Anxiety and Sleep Disorders Therapeutics Flashcards Preview

Pharmacy School 2016-17 > Anxiety and Sleep Disorders Therapeutics > Flashcards

Flashcards in Anxiety and Sleep Disorders Therapeutics Deck (83):

Medical Conditions with Secondary Anxiety Symptoms

Endocrine (thyroid or parathyroid disease, hypoglycemia, cushings)

Cardio-respiratory (angina, pulmonary embolism)

Autoimmune disorders

Neurological disorder (seizure disorder)

Substance related (nicotine, alcohol, benzos and opioids)


Medications which can cause anxiety

Stimulants, thyroid supplements, antidepressants, corticosteroids, oral contraceptives, bronchodilators, decongestants, abrupt withdrawal of CNS depressants (benzos, barbs, and alcohol)


Drug classes to treat anxiety

Antidepressants (SSRIs, SNRIs, TCAs, MAOIs)

Benzodiazepines and Z-drugs

Antihistamines, 5HT1a agonists and GABA agonists


Benzodiazepines by speed of onset

Very fast (diazepam)

Fast (Clorazepate)

Intermediate (alprazolam, chlordiazepoxide, clonazepam, lorazepam)

Slow (oxazepam)


Benzodiazepines by half-life

Short/Intermediate (alprazolam, oxazepam, lorazepam, chlordiazepoxide)

Intermediate/Long (clorazepate, diazepam)


Clomipramine is used for

OCD or panic disorder


GABA Agonist



5HT1a receptor agonist

Buspirone (GAD, SAD)



Phenelzine (SAD, Panic, PTSD, MDD)


GAD Criteria (DSM 5)

Presence of anxiety and worry for 6 months (worry when nothing is wrong or worry that is disproportionate)

With at least 3 of the following (edginess or restlessness, tiring easily/fatigued more than usual, impaired concentration, irritability, increased muscle aches or soreness, difficulty sleeping)



Generalized Anxiety Disorder

Psychic/subjective symptoms (worry, on edge, impaired concentration, concern over health)

Somatic symptoms (muscle tension, insomnia, fatigue, irritability, nausea or diarrhea, sweating, urinary frequency, palpitations, pain, GI distress)


GAD Comorbidity

90% have another psychiatric disorder

62% have lifetime MDD; 40% have dysthymia

Anxiety disorders predict greatest risk of secondary MDD

58% of patients with lifetime MDD have an anxiety disorder

Affects 6.8 million American adults (2.1%)


Overlapping MDD and GAD symptoms

Anxiety, sleep disturbance, psychomotor agitation, concentration difficulty, irritability, fatigue



Hamilton Anxiety Rating Scale

Good for both psychic and somatic symptoms

Pretreatment HAM-A scores of more than 18 indicate common index need for treatment



Generalized anxiety disorder severity scale

Specific probing in domains of worry, impairment of social and work functioning



PENN state worry questionnaire

Measures trait-like tendency to worry excessively

Useful to test severity of pathological worry

Discriminates among anxiety disorders - higher score indicate GAD among other disorders


Non-pharm for GAD

Relaxation techniques, biofeedback to reduce arousal, cognitive therapy, behavioral therapy


Cognitive Behavioral Therapy

Talk therapy helps change thinking patterns to find ways of coping; includes relaxation techniques, problem solving and challenging distorted beliefs


GAD Medication Treatment

Benzodiazepiens (acute; most effective for somatic symptoms)

Antidepressants (long term; most effective for psychic symptoms)


GAD Treatment Plan

1st Line (CBT with or without SSRI; if partial resposne augment with buspirone, hydroxyzine, pregabalin, or benzo)

2nd line (SNRI; duloxetine or venlafaxine)

3rd line (SSRI/SNRI + SGA (risperidone, quetiapine, olanzapine))

Continue medication/therapy treatment for at least 1 year


SSRI Concerns/Benefits

Stopped abruptly SSRIs can produce discontinuation syndrome (dizziness, insomnia, flu-like symptoms, seizures)


SNRIs Concerns/Benefits

abrupt withdrawal can cause anxiety, insomnia, flu like symptoms, headache, nausea, electrical shock like symptoms down limbs and scalp


TCAs Concerns/Benefits

Potential fatal toxicity after overdose


MAOIs Concerns/Benefits

Fatal overdose potential


Benzodiazepines Concerns/Benefits

Abrupt withdrawal may cause psychosis, delirium, confusion, seizures, insomnia and agitation


Anticonvulsants Concerns/Benefits

Discontinuation symptoms and abuse have been reported



Symptoms related to social or performance (as opposed to broad in GAD) situations in which you expect scrutiny or evaluations by others

