PM3PY2 Anxiety Disorders (2024-25) - PDF

School of Pharmacy This session is being recorded. For more information see the Learning Capture Student Essentials page: https://bit.ly/yujaessentials If you have any concerns, please speak to your...

School of Pharmacy This session is being recorded. For more information see the Learning Capture Student Essentials page: https://bit.ly/yujaessentials If you have any concerns, please speak to your session lead. PM3PY2: Anxiety Disorders Dr Angela Bithell [email protected] 2024-25 Trigger Warning: this session contains content on 1 mental health disorders, including associated suicide risk Copyright University of Reading Learning Outcomes At the end of this session you should be able to: Understand and define anxiety (as a disorder) Describe individual symptoms of anxiety and specific types of anxiety Explain the treatment (pharmacological and behavioural), side-effects and limitations associated with treatments for anxiety Discuss considerations that HCPs make in treating and advising patients with anxiety disorders Links with other PM3PY2 CNS & Mental Health topics 2 What is anxiety? Performance Anxiety serves a useful function in day to day life It becomes aberrant when: a threat is real but the response is disproportionate the threat is imagined Anxiety Level Definition: “prolonged or exaggerated response to a real or imagined threat, which interferes with normal life and cannot be attributed to any known neurological or organic dysfunction” Lifetime prevalence ~ 15% Anxiety, worry, despondency, sadness, somatic symptoms (PNS), sleep disturbance Life problems or reactions to stress or adjustment to circumstance Often seen by GPs Long term drug treatment not recommended Pathophysiology of Anxiety If we consider the sensory and reaction pathways in the CNS responsible for processing threatening situations, we can see where the potential for dysfunction (and therapeutic interventions) lies (see Lecture 1 – CNS Intro, including limbic system). Anxiety mediators: e.g. serotonin, noradrenaline, dopamine and GABA in CNS. Also PNS involvement Symptoms can be e.g. behavioural, physiological, cognitive or affective 4 Examples anxiety clinical features Cognitive/psychological: Somatic/physiological: Feelings of apprehension, tension, fear, Cardiovascular: palpitations, bradycardia or panic or terror, being ‘on edge’ tachycardia; elevated blood pressure; flushing Labile mood, outbursts of hostility, or pallor irritability Respiratory: rapid shallow breathing Circling thoughts, inability to (hyperventilation) or breathlessness (dyspnoea) concentrate, easily distracted, lapses of memory Gastrointestinal: diarrhoea, dyspepsia, dysphagia, churning stomach Musculoskeletal: agitation, restlessness, tremor, muscle tension Metabolic: elevated blood glucose and glucocorticoids Miscellaneous: excessive sweating, urge to defecate or urinate Insomnia 5 Types and Aetiology of Anxiety Disorders Generalised anxiety disorder (GAD) Social phobia Specific phobias Obsessive compulsive disorder (OCD) Panic disorder (PD) Post traumatic stress disorder (PTSD) Aetiology: Underlying cause of anxiety disorders not fully understood but likely risk factors may including genetic, environmental (including epigenetic), psychological and/or developmental factors Treatment aims and prognosis Prognosis is generally good if the external stressor can be eliminated Treatment aims to: Discover cause and address/remove it Assess the severity of the anxiety response Relieve distress Institute long-term measures to avoid same/related recurrence Institute long-term measures in cases of chronic anxiety Psychological Treatments Before looking at pharmacological interventions, we must consider psychotherapy as the principal means by which anxiety can be treated Commonly used and effective approaches include: Counselling Cognitive behavioural therapy (CBT) Exposure therapy Mindfulness and relaxation training 7 Treating Anxiety Disorders: Depends on type of disorder, stepped care model (NICE guidance – see later) e.g. Psychotherapy (+/- benzodiazepine/hypnotic) then long term antidepressant use Pharmacological: Acute Anxiety Benzodiazepines (e.g. lorazepam, alprazolam, diazepam) Positive allosteric modulators of GABA binding to GABA A receptor Fast-acting relief of severe anxiety (panic disorder, acute stress) Sedative and hypnotic, reduce muscle tone and coordination Amnesia Drug interactions (pharmaco-dynamic & -kinetic) Adverse effects Toxicity in overdose (reverse by flumazenil, competitive antagonist) Drowsiness, amnesia, confusion, impaired coordination, tolerance and dependence Restrict use - only use if anxiety is severely disabling or leading to extreme distress, short-term (2-4 weeks) Drugs to Treat Anxiety SSRIs first line for many anxiety disorders e.g. fluoxetine, escitalopram, paroxetine, sertraline, also SNRI (venlafaxine, duloxetine) Useful/licensed in certain anxiety disorders but may need to adjust dose (compared to antidepressant). Recommended for long term