Anxiety (and PD and PTSD) RW Exam 2

What are the diagnostic criteria for GAD?

Excessive anxiety or worry for at least 6 months + at least 3 of the following:

- Restlessness

- Easily fatigued

- Poor concentration

- Irritability

- Muscle tension

- Insomnia

The person finds it difficult to control the worry

Interferes with social or occupational functioning

Not caused by a drug, substance, medical, or psychiatric condition

Which medications/substances are associated with anxiety?

Antidepressants

Antiparkinson drugs

Bronchodilators

Corticosteroids

Decongestants

Stimulants

Thyroid hormones

Withdrawal of CNS depressants

What psychiatric disorders may cause anxiety?

Mood disorders

Hypochondriasis

Personality disorders

Alcohol or substance use, or withdrawal

Other anxiety disorders

What neurologic disorders may cause anxiety?

Cerebrovascular accident (CVA)

Seizure disorders

Dementia

Stroke

Migraine

Encephalitis

Vestibular dysfunction

What CV disorders may cause anxiety?

Angina

Arrhythmias

Congestive heart failure

Mitral valve prolapse

Myocardial infarction

What endocrine and metabolic disorders may cause anxiety?

Hypothyroidism or hyperthyroidism

Hypoglycemia

Cushing disease

Addison disease

Pheochromocytoma

Hyperadrenocorticism

Hyponatremia

Hyperkalemia

Vitamin B12 deficiency

What resp. disorders may cause anxiety?

Asthma

COPD

Pulmonary embolism

Pneumonia

Hyperventilation

What are the drugs of choice for GAD treatment?

Antidepressants

Why are antidepressants the drugs of choice for GAD treatment?

Tolerable side effect profile

No risk for dependency

Efficacy in common comorbid conditions

What component of anxiety do antidepressants decrease?

Mainly mind - reduce worry and apprehension

Some effect on body - somewhat decrease tremor, rapid HR, sweating

What is the onset of anti-anxiety effect with antidepressants?

2-4 weeks

What antidepressants are preferred for anxiety tx.?

SSRIs or SNRIs preferred

What are the names of the SSRI's?

Paroxetine

Escitalopram

Sertraline

Citalopram

Fluoxetine

Fluvoxamine

What are the names of the SNRIs?

Venlafaxine

Desvenlafaxine

Duloxetine

What are the 1st line antidepressants for GAD?

SNRI or SSRI

What is reccomended for GAD if 1st line pharmacotherapy fails?

Switch to another SSRI or SNRI, OR

Switch to a different agent, OR

(SSRI/SNRI, imipramine, buspirone, pregabalin)

Add augmentation agent

(SGA, antidepressant from diff. class, BZD, or therapy)

Which antidepressants are used in the management of GAD?

SSRIs: Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

SNRIs: Venlafaxine, Desvenlafaxine, Duloxetine

TCAs: Imipramine

What are other agents used in the management of GAD?

Hydroxyzine

Buspirone (azapirone)

Pregabalin (anticonvulsant)

Quetiapine (SGA)

What does the selection of an antidepressant for anxiety tx. depend on?

History of prior response,

Side effect and drug interaction profile,

Cost,

Formulary, etc.

What is the MOA of buspirone?

5-HT1A partial agonist

What is the onset of effect of buspirone?

Gradual onset - about 2 weeks

What are potential ADRs of buspirone?

Dizziness

Nausea

Headaches

What are drug interactions seen with buspirone?

CYP3A4 substrate

Other serotonergic medications

What are advantages of buspirone?

Not thought to have misuse potential, cause withdrawal symptoms, or potentiate sedative-hypnotic effects

What are disadvantages of buspirone?

Gradual onset of action (about 2 weeks)

Does not provide immediate anxiety relief

Inconsistent reports of efficacy

BZD use within 1 mo of starting buspirone is associated with dec. efficacy

What are examples of prescription medications that are commonly misused?

Opioids

Stimulants

Benzo's

Z-hypnotics

Quetiapine

Carisoprodol

Pregabalin + Gabapentin

Bupropion

Sildenafil

Diphenhydramine

Clonidine

What is hydroxyzine?

Antihistamine (active metab. is cetirizine)

Antihistaminergic and mild anticholinergic effects

What is the use of hydroxyzine in anxiety?

May be effective for acute reduction of somatic (physical) symptoms of anxiety

What is the MOA of BZDs?

Enhance GABA (major - NT)

Bind at distinct site from GABA on GABA-A receptors

Binding causes allosteric modification of the receptor, leading to increased activity

BZDs inc. freq. of channel opening events, leading to inc. Cl- conduction and inhibition of AP

What is the effect of BZDs in anxiety?

More effective for physical anxiety symptoms (decreasing tremor, rapid HR, and sweating)

Less effective for mental symptoms (worry and apprehension)

What are the properties of BZDs?

Anxiolytic

Sedative

Anticonvulsant

Muscle relaxant

When are BZD's recommended for acute treatment of anxiety?

Short-term relief is needed (about 2-4 weeks)

Adjunct during initiation of antidepressant therapy

People who have 3 treatment failures (treatment refractory)

How should BZDs be administered for anxiety?

Short term treatment

Scheduled dosing

What are the BBW's on BZDs?

Use w/ opioids can lead to resp. depression, coma, and death

Risk of abuse, misuse, and addiction; which can lead to overdose or death

May lead to physical dependence.

Abrupt d/c or dec. dose can precipitate withdrawal, which can be life threatening.

What are the advantages of BZDs use in anxiety?

Ease of use

Relatively low toxicity (when used alone)

Rapid onset

What are the disadvantages of BZDs use in anxiety?

Lack of antidepressant effects

Risk for withdrawal and need for taper

Potential interdose rebound anxiety

Possible cognitive and motor impairment

Increased fall risk

Risk for dependency and misuse

What is the average time to peak plasma level and the half life of Alprazolam?

