Updated Anxiety Lecture Week 6 PDF

Introduction to Psychiatry – Anxiety and Anxiety-related Disorders BMS 150 Week 6 Objectives Compare general anxiety disorder, phobia disorders, agoraphobia, social anxiety disorder and panic disorder in terms of: Signs and symptoms required for diagnosis T...

Introduction to Psychiatry – Anxiety and Anxiety-related Disorders BMS 150 Week 6 Objectives Compare general anxiety disorder, phobia disorders, agoraphobia, social anxiety disorder and panic disorder in terms of: Signs and symptoms required for diagnosis Time course of illness required for diagnosis Describe the clinical features of post-traumatic stress disorder, including: Types of exposures that render a person at risk for development of PTSD The general categories of signs and symptoms that characterize PTSD Typical signs and symptoms that correspond to each category Time course of illness required for diagnosis Objectives Describe the clinical features of obsessive compulsive disorder, including: The major features of obsessions and compulsions Signs and symptoms required for diagnosis Time course of illness required for diagnosis Describe the clinical features of eating disorders, including: Risk factors for their development Signs and symptoms required for diagnosis Important complications that accompany eating disorders Briefly describe the general neurobiological mechanisms underlying anxiety and obsessive compulsive disorders Objectives Differentiate between the use of BDZ as anxiolytics vs hypnotics, and provide examples of each type Outline the therapeutic mechanism of action of BDZ and flumazenil Discuss the adverse effects of BDZ, especially wrt hangover effects, rebound insomnia, tolerance and dependence Describe BDZ withdrawal symptoms from high vs low doses, and relate prescription length to the likelihood of developing withdrawal symptoms Discuss the warnings associated with use of BDZ for insomnia Provide therapeutic uses for flumazenil, and recognize the potential dangers of using it in a multi-drug overdose Anxiety A wide range of symptoms and signs, which everyone is familiar with because everyone has experienced it to some degree ▪ Can you name some? When is fear “pathologic”? ▪ Fear is out of proportion to risk/severity of threat ▪ Response lasts beyond the duration of the threat ▪ Response becomes generalized to other situations (similar or dis-similar) ▪ Social or occupational functioning is impaired Wide range of anxiety disorders ▪ 17% of adults report a lifetime history of one of the major anxiety disorders Anxiety Disorders “True” anxiety disorders: Panic disorder Agoraphobia Specific phobia Generalized anxiety disorder “Anxiety-like” disorders (no longer strictly considered as part of the anxiety disorder spectrum) Obsessive-compulsive disorder Post-traumatic stress disorder Panic disorder A type of anxiety disorder ▪ 1 - 2% prevalence Characterized by recurrent panic attacks ▪ What’s a panic attack? ▪ To be diagnosed with panic disorder, need to have periods in between attacks where patient a) fears another attack or b) does maladaptive things to avoid another attack Need at least 1 month history of avoidance or fear of another panic attack ▪ The panic can’t be due to a particular phobia or another anxiety-related disorder ▪ The panic symptoms cannot be due to an underlying medical disorder Panic Attacks - Features Four or more of the following: ▪ Palpitations, pounding heart, or accelerated heart rate ▪ Sweating ▪ Trembling or shaking ▪ Sensations of shortness of breath or smothering ▪ Feelings of choking ▪ Chest pain or discomfort ▪ Nausea or abdominal distress ▪ Feeling dizzy, unsteady, light-headed, or faint ▪ Chills or heat sensations ▪ Paresthesias (numbness or tingling sensations) ▪ Derealization (feelings of unreality) or depersonalization (being detached from oneself) ▪ Fear of losing control or “going crazy.” ▪ Fear of dying Generalized anxiety disorder GAD – generalized worry that occurs more days than not that is disproportionate to the severity of the event that is feared ▪ Common, prevalence is 3 – 8% ▪ Can be difficult to treat Often anxiety reduces with age Diagnostic criteria: ▪ Excessive anxiety for more days than not for 6 months ▪ Individual has difficulty controlling the anxiety ▪ Is accompanied by typical symptoms (see next slide) Generalized Anxiety Disorder - Symptoms 3 of 6 of the following must be present for diagnosis ▪ Restlessness or feeling “keyed up” or on edge ▪ Being easily fatigued ▪ Difficulty concentrating or mind going blank ▪ Irritability ▪ Muscle tension ▪ Sleep disturbance As with all psychiatric diagnoses, the anxiety, worry, or physical symptoms