Anxiety Disorders: Diagnosis and Management

ANXIETY DISORDERS Parna Haghparast, PharmD, BCPS Assistant Professor WCU School of Pharmacy Some slides has been adopted from Dr. Pondrom GAD = generalized anxiety disorder SAD = social anxiety disorder so 5-HT = serotonin Abbreviations NE = norepinephrine DA = dopamine CBT = cognitive behavioral therapy GABA = gamma-aminobutyric acid What is ANXIETY? • Anxiety is an emotional state commonly caused by the perception of real or perceived danger that threatens the security of an individual • Anxiety can produce uncomfortable and potentially debilitating psychological (eg, worry or feeling of threat) and physiologic arousal if it becomes excessive • Some individuals experience persistent, severe anxiety symptoms and possess irrational fears that significantly impair normal daily functioning. These persons often suffer from an anxiety disorder Emotional state ANXIETY Disorders • • • • The most frequent psychiatric disorder Often underdiagnosed and undertreated < 1/3 of patients receive appropriate treatment Develop CV, cerebrovascular, GI and respiratory disorders at a higher rate • Consequences: substance use, SI to suicide Anxiety Disorders Generalized Anxiety Disorder (GAD) Panic Disorder Social Anxiety Disorder (SAD or Social Phobia) Specific Phobias Common or Situational Anxiety • Normal response to stressful circumstance • Symptoms can be severe but temporary (no more than 2-3 wks) • PRN treatment with anxiolytics e.g. BZDs can provide relief I XD • Prolonged medication therapy not recommended Epidemiology Develops beforeage of • Approx. 34% of the population are affected by an anxiety disorder during their lifetime • 1-year prevalence for anxiety disorders: 21.3% (18+ years old) • • • • Specific phobias are most common – 10.1% SAD – 8% Panic – 3.1% GAD – 2.9% • Often develop another anxiety disorder, MDD or substance use disorder • More anxiety disorders among women compared to men (similar to PTSD and OCD) 30 1 Risk Factors for Anxiety Disorders 1. 2. 3. 4. 5. 6. Family history of anxiety Personal history of anxiety or mood disorder Childhood stressful life events or trauma Being female Chronic medical illness Behavioral inhibition • Consistent pattern of behavioral and emotional response to unfamiliar people/situations e.g. shy, timid, fearful • Dysfunctional parenting style (eg. Over protection) is associated with development of anxiety in children Etiology Anxiety Disorder Genetic Vulnerability Traumatic Experiences Childhood Adversity Occupational Stressors Neurobiological Adaptations Somatic Symptoms of Anxiety 39 in 4 D8 Abdominal Pain Palpitation/ Tachycardia Sweating Flushing Tremor Chest Pain Less specific: • HA • Muscle tension • Fatigue Medical disorders most closely associated with anxiety include: Cardiovascul ar e.g. MI no Respiratory e.g. asthma e Endocrine e.g. thyroid d/o GI issues e.g. Crohn’s disease Medication and Drug Induced Anxiety Is • CNS stimulants (dose-dependent) • Onset of medication-induced anxiety is usually rapid after the initiation of therapy • Thorough medication history • Recent initiation medications? • Any dose changes? • Use of unhealthy substances stimulating More Drug-Induced Anxiety wearatrine sertative CNS stimulants Anticonvulsants • Amphetamines • Methylphenidate • Nicotine • Carbamazepine Fluxitite Apna Antidepressants Antibiotics • Quinolones • Isoniazid • Phenytoin • SSRIs • SNRIs • Bupropion Unhealthy substances Bronchodilators Corticosteroids Dopamine agonists • Ecstasy • Albuterol • Theophylline • Prednisone • Levodopa • Cocaine • Amantadine • Cannabis Others • Pseudoephedrine/phenylephri ne • Levothyroxine • Ginseng • Clonidine Toxicity • Anticholinergics, • Antihistamines, • Digoxin Generalized Anxiety Disorder: Diagnostic Criteria • Criteria 1. Excessive anxiety and worry Rob (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities 2. The individual finds it difficult to control the worry Three or more of the following: Restlessness Fatigue Poor concentration or mind going blank Muscle tension Sleep disturbance Irritability At least some symptoms having been present for more days than not for the past 6 months Additional Criteria Significant distress or impairment • Social, occupational, or other areas of functioning two IF Not attributable to the