Kelly Kll M. Rock, DNP, CRNP 11/5/11 Objectives: Identify lifetime prevalence of depressive and anxious disorders. Recognize the social and economic burden of depressive and anxious disorders. Understand basic biological etiology of depressive and anxious disorders. Recognize symptoms of and anxiety across the lifespan. Identify appropriate FDA approved treatment modalities to treat depressive and anxious disorders. Lifetime prevalence Depressive disorders Major depressive disorder 16.9% highest of any psychiatric disorder Dysthymia 2.5% Anxious disorders Generalized anxiety disorder 5.7% Panic disorder 4.7% Obsessive compulsive disorder 2.3% National Comorbidity Survey retrieved September 2, 2011 at http://www.hcp.med.harvard.edu/ncs/publications.php#date2011 Social & Economic Burden of Leading cause of disability 4th leading contributor to the global burden of disease 15% of those with commit suicide Burden of crosses all domains of life Personal burden Family burden Mortality burden Disability burden Economic burden Etiology: Biological Factors of & Anxiety Neurotransmitters of interest Until recently, monoamine neurotransmitters (NTs) were the main focus of theories and research (serotonin, norepinephrine, dopamine) There has been a progressive shift in interest in favor of studying neurobehavioral systems, neural circuits and more intricate neuroregulatory mechanisms. 1
Biologic factors being reviewed in /anxiety research Autonomic nervous system stimulation i Genetic & Personality Factors Neuropeptide Y Galanin Alterations in Sleep Neurophysiology Neuroanatomical Considerations Immune Disturbances Second messengers & Intracellular cascades NTs Acetylcholine GABA Glutamate Glycine NMDA Alterations of Hormonal Regulation including HPA Thyroid DSM IV TR Criteria for MDD A. Five (or more) of the following symptoms have been present during the same 2 week period and represent a change from previous functioning; at least 1 of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. NOTE: Do not include symptoms that are clearly due to a general medical condition, or moodincongruent delusions or hallucinations (1) Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others. NOTE: In children and adolescents, can be irritable mood. (2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (3) Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day. NOTE: In children, consider failure to make expected weight gains. (4) Insomnia or hypersomnia nearly every day (5) Psychomotor agitation or retardation nearly every day (6) Fatigue or loss of energy nearly every day (7) Feelings of worthlessness or excessive or inappropriate guilt (8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (9) Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide MDD Continued B. The symptoms do not meet criteria for a mixed episode. C. The symptoms cause CLINICALLY SIGNIFICANT DISTRESS OR IMPAIRMENT in social, occupational, or other important areas of functioning D. The symptoms are not due to the direct physiological effects of a substance or a general medical condition E. The symptoms are not better accounted for by bereavement DSM IV TR criteria for Dysthymic disorder A. Depressed mood for most of the day, for more days than not, as indicted either by subjective account or observation by others, for at least 2 years. NOTE: In children and adolescents, mood can be irritable and duration must be at least 1 year. B. Presence, while depressed, or two (or more) of the following): (1) Poor appetite or overeating (2) Insomnia or hypersomnia (3) Low energy or fatigue (4) Low self esteem esteem (5) Poor concentration or difficulty making decisions (6) Feelings of hopelessness C. During the 2 year period (1 year for children/adolescents) of the disturbance, the person has never been without the symptoms in Criteria A and B for more than 2 months at a time D. No major depressive episode has been present during the first 2 years of the disturbance (1 year for children/adolescents) E. There has never been a manic episode, mixed episode