Anxiety disorders.pdf

2/14/2024 Anxiety Disorders Individualization of therapy & case-based approaches Nancy Ali Mahfouz, PharmD Head of Clinical Pharmacy , Department of Neuropsychiatry...

2/14/2024 Anxiety Disorders Individualization of therapy & case-based approaches Nancy Ali Mahfouz, PharmD Head of Clinical Pharmacy , Department of Neuropsychiatry Alexandria University Hospitals. Lecturer Practitioner – Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy Alexandria University 1 When is anxiety an Anxiety Disorder? Anxiety is a normal emotion under circumstances of threat and is thought to be part of the evolutionary “fight or flight” reaction of survival. It may be normal or even adaptive to be anxious when facing stressful or fearful situations. However, there are many circumstances in which anxiety is maladaptive and constitutes a psychiatric disorder. Anxiety as a psychiatric disorder is characterized by the core symptoms of excessive Fear and Worry. While MDD’s core symptoms are depressed mood or loss of interest. Anxiety disorders are frequently under-diagnosed conditions in primary care. The lifetime prevalence of anxiety disorders is about 29%. Patients with anxiety disorders are frequent users of emergency and primary medical services. Symptoms ,may be mild, transient and without associated impairment in function, but many patients are troubled by severe and persistent symptoms that cause significant personal distress, impair function and reduce quality of life. With adequate treatment, the quality of life of patients with these disorders may substantially be improved. The current conceptualization of anxiety disorders includes an interaction of a specific neurobiological vulnerability (genetic, childhood adversity) and environmental factors (stress, trauma). 2 1  2/14/2024 Fear response - Motor responses : Avoidance/freezing under threat , fight or to run away (flight) in order to survive threats. - Endocrine output of fear : Increases in Cortisol(stress hormone), which occur because of amygdala activation of the (HPA) axis. Prolonged activation can lead to increased risk of coronary artery disease, type 2 diabetes and stroke (*scared to death*). - Breathing output : Increases in the respiratory rate, shortness of breath, exacerbation of asthma, or a sense of being smothered. - Autonomic output of fear : Increases in heart rate and blood pressure, long- term effects (increased risk of atherosclerosis, cardiac ischemia, myocardial infarction, or even *sudden death*). Overactivation of worry or obsessions. Memory and re-experiencing Traumatic memories stored in the hippocampus can activate the amygdala and regenerate a fear response. 3 Key features of specific Anxiety and related disorders Panic disorder (PD) ‫اضطراب الهلع‬ Panic disorder is characterized by recurrent panic attacks. Panic attacks are discrete periods of intense fear or discomfort, accompanied by at least four somatic and psychic symptoms (palpitations, sweating, trembling, dyspnoea, choking sensations, chest pain, nausea, abdominal distress, dizziness, feeling of unreality, fear of dying, etc.). A panic attack reaches a peak within 10 min and lasts 30 – 45 min on average. Usually, the patient is afraid that he has a serious medical condition such as myocardial infarction. Agoraphobia ‫ رهاب الميادين‬/‫ الخوف من األسواق‬/‫رهاب الخالء‬ About two-thirds of all patients with panic disorder suffer from agoraphobia, which is defined as fear in places or situations from which escape might be difficult or in which help may not be available in the event of having an unexpected panic attack. These situations include being in a crowd or standing in a line, being outside the home alone, or traveling in a bus, train or automobile. These situations are avoided or endured with marked distress. Generalized anxiety disorder (GAD) ‫اضطراب القلق العام‬ The main features of generalized anxiety disorder are excessive fear and worry. The patients suffer from somatic anxiety symptoms as well as from restlessness, irritability, difficulty concentrating, muscle tension, sleep disturbances and being easily fatigued. Patient may express constant worry that the patient or a relative will shortly become ill or have an accident. Specific phobia ‫الخوف المرضى‬/‫الرهاب‬ Specific phobia is characterized by excessive or unreasonable fear of single objects or situations (e.g., flying, heights, animals, seeing blood, etc.). 