must: ▪ Cause clinically significant distress OR ▪ Impairment in social, occupational, or other important areas of function Agoraphobia In general, unreasonable fear of being out-of- doors or being in a crowd or being in a place where they can’t escape from or may suffer embarrassment ▪ The anxiety and its symptoms are typically present almost all of the time… even when the patient is somewhere comfortable to them ▪ Avoidance is prominent Very common disease, but again has a good prognosis if well-treated ▪ Rough estimate – about 1% of the population Agoraphobia – Symptoms Examples of situations that cause worry or fear in agoraphobia: ▪ Using public transportation ▪ Being in open spaces… or enclosed spaces ▪ Standing in line, being in a crowd, or being in other social situations ▪ Being outside of the home These situations should almost always provoke fear or anxiety ▪ Usually the patient fears that he/she cannot escape from the situation/environment or that they will experience a panic attack or other embarrassing symptom The fear or anxiety needs to be present for > 6 months and needs to cause significant distress or impairment in social or occupational function Specific Phobias fears of specific objects or situations that go beyond the true threat of the stimulus and cause avoidance and functional impairment ▪ Spiders, blood, clowns, etc. Surprisingly common – 12 - 16% Diagnostic criteria: ▪ exposure to stimulus provokes an immediate fear/anxiety response; may present as a panic attack ▪ phobic object/situation is actively avoided or endured with intense anxiety. ▪ fear/anxiety out of proportion to actual danger/sociocultural context ▪ person recognizes fear as excessive or unreasonable ▪ significant distress or impact on daily routine, occupational/ social functioning and/or marked distress ▪ Must be present > 6 months Social Anxiety Disorder marked and persistent (>6 mo) fear of social or performance situations in which: ▪ One is exposed to unfamiliar people or to possible scrutiny by others ▪ One is afraid that fearing he/she will act in a way that maybe humiliating or embarrassing e.g. public speaking, initiating or maintaining conversation, dating eating in public ▪ Out-of-proportion fear that they will be harshly judged by their interpersonal interactions ▪ Very common, 2 - 7% Post-traumatic stress disorder When does it happen? ▪ Exposure to actual death, threatened death, physical or sexual violence, serious injury Could have witnessed or received the violent act Can occur in people that are repetitively exposed to disturbing or violent events (i.e. police officer repeatedly exposed to details of an abuse situation) Often the sufferer feels helpless during the event ▪ In men, frequently associated with combat ▪ In women, abuse is frequently the causative factor ▪ First responders, healthcare personnel, law enforcement are a growing demographic affected by this disorder ▪ Lifetime prevalence estimated to be ~ 8% ▪ Diagnostic criteria and symptomatology are complex and specific – see next 3 slides Post-traumatic stress disorder Many different manifestations Symptoms divided into general categories: ▪ Intrusion symptoms Intrusive, distressing memories, flashbacks, dreams ▪ Avoidance behaviour Avoidance of situations or events that are associated with the inciting trauma Can also involve avoiding people, places, or conversations that arouse memories or feelings associated with the event ▪ Cognitive and mood symptoms Memory deficits, negative emotions, guilt, shame Detachment from others, loss of interest in people or activities ▪ Arousal and reactivity symptoms Difficulty sleeping, exaggerated startle responses Anger, irritability, increased risk-seeking behaviour Post-traumatic stress disorder - Symptoms Intrusion symptoms – examples ▪ Recurrent, involuntary distressing memories or dreams of a traumatic event (they “intrude” on the sufferer’s mind) ▪ Dissociative reactions where the individual feels as if the event was occurring Known as a flashback – different than a memory ▪ Marked physiological reactions or distress at exposure to cues that resemble the traumatic event Alterations in arousal and reactivity – examples ▪ Irritable behaviour or angry outbursts with little or no provocation ▪ Hypervigilance or exaggerated startle responses to everyday stimuli ▪ Sleep disturbances or difficulty concentrating ▪ Reckless or self-destructive behaviour Post-traumatic stress disorder - Symptoms Negative alterations in cognitions or mood – examples ▪ Inability to remember important aspects of the traumatic event ▪ Negative beliefs about oneself or the world in general These could be linked to or independent from