1. Psychological (mental)

• Apprehension
• Irritability
• Nervousness
• Worry
• Impending doom
• Fear
• Rumination
• Difficulty concentrating

2. Physiological (somatic)

• Tremor
• Restlessness
• HA
• Perspiration
• Muscle Tension
• Palpitations
• SOB

Cardiovascular

Angina, CHF, PE, MI

Endocrine

Hyperthyroidism, Hypoglycemia, Folate Deficiency, Adrenal Tumor, Parathyroid Disease

Neurological

Dementia/Delirium, Migraine, Parkinson's Disease, Seizures Strokes

Respiratory

Asthma, COPD

Other

Anemia, Lupus, Premenstrual Syndrome

CNS Stimulants

• Theophylline
• Albuterol
• Amphetamine
• Cocaine
• Pseudoephedrine
• Methylphenidate
• Nicotine
• Caffeine

CNS Depressant Withdrawal

• EtOH
• Barbiturates
• Benzodiazepines

Others

• Fluoxetine
• Levodopa
• Aripiprazole
• Steroids
• Levothyroxine
• Prednisone
• Levodopa

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Treatment of Anxiety Disorders: Antidepressants

Usefulness/Disadvantages

• More effective in treating psychological and cognitive symptoms (excessive worry)
• Tx of co-occuring depression
• No abuse potential
• Initial stimulation may worsen anxiety

Treatment of Anxiety Disorders: Benzodiazepines

Usefulness/Disadvantages

• More effective for somatic symptoms and for anticipatory fear/avoidant behavior
• Risk of tolerance and abuse potential
• Withdrawal symptoms: nervousness, insomnia, restlessness

• Clonazepam
• Alprazolam
• Lorazepam
• Diazepam
• Clorazepate
• Chlordiazepoxide
• Oxazepam

1. alpha1 (produces sedative effects)
2. alpha2 (produces anxiolytic effects)
3. alpha3
4. alpha5

1. Anxiolytic
2. Sedative-hypnotic
3. Muscle relaxant
4. Anticonvulsant

• Sedation
• Ataxia
• Psychomotor slowed
• Cognitive impairment
• Anterograde amnesia
• Respiratory depression
• Impaired coordination
• Slurred speech
• Paradoxical excitation

• Anxiety
• Insomnia
• Restlessness
• Agitation/Irritability
• Diaphoresis
• Nightmares
• Delusions/Hallucinations
• Seizures

Relapse

recurrence of original anxiety symptoms that follow d/c of tx

Rebound

anxiety symptoms are more intense

Withdrawal

implies a degree of physical dependence

Glucuronidation

No active metabolites

Glucuronidation

No active metabolites

Glucuronidation

No active metabolites

Nitroreduction

No active metabolites

N-desmethyldiazepam

Active metabolite

N-desmethyldiazepam

Active metabolite

N-desmethyldiazepam

Active metabolite

BZD Half-Life: Short

5-14 hrs

• Oxazepam
• No accumulation, severe withdrawal symptoms if d/c abruptly
• Safer with hepatotoxicity

BZD Half-Life: Intermediate

10-20 hrs

• Alprazolam, Lorazepam
• No accumulation, BID-TID dosing
• Clonazepam ~ 40 hrs = QD dosing -- makes it the perfect BZD

BZD Half-Life: Long

100 hrs

• Diazepam, Clorazepate, Chlordiazepoxide
• Have active metabolite that accumulates = less severe withdrawal symptoms
• QD dosing
• Avoid in elderly due to fall risk

• Diazepam, Clorazepate, Alprazolam
• Absorbed rapidly and distributed quickly
• Increased abuse potential

• Chlordiazepoxide
• Lorazepam
• Clonazepam
• Temazepam

• Oxazepam
• Absorbed slowly
• Abuse risk lower

• Excessive anxiety and worring occurring more days than not -- for > 6 mo about a # of events or activities
• Difficult to control worry
• Anxiety or worry is associated with > 3 of the following symp: restlessness, easily fatigued, difficulty conc., irritability, muscle tension, sleep disturbances
• Anxiety or worry not caused by another psychiatric illness (depression, mania, schizophrenia)
• Constant worry causing significant distress and impairment in social or occupational function
• Excessive worry and anxiety not caused by substance abuse or general medical condition