physiological effects of a substance or another medical condition Not explained by another mental disorder Characteristics of GAD Onset Gradual onset with average age of 21 Course of illness Chronic – episodes can last decade or longer High relapse / low recovery Likelihood of remission at 2 years is 25% Comorbid conditions Majority develop another mental disorder – anxious depression Treatment Goal: GAD Desired outcome: Long-term goal: • Reduce severity and duration of anxiety symptoms and • Improve overall functioning we with minimal or no • Remission anxiety symptoms, • No functional impairment, and • Increased QOL General Approach to Treatment Patient-oriented plan Modalities Psychotherapy + drug therapy Psychotherapy – least invasive & safest treatment modality 073 I Depends on severity, chronicity, age, drug history, comorbid medical & psychiatric conditions Anti-anxiety medications for symptoms severe enough to produce functional disability Controlled trials comparing the efficacy of combining medication and psychotherapy over long-term treatment are lacking Pharmacological Tx start atlowerdose thenfitrat up • Pharmacological treatment is often associated with a delay of about 2-8 weeks in onset of anxiolytic relief, with full response taking up to 12 weeks or more • Longer-term therapy has been associated with continued symptomatic improvement and the prevention of relapse • Therapy should be continued for at least 12-24 months for most patients per CANMAT guideline and at least 6-12 months after remission per WFSBP guideline Nonpharmacologic Treatments • Psychotherapy – to manage anxiety and worry • CBT most effective – less relapse • Alone or in combination w/ medications • Psychotherapy or medication alone has comparable efficacy in acute treatment • Psychoeducation • Short-term counseling • Stress management • Mindfulness-based therapy NBA Zxweek • Exercise Avoid: • Caffeine • Non-RX stimulants & diet pills • Excessive use of alcohol Pharmacologic Therapy - GAD weeks 1st line (SSRIs, SNRIs) e • • • • • 0 418ha Duloxetine Escitalopram Paroxetine Sertralineto NOTFDA appredfor Venlafaxine XR Er TID IBID nd 2 line • • • • • • • Benzodiazepines Buspirone Hydroxyzine Pfendative Quetiapine XR Imipramine Vortioxetine Bupropion SSRIs are first-line drugs for see thetotreatment of anxiety disorders, OCD and PTSD so so a ACUTE RELIEF 3rd Line • Citalopram • Divalproex • Fluoxetine • Mirtazapine • Pregabalin-not recommended in substance use All the SSRIs/SNRIs listed above are FDA approved for GAD except for sertraline From the second line agent, try bupropion last weybutrin Adjunctive Therapy Second-line: pregabalin turf Third-line: • aripiprazole • olanzapine • quetiapine, quetiapine XR • risperidone Not Recommended: GAD Propranolol Benzodiazepines No active metabolite: Lorazepam and Oxazepam semalapon After long-term treatment with benzodiazepines (e.g. over 2–8 months), tolerance to the therapeutic dose may occur in some patients The GABA-receptor model of anxiety theorizes that benzodiazepines ameliorate anxiety through potentiation of the inhibitory activity of GABA Benzodiazepines • No active metabolite: Lorazepam and Oxazepam and • Most improvement occur in first 2 weeks. • most common adverse reactions associated with benzodiazepine therapy involve CNS depression • drowsiness, sedation, psychomotor impairment, and ataxiaMa lossofmuscleintro • A transient mild drowsiness is experienced commonly by patients during the first few days of treatment; however, tolerance often develops. Disorientation, depression, confusion, irritability, aggression, and excitement are reported • The memory loss induced typically is limited to events occurring after medication ingestion (anterograde amnesia) • BBW: Risks From Concomitant Use With Opioids; Abuse, Misuse, and Addiction; and Dependence and Withdrawal Reactions: • the onset of withdrawal sx in patients using BZDs with short elimination half-lives occurs much earlier (within 24-48 hours) than in those taking BZDs with long elimination half-lives (within 3-8 days). • Other factors associated with an increased incidence and severity of withdrawal include high doses an long-term benzodiazepine therapy tear Buspirone • • • • • • • • • • adit MOA: partial agonist activity at the 5-HT1A presynaptic receptors 2nd line Lacks