self- blame about the traumatic incident ▪ Persistent inability to experience positive emotions ▪ Diminished interest or participation in general day-to-day, essential activities ▪ Detachment or estrangement from other people Time criteria: > 1 month for symptoms The disturbance must cause significant distress or impairment in social, occupational, or other important areas of function Obsessive-Compulsive disorder What is an obsession? A compulsion? Surprisingly difficult to treat ▪ Often refractory, a lot of work needs to be done by both patient and psychotherapist to get better Lifetime prevalence of 2-3% ▪ Subclinical OCD thought to be more prevalent, but few epidemiologic studies conducted  Obsessive Compulsive Disorder Obsession: intrusive and unwanted repetitive thoughts, urges, or impulses that lead to a marked increase in anxiety or distress Compulsion: repeated behaviors or mental acts that are done in response to obsessions, or in a rigid rule-bound way (i.e. ritual) ▪ Act may attempt to “suppress” the obsession Usually both are present Obsession Compulsion Fear of contamination Cleaning or washing rituals Pathological doubt (i.e. something was Repetitive checking missed leading to catastrophic consequences) Fear of causing harm to others Repetitive checking Need for symmetry or exactness Ordering, rearranging objects Superstitious obsessions (can include Superstitious rituals (i.e. repeating things religious obsessions) a certain number of times) Obsessive Compulsive Disorder Additional criteria ▪ Obsessions and compulsions must take > 1 hour/day or cause significant distress or impairment in social, occupational, or other areas of function Patients are usually aware that obsessions and compulsions are illogical and not based in fact ▪ This is known as insight ▪ Most patients with delusions and hallucinations have poor insight Other disorders may share a similar neurobiology with OCD, including: ▪ Hoarding disorder ▪ Skin-picking or trichitomania (hair-pulling/plucking) disorders ▪ Body dysmorphic disorder patient focuses on appearance in a negative way to the extent that it impairs social functioning  Neurobiology of Anxiety Disorders General concepts in fear and anxiety: Fear response: activation of the locus coeruleus (LC), a midbrain nucleus that contains neurons that release norepinephrine (NE) at the presynaptic terminal Activation of the LC ! release of norepinephrine (NE) ! ▪ Activation of the amygdala – emotional “fear” responses The amygdala is a prominent area that attaches an emotional weight to situations – this “weighting” can help prioritize and enhance learning ▪ Activation of the hypothalamus – activation of the sympathetic nervous system and cortisol release ▪ Activation of the reticular activating system in the brainstem – increased arousal Neurobiology of Anxiety Disorders The networks involved in anxiety-type disorders are complex ▪ i.e. ! in response to a fear-causing stimulus, the perception is sensed by the cortex ! communication to the amygdala via the thalamus ▪ The hippocampus can be “activated” or involved as part of the process of learning about the cause of the fear and how it can be avoided ▪ The pre-frontal cortex can exert a “top-down” control over how a patient (or any of us) regulates our cognitive responses or behaviours to a potential fear-causing stimulus ▪ The serotonin-releasing nucleus in the brainstem (the raphe nucleus) can also have a more “global” modulatory effect on mood, memory, and also fear + stress responses The noradrenergic, serotonergic and dopaminergic pathways all have important nuclei in the brainstem and all of them “cross-talk” to each other Noradrenergic Pathway Review Neurotransmitter: Noradrenaline (also known as norepinephrine) Origin: The cell bodies of noradrenergic neurons are located in the locus coeruleus in the brainstem. Function: Plays a key role in regulating mood, attention, arousal, and stress response. It is involved in the "fight or flight" response. Clinical Significance: Dysregulation of noradrenergic pathways is implicated in various psychiatric disorders such as depression, anxiety disorders, and attention deficit hyperactivity disorder (ADHD). Serotonergic Pathway Review Neurotransmitter: Serotonin (also known as 5- hydroxytryptamine or 5-HT) Origin: The cell bodies of serotonergic neurons are located in the raphe nuclei in the brainstem. Function: Regulates mood, emotion, appetite, sleep, and various cognitive functions. It is involved in modulating anxiety, aggression, and impulsivity. Clinical Significance: Imbalances in serotonin levels are associated with mood disorders such as depression and anxiety, as well as obsessive-compulsive disorder (OCD) and eating disorders. Dopaminergic Pathway Review Neurotransmitter: Dopamine Origin: Dopaminergic neurons have several nuclei in the brain, including the substantia nigra and the ventral tegmental area (VTA). Function: Plays a crucial role in reward, motivation, pleasure, movement, and reinforcement learning. Dopamine is involved in regulating mood, attention, and executive functions. Clinical Significance: Dysregulation of dopamine pathways is implicated in various psychiatric disorders such as schizophrenia, addiction, and Parkinson's disease.  