Affects 6% of adults


SAD Generalized vs non-generalized

Generalize (70% of cases), pervasive social fears and avoidance, early onset, familial, high comorbidity, more impairment, low remission, continual treatment (non-generalized is opposite)


SAD Treatment

Medication equally as effective as CBT (high effectiveness over year when used together)

CBT produces more significant results with lower rates of relapse; meds preferred if paralyzing symptoms or comorbid severe depression


SAD Treatment Plan

1st Line: SSRI
2nd Line: Different SSRI or SNRI (venlafaxine, mirtazapine); add benzo short term, augment with buspirone or beta blocker (for performance anxiety)

3rd Line (SGA - quetiapine, risperidone; MAIO - phenelzine; anticonvulsant/mood stabilizer - pregabalin, gabapentin)


Other treatment options for SAD

Combining meds (buspiron w/ SSRI or SNRI; Benzo with SSRI or SNRI; Med with CBT better than two meds)

Gabapentin is only modestly effective

Beta blockers ONLY for performance anxiety

Antipsychotics (quetiapine, risperidone) for cognitive impairment, weight gain and metabolic issues


PTSD Diagnostic criteria

History of exposure to traumatic event with attributes from each cluster:

Exposure (direct, indirect)
Intrusion (nightmares, flashbacks)
Avoidance of situations
Cognition and mood (recall problems, memory deficit)
Arousal and reactivity (irritable, aggressive, sleep disturbance)

Symptoms must last longer than 1 month, can't be attributable to substance or co-occurring medical conditions


PTSD Common Reactions/Behaviors

Fear, helplessness, anxiety

Reliving trigger events in form of thoughts, flashbacks or dreams



Hyperarousal and exaggerated startle resposne

Occurs on a continuum with some living their entire lives in a subthreshold PTSD state


Common PTSD Comorbidities

Substance abuse, traumatic brain injury, suicide, pain, major depression, PTSD


PTSD Treatment

Psychotherapy w/ or w/o medication (exposure therapy, CBT, stress inoculation, eye movement desensitization and reprocessing)

Alternative medicine therapy (CBT with pool, massage therapy, meditation, yoga, art therapy, marital/family therapy and acupuncture) -->more effective than lifelong disability


PTSD Medication

First Line (SSRI or SNRI or TCA)

Mood stabilizer (Depakote, Tegretol, Gabapentin)

Antipsychotic (Olanzapine, Risperidone, Quetiapine)

Nightmares (Clonidine, Prazosin)

Sleep (Trazodone, doxepine, nefazodone, mirtazapine)


Special PTSD Medication Considerations

Avoid benzos due to lack of effect on PTSD symptoms and abuse potential

Gabapentin, divalproex, augmented SSRI with atypical antipsychotic all useful in treatment-resistant cases

Avoid opiates/abusable medications


Anticonvulsants for PTSD

Valproate, Carbamazepine, Lithium (good evidence)

Gabapentine, Pregabalin (modest improvement)

Tiagabine (not proven)

Lamotrigine and Topiramate (not proven)


Atypical Antipsychotics for PTSD

Risperidone and Olanzapine (inherent anti-anxiety and antidepressant effects w/ 5HT2 and 5HT1A activity; high limbic activity; some effectiveness for intrusive thoughts and flashbacks; SE include weight gain, akathisia and sedation leading to high drop outs)

Quetiapine (possibly effective in treatment resistant PTSD; most useful if psychosis)


PTSD nightmare medications

Clonidine and Prazosin

Alpha-adrenergic activity associated with fear and startle response

Clonidine is centrally acting alpha 2 agonist resulting in reduced sympathetic outflow from CNS; reduces severity and duration of nightmares and improves quality of sleep

Prazosin acts peripherally and centrally as an alpha-1-adrenergic blocker; low doses (1mg) helpful within 7 days



Obsessive compulsive personality disorder characterized by (must have 4):

Excessive need for perfect, preoccupation with details, excessive devotion to work, rigidity of morals or values, inability to get rid of items that no longer have value, miserly or stingy, reluctance to work with others


OCP and OCPD Treatment


No medication unless physical or mental illness accompanies



Obsessive compulsive personality (strong values of order, organization, cautious, obeying rules)



Obsessive Compulsive Disorder

Anxiety disorder rather than a personality disorder at which you experience recurrent obsessions and compulsions


OCD Diagnostic Criteria

Must have obsessions and compulsions that significantly impact daily life

Patient usually realizes these are excessive compulsions; obsessions must be intrusive and persistent and include images that cause distress; compulsions must include excessive and repetitive or ritualistic behavior


