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Management of Anxiety Disorders Anxiety and Anxiety disorders Anxiety: subjective experience of fear and it’s physical manifestations (autonomic symptoms). It is important for clinicians to be able to distinguish normal anxiety from pathological anxiety. Anxiety disorders are caused by a combination of genetic, environmental, biological and psychosocial factors. Associated with neurotransmitter imbalances, including increase activity of norepinephrine and decrease activity of GABA and Serotonin. Normal vs pathological anxiety NORMAL • Situational • In response to existent threat • Temporary “short duration” • common PATHOLOGICAL • Chronic “recurrent course”. • No real source of fear or excess of provoking fear. • Multiple symptoms affecting daily life. Anxiety and Anxiety disorders Panic Disorder (PD) with/without Agoraphobia Phobic Disorder (social, specific) Obsessive- Compulsive Disorder (OCD) Post-traumatic Stress Disorder (PTSD) Acute Stress Disorder (ASD) Generalized Anxiety Disorder (GAD) Anxiety disorder secondary to general medical condition Substance-induced anxiety disorder Management of Anxiety in general : Pharmacotherapy Psychotherapy Pharmacotherapy Anti-depressants: Selective Serotonin Reuptake Inhibitors (SSRI) Tricyclic Antidepressatns (TCA) Monoamine Oxidase Inhibitors ( MAOI) Atypical anti-depressants Anxiolytics: Benzodiazepines Buspirone Beta blockers Anti-convulsants Psychotherapies Supportive psychotherapy Cognitive behavioral therapy Systematic desensitization Exposure and response prevention 1- Management of Panic Disorder Pharmacotherapy SSRI •The long-term treatment is SSRIs, especially paroxetine and sertaline. •Typically take 2-4 weeks to become effective and higher doses are required more than for depression). •Always start SSRIs at low dose and increase slowly because It can have side effects that may initially worsen anxiety. Benzodiazepines Effective immediately but are best used temporarily because of their risk of causing tolerance and dependency. Other Antidepressants (clomipramine, imipramine) may be used Treatment should continue for at least 8-12 months, as relapse is common after discontinuation of therapy. Psychotherapy 1. 2. 3. 4. For Relaxation training Biofeedback Cognitive therapy Insight-Oriented psychotherapy Agoraphobia when the coexisting panic disorder is treated usually it resolves. 2- Management of Specific Phobia Pharmacotherapy Has not been found effective. A short course of benzodiazepines or beta blockers may be used during desensitization to help control autonomic symptoms. Psychotherapy 1. Behavior therapy (most effective) 2. Systemic desensitization Gradual exposure to the feared object or situation with learning the patient relaxation techniques. 3-Management of Social Phobia Pharmacotherapy SSRI Paroxetine is FDA approved for the treatment of social anxiety disorder. Beta blockers Used to control symptoms of performance anxiety. Psychotherapy 1. 2. Cognitive therapy Behavioral therapy 4- Management of OCD Pharmacotherapy SSRI The first line of treatment. Higher than normal doses may be required to be effective. Tricyclic antidepressants Psychotherapy 1. Behavioral therapy -As effective as pharmacotherapy. -Best results when used with pharmacotherapy simultaneously. 2.Exposure and Response Prevention (ERP) Involves exposure to the ritual-eliciting stimulus and prevention of the relieving compulsion. (e.g., the patient must touch the dirty floor without washing his or her hands). 3.Relaxation techniques Last resort Electroconvulsive therapy (ECT) Surgery (cingulotomy) … lesioning of ant. cingulate gyrus which is part of limbic system 5- Management of PTSD & ASD Pharmacotherapy to reduce symptoms : Antidepressants SSRIs, TCA, MAOIs Anticonvulsants (For flashbacks and nightmares.) Psychotherapy 1. 2. 3. 4. cognitive-behavioral, support, psychodynamic therapy Relaxation training Support group, family therapy Eye Movement Desensitization and Reprocessing (EMDR) Addictive medications (benzodiazepines) should be avoided in the treatment of PTSD because of the high rate of substance abuse in these patients. 