Dopaminergic Neurobiology of Anxiety Disorders Noradrenergic, Dopaminergic, Serotonergic Pathways ! Brainstem Nuclei Serotonergic Noradrenergic Neurobiology of Anxiety Disorders A generalized model may be: Prolonged stress or genetic factors lead to a transition between “normal” anxiety and fear responses and “abnormal”, excessive anxiety and fear responses ▪ “Normal” – areas activated include the locus coeruleus, amygdala ! activation of the sympathetic nervous system and temporary increased release of cortisol Helps us deal with threats – the prefrontal cortex is able to regulate mood, negative cognition, and general worry Neurobiology of Anxiety Disorders A generalized model may be: Prolonged stress or genetic factors lead to a transition between “normal” anxiety and fear responses and “abnormal”, excessive anxiety and fear responses ▪ “Abnormal” – areas activated OR inactivated include an area close to the amygdala (stria terminalis) and other midbrain nuclei like the dorsal raphe nucleus as well as the locus coeruleus Poorer regulation of mood, fear/worry by the prefrontal cortex Excessive long-term activation of cortisol release by activation of the hypothalamic pituitary axis as well as excessive chronic activation of the sympathetic nervous system Obsessive Compulsive Disorder - Neurobiology OCD likely has a pathogenesis that is distinct from that of the anxiety disorders ▪ It likely involves circuits that involve the basal ganglia Remember the direct and indirect pathways as part of the extrapyramidal motor system? ▪ Research suggests that over-activation of the direct pathway and poor activation of the indirect pathway as they modulate activity of the orbitofrontal cortex Inhibitory dopaminergic transmission transmission (D2 receptors) may be implicated NOTE: this is a very simplified generalization for a disorder that has many different types of behaviour that are likely moderated by a range of different circuits ▪ The most effective medications are higher-dose SSRIs It is unclear how they mediate their positive impact on these circuits Recall - Nuclei of the basal ganglia General function Specific Nucleus Nucleus Function Input nuclei Putamen Control of limb and trunk (striatum) movements Caudate Cognition and eye movement control Nucleus accumbens Emotional regulation Associated nuclei Globus pallidus externa All are involved with limb/ Substantia nigra pars trunk movements, eye compacta movements, and Subthalamic nucleus emotional regulation Output nuclei Globus pallidus interna More involved with the putamen functions Substantia nigra pars More involved with the reticulata caudate functions Recall - Nuclei of the basal ganglia Frontal Input Output Thalamus lobe nucleus nucleus S.N.c. Ass. Nuclei Ass. Nuclei GPe STN Components of the direct and indirect pathway are illustrated here in a general fashion RED arrow = excitatory input BLUE arrow = inhibitory input Basics of eating disorders – anorexia nervosa and bulimia nervosa F:M ratio ~ 10:1 ▪ lifetime prevalence of around 1% in the female population for anorexia and 2-4% for bulimia Higher risk: ▪ display “perfectionist” traits ▪ Have a past history of sexual abuse ▪ feel that they lack control in other dimensions of their lives ▪ Expectations (i.e. athletic) regarding weight Gymnasts, dancers Wrestlers Anorexia diagnostic criteria A. intake and weight: restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. ▪ Significantly low weight ! a weight that is less than minimally normal B. fear or behaviour: intense fear of gaining weight or of becoming fat, or persistent behaviour that interferes with weight gain, even though at a significantly low weight C. perception: disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight Note: criteria A tends to be based on BMI criteria wrestlers, gymnasts, dancers (athletes) can have a lot of muscle mass but still have disordered eating habits Bulimia diagnostic criteria A. recurrent episodes of binge-eating; an episode of binge-eating is characterized by both of the following: ▪ eating, in a single period of time, an amount of food that