4 2  2/14/2024 Social phobia (social anxiety disorder; SAD) ‫الرهاب االجتماعي‬ This disorder is characterized by marked, persistent, and unreasonable fear of being observed or evaluated negatively by others in social performance or interaction situations and is associated with somatic and cognitive symptoms. The feared situations are avoided or else are endured with intense anxiety or distress. These situations include fear of speaking in public, speaking to unfamiliar people or being exposed to possible scrutiny by others. Obsessive-compulsive disorder (OCD) ‫الوسواس القهري‬ OCD is characterized by recurrent obsessions ‫ أفكار ملحة‬or compulsions ‫ أفعال قهرية‬or both, that cause impairment in terms of distress, time, or interference with functioning. Obsessions involving contamination, harm, hoarding, and sexual, somatic and religious preoccupations are the most common obsessions. Compulsions include washing, checking, repeating, ordering, counting, hoarding and touching (rare). Post-traumatic stress disorder (PTSD) ‫ الصدمة‬/‫اضطراب ما بعد الكرب‬ PTSD develops after a terrifying ordeal that involved physical harm or the threat of physical harm. The person who develops PTSD may have been the one who was harmed, the harm may have happened to a loved one, or the person may have witnessed a harmful event that happened to loved ones or strangers. The condition is characterized by recurrent and intrusive distressing recollections of the event, nightmares, a sense of reliving the experience with illusions, hallucinations, or dissociative flashback episodes, intense psychological or physiological distress at exposure to cues that resemble the traumatic event, avoidance of stimuli associated with the trauma, inability to recall important aspects of the trauma, loss of interest, estrangement from others, sleep disturbances, irritability, difficulty concentrating, hypervigilance, and exaggerated startle response. The full symptom picture must be present for more than 1 month. 5 ILLNESS ANXIETY DISORDER ‫اضطراب القلق من المرض‬ a somatic symptom related disorder characterised by excessive or disproportionate preoccupations with having or acquiring a serious illness, with excessive health-related behaviours and high levels of alarm about personal health status. SEPARATION ANXIETY DISORDER ‫اضطراب القلق من االن ِفصال‬ separation anxiety disorder is characterised by fear or anxiety concerning separation from those to whom an individual is attached: common features include excessive distress when experiencing or anticipating separation from home, and persistent and excessive worries about potential harms to attachment figures or untoward events that might result in separation. DIAGNOSTIC CRITERIA ARE CONSTANTLY CHANGING. THE LATEST VERSION OF THE DSM (DSM-5) REMOVED OCD & PTSD FROM THE CHAPTER OF ANXIETY DISORDERS AND NOW THEY ARE BEING IDENTIFIED AS SEPARATE DISORDERS. They may follow the general management guidelines for most anxiety disorders 6 3  ‫‪2/14/2024‬‬ ‫محاضرة احكي عن الوسواس القهري ‪ -‬د‪.‬محمد حسين استشاري الطب النفسي‬ ‫‪7‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪8‬‬ ‫‪4‬‬  ‫‪2/14/2024‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪9‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪10‬‬ ‫‪5‬‬  ‫‪2/14/2024‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪11‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪12‬‬ ‫‪6‬‬  ‫‪2/14/2024‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪13‬‬ ‫الفكرة الملحة‬ ‫أو المتكررة‬ ‫أعراض تجنبيه‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪14‬‬ ‫‪7‬‬  ‫‪2/14/2024‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي ‪ ,‬من كتاب " الوسواس القهري" لدكتور محمد شريف سالم‬ ‫‪15‬‬ ‫‪minutes‬‬ ‫محاضرة احكي عن الوسواس القهري د‪.‬محمد حسين استشاري الطب النفسي‬ ‫‪16‬‬ ‫‪8‬‬  2/14/2024 Linking Anxiety Symptoms To Circuits & Neurotransmitters Worry loops that feedback from prefrontal cortex Amygdala-centered circuits 17 General Treatment Outlines of Anxiety Disorders 18 9  2/14/2024 “Hierarchy of diagnosis” exclude anxiety due to medical condition or drugs. COMBINED THERAPY (Pharmacological + PSYCHOTHERAPY “CBT”) is SUPERIOR in anxiety disorders. Pharmacological treatment depends on three drug categories: - Short-term (for the first few weeks of treatment- maximum 4 weeks) a) Benzodiazepines …. to control acute symptoms **(dependance/tolerance) used cautiously then gradually withdrawn - Long-term (at least 12-24 months) b) Antidepressants with anxiolytic effects c) Beta-blockers for autonomic hyperactivity (sweating, palpitations etc.) Adequate follow up plan with psychiatrists and psychotherapists. 