therapy Pregabalin (also for epilepsy, similar gabapentin, MoA inhibition at auxillary a2d subunit voltage-gated calcium channels, VGCC). Class 3 controlled substance, Schedule 3 drug Can be used for GAD Tricyclic antidepressants e.g. Clomipramine – obsessions, phobias Common side effects (often muscarinic): dry mouth, dry nose, blurry vision, lowered gastrointestinal motility or constipation, urinary retention Buspirone (hydrochloride) - 5-HT1A receptor partial agonist Slow onset of action but no withdrawal effects Generalised anxiety disorder short-term, acute anxiety Side effects: nausea, dizziness, headache, restlessness Beta blockers e.g. propranolol Treats somatic symptoms. Useful for anxiety disorder with strong somatic symptoms e.g. social phobias, panic disorder Generalised Anxiety Disorder – GAD Full NICE guidance CG113 10 GAD: diagnosis As for depression, international diagnostic criteria can be used to aid diagnosis, including both the DSM-V or ICD-11 criteria. Some overlap and some differences (see NICE CKS for GAD): The DSM-V diagnostic criteria include: Excessive anxiety and worry occurring more days than not for at least 6 months, about a number of events and activities The individual finds it difficult to control the worry Anxiety and worry are associated with 3 or more of the following symptoms with at least some symptoms having been present for more days than not for the past 6 months: restlessness/nervousness, being easily fatigued, poor concentration, irritability, muscle tension, or sleep disturbance The anxiety, worry or physical symptoms cause significant distress or impairment in social, occupational or other areas of functioning The disturbance is not attributable to physiological effects of a substance or another medical condition The disturbance is not explained by another mental disorder GAD: diagnosis 2 The ICD-11 diagnostic criteria include: Marked symptoms of anxiety manifested by either general apprehensiveness that is not restricted to any particular environmental circumstance or excessive worry about negative events occurring in several different aspects of everyday life Anxiety and general apprehensiveness or worry are accompanied by additional characteristic symptoms, such as: muscle tension or motor restlessness, sympathetic autonomic overactivity as evidenced by frequent gastrointestinal symptoms such as nausea and/or abdominal distress, heart palpitations, sweating, trembling, shaking, and/or dry mouth, subjective experience of nervousness, restlessness, or being ‘on edge’, difficulty concentrating, irritability, sleep disturbances (difficulty falling or staying asleep, or restless, unsatisfying sleep). The symptoms are not transient and persist for at least several months, for more days than not; are not better accounted for by another mental disorder (e.g., a Depressive Disorder); are not a manifestation of another medical condition (e.g., hyperthyroidism) and are not due to the effects of a substance or medication on the central nervous system The symptoms result in significant distress about experiencing persistent anxiety symptoms or significant impairment in personal, family, social, educational, occupational, or other important areas of functioning. If functioning is maintained, it is only through significant additional effort. NICE: Need take medical history, assess risk suicide and physical exam. Other tools such as GAD-7 can be used to assess symptom severity (see next slide) Generalised Anxiety Disorder (GAD): GAD-7 questionnaire tool Can use tools to assist in diagnosis such as GAD-7 questionnaire that can also help to assess severity (7 questions self-scored as follows): Scores assigned to the response categories of 'not at all’ - 0, 'several days’ - 1, 'more than half the days’ - 2 and 'nearly every day' – 3, with a possible total of 21 (i.e. 7Q x 3 points). Scores of 5, 10, and 15 are taken as cut-off points for mild, moderate, and severe anxiety respectively. The person is asked 'over the last 2 weeks, how often have you been bothered by any of the following problems'?: 1. Feeling afraid, as if something awful might happen. 2. Becoming easily annoyed or irritable. 3. Being so restless that it is hard to sit still. 4. Trouble relaxing. 5. Worrying too much about different things. 6. Not being able to stop or control worrying. 