1st line

• Venlafaxine XR
• Paroxetine
• Escitalopram
• Duloxetine
• Sertraline

Initially, pts anxiety may worsen due to increase availability of 5-HT in the neuronal synapse --- START AT LOWER DOSES

Response is gradual over 8-12 wks

Continue tx for at least 6-12 mo

Additional Options

BZDs, Buspirone, Beta-Blockers

BZDs are 1st line when rapid onset is essential and substance abuse is not an issue (limit use to 2-6 wks)

• Clonazepam
• Lorazepam
• Alprazolam (hardest to d/c)

5-HT1A partial agonist

ADRs

• jitteriness
• dizziness
• nausea
• HA

Benefits

Lacks sedative effects of BZDs, no abuse potential, safer in overdose

Patient Counseling

• Must be taken QD, NO prn use
• Takes several weeks for effects
• No abuse potential
• Does not affect sexual function
• Given with food increases bioavailability

Obsessions

recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate and that cause marked anxiety or distress

Compulsions

repetitive behavior or mental acts aimed at preventing or reducing distress

• The person has recognized that the obsessions or compulsions are excessive or unreasonable
•  The obsessions or compulsions cause marked distress, are time consuming (>1hr/day) or impair occupational social functioning
• The content of the obsessions or compulsions not restricted to another Axis I diagnosis, substance abuse, or medical condition

• Depression
• Other Anxiety Disorders
• Schizophrenia
• Eating Disorders

1st Line

SSRIs and Behavioral Therapy

• Fluoxetine
• Sertraline
• Fluvoxamine

5-HT selectivity is ESSENTIAL for response to OCD

Full tx trial at max dose of 8-12 wks

Relapse is > 90% upon medication d/c

2nd Line

TCAs and Antipsychotics (for comorbid tics)

Clomipramine

• max dose: 250 mg due to seizure risk
• Adv: several studies have demonstrated > efficacy over SSRIs, plasma leves can be drawn to aid in dosing
• Disadv: tolerability -- sedation, dry mouth, dizziness, constipation, nausea, blurry vision, HA, weight gain, sex dysfunction

• Presence of at least 2 unexpected panic attacks
• At least 1 of the attacks has been followed by at least 1 month of persistent concern about having another attack of significant change in behavior because of the attack
• Attacks not due to direct physiological effects of substance abuse or medical condition
• Attacks not better accounted for by another mental disorder (social phobia, specific phobia, OCD, PTSD)
• Presence or absence of agoraphobia

1st Line

CBT, exposure tx, relaxation tx

SSRIs

• paroxetine, sertraline, fluoxetine, venlafaxine XR = decrease in frequency of panic attacks, anticipatory anxiety, and depression
• Start low with SSRI dosing
• 4-6 wks for efficacy

BZDs

• Alprazolam, clonazepam (preferred)
• BZDs allow for more rapid relief -- give on schedule and NOT prn to prevent attacks
• Panic disorder pts have increased BZD withdrawal -- taper slowly over 4-9 mo

TCAs

• Imipramine, clomipramine
• Very effective but increased risk for ACh side effects and cardiac effects
• Imipramine most studied TCA -- alleviates attacks 75% of the time
• Continue tx for at least 12-24 mo
• 25-40% of pts relapse after d/c meds

• Person witnessed or experienced event involving death or serious injury OR was confronted with actual or threatened death and peron's response involved intense fear, helplessness, or horror
• Traumatic event is persistently re-experienced
• Persistent avoidance of stimuli associated with the trauma
• Persistent symptoms of increased arousal (insomnia, irritability, anger outbursts, hypervigilance)
• Duration of disturbance > 1 mo
• Disturbance causes significant distress or impairment to pts social, occupational functioning

1. Re-experiencing
2. Avoidance/numbing
3. Autonomic hyperarousal