is larger than what most individuals would eat during a similar period of time and under similar circumstances ▪ a sense of lack of control over eating during the episode B. recurrent inappropriate compensatory behaviour in order to prevent weight gain such as: ▪ self-induced vomiting ▪ misuse of laxatives, diuretics, enemas, or other medications ▪ Fasting ▪ excessive exercise C. the binge-eating and inappropriate compensatory behaviours both occur, on average, at least once a week for 3 mo D. self-evaluation is unduly influenced by body shape and weight E. the disturbance does not occur exclusively during episodes of AN Dangers of eating disorders Eating disorders can cause significant physical harm – a short list below for anorexia and bulimia Starvation/Calorie Restriction Binging + Purging Hypotension, bradycardia Gastric dilation or rupture Dysrhythmias, congestive heart Esophageal damage/tearing failure Pancreatitis Vitamin deficiencies Dysrhythmias (due to K+ loss from Constipation, delayed gastric vomiting or use of laxatives) emptying Damage to teeth (purging) Decreases thyroid hormone, Aspiration pneumonia amenorrhea, osteoporosis Gastric contents cause Increased risk of seizure due to pneumonia when they are electrolyte abnormalities accidentally “breathed in” Severe restriction can cause renal failure and edema Benzodiazepines Act as anxiolytics or hypnotics BDZ commonly ▪ Anxiolytic example: Diazepam (Valium®) have “zepam” Also used for certain types of seizures and “zolam” ▪ Hypnotic example: Triazolam (Halcion®) endings What is their mechanism of action? ▪ Facilitate binding of GABA to GABA-R How could this explain their anxiolytic, hypnotic, and anti-seizure effects? Benzodiazepine Adverse Effects Selected adverse effects (most common with hypnotic use): Hangover effects ▪ Wake up feeling groggy ▪ More common with long half-life agents Early morning rebound insomnia ▪ Wake up too early ▪ More common with short half-life agents ▪ Can lead to taking a second pill during the same sleep cycle, which makes tolerance more likely to develop Benzodiazepine Adverse Effects Tolerance ▪ Usual dose of drug no longer sufficient to get therapeutic effect ▪ May be due to downregulation of ? How can you still get a therapeutic effect once tolerance occurs? ▪ Unfortunately, this increases likelihood of dependence Dependence ▪ Brain requires the drug to generate normal amounts of GABA activity ▪ Leads to more severe withdrawal symptoms when drug is discontinued Benzodiazepine Adverse Effects Withdrawal symptoms ▪ Mild symptoms can occur after short-term use and/ or low-doses, including: Extra-sensory awareness ▪ Ex acute hearing Muscle twitching or tremors Rebound excitation ▪ Patients should be counselled to expect a few nights bad sleep at the end of a course of BDZ During this time, a new prescription should not be given * Use of BDZ’s more than 14-21 nights in a row makes tolerance/ dependence/several withdrawal symptoms more likely Benzodiazepine Adverse Effects Withdrawal symptoms ▪ Severe symptoms usually occur on abrupt discontinuation after long-term use and/or high doses, and include: Increased blood pressure, Can you rationalize temperature and pulse this group of Rage symptoms? Hallucinations and paranoia Seizures ▪ Withdrawal symptoms can also occur during chronic drug use – why? Benzodiazepines Adverse Effects General warnings/precautions associated with the use of hypnotics to treat insomnia include: ▪ Abnormal thinking and behavioral changes Visual and auditory hallucinations, “sleep-X” events ▪ The need to evaluate for an underlying primary psychiatric and/or medical illness for the insomnia Hypnotic use coupled with an underlying primary disorder can cause: ▪ Worsening of insomnia, worsening of depression (including suicidal thoughts), etc BDZ Antagonist Flumazenil = BDZ antagonist ▪ Competitive inhibitor of BDZ ▪ Therapeutic uses include: Removal of effects of BDZ once therapeutic effects no longer needed ▪ Ex after an in-office procedure Treatment of BDZ OD ▪ Caution with multi-drug overdose ▪ Shorter duration of action than BDZ What is the implication for someone who had a BDZ for an in-office procedure, then was given flumazenil to reverse its effects? Case: Discuss with a partner/small group A patient is admitted to the emergency room with severe CNS depression from a probable drug overdose ▪ Signs include including ataxia, hypotonia, and respiratory distress ▪ Empty bottles of diazepam, amitriptyline, and bupropion were found at his bedside An intern starts to prepare a flumazenil IV ▪ Do you stop her and ask her to re-evaluate the treatment, or do you go ahead with administering flumazenil?