Pr. Peivand Pirouzi - Challenges in Clinical Research in CNS - Anxiety Disorders - Publication, Canada 2015

1. Challenges in Clinical Research
Studies Performed in the CNS
field: Anxiety disorders
Presented by guest speakers:
Dr. Ghada Zaied, Ph.D.
&
Hussain Ahmad, B.Sc.
Toronto - Canada - 2015
Clinical Research Postgraduate Program, Humber
Facilitator: Professor Peivand Pirouzi, Ph.D., M.B.A.

2. What is Anxiety?
 Anxiety is a normal human emotion that everyone experiences
at times. Many people feel anxious, or nervous, when faced
with a problem at work, before taking a test, or making an
important decision
 Anxiety disorders, however, are different. They can cause such
distress that it interferes with a person's ability to lead a normal
life
 An anxiety disorder is a serious mental illness. For people
with anxiety disorders, worry and fear are constant and
overwhelming, and can be crippling

3. Anxiety as a Disorder
When does anxiety become a disorder?
 Greater intensity and/or duration than expected given the
circumstances
 Leads to impairment or disability
 Daily activities are disrupted by avoidance of certain situations
or objects to decrease anxiety
 Includes clinically significant unexplained physical symptoms,
obsessions, compulsions, or intrusive recollections of trauma

4. Causes of Anxiety
 The exact cause of anxiety disorders is unknown but anxiety
disorders like other forms of mental illness are not the result of
personal weakness, a character flaw, or poor upbringing
 As scientists continue their research on mental illness, it is
becoming clear that many of these disorders are caused by a
combination of factors, including changes in the brain and
environmental stress
 May be caused by a mental condition, a physical condition, the
effects of drugs, or a combination of these

5. Causes of Anxiety cont.
 Like other brain illnesses, anxiety disorders may be caused by problems in
the functioning of brain circuits that regulate fear and other emotions
 Studies have shown that severe or long-lasting stress can change the way
nerve cells within these circuits transmit information from one region of
the brain to another
 Other studies have shown that people with certain anxiety disorders have
changes in certain brain structures that control memories linked with strong
emotions
 Anxiety disorders run in families, which means that they can at least partly
be inherited from one or both parents, like the risk for heart disease or cancer
 Certain environmental factors such as a trauma or significant event may
trigger an anxiety disorder in people who have an inherited susceptibility to
developing the disorder

6. Causes of Anxiety cont.
 Anxiety disorders are partly genetic but may also be due to drug use
including alcohol and caffeine, as well as withdrawal from certain
drugs. They often occur with other mental disorders,
particularly major depressive disorder, bipolar disorder,
certain personality disorders, and eating disorders
 The term anxiety covers four aspects of experiences that an individual
may have mental apprehension, physical tension, physical symptoms
and dissociative anxiety
 The emotions present in anxiety disorders range from simple
nervousness to bouts of terror
 There are other psychiatric and medical problems that may mimic the
symptoms of an anxiety disorder, such as hyperthyroidism

7. Causes of Anxiety cont.
 Most anxiety disorders begin in childhood, adolescence, and
early adulthood
 They occur slightly more often in women than in men, and
occur with equal frequency in whites African-Americans, and
Hispanics

8. Types of Anxiety Disorders
• Panic Attacks and Panic Disorder
• Phobias
• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Post-traumatic stress disorder
• Social anxiety disorder
Each has its own characteristics and symptoms, they all
include symptoms of anxiety

9. Panic Attacks and Panic Disorder
 A panic attack is a sudden surge of overwhelming anxiety and
fear. Your heart pounds and you can’t breathe
 You may even feel like you’re dying or going crazy
 Left untreated, panic attacks can lead to panic disorder and
other problems

10. Signs and symptoms of panic attack
 Panic attacks often strike when you’re away from home, but
they can happen anywhere and at any time
 You may have one while you’re in a store shopping, walking
down the street, driving in your car, or sitting on the couch at
home
 The signs and symptoms of a panic attack develop abruptly and
usually reach their peak within 10 minutes
 Most panic attacks end within 20 to 30 minutes, and they rarely
last more than an hour

