence and consequences of abrupt discontinuation. Slide 2Slide 2

8. Objectives for MS II At the end of this lecture, the student will: Be able to articulate the basic mechanism of action of the anxiolytic drugs Be able to name the basic drugs in this class and their clinical indications

9. Objectives for MS III At the end of this lecture, the student will: Be able to list appropriate dose ranges for at least 3 drugs in this class Be able to elucidate the major side effects seen in the use of the various types of anxiolytic drugs

10. Outline For each disorder: Definition of the disorders (with DSM criteria) Review of the phenomenology and epidemiology of the disorder The clinical psychopharmacology Pitfalls and Pearls Questions

11. Slide 15Slide 15

12. Recognition and Treatment of Gernalized Anxiety Disorder

13. Generalized Anxiety Disorder (GAD) In earlier versions of the DSM there was a residual anxiety category Emphasis has changed from somatic to psychic manifestations Increased duration of symptoms to 6 months Virtually a new disorder as currently defined Perceptions of psychiatrists and PCPs differ

14. Generalized Anxiety Disorder (GAD) Excessive anxiety and worry about a number of events for the majority of days over 6 months Difficulty in controlling the worry Associated physical and psychological symptoms Causes significant distress or impairment Not due to a substance or a general medical condition Slide 2Slide 2

15. GAD Symptoms Psychic symptoms worry insomnia fatigue irritability feeling �on edge� poor concentration Somatic symptoms muscle tension nausea or diarrhea sweating urinary frequency palpitations The presentation of GAD is characterized by a cluster of psychic and somatic symptoms. The predominant psychic symptom of GAD is worry. However, other symptoms of anxiety are present, including insomnia, fatigue, irritability, feelings of edginess, and poor concentration. Somatic symptoms include muscle tension, which is a hallmark physical feature, and gastrointestinal distress, sweating, urinary frequency, and palpitations.The presentation of GAD is characterized by a cluster of psychic and somatic symptoms. The predominant psychic symptom of GAD is worry. However, other symptoms of anxiety are present, including insomnia, fatigue, irritability, feelings of edginess, and poor concentration. Somatic symptoms include muscle tension, which is a hallmark physical feature, and gastrointestinal distress, sweating, urinary frequency, and palpitations.

16. Generalized Anxiety Disorder (GAD)

17. Epidemiology of GAD

18. GAD Patients: Comorbidity 90% have another psychiatric disorder In patients with GAD 62% have lifetime major depression 40% have dysthymia Anxiety disorders predict greatest riskof secondary MDD 58% of patients with lifetime MDDhave anxiety disorder

19. Overlapping Symptoms of Depression and GAD Slide 8Slide 8

20. GAD: Complications

21. Lifetime Prevalence of Comorbid Disorders in Patients with GAD

22. Differential Diagnosis Medications Which Can CauseAnxiety Symptoms Thyroid supplementation Antidepressants Corticosteroids Oral contraceptives Stimulants (caffeine) Bronchodilators Decongestants Abrupt withdrawal of CNS depressants Alcohol Barbiturates Benzodiazepines

23. Differential Diagnosis Medical Conditions with Secondary Anxiety Symptoms Endocrine disorders Thyroid disease Parathyroid diseases Hypoglycemia Cushings Disease Cardio-respiratory disorders Angina Pulmonary embolism Autoimmune disorders Neurological Seizure disorder Substance-related dependence/ withdrawal Nicotine Alcohol Benzodiazepines Opioids

24. General Recommendations for Treating Patients With Anxiety Disorders Avoid caffeine Avoid excess alcohol consumptionand nicotine Exercise moderately to relieve tension and improve sleep Monitor over-the-counter medications Adhere to prescribed treatment regimen

25. �Pure� GAD: Treatment Options

28. Benzodiazepines Advantages Rapid onset Effective Well-tolerated General anti-anxiety effects Safe in overdose Generics available Disadvantages Withdrawal reactions Sedation Multiple daily dosing often required Abuse potential in patients with a history of substance abuse Poor antidepressant effect

29. Benzodiazepines Medication Daily Dosage Range (mg) Alprazolam 2-6 Clonazepam* 1-3 Lorazepam 4-10 Diazepam* 15-20

30. Benzodiazepine Approximate Clinical Equivalents Clonazepam 0.5 Alprazolam 1 mg Lorazepam 1.5 mg Diazepam 10 mg

35. Other GAD Medication Treatments Tricyclic antidepressants (TCAs) Advantages Single daily dose Antidepressant effects No abuse potential Well studied Effective Generics available Disadvantages Delayed onset Anticholinergic side-effects Postural hypotension Weight gain Sexual side-effects Initial stimulation Dangerous in overdose

36. GAD Treatments Newer Antidepressants Venlafaxine and SSRIs (Venlafaxine, escitalopram and paroxetine have FDA approval for GAD) Advantages Effective Benign side-effect profile Safety No dependence issues Once a day dosing Disadvantages Delayed onset of action Early anxiogenic effect Sexual side-effects Usually requires dose titration