or hypomanic episode and criteria have never been met for cyclothymic disorder F. The disturbance does not occur exclusively during the course of a chronic psychotic disorder G. The symptoms are not due to the direct physiological effects of a substance or general medical condition. H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Other symptoms of often noted in children/adolescents Somatic complaints Psychomotor agitation Mood congruent hallucinations Anhedonia ( blah mood) Negativistic attitude Restlessness Grouchiness Aggression Sulkiness Reluctance to cooperate in family ventures Withdrawal from social activities Desire to leave home School difficulties Inattentive to personal appearance Increased emotionality DSM IV TR Criteria for GAD A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance. B. The person finds it difficult to control the worry. C. The anxiety and worry are associated with 3 (or more) of the following 6 symptoms (with at least some symptoms present for more days than not for the past 6 months). NOTE: Only 1 item is required in children. (1) Restlessness or feeling keyed up or on edge (2) Being easily fatigued (3) Difficulty concentrating or mind going blank (4) Irritability (5) Muscle tension (6) Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep) D. The focus of the anxiety and worry is not confined to features of an Axis I disorder E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupations, or other important areas of functioning. F. The disturbance is not due to the direct physiological effects of a substance or general medical condition and does not occur exclusively during a mood disorder, a psychotic disorder, or a pervasive developmental disorder. 2
DSM IV TR Criteria for PD A. (1). Recurrent and unexpected panic attacks defined as: A discrete period of intense fear or discomfort, in which 4 (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: a. Palpitations, pounding heart, or accelerated HR b. Sweating c. Trembling or shaking d. Sensations of SOB or smothering e. Feeling of choking f. CP or chest discomfort g. Nausea or abdominal distress h. Feeling dizzy, unsteady, lightheaded or faint i. Derealization (feelings of unreality) or depersonalization (being detached from oneself) j. Fear of losing control or going crazy k. Fear of dying l. Paresthesias m. Chills or hot flashes PD Continued (2). At least one of the attacks has been followed by 1 month (or more) of one (or more) of the following: a. Persistent concern about having additional attacks b. Worry about the implications of the attack or its consequences c. A significant change in behavior related to the attacks B. Presence or absence of agoraphobia C. The panic attacks are not due to the direct physiological effects of a substance or a general medical condition D. The panic attacks are not better accounted for by another mental disorder. DSM IV TR Criteria for OCD A. Either obsessions or compulsions: Obsessions defined as: (1) recurrent and persistent thoughts, impulses, or images that are experienced at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress (2) the thoughts, impulses, or images are not simply excessive worries about real life problems (3) the person attempts to ignore or suppress such thoughts, impulses, or images or to neutralize them with some other thought or action (4) the person recognizes that the obsessional thoughts, impulses, or images are a product of his ore her own mind. Compulsions defined as: (1) repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly (2) the behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize ore prevent ore are clearly excessive. B. At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable. NOTE: This does not apply to children C. The obsessions or compulsions cause marked distress, are time consuming (taking more than 1 hour a day), or significantly interfere with the person s normal routine, occupational or academic functioning, or usual social activities or relationships. D. If another Axis I disorder is present, the