muscle relaxing, hypnotic, and physical dependence of BZDs Inconsistent reports on efficacy Lack of efficacy for other concurrent disorders: depression, other anxiety d/o Effective for psychological sx Delayed onset of effect (2 wks or longer). Max effect take 4-6 wks Dosed BID/TID ADR: dizziness, nausea, and headaches Not useful for PRN dosing or if need rapid relief Dosing, administration and Side Effects • The antianxiety response of antidepressants is delayed by 2 to 4 weeks or longer • Antidepressants are effective in the acute and long-term management of GAD • For SSRIs/SNRI, GI and sleep disturbances are the most common side effects. Headaches and diaphoresis occur early in treatment and are often transient, whereas weight gain and sexual dysfunction may continue in long-term treatment. • The use of TCAs in clinical practice is limited by troublesome adverse reactions e.g. anticholinergics and toxicity in overdose • Start w/ low dose in week one for the antidepressant (due to transient increased anxiety) • Anxiety will dissipate with time and slow titration say Evaluation of Therapeutic Outcomes Reduction in frequency, duration & severity of anxiety Improvement in functioning Length of therapy should be individualized, with some patients requiring up to 1 year of antidepressant treatment Patient case • Difficulty sleeping He also continues to drink heavily. Patient Case • Mirtazapine two years ago for depression. • Discontinued due to weight gain. • He is currently taking OTC diet pills to lose weight. • He has been drinking coffee continuously to help him stay awake later so that he can exercise. • He would like to stop drinking, but the last time he tried, it gave him “the shakes”. Current Medications: PSE 60 mg BID for congestion Naproxen 500 mg BID for muscle aches Hydrocodone/APAP 7.5/325 TID for pain Loperamide 2 mg QID PRN diarrhea OTC diet pills DX: Generalized Anxiety Disorder, EtOH abuse forTreatment Recommendations? SSR line Natron on complor ptusingnorco• Patient Education dose startlow Tengoup SOCIAL ANXIETY DISORDER MIKE • 20 year-old man who reports that he feels depressed and is experiencing a significant amount of stress about school, noting that he’ll “probably flunk out.” • He spends much of his day in his dorm room playing video games and has a hard time identifying what, if anything, is enjoyable in a typical day. • He rarely attends class and has avoided reaching out to his professors to try to salvage his grades this semester. MIKE • Has always been a self-described shy person • Very small and cohesive group of friends from elementary through high school • Stress level significantly amplified when he began college • When meeting new people, he has a hard time concentrating on the interaction because he is busy worrying about what they will think of him – he assumes they will find him “dumb,” “boring,” or a “loser.” MIKE • When he loses his concentration, he stutters, is at a loss for words, and starts to sweat, which only serves to make him feel more uneasy. • After the interaction, he replays the conversation over and over again, focusing on the “stupid” things he said. Similarly, he has a long-standing history of being uncomfortable with authority figures and has had a hard time raising his hand in class and approaching teachers. • Since starting college, he has been isolating more, turning down invitations from his roommate to go eat or hang out, ignoring his cell phone when it rings, and habitually skipping class. His concerns about how others view him are what drive him to engage in these avoidance behaviors. Social Anxiety Disorder (Social Phobia) Key Features: • Marked, excessive or unrealistic fear or anxiety about social situations in which there is possible exposure to scrutiny by others • Active avoidance of feared situation Epidemiology: • Lifetime prevalence estimates ranging from 8-12% among the international general population • More common in women than men • SAD has an early age of onset, typically during adolescence (mean 12 years), and tends to have a chronic and unremitting course DSM-5 Criteria: SAD Some Feared Situations •Speaking in public •Addressing a group of people • Eating or writing in front of others • Use of public toilets • Interacting with authority figures • Talking with strangers Physical symptoms