6-Management of GAD Pharmacotherapy Antidepressants SSRIs, Venlafaxine(snri) Anxiolytics: Benzodiazepines, Buspirone Psychotherapy Cognitive-behavioral therapy The most effective treatment approach is a combination of psychotherapy and pharmacotherapy In Details: Pharmacotherapy Anti-depressants Selective Serotonin Reuptake Inhibitors (SSRI) Tricyclic Antidepressatns (TCA) Monoamine Oxidase Inhibitors ( MAOI) MOA: SSRIs inhibits presynaptic serotonin pumps that take up serotonin, which will increase availability in synaptic cleft. The most commonly prescribed antidepressant due to: Low incidence of side effects, most of which resolve with time. No food restrictions. Safer in overdose. Fluoxetine: Sertaline: Longest half life with active metabolites; therefore, no need to taper. Safe in pregnancy, approved for use in children. Can elevate levels of neuroleptics, leading to increase side effects. Highest risk for GI disturbances. Very few drug interactions. Proxetine: High protein bound, leading to several drug interactions. More anticholinergic effects like sedation, constipation, weight gain. Short half-life leading to withdrawal phenomena if not taken consistently Fluvoxamine: Citalopram: Nausea and vomiting more common. Lots of drug interactions. Fewest drug interactions. Possibly fewer sexual side effects. Escitalopram: Levo-enantiomer of citalopram; similar efficacy, fewer side effects. More expensive than citalopram. Indications : Depression in children above 6 years (fluoxetine) and adults Premenstrual dysphoric disorder (sertraline) Impulse control disorder Hypochondriasis and body dysmorphic disorder (fluoxetine) Premature ejaculation (fluoxetine/sertraline) Autism and ADHD/obesity/eating disorder/migraine/IBS In anxiety disorders: Panic disorder paroxetine and sertraline OCD all are effective. But if a child has OCD our first choice will be sertraline then fluvoxamine and finally citalopram. Agoraphobia, social anxiety, Posttraumatic stress disorder (PTSD),Acute stress disorder paroxetine Sexual decrease interest, anorgasmia, delayed ejaculation. These typically do not resolve in a few weeks. Treated by augmenting the regimen with buproprion, changing to non- SSRI or by adding another medications like sildenafil for men. GI dysfunction (25-30%): disturbances: mostly nausea and diarrhea giving food can help. Insomnia: also vivid dreams, often resolves over time Headache. Anorexia, weight loss. Restlessness An akathisia-like state has been reported at initiation and termination of SSRIs. Benzodiazepine or B-blocker or anticholinergic Seizure Rate of 0.2% Slighty lower than TCAs. • Serotonin syndrome • Caused by taking 2 drugs, both of which increase serotonin too much serotonin in the brain; like when used with MAOI • Symptoms: nausea, diarrhea, palpitations, chills, rigor, restlessness, confusion and lethargy, Hyperreflexia. • Drugs that increase the serotonin maybe found over the counter cold remedies, possibly serotonin syndrome. • Management of Serotonin Syndrome stop the drug ABC Gastric lavage if overdose IV fluid and NaHCO3 Benzodiazepines (calm the pt, muscle relaxant and prevent seizure) B-blocker Mirtazapine (Nassa) ECT SSRIs increase suicidal thinking and behavior, this is most documented in children and adolescents but may be accurate for adults as well. You should give a patient an adequate trial of antidepressants, usually between 1 and 2 months at full dose, before considering changing medication. MOA: Inhibits the reuptake of norepinephrine and serotonin, which leads to increase availability of monoamines in the synapse. Because of the long half lives, most are dosed once daily. They are rarely used as first-line agents because they have a higher incidence of side effects, require greater monitoring of dosing, and can be lethal in overdose. Tertiary amines: (highly anticholinergic, more sedating, greater lethality in overdose) Amitriptyline Imipramine Has intramuscular form Useful in enuresis and panic disorders Clomipramine Useful in chronic pain, migraines, and insomnia. Most serotonin specificm useful in treatment of OCD. Doxepin Useful in treating chronic pain Emerging use as a sleep aid in low doses Secondary amines: (metabolites of tertiary amines) Nortriptyline Least likely to cause othostatic hypotension Useful therapeutic blood levels Useful in treating chronic pain Desipramine More activating; least sedating Least anticholinergic Indications: Depression Anxiety disorders OCD clomipramine PTSD imipramine and doxepin Pain syndrome Nocturnal enuresis Eating disorder Attention Deficit Hyperactive Disorder Insomnia Compulsive