Anxiety Disorders and Antianxiety Medications Overview

DSM-5

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, which groups anxiety disorders into three major categories based on suspected etiology and type of symptoms.

Anxiety Disorders

A category of mental health disorders characterized by excessive fear or anxiety.

Obsessive-Compulsive and Related Disorders

A category of disorders that includes obsessive thoughts and compulsive behaviors.

Trauma and Stressor-related Disorders

Disorders that occur following exposure to a traumatic or stressful event.

Separation Anxiety Disorder

A disorder characterized by excessive fear or anxiety concerning separation from those to whom the individual is attached.

Selective Mutism

A disorder where a person consistently fails to speak in specific social situations despite speaking in other situations.

Specific Phobia

An intense, irrational fear of a specific object or situation that leads to avoidance behavior.

Social Anxiety Disorder (Social Phobia)

A disorder characterized by significant anxiety and discomfort in social situations.

Panic Disorder

A disorder characterized by recurrent unexpected panic attacks and persistent concern about having more attacks.

Panic Attack Specifier

A feature of panic disorder that indicates the presence of panic attacks.

Agoraphobia

An anxiety disorder characterized by fear of being in situations where escape might be difficult or help unavailable.

Generalized Anxiety Disorder

A disorder characterized by excessive anxiety and worry about various aspects of life.

Obsessive-Compulsive Disorder

A disorder characterized by unwanted repetitive thoughts (obsessions) and/or actions (compulsions).

Body Dysmorphic Disorder

A disorder characterized by an obsessive focus on a perceived flaw in appearance.

Hoarding Disorder

A disorder characterized by persistent difficulty discarding or parting with possessions, regardless of their actual value.

Trichotillomania (Hair-Pulling Disorder)

A disorder characterized by recurrent, irresistible urges to pull out hair from one's scalp, eyebrows, or other areas of the body.

Excoriation (Skin Picking) Disorder

A disorder characterized by recurrent skin picking resulting in skin lesions.

Reactive Attachment Disorder

A disorder characterized by a consistent pattern of inhibited, emotionally withdrawn behavior toward adult caregivers.

Disinhibited Social Engagement Disorder

A disorder characterized by a pattern of behavior in which a child actively approaches and interacts with unfamiliar adults.

Posttraumatic Stress Disorder (PTSD)

A disorder that develops after exposure to a traumatic event, characterized by intrusive memories, avoidance, and hyperarousal.

Acute Stress Disorder

A disorder characterized by severe anxiety and dissociative symptoms that occur within three days to one month after exposure to a traumatic event.

Adjustment Disorders

A group of conditions that can occur when a person has difficulty coping with a stressful event.

Prevalence of Anxiety Disorders

29-31% of people will experience a diagnosable anxiety disorder.

Gender Differences in Anxiety

Females have 1.5x the rate of anxiety compared to males.

Social Anxiety Disorder Prevalence

12.1% in the U.S., with rates as high as 36% among late teens and young adults.

Panic Disorder Prevalence

4.7% in the U.S., more common in females than males.

Generalized Anxiety Disorder (GAD)

Prevalence - 5.0-5.7% in U.S. (more common in females)

Sub-clinical symptoms of GAD

15.6% will experience sub-clinical symptoms of GAD

Age prevalence of GAD

More common in young adults than older adults

Heritability of GAD

30%

Focus genes for GAD

Main focus is on 5HT genes, especially for transporters and receptors, along with DA transporters, MAO-A, and BDNF genes

Obsessive-Compulsive Disorder (OCD)

Prevalence - 2.3% in U.S. (twice as common in females)

Average age of onset for OCD

Average age of onset is 19.5, but for males it is 17 and 21 for females (25% of males will have onset prior to age 10)

Common compulsions in OCD

Checking and ordering are the two most common compulsions (hoarding used to be #2 until it became its own disorder)

Obsessions and compulsions in OCD

Almost 100% have both obsessions and compulsions (mental acts such as counting and repeating words are considered compulsions, though many think they are obsessions)