11. Signs and symptoms of panic attack cont.
• Shortness of breath or
hyperventilation
• Heart palpitations or a racing
heart
• Chest pain or discomfort
• Trembling or shaking
• Choking feeling
• Feeling unreal or detached from
your surroundings
• Sweating
• Nausea or upset stomach
• Feeling dizzy, light-headed, or
faint
• Numbness or tingling
sensations
• Hot or cold flashes
• Fear of dying, losing control, or
going crazy

12. Signs and symptoms of Panic disorder
 Panic disorder is characterized by repeated panic attacks,
combined with major changes in behaviour or persistent
anxiety over having further attacks
 Experience frequent, unexpected panic attacks that aren’t tied
to a specific situation
 Worry a lot about having another panic attack
 Are behaving differently because of the panic attacks, such as
avoiding places where you’ve previously panicked

13. Causes of panic attack and panic
disorder
Although the exact causes of panic attacks and panic disorder are
unclear, the tendency to have panic attacks runs in families.
• Severe stress, such as the death
of a loved one, divorce, or job
loss can also trigger a panic
attack
• Panic attacks can also be caused
by medical conditions and other
physical causes
• Mitral valve prolapse, a minor
cardiac problem that occurs
when one of the heart’s valves
doesn't close correctly
• Smoking and caffeine
• Hyperthyroidism (overactive
thyroid gland)
• Hypoglycemia (low blood
sugar)
• Alcohol and sedatives
• There also appears to be a
connection with major life
transitions such as:
• graduating from college
• entering the workplace
• getting married,
• and having a baby

14. Panic attack and panic disorder
Mechanism and treatment
 Some individuals with panic disorder having a chemical
imbalance within the limbic system and one of its regulatory
chemicals GABA-A
 The reduced production of GABA-A sends false information to
the amygdala which regulates the body's "fight or flight
response" mechanism and in return, produces the physiological
symptoms that lead to the disorder
 Clonazepam, an anticonvulsant benzodiazepine with a long
half-life, has been successful in keeping the condition in check

15. panic attack and panic disorder
Treatment cont.
 Cognitive behavioural therapy(CBT) and Positive Self Talk specific
for panic are the treatment of choice for panic disorder. Several studies
show that 85 to 90 percent of panic disorder patients treated with CBT
recover completely from their panic attacks within 12 weeks
 Selective serotonin reuptake inhibitors
 Antidepressants(SSRIs, MAOIs, tricyclic
antidepressants and norepinephrine reuptake inhibitors): alter
neurotransmitter configurations which in turn can help to block
symptoms
 Anti-anxiety drugs (benzodiazepines that this is offset by the risk of
developing a benzodiazepine dependence
 For some people, anxiety can be greatly reduced by discontinuing the use
of caffeine

16. Phobias
 The single largest category of anxiety disorders
 A phobia is an intense fear of something that, in reality, poses little or
no actual danger
 Common phobias and fears include closed-in places, heights, highway
driving, flying insects, snakes, and needles. However, we can develop
phobias of virtually anything. Most phobias develop in childhood, but
they can also develop in adults
Normal fear vs. phobias
 Fear is an adaptive human response. It serves a protective purpose,
activating the automatic “fight-or-flight” response. With our bodies and
minds alert and ready for action, we are able to respond quickly and
protect ourselves

17. Phobias
 phobias the threat is greatly exaggerated or nonexistent
 Feeling a little queasy when getting a shot or when your blood is
being drawn (fear)
 Avoiding necessary medical treatments or doctor’s check-ups
because you’re terrified of needles (phobia)
 Experiencing butterflies when peering down from the top of a
skyscraper or climbing a tall ladder (fear)
 Turning down a great job because it’s on the 10th floor of the
office building (phobia)

