1. Management of Anxiety Disorders

2. 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.

3. Normal vs pathological anxiety
Situational
In response to existent threat
Temporary “short duration”
common
Chronic “recurrent course”.
No real source of fear or excess of provoking fear.
Multiple symptoms affecting daily life.

4. 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

5. Management of Anxiety in general :
Pharmacotherapy
Psychotherapy

6. Pharmacotherapy Anxiolytics: Anti-convulsants Anti-depressants:
Selective Serotonin Reuptake Inhibitors (SSRI)
Tricyclic Antidepressatns (TCA)
Monoamine Oxidase Inhibitors ( MAOI)
Atypical anti-depressants
Anxiolytics:
Benzodiazepines
Buspirone
Beta blockers
Anti-convulsants

7. Psychotherapies Supportive psychotherapy Cognitive behavioral therapy
Systematic desensitization
Exposure and response prevention

8. 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.

9. Psychotherapy
Relaxation training
Biofeedback
Cognitive therapy
Insight-Oriented psychotherapy
For Agoraphobia when the coexisting panic disorder is treated usually it resolves.

10. 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
Behavior therapy (most effective)
Systemic desensitization
Gradual exposure to the feared object or situation with learning the patient relaxation techniques.

11. 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
Cognitive therapy
Behavioral therapy

12. 4- Management of OCD Pharmacotherapy Psychotherapy SSRI
The first line of treatment.
Higher than normal doses may be required to be effective.
Tricyclic antidepressants
Psychotherapy
Behavioral therapy
-As effective as pharmacotherapy.
-Best results when used with pharmacotherapy simultaneously.

13. 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

14. 5- Management of PTSD & ASD
Pharmacotherapy to reduce symptoms :
Antidepressants
SSRIs, TCA, MAOIs
Anticonvulsants
(For flashbacks and nightmares.)
Psychotherapy
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.

15. 6-Management of GAD Pharmacotherapy Psychotherapy
Antidepressants
SSRIs, Venlafaxine(snri)
Anxiolytics: Benzodiazepines, Buspirone
Psychotherapy
Cognitive-behavioral therapy
The most effective treatment approach is a combination of psychotherapy and pharmacotherapy

16. In Details: Pharmacotherapy

17. Anti-depressants Selective Serotonin Reuptake Inhibitors (SSRI)
Tricyclic Antidepressatns (TCA)
Monoamine Oxidase Inhibitors ( MAOI)

18. Selective Serotonin Reuptake Inhibitors (SSRI)
MOA:
SSRIs inhibits presynaptic serotonin pumps that take up serotonin, which will increase availability in synaptic cleft.
The most commonly prescribed anti-depressant due to:
Low incidence of side effects, most of which resolve with time.
No food restrictions.
Safer in overdose.

19. SSRI’S : Fluoxetine: Sertaline: Proxetine:
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.
Sertaline:
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

20. SSRI’S : Nausea and vomiting more common. Lots of drug interactions.
Fluvoxamine:
Nausea and vomiting more common.
Lots of drug interactions.
Citalopram:
Fewest drug interactions.
Possibly fewer sexual side effects.
Escitalopram:
Levo-enantiomer of citalopram; similar efficacy, fewer side effects.
More expensive than citalopram.

21. SSRIS :
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

22. SSRI side effects and management :
Sexual dysfunction (25-30%):
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 disturbances:
mostly nausea and diarrhea
giving food can help.
Insomnia:
also vivid dreams,
often resolves over time
Headache.

23. SSRI side effects and management :
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.
Akathisia :is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting.

24. SSRI 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.

25. SSRI 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
Nassa : non adrenergic and selective seratonin antidepressent

26. SSRI
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.

27. Tricyclic Antidepressants (TCA)
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.

28. TCA
Tertiary amines: (highly anticholinergic, more sedating, greater lethality in overdose)
Amitriptyline
Useful in chronic pain, migraines, and insomnia.
Imipramine
Has intramuscular form
Useful in enuresis and panic disorders
Clomipramine
Most serotonin specificm useful in treatment of OCD.
Doxepin
Useful in treating chronic pain
Emerging use as a sleep aid in low doses

29. TCA 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

30. TCA Indications: Depression Pain syndrome Nocturnal enuresis
Anxiety disorders OCD clomipramine PTSD imipramine and doxepin
Pain syndrome
Nocturnal enuresis
Eating disorder
Attention Deficit Hyperactive Disorder
Insomnia
Compulsive behaviors in children

31. TCA Side effects : 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%)

32. Monoamine Oxidase Inhibitors
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.

33. MAOI Side Effects: 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

34. Anxiolytics
Benzodiazepines
Buspirone
Beta blockers

35. Benzodiazepines MOA First-line anxiolytics.
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.

36. 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.

37. Diazepam
Cautions: - Respiratory disease - Muscle weakness - Myasthenia Gravis - History of drugs and alcohol abuse - Marked personality disorder - Acute porphyria
Contraindications:
- Respiratory depression
- Unstable Myasthenia Gravis
- Pulmonary insufficiency
- Sleep apnea syndrome

38. Benzodiazepines Intermediate acting (half-life 6-20 hours) Alprazolam
Treatment of anxiety; including panic attacks
Short onset of action leads to euphoria, high abuse potential.
Lorazepam
Treatment of panic attacks, alcohol and sedative-hypnotic-anxiolytic detoxification, agitation
Oxazepam
alcohol and sedative-hypnotic-anxiolytic detoxification
Not metabolized by the liver.
Temazepam
Decreasingly used for treatment of insomnia due to dependence.

39. Benzodiazepines Short acting (half-life < 6 hours) Triazolam
Treatment of insomnia.
Primarily used in medical and surgical settings.
Midazolam

40. 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

41. Benzodiazepines Special cases Hepatic Impairment Renal impairment
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 )
Renal impairment
patients with renal impairment have increased cerebral sensitivity to these drugs.
Pregnancy
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.

42. 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.

43. Buspirone Side effects:
Nausea
Dizziness
Headache
Nervousness
Excitement
Rarely …… dry mouth , tachycardia , chest pain , drowsiness , confusion , seizure , fatigue and sweating

44. Buspirone Special cases Hepatic Impairment Renal impairment
Reduce dose in mild and moderate disease
Avoid it in severe disease
Renal impairment
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.

45. 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).

46. 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.

47. In Details: Psychotherapy

48. 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.

49. 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.

50. 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.

51. 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.

52. 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.

53. 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 long-term reduction in obsessive and compulsive symptoms.
Relaxation techniques are employed to help the patient manage the anxiety that occurs when the compulsion is prevented.

54. 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.

55. summary Panic disorder: OCD: PTSD: GAD:
-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

56. Thank you 