19 “This table is an overview on agents used across different types of anxiety disorders , but the use of Individual agents (on or off-the label) may slightly vary across different guidelines (Canadian, European or American)” 20 10  2/14/2024 General pharmacological recommendations First-line pharmacological treatments for these disorders are SSRIs (for all disorders), SNRIs (for some) and pregabalin (for generalized anxiety disorder only) some TCA (clomipramine) for OCD. Although treatment with SSRIs and SNRIs is usually well tolerated, nausea , restlessness, jitteriness, an increase in anxiety symptoms, insomnia or headache in the first days or weeks of treatment may jeopardize compliance with treatment. Lowering the starting dose of SSRIs may reduce this overstimulation. It is important to discuss potential adverse effects early in treatment and review patient progress carefully over the first few weeks of treatment. The anxiolytic effect may start with a delay of 2 – 4 weeks (in some cases up to 6 or 8 weeks) ex. OCD The anxiolytic effect of Benzodiazepines starts within minutes after oral or parenteral application. In general, they have a good record of safety. Due to CNS depression, benzodiazepines treatment may be associated with sedation, dizziness, and prolonged reaction time. Accordingly, cognitive functions and driving skills are affected. After a couple of weeks or months of continuous treatment with benzodiazepines, low-dose dependency may occur in a substantial number of patients. Patients with a history of benzodiazepine, alcohol or other psychoactive substance abuse should generally be excluded from treatment or be closely monitored in specialized care settings. 21 General pharmacological recommendations Benzodiazepines: may also be used in combination with serotonergic medications during the first weeks of treatment to suppress increased anxiety. In general, benzodiazepines should be used with a regular dosing regimen. One should be aware that benzodiazepines were not found to be effective conditions with depression comorbidity or OCD. Pregabalin & TCAs The efficacy in some anxiety disorder is well proven. However, Compliance may be reduced by adverse effects. TCAs should be avoided in patients considered to be at risk of suicide, due to their potentially fatal toxicity after overdose. Antihistamines The antihistamine hydroxyzine is effective in GAD. Because of sedating effects, the antihistamine should only be used when other medications have not been successful or not tolerated. The azapirone drug “Buspirone” is efficacious in the acute treatment of GAD as is the anti-histamine drug hydroxyzine, though neither of them has published evidence of efficacy in the prevention of relapse. Atypical antipsychotics are used as add-on augmentation treatment for non-responsive cases of anxiety disorders, OCD and PTSD. Due to The tolerability profile of antipsychotic drugs is such that they should generally be reserved for treatment after a non-response to other interventions. Psychotherapy, HPA-axis and stress regulation A combination of medication and cognitive behavioural/exposure therapy was shown to be a clinically desired treatment strategy. 22 11  2/14/2024 Dosing Approximately 75% of patients respond to the initial low dose of antidepressants. The dose should be increased to the highest recommended therapeutic level if the initial treatment with a low or medium dose fails. (with the exception of OCD , medium to high doses are recommended). In some patients, such as the elderly, treatment should be started with half the recommended dose or less in order to minimize initial adverse drug events. In particular, patients with panic disorder may be sensitive to serotonergic stimulation and may easily discontinue treatment because of initial jitteriness and nervousness. Regarding SSRIs and SNRIs, the same doses are usually prescribed in the maintenance treatment as in the acute treatment phase. “What gets you well keeps you well”. If the patient does not respond to treatment in an adequate dose after 4 – 6 weeks (8 – 12 weeks in OCD or PTSD), medication should be changed. 23 Psychological treatments in anxiety disorders Psychological and Pharmacological treatments are often concomitant therapies, rather than alternative therapies. The efficacy of both approaches is broadly similar in the acute treatment of anxiety disorders. Exposure therapy, cognitive and cognitive behavioural therapy (CBT), have largely consistent evidence of efficacy in the treatment of anxiety disorders. Exposure therapy (e.g., gradual exposure) and response prevention were found to be very effective in specific phobia, agoraphobia, social phobia and OCD. However, have high rates of therapy refusal due to unpleasant experience during sessions and related anticipatory anxiety. A general range of 8–20 h of sessions of CBT may be needed in the treatment of anxiety. In GAD and panic disorder: a typical treatment course consists of 16–20 hrs, up to half of which can be conducted by the patient in supervised ‘homework’ sessions, over a period of approximately four months. In social anxiety disorder: a standard course should consist of up to 14 sessions of 90 min duration over the course of four months. In PTSD: a standard course involve 8–12 sessions of trauma-focused CBT, delivered at weekly intervals. In OCD: a typical initial treatment course might include approximately 16 hrs of intervention based on exposure and response prevention, with longer and more intensive treatment in housebound patients. Remind patients that response to psychological treatment is not immediate and that a prolonged course is usually needed to maintain an initial treatment response. 