18. Common types of phobias and fears
 Animal phobias. Examples include fear of snakes, fear of spiders, fear
of rodents, and fear of dogs etc.
 Natural environment phobias. Examples include fear of
heights(Acrophobia), fear of storms(Astraphobia), fear of water
(Aquaphobia), and fear of the dark
 Situational phobias ( fears triggered by a specific
situation). Examples include fear of enclosed spaces (claustrophobia),
fear of flying , fear of driving, fear of tunnels, and fear of bridges
(Gephyrophobia)
 Blood-Injection-Injury phobia. The fear of blood, fear or injury, or a
fear of needles or other medical procedures

19. Social phobia and fear of public
speaking
 Also called social anxiety disorder, is fear of social situations
where you may be embarrassed or judged. If you have social
phobia you may be excessively self-conscious and afraid of
humiliating yourself in front of others
 Your anxiety over how you will look and what others will think
may lead you to avoid certain social situations you’d otherwise
enjoy
 Fear of public speaking, an extremely common phobia, is a
type of social phobia. Other fears associated with social phobia
include fear of eating or drinking in public, talking to strangers,
taking exams, mingling at a party, and being called on in class

20. Agoraphobia (fear of open space)
 Agoraphobia develops as a complication of panic attacks
 Afraid of having another panic attack, you become anxious
about being in situations where escape would be difficult or
embarrassing, or where help wouldn't be immediately available
 For example, you are likely to avoid crowded places such as
shopping malls and movie theaters
 You may also avoid cars, airplanes, subways, and other forms
of travel. In more severe cases, you might only feel safe at
home

21. Physical signs and symptoms of
phobias
 Difficulty breathing
 Racing or pounding heart
 Chest pain or tightness
 Trembling or shaking
 Feeling dizzy or lightheaded
 A churning stomach
 Hot or cold flashes; tingling sensations
 Sweating

22. Emotional signs and symptoms of
phobia
 Feeling of overwhelming anxiety or panic
 Feeling an intense need to escape
 Feeling “unreal” or detached from yourself
 Fear of losing control or going crazy
 Feeling like you’re going to die or pass out
 Knowing that you’re overreacting, but feeling powerless to
control your fear

23. Causes of agoraphobia
 Although the exact causes of agoraphobia are currently
unknown, there are some hypotheses. The condition has been
linked to the presence of other anxiety disorders, a stressful
environment or substance abuse
 Chronic use of tranquilizers and sleeping pills such
as benzodiazepines has been linked to onset of agoraphobia
 Tobacco smoking has also been associated with the development
and emergence of agoraphobia
 alcohol use disorders are associated with panic with or without
agoraphobia; this association may be due to the long-term effects
of alcohol misuse causing a distortion in brain chemistry

24. Agoraphobia treatments and
medications
 Agoraphobia is best understood as an adverse behavioural
outcome of repeated panic attacks and subsequent anxiety and
preoccupation with these attacks that leads to an avoidance of
situations where a panic attack could occur
Cognitive and behavioral treatments
1. Exposure treatment
2. Cognitive restricting
3. Relaxation techniques

25. Agoraphobia treatments and
medications cont.
Medications
 Anti-depressant medications most commonly used to treat
anxiety disorders are mainly in the selective serotonin reuptake
inhibitor (SSRI). Benzodiazepines, MAO inhibitors and
tricyclic antidepressants are also sometimes prescribed for
treatment of agoraphobia

26. General anxiety disorder (GAD)
 General anxiety disorder (or GAD) is characterized by
excessive, exaggerated anxiety and worry about everyday life
events with no obvious reasons for worry
 People with symptoms of generalized anxiety disorder tend to
always expect disaster and can't stop worrying about health,
money, family, work, or school. In people with GAD, the
worry is often unrealistic or out of proportion for the situation
 Daily life becomes a constant state of worry, fear, and dread
 Eventually, the anxiety so dominates the person's thinking that
it interferes with daily functioning, including work, school,
social activities, and relationships

27. Symptoms of (GAD)
• Hot flashes
• restlessness
• fatigue
• concentration problems
• irritability
• muscle tension
• sleep disturbance
• Sweating
• Nausea
• Headaches
• Numbness hand & feet
• Difficulty swallowing
• Rashes
• In children GAD may be
associated with headaches,
restlessness, abdominal pain,
and heart palpitations
In addition, people with GAD often have other anxiety disorders
(such as panic disorder or phobias), obsessive-compulsive
disorder, clinical depression, or additional problems with drug or
alcohol misuse.