content of the obsessions or compulsions is not restricted to it. E. The disturbance is not due to the direct physiological effects of a substance or general medical condition. Other symptoms of anxiety often noted in children/adolescents Fear of the dark Imaginary, bizarre worries Separation anxiety is prominent Somatic symptoms are common (GI, headaches, CV, and respiratory) High sensitivity to changes in their bodies More sensitive and easily brought to tears Treatment for depressive & anxious disorders Hospitalization Psychotherapy Pharmacotherapy ECT Trans cranial Magnetic Stimulation (TMS) Deep Brain Stimulation (DBS) Pharmacotherapy in children through young adults aged 24 Educate and DOCUMENT that pt (and family members) are aware of BLACK BOX WARNING with ALL ANTIDEPRESSANTS Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Insert established name] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Insert Drug Name] is not approved for use in pediatric patients. [The previous sentence would be replaced with the sentence, below, for the following drugs: Prozac: Prozac is approved for use in pediatric patients with MDD and obsessive compulsive disorder (OCD). Zoloft: Zoloft is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). Fluvoxamine: Fluvoxamine is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).] (See Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use) 3
Selective Serotonin Reuptake Inhibitors (SSRI) Fluoxetine Prozac 20 daily 20-80 for ages 8+, OCD for ages 7+, bulimia nervosa, PD Paroxetine Paxil 20 daily 10-60, OCD, PTSD, PD, SAD, GAD Paroxetine CR Paxil CR 12.5mg daily 12.5-62.5, PD Fluvoxamine Fluvoxamine CR Luvox Luvox CR 50 daily 50-300 100-300 OCD in children, adolescents and adults OCD, Social anxiety disorder Citalopram Celexa 20 daily 20-60 Sertraline Zoloft 50 daily 50-200, OCD, PD, PTSD, PMDD Escitalopram Lexapro 10 daily 10-20, GAD Vilazodone Viibryd Follow protocol 40mg MDD Clinical challenges in using SSRIs Side effect profile sexual, GI, electrolyte, PT/PTT Discontinuation syndromes Drug drug interactions *New FDA BB warning with citalopram/celexa > 40mg/day Serotonin Norepinephrine Reuptake Inhibitors (SNRI) Venlafaxine Effexor 37.5 BID 75-375 Venlafaxine XR Effexor XR 37.5-75 daily 75-225, GAD, SAD, PD Desvenlafaxine Pristiq 50 daily 50-100 Duloxetine Cymbalta 60 daily 60-120, GAD Clinical challenges in using SNRIs Dosing venlafaxine to reach norepinephrine receptor Risk of HTN Discontinuation syndrome Drug drug interactions Norepinephrine Dopamine Reuptake Inhibitors (NDRI) Bupropion Wellbutrin 100 BID 200-450 Bupropion SR Wellbutrin SR/ Zyban 150 QAM 150-400, smoking cessation Clinical challenges in using NDRIs Risk of seizures with bupropion above 400mg/day s (not used in those with seizure disorder) Not drug of choice in pts with ETOH abuse/dependence Bupropion XL Wellbutrin XL 150 300-450 4
Serotonin Norepinephrine Disinhibitor (SNDI) Clinical challenges in using SNDIs Sedation and increased appetite/weight Mirtazapine Remeron 15 QHS 15-45 Serotonin Antagonist Reuptake Inhibitors (SARI) Nefazodone Serzone 100 BID 200-600 Trazodone Desyrel 50 TID 150-600 Clinical challenges in using SARIs Sedation and priaprism with trazodone /oleptra Liver failure (1:250,000 300,000) with nefazodone. Monitor LFTs. Drug drug interactions Trazodone ER Oleptro 150 daily 225-375 Monoamine Oxidase Inhibitors (MAOIs) Generic Trade Typical starting FDA Indication Phenelzine Nardil 15mg TID 15-90 ; atypical Tranylcypromine Parnate Individualized 30-60 ; without melancholia Clinical challenges in using MAOIs Significant adverse reactions Di t titi d t ti l f h t i ii Dietary restriction and potential for hypertensive crisis Fatal over risk Drug to drug interactions (significant and can be fatal) Isocarboxazid Marplan 10mg daily 20-60 *Selegiline transdermal Emsam 6mg/24hr patch 6-12mg patch MDD 5