37. Recognition and Treatment of Panic Disorder

38. Panic Disorder One or more unexpected panic attacks as characterized by at least 4 symptoms that are described in the next slide, generally peaking in 10-20 minutes: At least one month of worry, including change in cognition or behavior With or without agoraphobia

39. Panic attack symptoms Palpitations, pounding heart Chest Pain or discomfort Shortness of breath Feeling of choking Feeling of dizzy, unsteady, lightheaded or faint Paresthesias (numbness or tingling sensations) Chills or hot flushes Trembling or shaking Sweating Nausea or abdominal stress Derealization (feelings of unreality) or depersonalization (being detached) Fear of losing control or going crazy Fear of dying

40. Medical Utilization Top 10% of Users Odds ratio 5 MD visits Males Females Major depression 1.5 3.4 Panic disorder 8.2 5.2 Phobic disorder 2.7 1.6

41. Percent Using Emergency Room for Emotional Problems Past Year

42. Medical conditions with increased frequency of co morbid diagnoses of panic disorder Mitral valve prolapse Migraine Irritable bowel syndrome Chronic fatigue syndrome Vertigo Hyperventilation syndrome Premenstrual syndrome

43. Panic Disorder Treatment:General Principles Pharmacotherapy Cognitive-Behavior Therapy (CBT) Manual-driven CBT treatment to normalize �catastrophic thinking� Exposure to panic symptoms and other feared situations

44. Panic Disorder Treatment:General Principles Pharmacotherapy Selective serotonin reuptake inhibitors first line due to favorable side effect profile Other antidepressant classes work also Venlafaxine (Effexor) is effective Nefazodone(Serzone) no longer on US market due to liver toxicity Benzodiazepines and Beta-blockers useful adjunctive treatments for residual symptoms

46. Recognition and Treatment of Obsessive Compulsive Disorder

47. Obsessive-Compulsive Disorder Obsessions: recurrent or persistent thoughts, impulses, or images are experienced as intrusive or inappropriate and cause distress not simply excessive worries about real-life problems person attempts to ignore or suppress thoughts or neutralize them with another thought or action person recognizes that obsessions are product of his/her mind, not imposed from without Compulsions: repetitive behaviors or mental acts performed in response to an obsession or according to certain rules designed to neutralize or prevent discomfort or some dreaded event or situation The obsessions and compulsions cause marked distress, are time-consuming, or significantly interfere with normal routine, occupational functioning, or usual social activities or relationships with others

48. Common obsessions in OCD Contamination Pathological doubt Aggressive impulse Somatic concerns Need for symmetry Sexual impulse

49. Common Compulsions in OCD Washing Checking Counting Symmetry and precision Need to ask or confess Hoarding

50. Differentiating Obsessions vs. Delusions Obsessions Doubt Minute possibility Insight Delusions Certainty False/bizarre/impossible No insight

51. OCD Treatments Behavior Therapy (Exposure and Response Prevention) Pharmacotherapy (SSRI) Combination

52. Behavior Therapy for OCDExposure and Response Prevention Systematic and intensive treatment Stimuli for rituals and avoidance identified and assigned a place in a hierarchy of anxiety provocation Intensive exposure to stimuli is done both with therapist and as homework Exposure is graded from easiest to most difficult Rituals omitted or, if not possible, delayed

53. Serotonergic antidepressants for OCD Minimum duration of treatment: 10-12 weeks Therapeutic doses: clomipramine 250 mg/day fluoxetine 60 mg/day fluvoxamine 300 mg/day sertraline 50-200 mg/day paroxetine 60 mg/day Maintenance therapy prevents relapse Risk of relapse 2.7 times greater with placebo than paroxetine

54. Medication Choice Fluoxetine 20mg 40-60mg 80mg long half-life 4-16 days Fluvoxamine 50mg 200mg 300mg short half-life 13-15 hrs Paroxetine 20mg 50mg 60mg half-life 21 hours Sertraline 50mg 150mg 225mg half-life 26 hours

55. Recognition and Treatment of Posttraumatic Stress Disorder(PTSD)

56. Posttraumatic Stress Disorder A characteristic set of symptoms following exposure to extreme traumatic stress Experience, witness, or confronted with actual or threatened death or injury Response involves intense fear, helplessness, or horror These symptoms include experiencing symptoms, avoidance symptoms and arousal symptoms Duration more than one month Significant functional impairment

57. Experiencing symptoms (1 necessary) intrusive recollections recurrent dreams flashbacks psychological distress with reminders physiologic reactivity with reminders Posttraumatic Stress Disorder

58. Avoidance symptoms (3 necessary) avoid thoughts/feelings/conversations avoid activities, places, people inability to remember diminished interest feelings of detachment restricted affect foreshortened future Posttraumatic Stress Disorder