28. Symptoms of (GAD)

29. Causes of GAD
 The exact cause of GAD is not fully known, but a number of
factors appear to contribute to its development
 Genetics: Some research suggests that family history plays a
part in increasing the likelihood that a person will develop
GAD. This means that the tendency to develop GAD may be
passed on in families
 Environmental factors: Trauma and stressful events, such as
abuse, the death of a loved one, divorce, changing jobs or
schools, may lead to GAD
 GAD also may become worse during periods of stress. The use
of and withdrawal from addictive substances, including
alcohol, caffeine, and nicotine, can also worsen anxiety

30. Causes of GAD cont.
 Brain chemistry: GAD has been associated with abnormal
functioning of certain nerve cell pathways that connect particular
brain regions involved in thinking and emotion
 These nerve cell connections depend on chemicals called
neurotransmitters that transmit information from one nerve cell
to the next
 If the pathways that connect particular brain regions do not run
efficiently, problems related to mood or anxiety may
result. Medicines, psychotherapies, or other treatments that are
thought to "tweak" these neurotransmitters may improve the
signalling between circuits and help to improve symptoms
related to anxiety or depression

31. GAD treatments and medications
 Cognitive behavioral therapy (CBT): is more effective in the
long term than medications
 Among the cognitive–behavioural orientated psychotherapies
the two main treatments are cognitive behavioural therapy and
acceptance and commitment therapy
(CBT) for GAD includes :
 psychoeducation

32. GAD treatments and medications
CBT treatment
 self-monitoring
 stimulus control techniques
 relaxation
 self-control desensitization
 cognitive restructuring
 worry exposure
 worry behaviour modification
 problem-solving

33. GAD treatments and medications cont.
Intolerance of uncertainty therapy(IUT)
 IUT focuses on helping patients in developing the ability to
tolerate, cope with and accept uncertainty in their life in order
to reduce anxiety
Motivational interviewing(MI)
 Motivational Interviewing is a strategy centered on the patient
that aims to increase intrinsic motivation and decrease
ambivalence about change due to the treatment

34. GAD treatments and medications cont.
MI contains four key elements
1. Express empathy
2. Heighten dissonance between behaviours that are not desired
and values that are not consistent with those behaviours
3. Move with resistance rather than direct confrontation
4. Encourage self-efficacy

35. GAD treatments and medications cont.
 SSRIs
 Benzodiazepines
 Pregabalin and gabapentin
 Pregabalin (Lyrica) acts on the voltage-dependent calcium
channel in order to decrease the release of neurotransmitters
such as glutamate, norepinephrine and substance P. Its
therapeutic effect appears after 1 week of use and is similar in
effectiveness to lorazepam, alprazolam and venlafaxine
 Gabapentin (Neurontin), a closely related drug to pregabalin
with the same mechanism of action

36. GAD treatments and medications cont.
 Psychiatric drugs 5-HT1A receptor partial agonists, such
as buspirone (BuSpar) and tandospirone (Sediel)
 Serotonin-norepinephrine reuptake inhibitors (SNRIs),
such as venlafaxine (Effexor) and duloxetine (Cymbalta)
 Newer, atypical serotonergic antidepressants, such
as vilazodone (Viibryd), vortioxetine (Brintellix),
and agomelatine (Valdoxan)
 Tricyclic antidepressants (TCAs), such
as imipramine (Tofranil) and clomipramine (Anafranil)
 Certain monoamine oxidase inhibitors (MAOIs), such
as moclobemide (Marplan) and, rarely, phenelzine (Nardil)