Heritability of OCD

Around 50%

Research focus for OCD

5HT transporter genes have received most research due to efficacy of serotonin drugs, but glutamate receptor and transporter genes also appear to play a role within basal ganglia

Post-Traumatic Stress Disorder (PTSD)

Prevalence - 3.0-27.0% (significant differences across groups and different determinants of a 'trauma' make it difficult to determine rates)

Trauma experience in life

70% of people experience at least one trauma in life (e.g., witnessing family or other person trauma, being involved in accident, violence on self)

Development of PTSD after trauma

4% will develop PTSD after a traumatic event, though it differs by type of trauma, with personal trauma more likely to develop PTSD than impersonal trauma (e.g., rape vs house destroyed in hurricane)

PTSD

Post-Traumatic Stress Disorder, likely to develop from experiences such as rape (19%), physical abuse by romantic partner (11.7%), kidnapping (11%), and any sexual assault besides rape (10.5%).

Heritability

The genetic contribution to a trait, specifically in this context, ranges from 5-20% for PTSD.

Non-coding RNA

A type of RNA that regulates gene expression and may play an important role in the neurobiology of anxiety.

Fear

An emotional response that includes cognitive and physical responses to current danger or threat.

Anxiety

An emotional response that includes cognitive and physical responses to perceived future danger or threat.

Panic

A sudden, unexpected emotional response that includes cognitive and physical responses in the absence of obvious danger or threat.

HPA Axis

Hypothalamic-pituitary-adrenal axis, a central stress response system that plays a crucial role in the neurobiology of anxiety.

Anterior Cingulate Cortex

A brain region involved in the emotional experience of fear or anxiety.

Amygdala

A brain structure that plays a key role in processing emotions, particularly fear and anxiety.

Orbitofrontal Cortex

A brain region involved in decision-making and emotional regulation related to fear and anxiety.

Periaqueductal Gray

A brain region involved in the modulation of pain and defensive behavior, associated with the amygdala.

Hypothalamus

A brain region that influences endocrine effects, including increased cortisol in response to fear.

Parabrachial Nucleus

A brain region involved in breathing responses such as shortness of breath and hyperventilation, connected to the amygdala.

Locus Coeruleus

A brain region associated with arousal, increased heart rate, and blood pressure, linked to the amygdala.

Dorsolateral Prefrontal Cortex

A brain region associated with cognitive functions such as worry and obsessions.

Thalamus

A brain structure involved in sensory perception and regulation of motor functions, associated with compulsions.

Cingulate Cortex

A brain region involved in emotional regulation and processing, connected to the striatum.

Hippocampus

A brain structure involved in memory formation, particularly in remembering and reexperiencing fear.

Serotonin (5HT)

A neurotransmitter that plays a primary role in anxiety regulation.

5HT-1A receptors

Presynaptic receptors that, when overactive, decrease the release of serotonin in anxiety.

GABA

The primary inhibitory neurotransmitter that slows firing in the amygdala and prefrontal cortex, reducing fear.

Anxiolytics

Medications used to reduce anxiety, with a historical context including the use of alcohol, opium, and barbiturates.

Chlordiazepoxide

The first benzodiazepine marketed as an anxiolytic and anticonvulsant in 1960.

Meprobamate

A tranquilizer known as 'mother's little helper', best-selling psychotropic drug in 1955.

Barbiturates

A class of drugs that were primary sedative/hypnotics until the introduction of benzodiazepines.

Lethal dose of barbiturates

10X effective dose of barbiturates is lethal.

Lethal dose of benzodiazepines

About 100X effective dose of benzodiazepines is lethal.

FDA recognition of benzodiazepines

In 1975, the FDA recognized that benzodiazepines cause dependence and should be prescribed for no more than 4 weeks.

Fluoxetine (Prozac)

Introduced in 1987, fluoxetine has both antidepressant and antianxiety effects.

SSRIs and SNRIs

SSRIs and SNRIs quickly followed fluoxetine and became primary drugs in the treatment of anxiety.