Tricyclic/Tetracyclic Antidepressants (TCAs) Imipramine Tofranil 25 TID 75-300, childhood enuresis Desipramine Amitriptyline Norpramin Elavil 25 BID or 50 QHS 25 BID or 50 QHS 100-300 50-300 Various depressive syndromes, especially endogenous Nortriptyline Pamelor 25 TID 75-150 Amoxapine Asendin 50 BID/TID 50-600 in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic s; accompanied by anxiety or agitation Doxepin Sinequan 25 BID or 50 QHS 75-300, anxiety, psychotic with anxiety Clinical challenges in using TCAs Significant adverse reactions Death in over Drug drug interactions Laboratory and EKG monitoring Clomipramine Anafranil 25-100 daily in divided s 25-250 OCD in children, adolescents and adults Second Generation Atypicals (SGAs) Clinical challenges in using SGAs Aripiprazole Ability 2mg 2-5mg Adjunctive tx in MDD Quetiapine XR Seroquel XR 50mg 150-300mg Adjunctive tx in MDD Fluoxetine + Olanzapine Symbyax 6/25mg 6-18/25-50mg Treatment resistant MDD Monitor and document presence/absence of metabolic SE. Be sure to include weight, glucose/hgba1c, and lipids at baseline, in 3 months after initiation and Q 6 12 months thereafter depending on risk factors! Potential for movement disorders and EPS (akathisia, TD, etc) Benzodiazepines Generic name Trade name Approval oral adult Half-life of Peak plasma Active FDA Indication dosage in parent drug level in hours metabolite mg/day Alprazolam Xanax GAD 0.75-4.0 6.3-26.9 1-2 None GAD, PD PD 1-10 Xanax XR 3-6 10.7-15.8 Chlordiazepoxide Librium 15-100 24-48 Several hours Four Anxiety disorders Clonazepam Klonopin 1.5-4 18-50 1-2 None PD Clinical challenges in using benzos Risk of abuse, dependence, diversion, and tolerance Psychological dependence vs. physical dependence Blunts efficacy of psychotherapy h Clorazepate Tranxene 15-60 Prodrug 1-2 Two Anxiety disorders Diazepam Valium 4-40 20-80 0.5-2 Three Anxiety disorders Lorazepam Ativan 1-10 12 2 None Anxiety disorders; Anxiety associated with Oxazepam Serax 30-120 5.7-10.9 3 None Anxiety disorders; Anxiety associated with 6
Serotonin 1A partial agonist (5HT 1A) Generic Trade Buspirone BuSpar 5-20mg TID or 15-30mg BID FDA Indication Anxiety disorders or short-term relief of the symptoms of anxiety Clinical challenges in using 5HT 1A partial agonists MUCH BETTER results with benzo nieve patients Anti anxiety effects not seen for a few weeks Requires BID TID daily dosing ATC (not prn) Pharmacotherapy for MDD Monotherapies 1 st Line SSRI NDRI SNRI Monotherapies 2 nd Line Mirtazepine (Remeron) NRI TCA SARI MAOI Augmentation Buspirone (Buspar) Lithium(low ) Benzos Cytomel(T3) Stimulant SGA Deplin(folic acid) Ancillary Cognitive therapy ECT Inpatient Vagus nerve stimulation (VNS) Adapted from: Stahl, Stephen. (2008). Stahl s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications (3 rd ed.). Cambridge University Press. Pharmacotherapy for GAD 1 st Line SSRI Buspirone (Buspar) SNRI Benzos 2 nd Line TCA Mirtazapine (Remeron) Trazodone (Desyrel) Gabapentin (Neurontin) Adjunctive Cognitive behavioral therapy SGA(esp. quetiapine) Adapted from: Stahl, Stephen. (2008). Stahl s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications (3 rd ed.). Cambridge University Press. Pharmacotherapy for PD Pharmacotherapy for OCD 1 st Line 2 nd Line Adjunctive 1 st Line 2 nd Line Adjunctive SSRI SNRI Benzos MAOI TCA Mirtazapine (Remeron) Trazodone (Desyrel) Gabapentin (Neurontin) Cognitive behavioral therapy SGA Lamotrigine (lamictal) Topiramate (Topamax) SSRI Clomipramine (Anafranil) MAOI SNRI Lithium Benzos SGA Buspirone (Buspar) Deep brain stimulation Neuro surgery Adapted from: Stahl, Stephen. (2008). Stahl s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications (3 rd ed.). Cambridge University Press. Adapted from: Stahl, Stephen. (2008). Stahl s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications (3 rd ed.). Cambridge University Press. 7
Thank you for your attention! Questions, clinical consultations, or needing additional information or resources: Kelly M. Rock, DNP, CRNP Family Counseling Center of Armstrong County 300 S. Jefferson St. Kittanning, PA 16201 724 545 4649 kmrock@fccac.org Conference Evaluation Online evaluations at: www.pacnp.org/conference 8