37. Obsessive-Compulsive Disorder (OCD)
 Is an anxiety disorder characterized by intrusive thoughts that
produce uneasiness, apprehension, fear or worry (obsessions),
repetitive behaviours aimed at reducing the associated anxiety
(compulsions), or a combination of such obsessions
and compulsions
 Symptoms of the disorder include excessive washing or
cleaning, repeated checking, extreme hoarding, preoccupation
with sexual, violent or religious thoughts, relationship-related
obsessions, aversion to particular numbers and
nervous rituals such as opening and closing a door a certain
number of times before entering or leaving a room

38. Obsessive-Compulsive Disorder (OCD)
 These symptoms are time-consuming, might result in loss of
relationships with others, and often cause severe emotional and
financial distress. The acts of those who have OCD may
appear paranoid and potentially psychotic
 However, people with OCD generally recognize their
obsessions and compulsions as irrational and may become
further distressed by this realization
 Despite the irrational behavior, OCD is associated with above-
average intelligence

39. Causes of obsessive-compulsive
Disorder (OCD)
Biological
 OCD has been linked to abnormalities with
the neurotransmitter serotonin, although it could be either a
cause or an effect of these abnormalities
 Serotonin is thought to have a role in regulating anxiety. To
send chemical messages from one neuron to another, serotonin
must bind to the receptor sites located on the neighbouring
nerve cell
 A possible genetic mutation may contribute to OCD.
A mutation has been found in the human serotonin transporter
gene

40. Causes of obsessive-compulsive
Disorder (OCD) cont.
 Researchers have yet to pinpoint the exact cause of obsessive-
compulsive disorder (OCD), but brain abnormalities, genetic
(family) influences and environmental factors are being studied
 Some experts believe that a problem related to streptococcal
infections, such as strep throat and scarlet fever, can suddenly
bring on the disorder or make its symptoms worse in some
children.

41. Treatments and Medications of
(OCD)
 Behavioral therapy (BT)
 Cognitive behavioral therapy (CBT)
 Medication: medications as treatment include selective serotonin
reuptake inhibitors (SSRIs) and the tricyclic antidepressants, in
particular clomipramine
 Electroconvulsive therapy (ECT): has been found to have
effectiveness in some severe and refractory cases
 Psychosurgery: a surgical lesion is made in an area of the brain
(the cingulate cortex)

42. Post-Traumatic Stress Disorder (PTSD)
 PTSD was first brought to public attention in relation to war
veterans, but it can result from a variety of traumatic incidents,
such as mugging, rape, torture, being kidnapped or held captive,
child abuse, car accidents, train wrecks, plane crashes, bombings,
or natural disasters such as floods or earthquakes
 May develop after a person is exposed to one or more traumatic
events, such as major stress, sexual assault, terrorism, or other
threats on a person's life

43. Signs and symptoms of (PTSD)
PTSD can cause many symptoms. These symptoms can be grouped into
three categories:
1. Re-experiencing symptoms
 Flashbacks—reliving the trauma over and over, including physical
symptoms like a racing heart or sweating
 Bad dreams
 Frightening thoughts
 Re-experiencing symptoms may cause problems in a person’s
everyday routine. They can start from the person’s own thoughts and
feelings. Words, objects, or situations that are reminders of the event
can also trigger re-experiencing

44. Signs and symptoms of (PTSD) cont.
2. Avoidance symptoms
 Staying away from places, events, or objects that are reminders of the
experience
 Feeling emotionally numb
 Feeling strong guilt, depression, or worry
 Losing interest in activities that were enjoyable in the past
 Having trouble remembering the dangerous event.
 Things that remind a person of the traumatic event can trigger avoidance
symptoms. These symptoms may cause a person to change his or her
personal routine. For example, after a bad car accident, a person who usually
drives may avoid driving or riding in a car