Hydroxyzine (Atarax)

An antihistamine introduced in the 1950s that has been used for anxiety.

Buspirone (BuSpar)

A serotonin agonist introduced in 1975 that has been used for anxiety.

Agomelatine

A melatonin agonist that also has SSRI effects and is in Phase III studies.

MDMA (ecstasy)

Currently in Phase III trials for therapy-assisted PTSD treatment.

Esketamine (Spravato)

Early research indicates it is effective with PTSD.

Psilocybin, LSD, and DMT

Trials indicate they are effective with PTSD and GAD, with psilocybin having a more favorable side effect profile.

Primary categories of anxiolytics

Six primary categories include Benzodiazepines, Antidepressants, Serotonin agonist, Antihypertensives, Alpha-2-delta ligands, and Antihistamines.

Alprazolam (Xanax)

Dosage: 0.25-1.0 mg, Number of dosages per day: 3, Full Onset of Effect: 1-2 hours, Duration of Effect: 6-26 hours.

Chlordiazepoxide (Librium)

Dosage: 10-20 mg, Number of dosages per day: 2-4, Full Onset of Effect: 2 hours, Duration of Effect: 5-30 hours.

Clonazepam (Klonopin)

Dosage: 0.5-2.0 mg, Number of dosages per day: 3, Full Onset of Effect: 1-4 hours, Duration of Effect: 18-50 hours.

Clorazepate (Tranxene)

Dosage: 7.5-15 mg, Number of dosages per day: 2-3, Full Onset of Effect: 0.5-2 hours, Duration of Effect: 40-50 hours.

Diazepam (Valium)

Dosage: 2-10 mg, Number of dosages per day: 3-4, Full Onset of Effect: 0.5-1.5 hours, Duration of Effect: 20-80 hours.

Lorazepam (Ativan)

Dosage: 0.5-1.0 mg, Number of dosages per day: 3-4, Full Onset of Effect: 1-2 hours, Duration of Effect: 10-20 hours.

Oxazepam (Serax)

Dosage: 10-30 mg, Number of dosages per day: 3-4, Full Onset of Effect: 3 hours, Duration of Effect: 5-11 hours.

Prazepam (Centrax)

Dosage: 10-30 mg, Number of dosages per day: 1-2, Full Onset of Effect: 4-6 hours, Duration of Effect: 36-200 hours.

GABA-A receptors

Benzodiazepines target GABA-A receptors, which are ligand-gated ion channels.

Long-term use of benzodiazepines

Long-term use (>1 year) is associated with impaired working and recent memory, slower processing speed, and expressive language difficulties.

Onset of action for benzodiazepines

Shortest onset is for clorazepate (Tranxene) and diazepam (Valium); longest is for oxazepam (Serax) and prazepam (Centrax).

Duration of action for benzodiazepines

Shortest duration is for lorazepam (Ativan) and oxazepam (Serax); longest is for diazepam (Valium) and prazepam (Centrax).

Lipophilicity of benzodiazepines

Most are lipophilic, especially alprazolam (Xanax) and diazepam (Valium); lorazepam (Ativan) is most lipophobic.

Benzodiazepines Side Effects

drowsiness, confusion, orthostatic hypotension (drop in blood pressure causing dizziness when standing), slurred speech, muscle weakness, memory problems, constipation, nausea, dry mouth, blurred vision

Escitalopram (Lexapro)

10-20 mg for GAD, 20-80 mg for PD, OCD

Fluoxetine (Prozac, Sarafem)

Dosage not specified

Fluvoxamine (Luvox)

50-300 mg for SAD, OCD

Paroxetine (Paxil)

20-50 mg for SAD, PD, GAD, OCD, PTSD

Sertraline (Zoloft)

50-200 mg for SAD, PD, OCD, PTSD

Duloxetine (Cymbalta)

20-80 mg for GAD

Venlafaxine (Effexor)

75-350 mg for SAD, PD, GAD

Clomipramine (Anafranil)

150-300 mg for OCD

SAD

social anxiety disorder