1-2 hrs to peak

12-15 hrs t1/2

What is the average time to peak plasma level and the half life of Chlordiazepoxide?

1-4 hrs to peak

5-30 hrs t1/2

What is the average time to peak plasma level and the half life of Clonazepam?

1-4 hrs to peak

18-50 hrs t1/2

What is the average time to peak plasma level and the half life of Diazepam?

0.5-2 hrs to peak

20-80 hrs t1/2

What is the average time to peak plasma level and the half life of Lorazepam?

2-4 hrs to peak

10-20 hrs t1/2

How are most BZDs eliminated?

Most undergo hepatic oxidation and glucuronide conjugation

Which BZDs are only conjugated?

Lorazepam

Oxazepam

Temazepam

(L-O-T)

Which benzodiazepines are preferred for patients with reduced hepatic function secondary to aging or disease?

Lorazepam and Oxazepam

What are potential ADRs of BZDs?

Sedation

Motor and cognitive impairment

Ataxia (lack of coordination/balance)

Anterograde amnesia

Paradoxical agitation, irritability, and aggression

Disorientation

Slurred speech

Resp. depression

(inc. GABA -> slowing body down -> tired, balance issues)

What are contraindications to BZD use?

Alcohol intoxication

Pulmonary disease

Hepatic disease

Sleep apnea

Current or hx. of substance use disorders

Older adults (fall risk)

What are pharmacodynamic drug interactions of BZDs?

Alcohol

Opioids

Antipsychotics

Antihistamines

Anticonvulsants

Certain antidepressants (sedating)

How long should BZDs be used for acute anxiety managment?

Limit use for acute management to 2-4 weeks if possible

How should BZDs be dosed?

Start low and go slow

Limit use for acute management to 2-4 weeks if possible

What are withdrawal symptoms from BZDs?

Anxiety

Insomnia

Muscle tension

Seizures

What BZD effects does tolerance develop to?

Sedative

Muscle relaxant

Anticonvulsant

How should BZDs be discontinued?

25% reduction per week until 50% of dose is reached, then reduce by 10% per week until d/c

Therapy > 8 weeks: 2-3 weeks

Therapy > 6 months: 4-8 weeks

Therapy > 1 year: slow taper over 2-4 months

Taper will not prevent withdrawal symptoms, but should prevent severe withdrawal

What is a major possible neurologic ADR of BZDs?

Benzodiazepine-Induced Neurological Dysfunction (BIND)

What is BIND?

Functionally limiting neurologic symptoms (phys. and psych.) due to neuroadaptation and/or neurotoxicity from BZD exposure

Symptoms can begin while taking or tapering BZDs, and can persists for weeks, months, or years after d/c

What is the median length of withdrawal symptoms from BZDs, according to the FDA?

9.5 months

When does physical dependence occur with BZDs, according to the FDA?

Physical dependence can occur within days to weeks

Median time to onset - 14 days

What is panic disorder (PD)?

Begins as a series of panic attacks

Attacks are followed by at least 1 month of persistent concern about having another panic attack

Patients often seek medical assistance for what they believe to be a medical problem

Patients often develop agoraphobia secondary to the attacks

What is the clinical presentation of panic attacks?

Discrete period of intense fear or discomfort, in which at least 4 of the following appear & disappear quickly:

- Palpitations

- Sweating

- Shaking

- Shortness of breath

- Feeling of choking

- Chest pain

- Nausea

- Dizziness

- Chills or hot flashes

- Numbness

- Feeling detached from oneself

- Fear of losing control

- Fear of dying

What pharmacotherapy is recommended for PD?

SSRIs

Venlafaxine may also be used

Selected BZDs in certain cases

When is response seen with SSRIs in PD tx.?

Antipanic effects start to be seen around 4 weeks

Optimal response takes 6-12 weeks

How should SSRIs be dosed for PD tx.?

Start at 1/4-1/2 normal starting dose

Titrate up to max tolerated dose slowly

(Pt.'s w/PD are very sensitive to stimulant ADRs)

When are BZDs used in PD?

Patients requiring rapid relief of anticipatory anxiety

Patients who are unable to tolerate antidepressants

What is the onset of BZD effect in PD tx.?

Antipanic effects usually seen within 1 week

What is the clinical presentation of PTSD?

Exposure to threatened or actual death, violence, or serious injury

Presence of at least 1 intrusive symptom

- Distressing, recurrent dreams related to the trauma

- Dissociative reactions (flashbacks) where patient feels as if trauma is reoccurring

Avoidance of stimuli associated with traumatic event

Negative alterations in mood or cognition associated with traumatic event

Changes in reactivity & arousal associated with traumatic event

What is the general approach to PTSD treatment?

Trauma-focused psychotherapy preferred

If trauma-focused psychotherapy unavailable: pharmacotherapy (antidepressants) or non-trauma-focused psychotherapy

What antidepressants are first line for PTSD?

SSRIs - Fluoxetine, Paroxetine, and Sertraline

SNRI - Venlafaxine

What antidepressants are second line for PTSD?

Mirtazapine

Imipramine (TCA)

Phenelzine (MAOI)

What are adjunctive therapies for symptoms of PTSD?

Prazosin

Risperidone, quetiapine, aripiprazole

What is the use of Prazosin as an adjunctive therapy for symptoms of PTSD?

Used for treatment of nightmares

What is the use of antipsychotics as an adjunctive therapy for symptoms of PTSD?

Used for intrusion symptoms

Benefit in treatments weighed against ADRs

(Risperidone, quetiapine and aripiprazole)

Can BZDs be used as adjunctive therapies for PTSD symptoms?

NOT recommended for PTSD symptoms