45. Signs and symptoms of (PTSD) cont.
3. Hyperarousal symptoms
 Being easily startled
 Feeling tense or “on edge”
 Having difficulty sleeping, and/or having angry outbursts
 Hyperarousal symptoms are usually constant, instead of being
triggered by things that remind one of the traumatic event.
They can make the person feel stressed and angry. These
symptoms may make it hard to do daily tasks, such as sleeping,
eating, or concentrating

46. Causes of (PTSD)
 Genetics there is evidence that susceptibility to PTSD is
hereditary. Approximately 30% of the variance in PTSD is
caused from genetics alone
 Trauma such as interpersonal violence and sexual assault
 Domestic violence
 Military experience
 Foster care
 Drug misuse Alcohol abuse and drug abuse commonly co-occur
with PTSD

47. What happen in the brain (PTSD)
 Three areas of the brain in which function may be altered in
PTSD have been identified: the prefrontal cortex, amygdala, and
hippocampus
 PTSD symptoms may result when a traumatic event causes an
over-reactive adrenaline response, which creates deep
neurological patterns in the brain. These patterns can persist long
after the event that triggered the fear, making an individual hyper-
responsive to future fearful situations During traumatic
experiences the high levels of stress hormones secreted
suppress hypothalamic activity that may be a major factor toward
the development of PTSD

48. What happen in the brain (PTSD)

49. Treatments and Medications of
(PTSD)
 Cognitive behavioral therapy (CBT) seeks to change the way a
trauma victim feels and acts by changing the patterns of thinking or
behaviour, or both, responsible for negative emotions
 A variety of medications has shown adjunctive benefit in reducing
PTSD symptoms, but there is no clear drug treatment for PTSD
 Some studies have shown that treatment with hydrocortisone shortly
after a traumatic event, in comparison to a placebo, decreases the
likelihood that the person will develop PTSD
 Propranolol administered within 6 hours of a traumatic event
decreases the physiological reactivity to a reminder of the traumatic
event

50. Treatments and Medications of
(PTSD) cont.
 Symptom management
 SSRIs (selective serotonin reuptake inhibitors). SSRIs are
considered to be a first line drug treatment
 Tricyclic antidepressants: Amitriptyline has shown benefit for
positive distress symptoms and for avoidance
 Alpha-adrenergic antagonists: Prazosin, , has shown
substantial benefit in relieving or reducing nightmares
 Anti-convulsants, mood stabilizers, anti-aggression
agents: Carbamazepine has likely benefit in reducing arousal
symptoms involving noxious affect

51. Medical conditions that mimic or
worsen anxiety symptoms
Cardiovascular
• Acute Coronary Syndrome
• Arrhythmia
• CHF
• Hypertension
Endocrine conditions
• Hyperthyroidism
• Hypothyroidism
• Pheochromocytoma
• Cushing’s disease
• Addison’s disease
• Menopause
• Mitral Valve Prolapse

52. Medical conditions that mimic or
worsen anxiety symptoms cont.
Neurological
• Epilepsy
• Cerebrovascular disease
• Meniere’s disease
• Multiple Sclerosis
• Migraine
• Encephalitis
• Early dementia
Metabolic
• Porphyria
• Diabetes
Pulmonary
• Asthma
• COPD
• Pulmonary Embolism
• Pneumonia

53. Medical conditions that mimic or
worsen anxiety symptoms cont.
Other
 Anemia
 UTI (in elderly)
 Irritable Bowel Syndrome
 Heavy metal poisoning
 B12 deficiency
 Electrolyte disturbances

54. Substance Abuse and Anxiety
 Substance abuse is often co-morbid with anxiety disorders as patients
often try to self-medicate to cope with anxiety
 37% of patients with GAD and 20-40% of patients with Panic
Disorder have alcohol abuse/dependence
 Drug intoxication can mimic anxiety:
- Amphetamines - Marijuana
- Caffeine - Hallucinogens
- Nicotine - Ecstasy
- Cocaine - Excessive alcohol consumption
- Phencyclidine