Blushing Discomfort • Diarrhea • Sweating • Tachycardia • Trembling “Butterflies in the stomach” OH TYPES of SAD • Generalized type: fear & avoidance extend to a wide range of social situations • Non-generalized: limited to one or two situations Goal of Therapy Acute 1. Reduce physiologic symptoms (e.g. tachycardia, flushing, sweating) 2. Reduce social anxiety 3. Reduce phobic avoidance 1. Ability to participate in social activities Continuation/ 2. Remission maintenance 3. Improve QOL General Approach to Treatment • SAD associated with significant morbidity • Response can be slow • Symptoms, prior treatments, concurrent conditions, and history of substance abuse direct treatment selections • Both CBT and pharmacotherapy (more practical) are effective in the treatment of SAD Pharmacologic Therapy - SAD MID First line • • • • • Fluvoxamine XR Escitalopram Paroxetine Sertraline Venlafaxine XR Second line • Citalopram • Gabapentin • Pregabalin • Clonazepam Third Line • • • • • • • • Bupropion SR Duloxetine Fluoxetine-inconclusive Mirtazapine Olanzapine Divalproex Topiramate Phenelzine TCA’s generally NOT effective for SAD Buspar may be used as adjunct but not as monotherapy per CANMAT, 2014 Adjunctive Therapy: SAD aripiprazole risperidone buspirone paroxetine Pharmacologic Therapy • Initiate SSRI at doses similar to depression • Dose response curve is relatively flat • If co-morbid panic d/o, start SSRI dose at ¼ or ½ of the dose • Benzodiazepines • Not considered 1st line • Beta Blockers e.g. Propranolol • Situational anxiety • Helps with autonomic sx (palpitation, sweating, blushing, tremor) Panic Disorder This Photo by Unknown Author is licensed under CC BY-SA DAVE • Dave is a 41-year-old male who was referred by his primary care physician after presenting to the ER with difficulty breathing. Dave’s physician was unable to find a medical explanation for his symptoms, which left Dave feeling confused, stressed, and angry. • Over the last 6 months, Dave has had several instances where he felt an intense fear that would reach a peak within a few minutes. During these instances, he would also experience sweating, heart palpitations, chest pain and discomfort, and shortness of breath. • At times, Dave worried that might die. As a result, Dave has persistent worry about having another attack. • In addition, he has begun to avoid unfamiliar places and people where it may be difficult to get help in the event of another panic attack. • The panic and associated avoidance are significantly impacting Dave’s life as he has been turning down social invitations, making excuses to stay at home whenever possible, and relying on his wife to drive their children to their various activities. Although she was understanding at first, Dave’s wife has grown frustrated with what she perceives as his irrational fear of panic attacks. soRandom Panic Attack Key Features: • Recurrent unexpected panic attacks, in the absence of triggers • Persistent concern about additional panic attacks and/or maladaptive change in behavior related to the attacks Epidemiology: • • • Estimated lifetime prevalence is 28.3% About 40-70% of patients with panic disorder experience nocturnal panic (waking from sleep in a state of panic) Risk higher among: o Women o Widowed/divorced o Middle-aged • Common co-morbidities: other anxiety d/o, mood disorder, impulse control d/o, SUD DSM-5 Criteria: Panic Attacks 1. Must have recurrent unexpected panic attacks 2. At least 1 month of persistent concern/worry about future attacks or maladaptive behavioral change related to attack 3. An abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and includes ≥4 of symptoms ◦Dizziness / Lightheadedness Nausea Abdominal distress Psychological symptoms Impact of Panic Disorder • Patients may develop agoraphobia • Anxiety about places or situations in which escape might be difficult • Patients will avoid specific situations • Adverse impact of QOL • Social and work impairment • Complications • Depression, alcohol abuse, high use of health services and emergency rooms • High lifetime suicide risk compared to general population Treatment: Panic Disorder Desired outcome 8 • Goal is remission – free of panic attacks, no/minimal anticipatory anxiety & agoraphobia, and no functional impairment General Approach to treatment • Single