59. Arousal symptoms (2 necessary) sleep difficulty irritability concentration hyper vigilance exaggerated startle Posttraumatic Stress Disorder

60. Lifetime prevalence in community of 1% to 14% One of the least well-studied anxiety disorders Combat-related PTSD is best studied PTSD is associated with sexual abuse, physical assault, torture, accidental trauma, natural or man-made disasters, diagnosis of threatening illness Posttraumatic Stress Disorder

61. PTSD Risks of Specific Traumasin the US Population

62. PTSD Treatment Options Talk: Managing PTSD Speaker: Randall D. Marshall, M.D. Meeting: Addressing the Symptom Cluster Triad: Diagnosing and Treating PTSD / GSK 2001 T2Talk: Managing PTSD Speaker: Randall D. Marshall, M.D. Meeting: Addressing the Symptom Cluster Triad: Diagnosing and Treating PTSD / GSK 2001 T2

63. Recognition and Treatment of Social Anxiety Disorder

64. Social Anxiety Disorder Fear that performance will prove humiliating or embarrassing Not related to other axis I or III disorders Exposure to feared situation ? anxiety Avoidance or distress Social or occupational problems or worried about fear Knows fear is excessive

65. Social Anxiety Disorder Subtypes Generalized Almost all domains affected Non-generalized One or two social situation--usually public speaking only

66. Symptoms of social anxiety disorderFeared situations Social Attending parties, weddings etc Conversing in a group Speaking on telephone Interacting with authority figure (eg teacher or boss) Making eye contact Ordering food in a restaurant Performance Public speaking Eating in public Writing a check Using public toilet Taking a test Trying on clothes in a store Speaking up at a meeting

67. Symptoms of social anxiety disorder Precipitating situations Being introduced Meeting people in authority Using the telephone Receiving visitors Being watched doing something Writing in front of others Speaking in public

68. Symptoms of social anxiety disorder Cognitive patterns  Overestimation of scrutiny by others Overestimating possible rejection, embarrassment or humiliation Misinterpretation of response of others Exaggerated response to rejection Discounting personal achievements / overemphasizing failures

69. Social anxiety disorderTreatment options

70. Social anxiety disorder Treatment goals Control anxiety and phobic avoidance Reduce associated disability Treat depression / other comorbid disorders Tolerability over long term Eventual medication-free status

71. Pharmacological management of social anxiety disorder Consider initial choice of an SSRI Initial dose for 2-4 weeks, then increase if necessary example sertraline: 100mg/day with increase to 200mg/day Some benefit evident by 2-4 weeks If no response by 6-8 weeks, switch to drug of another class or augment Consider psychosocial treatments Continue pharmacotherapy for at least 1 year

72. Social Anxiety Disorder: Pharmacological Treatments Monoamine oxidase inhibitors (standard/RIMAs) Benzodiazepines SSRIs--leading choice as sertraline and paroxetine are FDA approved for this disorder

73. Pitfalls and Pearls Pitfalls Anxiety is a difficult condition to treat, as individuals often overestimate the level of their anxiety Building a tolerance to anxiolytics and sedative hypnotics always happens. This easily can turn into addiction in high risk individuals. Anxiolytics with longer half-lives are less likely to cause dependence.

74. Pitfalls and Pearls Pearls Because of the pitfalls, most of these medications are used only sparingly by psychiatrists. buspirone is an exception to the pitfalls. However, it may not be as effective as the usual anxiolytics. Withdrawal from anxiolytics/sedative hypnotics is similar to that from alcohol (with which they are cross=tolerant), but is more insidious and life-threatening Never use combinations of these drugs

75. Question 1 In an average primary care practice, what percentage of patients will have GAD? A. about 2 percent B. about 4 percent C. about 6 percent D. about 8 percent E. about 10 percent

76. Question 2 Which of these is not a good recommendation for someone with an anxiety disorder? A. drink less coffee B. monitor over-the-counter medications C. have a glass of wine before bedtime D. exercise moderately E. pay attention to sleep hygiene

77. Question 3 What would be most useful for a person who is dependent on alprazolam? A. Tell the patient to stop the drug at once B. Add a longer acting benzodiazepine C. Tell the patient not to drink alcohol D. Monitor the patient for liver failure E. Change the patient to clonazepam

78. Question 4 Buspirone is most like what other drug class with regard to mechanism of action? A. �Typical� antipsychotics B. Benzodiazepines C. Antidepressants D. Analeptic mood stabilizers E. Beta blockers

79. Question 5 Which agent is most likely to abort an acute panic attack? A. alprazolam B. clonazepam C. buspirone D. amitriptyline E. diazepam

80. Question 6 What is a good treatment option for PTSD? A. SSRIs B. MAOIs C. Mood stabilizers D. Antianxiety agents E. All of the above

81. Answers to Questions 1. D 2. C 3. E 4. C 5. A 6. E

82. End of Lecture