Common OCD Obsessions

Germs or dirt, intruders, preoccupation with violent acts, unwanted sexual images and acts, unwanted religion thoughts, neatness or symmetry, continual thinking of certain words/sounds/images/numbers


OCD Compulsions

Behaviors that patient feels they must carry out over and over

Behaviors which provide order and symmetry

Behaviors aimed at getting rid of anxiety or to stop a feared situation

Have unrealistic solutions



Obsessions and compulsions known to be problematic and non-beneficial (no obsessions or compulsions)

Use tasks to reduce anxiety caused by obsessive thoughts (justify tasks as being beneficial)

Medication used for Tx (no meds for Tx)


Borderline Personality Disorder

Often caused by childhood sexual trauma

Verbal abuse by mothers increases likelihood


Antisocial Personality Disorder


Lack of fathers affection or lack of boundaries in early childhood increase risk


Anxious Personality

High reactivity - sensitive to light, noise, texture or other stimuli

Likely to develop anxious personalities


OCD Non-Pharm Treatment

Psychotherapy (CBT; ERP - exposure and response prevention)



OCD Pharm Treatment


Step 1: Fluvoxamine or Clomipramine, or other SSRI/SNRI

Step 2: If no partial response, choose different SSRI or TCA

Step 3: SSRI/TCA + Mirtazapine or atypical antipsychotic

Step 4: SSRI + Clomipramine OR SSRI/TCA + Buspirone OR SSRI?TCA + Pindolol


OCD Treatment for Resistant Cases

70% respond to CBT with or without medication

ECT not effective - consider transcranial magnetic stimulation or deep brain stimulation

Riluzole used to lower high brain glutamate levels (Memantine also does this)

N-acetylcycsteine may be used as antioxidant


Define Panic Disorder

Spontaneous and unexpected occurence of panic attacks (4 or more in a 4 week period OR 1 followed by at least 1 month of fear of another attack)

Intense fear with abrupt onset of 4/13 symptoms with peak less than 10 minutes from onset


Panic Disorder Diagnostic Symptoms

Palpitations, pounding heart or increased HR


Trembling or shaking

Sense of SOB or smothering

Feeling of choking

Chest pain or discomfort

Nausea/abdominal distress

Feeling dizzy, unsteady, lightheaded or faint

Derealization or depersonalization

Fear of losing control or going crazy

Fear of dying

Numbness or tingling

Chills or hot flashes


Panic Triggers

Injury, illness, conflict, use of cannabis, use of stimulants, SSRI discontinuation


Describe panic attack

Patients have urge to flee or escape and have sense of impending doom

After attack they worry about next attack or going crazy, avoid situations or locations and are more passive/withdrawn


Panic attack comorbidities

Alcohol use, increased suicidality

80% have some other psychiatric disorder and 50-60% have depression

Association between panic disorder and psychiatric disorders in first-degree relatives

Medical comorbidities include: IBS, migraines, COPD, asthma, mitral valve prolapse, cardiomyopathy, restless leg syndrome, epilepsy and fatigue


Neurotransmitter targeted in panic disorder

Serotonin (5HT2 receptor antagonist increasing serotonergic activity)

Alpha 2 adrenergic antagonism (increases synaptic NE and 5HT)


Panic Disorder Treatment

CBT is best choice

SSRIs and SNRIs | TCAs | MAIOs | Benzos


Which antidepressant has cardiac concerns

Citalopram in doses greater than 40mg/day

20 is max dose

Potential interaction with cimetidine (decreasing metabolism)

TCAs also have risk of arrhythmias


Insomnia Etiology

More females than males

Young adults more likely to have trouble initiating sleep, older adults staying asleep

Alcohol, stimulants, steroids and diuretics

Stress or poor sleep hygiene also factors


Prevalence of Insomnia

50% of population (80% of elderly)

35% have occasional sleep disturbance with self-recovery occurring most-often

Chronic insomnia in 15% and leads to daytime impairment; later in life will increase risk for depression and anxiety; requires treatment


Insomnia diagnostic criteria

Problems getting to sleep between 3-7 nights a week and taking more than 30 minutes to get to sleep those nights (present for 3 months)

Waking 3 or more times per night or waking up 30 minutes or more early

Feeling unrefreshed in the AM between 3-7 days a week with at least 7 hours of sleep

Can't be due to another medical disorder or substance abuse


Conditions associated with insomnia

Mood or anxiety disorders, delirium, dementia, eating disorders, somatoform disorders, personality disorders