24 12  2/14/2024 Recommendations: deciding when and which treatment is required Assess the severity and duration of anxiety symptoms, and the associated distress and impairment, when deciding which patients should be offered pharmacological or psychological treatment or both. Coexisting depressive symptoms and other comorbid disorder. Presence of physical illness. Concomitant medication. History of good response or poor tolerability of previous treatments. Local availability of any proposed intervention Cost issues. 25 Natural course of anxiety symptoms and disorders 26 13  2/14/2024 Natural course of anxiety symptoms and disorders Many individuals with anxiety symptoms experience an episodic condition with prolonged periods of remission. The reappearance or worsening of symptoms is associated with adverse life events and other psychosocial stressors. By contrast, in some patient groups anxiety disorders tend to run a chronic course, often over many years, with symptoms fluctuating in severity between periods of remission and relapse, the course of illness varying between disorders. Generalised anxiety disorder tends to run a waxing and waning course but may also ‘switch’ to other diagnoses particularly depression and somatoform disorders. Social anxiety disorder tends to run a chronic course. For panic disorder prospective studies reveal high degrees of symptom chronicity ,relapse after remission and ‘switching’ to other diagnoses. Childhood separation anxiety disorder often resolves with entry into adolescence. Obsessive-compulsive disorder tends to run a chronic course. Post-traumatic stress disorder emerges in only a minority of affected individuals, though a chronic course was seen in almost one-half of adolescents and young adults. 27 Phases of treatment Anxiety and related disorders are often chronic disorders. Pharmacological treatment Acute phase: onset of symptom relief is often delayed (about two to eight weeks), with full response taking up to 12 weeks or more. Longer-term therapy : (continued symptomatic improvement and relapse prevention) therapy should be continued for at least 12-24 months for most patients after remission has occurred to reduce the risk of relapse, and may be stopped only if all, or almost all, symptoms disappear. Follow up: should occur at two-week intervals for the first six weeks then monthly. Psychotherapy Treatment schedule is structured around weekly contact with a therapist for about 12-20 weeks, although shorter protocols have also proven effective. A follow up appointment four weeks later and then every two to three months is usually sufficient. 28 14  2/14/2024 SPECIAL CONSIDERATIONS FOR INDIVIDUAL DISORDERS 29 Management of GAD GAD is amongst the most common of mental disorders in primary medical care and is associated with increased use of health services. However, it is often not recognised, possibly because most patients present with physical symptoms and anxiety is overlooked. Beta-blockers are often used in primary medical management of physical symptoms of anxiety. Management of Panic disorder Initial side effects can be minimised by slowly increasing the dose or by adding a benzodiazepine for a few weeks In acute panic attacks: reassurance of the patient may be sufficient in most cases. In severe attacks: short-acting benzodiazepines may be needed (e.g., melting tablets). A combination of CBT and medication treatment has been shown to have the best treatment outcomes. Social anxiety disorder (social phobia) Assess the level of distress and disability to help distinguish social anxiety disorder from shyness. SAD is generally a chronic disorder and requires long-term treatment. Continue drug treatment for at least six months in patients who have responded to treatment. Consider cognitive therapy with exposure as this may reduce relapse rates better than drug treatment. 