or combined medications, concurrent psychotherapy or psychotherapy followed by pharmacotherapy Nonpharmacologic Therapy • Patient education • Avoid substances that can precipitate panic attacks • (caffeine, drugs of abuse, stimulants) • CBT – 89-90% short-term improvement Pharmacologic Therapy – Panic Attack First line • • • • • • • Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline Venlafaxine XR Second line Rightnow • Benzodiazepines • Imipramine • Mirtazapine Third Line • Bupropion SR • Duloxetine • Olanzapine • Gabapentin • Divalproex • Topiramate • Quetiapine • Risperidone • Phenelzine • Levetiracetam • Milnacipran Adjunctive Therapy Second-line: BZD Third-line: • aripiprazole • olanzapine • risperidone • divalproex Pharmacologic Therapy Treatment options • • • • SSRI antidepressants or venlafaxine Benzodiazepines Mirtazepine Imipramine Antidepressants are considered 1st line • Long-term efficacy • Tolerability and safety profile Benzodiazepines are 2nd line • Risk of dependency • Avoid with history of substance abuse Panic Disorder Acute therapy Antidepressant therapy Maintenance therapy • Reduce symptoms • 1-3 months • 12 weeks for antidepressants • 4 weeks benzodiazepines • Use ¼ - ½ dose used for depression • Avoid activating effects • May need dosing at upper end for effect • 12-24 months Discontinuation Monitor Scales • Taper over 4-6 months • Panic symptoms • Adverse events • Panic Disorder Severity Scale • Sheehan Disability Scale Key Features: Specific Phobia: Marked, unreasonable fear or anxiety about a specific object or situation, which is actively avoided (e.g., flying, heights, animals, receiving an injection, seeing blood) Epidemiology • Lifetime prevalence estimates of 10-13% based on US and European study • Rates among adolescents may be particularly high with lifetime prevalence estimates of 36.5% • The most prevalent phobia types include: • • • • Animal (e.g., insects, snakes) Natural environment (e.g., heights, storms, water) Situational (e.g., flying, enclosed spaces), blood-injection-injury (blood, dentist, hospitals) • Women > men • Age of onset 5-12 yo (but differs based on type of phobia) • Tend to have other specific phobias as well DSM-5 Criteria: Specific Phobia Treatment • Treatment of choice: Exposure therapy for specific phobias o More effective if o sessions are grouped closely together o Exposure is prolonged o Some degree of therapist involved o Virtual reality can be helpful • Minimal role for pharmacotherapy due to o Lack of research on medications o Success of exposure-based therapies o BZD may be used acutely (e.g. MRI, dentist) o Nasal midazolam has been used (claustrophobic in MRI) Anxiety Disorders Panic Disorder Recurrent, unexpected panic attacks, in absence of triggers Persistent concern about additional panic attacks and/or maladaptive behaviors related to attacks Specific Phobia Marked, unreasonable fear or anxiety about a specific object or situation, which is actively avoided (e.g., flying, heights, animals, receiving an injection, seeing blood) Social Anxiety Disorder Marked, excessive or unrealistic fear or anxiety about social situations in which there is possible exposure to scrutiny by others Generalized Anxiety Disorder Excessive, difficult to control anxiety and worry (apprehensive expectation) about multiple events or activities (e.g., school/work difficulties) Active avoidance of feared situation Accompanied by symptoms such as restlessness/feeling on edge or muscle tension Key Points • Anxiety Disorders more common in females • With the exception of panic attacks, anxiety sx must be present for at least 6 months for diagnosis • Often co-morbid psychiatric conditions • CBT and exposure therapy (phobia) play an important role in management of anxiety • Stimulants can exacerbate anxiety • Generally, SSRIs and Venlafaxine are first line pharmacotherapy • BZD are second line pharmacotherapy and can provide acute relief o Risk of abuse, misuse, addition, withdrawal and CNS depression • Buspirone may be used in GAD • Antipsychotics are NOT first line o May be good option if psychosis or bipolar d/o • If not responding to first agent, switch to another agent within the first class o May also augment with adjunct medications for partial responders • Most patient may require 12-24 months of treatment