Substance abuse or withdrawal

Sleep disorders (apnea, restless leg, circadian rhythm)

Jet-lag, shit work

Angina, CV problems, Parkinson's, GERD, menopause (everything)


Substances and medications associated with insomnia

Alcohol, amphetamine/stimulants, antipsychotics, anticonulsants, appetite suppressants, b-agonists, b-blockers, antidepressants, caffeine, cocaine, corticosteroids, decongestants, diuretics, hypnotics, interferon, LDOPA, modafanil, nicotine, phenytoin, thyroid


Neurotransmitters promoting sleep

GABA, Melatonin (released when dark), Adenosine (may inhibit wake promoting neurons)


Neurotransmitters promoting wakefulness

NE, ACh, Histamine, 5HT, DA, Orexin


Insomnia treatment guidelines

First line (CBT, sleep hygiene, relaxation)

Second (short-trial antihistamine, Benzos or Z-drugs, sedating antidepressants (trazodone or doxepine; mirtazapine, paroxetine or venlafaxine if depressed))

Third (Ramelteon, sedating antipsychotic - low dose quetiapine or olanzapine; other sedating agents such as gabapentin or tiagabine)


Herbal insomnia products

Valerian, cham


OTC Melatonin

Minimal benefit in sleep onset

Recommended dose dropped from 6 to 0.5-2 mg


Prescription Medications for Insomnia

Melatonin receptor agonists (Ramelteon; Tasimelteon - spendy and used for non-24 hour sleep-wake disorder in the blind)

Antihistamines (hydroxyzie)

Sedating antidepressants (trazodone, doxepin, mirtazapine)

Buspirone (5HT1A agonist)


Sedative Hypnotics based on half-life

Short acting (Phenobarbital injection and secobarbital)

Intermediate (Amobarbital, Butabarbital)

Long acting (Mephobarbital, phenobarbital)


Sedative Hypnotics Barbiturates

Addictive so use short term (except phenobarbital for seizures)

Lose effectiveness after 2 weeks and can cause seizure if stopped abruptly in seizure patients

Can cause depression, delirium, emotional disturbances, excitement/agitation, irritability, hyperactivity and stupor

Can be lethal with alcohol

Sometimes used pre-anesthetic as sedative (secobarbital and butalbital)


Chloral Hydrate

GABA-A agonist

500 mg - 1 g = hypnotic
250-500 mg = sedative

Onset usually 30 minutes; half-life 7-10 hours

Used in resistant insomnia, pre-operative sedation or for post-operative pain as adjunct with opioids


Benzodiazepines for insomnia

Addictive (use 5-10 days only)

GABA agonists

Avoid in elderly (65 up) or younger if comorbid cognitive conditions

Short acting, avoid in elderly (alprazolam, triazolam)

Intermediate (temazepam, lorazepam, oxazepam)

Long (diazepam, flurazepam, clonazepam)


Z-drugs for Insomnia

Non-benzo sedative hypnotics

Addictive (use 10-14 days)

Zolpidem (good for onset and maintenance, intermediate acting, need at least 8 hours, no clinical difference between IR and CR formulation, Edular SL only needs 4 hours and can be used for up to 35 days)

Eszopiclone (intermediate for onset and maintenance, need at least 8 hours, metallic after-taste)

Zaleplon (quick onset for sleep onset only, need at least 4 hours, administer immediately before bed, loses effectiveness after 30 days, may result in rebound insomnia)


Insomnia - Sedating Antipsychotics

Low dose Quetiapine (25-150 gm) works at H1 over D2 (not recommended for sleep aid due to akathisia, weight gain, increased triglycerides, abuse, and hepatotoxiciy)

Doxepin (used for maintenance, avoid in elderly, take on empty stomach, ACh side effects)

Mirtazapine (Low ACh, antihistamine at low dose; SEs include movement in sleep, increased appetite)

Trazodone (low ACh; SEs include priapism, hypotension and cardiac arrhythmias)



Orexin receptor antagonist blocks orexin A and B suppressing wake drive

Promotes faster sleep onset and less waking

5-20mg qHS (10 dollars each)

Can impair daytime wakefulness and cognition, may worsen depression and become addictive; inhibits CYP3A


General insomnia medication guidelines

all short term only (3-10 days)

Can cause cognitive impairment (hangover, auto accidents)

Need to be taken at proper time for effectiveness


Zolpidem FDA warnings

Half-life longer in women


FDA approved antidepressant for sleep

Doxepine (strong H1 blocker)

Anticholinergic, memory impairment, substantial next day sedation (SEs)