30 15  2/14/2024 Specific phobia Assess the number of fears, the level of anxiety, and the degree of impairment to judge severity. Use psychological treatments based on exposure therapy and CBT as first-line treatment. Pharmacological drugs are NOT recognized as a standard treatment in simple cases of specific phobia. Consider SSRI treatment for severe cases who have not responded to psychological interventions. Usually, patients with specific phobia do not consult medical professionals, especially if they can cope with their phobia by avoiding the specific feared situations or objects. OCD Assess the time engaged in obsessive-compulsive behaviour, the associated distress and impairment, and the degree of attempted resistance to confirm the diagnosis. Acute treatment: - Advise the patient that initial treatment periods beyond 12 weeks may be needed to assess efficacy. - It is recommended to use the medium to upper dose range. - Pharmacological: clomipramine and all SSRIs. - Psychological: exposure therapy, cognitive-behaviour therapy Longer-term treatment: OCD requires long-term treatment at an effective dose-level. Continue drug treatment for at least 12 months in patients who have responded to treatment. 31 PTSD Longer-term treatment: - PTSD is often a chronic disorder and needs long-term treatment for at least 12 – 24 months. Only a minority (10 – 20%) of persons subject to severe traumatic events develop PTSD. The current recommendation in the first month is summarized by three Ps: Don’t Pathologize (this is a normal response to an abnormal situation), Don’t Psychologize (don ’ t facilitate emotional reaction via group therapy, or stressful debriefing) as they might interfere with the potent spontaneous recovery process, and Don’t Pharmacologize (there is no evidence that prophylactic medication treatment may prevent the development of PTSD). CBT is indicated only several months after exposure to trauma and for individuals who have developed PTSD. 32 16  2/14/2024 Monitoring patient’s response Monitor effectiveness and acceptability regularly over the course of treatment. When stopping treatment, reduce the dose gradually over an extended period to avoid discontinuation and rebound symptoms. In the absence of evidence, a minimum of three months is recommended for this taper period When initial treatments fail Check for compliance. Consider raising the dosage of if the current dosage is well tolerated. Consider switching to another evidence-based treatment. Consider combining evidence-based treatments when there are no contraindications. Consider combining evidence-based pharmacological and psychological treatments. GAD: Consider pregabalin augmentation after a non-response to initial SSRI or SNRI treatment. Social anxiety: Consider benzodiazepines in patients who have not responded to other approaches. OCD: Consider augmentation of an SSRI or clomipramine with an antipsychotic drug. In severe OCD cases, where all other available therapeutic approaches have been tried without success, deep brain stimulation may be a treatment option. PTSD: Consider augmentation of antidepressants with olanzapine, risperidone or prazosin. 33 What is an ideal Anxiolytic ?? Efficacy in short term use for acute onset symptoms of anxiety. Efficacy in long term use in maintenance phase of anxiety. No agent up till now can do both functions GABA is the principal inhibitory neurotransmitter in the brain. GABA receptors are regulated not only by GABA itself, but also benzodiazepines at a highly specific binding site. “Not All GABAA Receptors Are The Same” GABA a receptors with : α2/3 subtypes …. exert an ANXIOLYTIC effect α1 subunits ….. important for regulating SLEEP (hypnotic) Benzodiazepines : binds non-selectively to different α subunits, so they have Sedative/Anxiolytic + Hypnotic effects. Selective α1-agents “the Z-drugs “ (zopiclone, zolpidem & eszopiclone) : non-benzodiazepine Hypnotics with no anxiolytic effects Ongoing research for; - Selective α2/3 agents that could be utilized in situations that require immediate anxiety relief without sedation ex. Exams and less dependence. 34 17  2/14/2024 Benzodiazepines’ Classification High potency benzodiazepines Short to intermediate acting Long acting “Better for acute symptoms and sleep initiation ” “More sustained anxiolytic action” “Easier withdrawal” * Aloprazolam (Xanax ® , Zolam ®) * Clonazepam (Apetryl®) * Bromazepam (calmipam ®) * Lorazepam (Ativan ®) Low potency benzodiazepines Short acting Long acting * Oxazepam * Diazepam (Valium®, Neuril ®, Epival ®) * Temazepam * Chlordiazepoxide (Clolverin®, Librax ®) BNZ are Only for short-term use in acute symptoms (not longer than one month) **** Not proven for long-term use like SSRIs or SNRIs + Dependance risk 35 Off-label use of some cardiovascular drugs in anxiety Propranolol: a Lipophilic beta blocker that crosses BBB Peripheral: Performance Anxiety, autonomic arousal Central: PTSD ‘amnesic agent’ Prazosin: Central alpha-1 adrenergic receptors Reduce severity & frequency Nightmares in PTSD Thank you 36 18