55. Substance Abuse and Anxiety cont.
Drug withdrawal also associated with anxiety
 Alcohol
 Benzodiazepines
 Opiate
 Barbiturate
 Anti-hypertensive

56. Recent trend in therapeutics
Canada

57. Cognitive Therapy for Anxiety
Disorders
 The challenges for the future development of CBT for anxiety
disorders relate to the efficacy, the effectiveness and the cost-
effectiveness of the treatment
1. Efficacy
 While current CBT treatments for anxiety disorders have
demonstrated efficacy, there remains room for improvement as
many patients do not achieve high end state functioning,
particularly at longer term follow-up

58. Cognitive Therapy for Anxiety
Disorders cont.
2. Effectiveness
 It has been estimated that fewer than 30% of patients treated in
routine clinical settings currently receive evidence-based
treatments
 Furthermore, even when evidence-based treatments are applied
the reported effect sizes and drop-out rates are often less
favourable than those reported in the original research trials
 Hence, a future challenge for CBT for the anxiety disorders is
its successful dissemination

59. Cognitive Therapy for Anxiety
Disorders cont.
 Two issues to be tackled in disseminating CBT for anxiety
disorders into routine clinical practice are
 First, whether CBT protocols delivered in RCTs (randomized
controlled trial) can generalize to the patients seen in routine
clinical practice
 Second, whether it is possible to train therapists to the standards
necessary to achieve the same effects as seen in clinical trials

60. Cognitive Therapy for Anxiety
Disorders cont.
3. Cost-effectiveness
 It is recommended CBT is to be delivered to the majority of
patients with anxiety disorders who may benefit from it
 It will be necessary to take a stepped care approach, working
up from the lower intensity interventions to higher intensity
treatments
 At the lowest level of intervention, there are a vast number of
self-help books for anxiety disorders
 There is little evidence for their efficacy as a stand-alone
treatment for any anxiety disorder

61. Conclusions
Conclusions
 As discussed above, there is a great deal of evidence that CBT
is an efficacious treatment for anxiety disorders. CBT’s
empirical stance means that it is well placed to continue to
incorporate theoretical and practical developments (both from
within and outside CBT) to continue to increase its efficacy
 The biggest challenge currently facing CBT for anxiety
disorders is how best to achieve the increase in provision that is
needed to meet current demand for CBT, whilst retaining high
levels of efficacy and effectiveness

62. Clinical trials
 Efficacy and Safety of Vortioxetine for Treatment of
Generalized Anxiety Disorder in Adults
 Study design: A Randomized, Double-Blind, Parallel-Group,
Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy
and Safety of a Single Dose of in Acute Treatment of Adults
With Generalized Anxiety Disorder
 The HAM-A is an anxiety rating scale consisting of 14 items
that assess anxious mood, tension, fear, insomnia, intellectual
(cognitive) symptoms, depressed mood, behaviour at interview,
somatic (sensory), cardiovascular, respiratory, gastrointestinal,
genitourinary, autonomic and somatic (muscular) symptoms.
Each symptom is rated from 0 (absent) to 4 (maximum severity

63. Clinical trials
 The study enrolled 301 patients. Participants were randomly
assigned to one of the two treatment groups
 Vortioxetine 5 mg
 Placebo (dummy inactive pill)
 There were no statistically significant differences in any key
secondary efficacy outcome between vortioxetine and placebo.
 In conclusion, in this trial, vortioxetine did not improve
symptoms of GAD (compared with placebo) over 8 weeks of
treatment. Vortioxetine was well tolerated in this study

64. References
 Anxiety Disorders Association of Canada:
www.anxietycanada.ca Anxiety Disorders Association of
America: www.adaa.org National Institutes of Mental Health
(United States)
 www.nimh.nih.gov/anxiety Anxiety Research and Treatment
Centre (Canada): www.anxietytreatment.ca Obsessive-
Compulsive Foundation (United States):www.ocfoundation.org

65. References
 American Psychiatric Association (2004). Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition (DSM-IV). Washington, DC: APA.
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67. Thank you