behaviors in children Anti-histaminic properties (sedation) Anti-adrenergic properties (arrhythmias, tachycardia, postural hypotension) Anticholinergic effects ( dry mouth, constipation, urinary retention, blurred vision) Weight gain Major complications 3Cs (Convulsion, Coma, Cardiotoxicity) Lethal in overdose Seizures (0.3%) MOA Prevent the inactivation of biogenic amines such as norepinephrine, serotonin, dopamine and tyramine. Examples of MAOIs Phenelzine, tranylcypromine, isocarboxazid. Uses Depression, panic disorder, posttraumatic stress disorder, acute stress disorder. Serotonin syndrome if taken with SSRI Hypertensive crisis when taken with tyramine-rich foods or sympathomimetics. Postural hypotension, drowsiness, weight gain Sexual dysfunction, dry mouth, sleep dysfunction Anxiolytics Benzodiazepines Buspirone Beta blockers Benzodiazepines MOA Works by potentiating the effects of gammaamino-butyric acid GABA. First-line anxiolytics. Many patients become dependent and addicted. Choice of BDZs is based on time to onset of action, duration of action, and method of metabolism. Benzodiazepines should not be used as sole treatment for chronic anxiety. Benzodiazepines Long acting (half-life >20 hours) Diazepam Rapid onset. Used during detoxification from alcohol or sedative-hypnotic-anxiolyticx and for seizure. Clonazepam Treatment of anxiety, including panic attacks. Avoid with renal dysfunction; longer half-life allows for once daily dosing. Diazepam Cautions: Contraindications: - Respiratory disease - Respiratory depression - Muscle weakness - Myasthenia Gravis - Unstable Myasthenia Gravis - History of drugs and alcohol abuse - Pulmonary insufficiency - Marked personality disorder - Acute porphyria - Sleep apnea syndrome Benzodiazepines Intermediate hours) Alprazolam Treatment of panic attacks, alcohol and sedative-hypnoticanxiolytic detoxification, agitation Oxazepam Treatment of anxiety; including panic attacks Short onset of action leads to euphoria, high abuse potential. Lorazepam acting (half-life 6-20 alcohol and sedative-hypnotic-anxiolytic detoxification Not metabolized by the liver. Temazepam Decreasingly used for treatment of insomnia due to dependence. Not metabolized by the liver. Benzodiazepines Short acting (half-life < 6 hours) Triazolam Treatment of insomnia. Primarily used in medical and surgical settings. Midazolam Primarily used in medical and surgical settings. Benzodiazepines Side effects: Drowsiness Impairment of intellectual function* Reduced motor coordination (careful in elderly) Anterograde amnesia Withdrawal can be life threatening and causes seizure Toxicity with alcohol: Respiratory depression Benzodiazepines Special cases Hepatic Impairment Renal impairment patients with renal impairment have increased cerebral sensitivity to these drugs. Pregnancy benzodiazepines can precipitate Coma if used in hepatic impairment , so use benzodiazepines that are not metabolized by the liver: Lorazepam, Oxazepam, Temazepam . ( L.O.T ) There is a risk of neonatal withdrawal symptoms when these drugs are used during pregnancy. So avoid regular use and use only if there is a clear indication such as seizure control high doses administrated during late pregnancy or labor may cause neonatal hypothermia , hypotonia , and respiratory depression . Teratogenic - especially in the 1st trimester- Cleft palate. Breast-feeding should be avoided if possible during breast-feeding. Buspirone The anxiolytic action is at 5HT-1A receptor (partial agonist) It has a slower onset of action than BDZs (takes 1-2 weeks for effect). Not considered as effective as other options, and so it is often used in combination with another agent (SSRI), for treatment of anxiety. It idoes not potentiate the CNS depression of alcohol (useful in alcoholics), and has a low potential for abuse/addiction. Buspirone Side effects: Nausea Dizziness Headache Nervousness Excitement Rarely …… dry mouth , tachycardia , chest pain , drowsiness , confusion , seizure , fatigue and sweating Buspirone Special Hepatic Impairment Reduce dose in mild and moderate disease Avoid it in severe disease Renal impairment cases Reduce dose in mild and moderate cases Avoid it if eGFR less than 20 ml/min/1.73 m2 Pregnancy and breastfeeding avoid this drug. B-blockers (propranolol) Useful for treating the autonomic effects of panic attacks or performance anxiety, such as palpitations, sweating