7. Feeling nervous, anxious, or on edge. Stepped Care for GAD Step 4 Step 3 Step 2 STEP 1: All known and suspected presentations of GAD Step 1 Identification and assessment; education about GAD and treatment options; active monitoring STEP 2: Diagnosed GAD that has not improved after education and active monitoring in primary care (for those without marked functional impairment – based on assessment of severity) Low-intensity psychological interventions: individual non-facilitated self-help, individual guided self- help and psychoeducational groups STEP 3: GAD with an inadequate response to step 2 interventions or marked functional impairment Choice of a high-intensity psychological intervention* (CBT/applied relaxation) or a drug treatment (typically SSRI sertraline) – see next slide STEP 4: Complex treatment-refractory GAD and very marked functional impairment, such as self- neglect or a high risk of self-harm Highly specialist treatment, such as complex drug and/or psychological treatment regimens; input from multi-agency teams, crisis services, day hospitals or inpatient care *in pregnancy, recommend psychological intervention as first line Taken and adapted from full NICE Drug Treatment For GAD Can be treated effectively with CBT or other psychological interventions If drug therapy used, first line drug: SSRI e.g. sertraline*, escitalopram, paroxetine *NICE recommends sertraline first-line (cost-effective, less interactions and risks than some other SSRIs, including discontinuation symptoms e.g., compared to paroxetine) but not licensed for this indication so needs consent. Escitalopram not for those with (or suspected) QT interval prolongation. Common side effects and interactions – see Lecture 2 and workshops 12 weeks then assess, possibly 6-12 months+ SNRIs also recommended alternatives e.g. duloxetine, venlafaxine SSRIs and SNRIs – in a minority of those risk] Benzodiazepines only if necessary (typically not in primary care except in crisis) Fast-acting, short-term relief, 2-4 weeks e.g., Alprazolam, Lorazepam, Oxazepam, Diazepam Buspirone hydrochloride, short-term use only (specialist)  Mechanisms of Action DAT SSRIs inhibit SERT, some SERT SERT differences may reflect SSRIs Sertraline individual properties s SNRIs inhibit both SERT and SERT SERT NET, duloxetine NET inhibition Venlafaxine Duloxetine > than venlafaxine NE NE 5H H1 T T T 2C 5HT 2A SERT TCAs almost all inhibit SERT, s TCAs NET, H1 (and H2), a1, mACh NE (M), 5HT (and agonists s1 & 2 M T and sodium channel blockers) 1 a1 Pregabalin: inhibits a2d subunit voltage-gated calcium channels (sim. gabapentin) Benzodiazepines: positive modulators GABAAR (increase action) Buspirone hydrochloride: main action as 5-HT1A receptor partial agonist Note: Dose can be important for which receptors are acted at  Mechanisms of Action Typical antipsychotics (e.g., haloperidol) block D2 receptor Most atypicals (2nd gen) have additional 5HT, H1 and adrenergic actions in addition to D2 (some also act at other D receptors). Differences between individual agents Some (e.g., clozapine and olanzapine and to a lesser extent quetiapine) also block M1/M3 (mACh) MOAIs: block action MOA – thus block breakdown of monoamines Anticonvulsants: typically sodium channel blockers Pregabalin: inhibits a2d subunit voltage-gated calcium channels (sim. gabapentin) Benzodiazepines: positive modulators GABAAR (increase action) Buspirone hydrochloride: main action as 5-HT1A receptor partial agonist Image Top (A and B, antipsychotics, Grinchii & Dremencov 2020. Int. J. Mol. Sci., 21(24), 9532 CC-BY 4.0 STEP 3 Examples for Patient considerations: pharmacotherapy Expected effects of drug prescribed (e.g. SSRI) Gradual development of anxiolytic effect (1 week +) Risk activation from SSRI/SNRIs (anxiety, agitation, insomnia) Important to take as prescribed and continue after remission (1yr+) to avoid relapse Potential side effects of drug, interactions and withdrawal Risk suicidal ideation Monitoring Follow-up: within 1 week, then every 2-4 weeks (3 months) then 3-monthly Changes: Considered if no improvement, significant side effects, patient preference. If switching, many considerations (wash-out, interactions etc.) Refer to information Lecture 2/workshops such as tapering/switching from SSRIs Note: If patient chose high-intensity psychological intervention but fails to improve, can offer drug therapy and vice versa. Can add non-pharmacological intervention if only partial improvement with drug therapy 18 Learning Outcomes: RECAP At the end of this session you should be able to: Understand and define anxiety (as a disorder) Describe individual symptoms of anxiety and specific types of anxiety Explain the treatment (pharmacological and behavioural), side-effects and limitations associated with treatments for anxiety Discuss considerations that HCPs make in treating and advising patients with anxiety disorders Links with other PM3PY2 CNS & Mental Health topics (depression, epilepsy) 19 Reference Material PM3PY2 Reading list text books in the ‘Neurological disorders and mental health’ section, e.g., ‘Fundamentals of clinical psychopharmacology’ (4th Edition, 2016, ed. Anderson & McAllister-Williams) – Chapters 4, 6 & 11 Relevant NICE guidance pages for anxiety disorders, GAD and CKS (summary) DSM-V – the Diagnostic and Statistical Manual of Mental Disorders (5th Edition). Used in the US and published by the American Psychiatric Association ICD-11 – the WHO 10th revision of the International Statistical Classification of Diseases and Related Heath Problems, https://icd.who.int/browse11/l-m/en BNF BNF section on antidepressants - covers many of drugs discussed in this session BNF section on anxiolytics and hypnotics covered in this session 20