Anxiety and Sleep Disorders Therapeutics Flashcards
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
Meprobamate
5HT1a receptor agonist
Buspirone (GAD, SAD)
MAOI
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)
GAD
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
HAM-A
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
GADSS
Generalized anxiety disorder severity scale
Specific probing in domains of worry, impairment of social and work functioning
PSWQ
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
SAD
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
Disassociation
Avoidance
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
OCPD
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
Psychotherapy
No medication unless physical or mental illness accompanies
OCP
Obsessive compulsive personality (strong values of order, organization, cautious, obeying rules)
OCD
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
OCD (vs OCPD)
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
Environmental/parental
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)
Relaxation
OCD Pharm Treatment
Antidepressants
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
Sweating
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)
Belsomra
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)