and tachycardia. Can also be used for treating Akathisia (side effect of typical antipsychotics). Other Medications Venlafaxine (atypical antidepressant) It is a SNRI, so it increases serotonin and norepinephrine availability in the synaptic cleft. Useful in treating generalized anxiety disorder, panic disorder and social anxiety. Main side effect: increase the blood pressure. Topiramate (An anticonvulsant) Blocks sodium channels, inhibits glutamate and enhances GABA One of the new generations of mood stabilizers Useful in treating the flashbacks and nightmares associated with Posttraumatic stress disorder. In Details: Psychotherapy Supportive psychotherapy Supportive psychotherapy is commonly used as an adjuvant treatment even in the most severe mental disorders. Purpose is to help the patient feel safe during difficult times. It is not insight-oriented but instead focuses on empathy, understanding, and education. Helps build up the patient’s healthy defenses and lessens the anxiety through specific techniques such as reassurance, advice and encouragement. Supportive psychotherapy Techniques of supportive psychotherapy: Praising (reinforcing positive behavior). Reassurance. Normalizing (reassure the patient that their thoughts and feelings are not unusual or pathological). Encouragement. Reframing. Advice and teaching. Careful use of language. Cognitive-Behavioral Therapy (CBT) CBT combines ideas from cognitive therapy and behavior therapy. Cognitive therapy: seeks to correct faulty assumptions and negative feelings that exacerbate psychiatric symptoms. The patient is taught to identify maladaptive thoughts and replace them with positive ones. Behavior therapy: helps the patient to change their behaviors that contribute to their symptoms. It can be used to extinguish maladaptive behaviors by replacing them with healthy alternatives. Cognitive-Behavioral Therapy (CBT) Treatment follows a protocol or manual with homework assignments between therapy sessions. During therapy sessions, the patient and the therapist set an agenda, review homework, and challenge cognitive distortions. The patient learns how his behavior is influenced by his thoughts. Treatment is usually brief and may last from 6 weeks to 6 months. Research has shown than CBT is effective for many psychiatric illnesses, including depression, anxiety, and substance abuse. Systematic desensitization Used mostly to help effectively overcome specific phobias. When persons experience such phobias (for example fears of heights, dogs, snakes, closed spaces, etc.), they tend to avoid the feared stimuli; this avoidance, in turn, can temporarily reduce anxiety but is not necessarily an adaptive way of coping with it. In this regard, patients' avoidance behaviors can become reinforced. The goal of systematic desensitization thus, is to overcome avoidance by gradually exposing patients to the phobic stimulus, until that stimulus can be tolerated. Exposure and response prevention Used mostly in the management of obsessive– compulsive disorder. Helps to resist carrying out compulsions. Therapeutic effect is achieved as subjects confront their fears and discontinue their escape response. Uses some short-term anxiety, this facilitates longterm reduction in obsessive and compulsive symptoms. Relaxation techniques are employed to help the patient manage the anxiety that occurs when the compulsion is prevented. Exposure and response prevention The Exposure in ERP refers to confronting the thoughts, images, objects and situations that make a person with OCD anxious. The Response Prevention in ERP refers to making a choice not to do a compulsive behavior after coming into contact with the things that make a person with OCD anxious the response is delayed or prevented The natural drop in anxiety that happens when you stay “exposed” and “prevent” the “response” is called habituation. summary Panic disorder: -In acute case : short term course BDZ -Maintenance :SSRI (paroxetine/ sertraline) OCD: -Pharmacotherapy: high dose SSRI (fluvoxamine), TCA (clomipramine) -Behavioral therapy: exposure and response prevention -For resistant cases: ECT/ Cingulotomy PTSD: -Pharmacotherapy: TCA (imipramine, doxepin), SSRI, MAOI/ anticonvulsants -Psychotherapy: Relaxation and family and group therapy GAD: -Pharmacotherapy: SSRI, Buspirone, BDZ, venlafaxine -Psychotherapy and behavioral therapy Thank you
