Term
| Most common reason for inadaquate response? |
|
Definition
| Inadequate “standard” treatment |
|
|
Term
| Other reasons ofr inadequate response |
|
Definition
Permanent neurologic impairment
Un-addressed psychological issues
Toxic living environment |
|
|
Term
| What to do with inadequate response |
|
Definition
| Optimizing, Augmenting, Switch |
|
|
Term
|
Definition
| Improve adherence (psychotherapy), Check DDI's, increase dose or just give it enought time. |
|
|
Term
|
Definition
| Add another antidepressant from a different class (commonly NDRI or 5-HT1A partial agonist to SSRI). |
|
|
Term
| How psychotherapy supports psychopharmocology: |
|
Definition
Increase or prolong therapeutic effects
Decrease probability of relapse or recurrence |
|
|
Term
| If no remission after third trial: |
|
Definition
| Try Remeron + Effexor = “California rocket fuel” or MAOI |
|
|
Term
| Better to use more than one to: |
|
Definition
| get full remission if pt suffers from residual sxs, with evidence that full remission decreases relapse or recurrence |
|
|
Term
| Switching to another antidepressant (AD) |
|
Definition
No more than 1-2 times to ADs of same class
Usually better to go to a different class if one has rationally considered which class may be optimal for this particular pt |
|
|
Term
| bipolar in children may manifest as: |
|
Definition
Severe irritability, “affective storms” w/ severe, persistent anger & violent outbursts
Chronic sx’s more than discrete episodes
Euphoria rarely
Comorbid w/ ADHD |
|
|
Term
| bipolar in adolescents may manifest as: |
|
Definition
| May show “mixed mania” sx’s w/ high suicidality, poor response to tx, and early hx of cognitive sx’s similar to ADHD. (Similar to children) |
|
|
Term
|
Definition
Sitimulating brain with glutimate. Hypothesised to occur in:
Bipolar mania
Bipolar depression
Schizophrenia
Chronic pain
“Unipolar” depression
Anxiety
Insomnia
Thus with each episode, the likelyhood of another episode increases. |
|
|
Term
| Pathological learning from "Kindling" |
|
Definition
Neuroplastic strengthening of abnormal synapses
Recruitment of other neurons
Eliminating compensatory mechanisms |
|
|
Term
| Main idea for treating Bipolar |
|
Definition
Treat these disorders/symptoms aggressively and appropriately w/ a biopsychosocial model to:
Relieve suffering
Increase well-being and productivity
Prevent further episodes |
|
|
Term
| FDA-approved drugs for acute mania/mixed episodes |
|
Definition
lithium (Lithobid, Eskalith)
divalproex sodium (Depakote, Depakote ER), valproic acid (Stavzor)
carbamazepine (Equetro)
chlorpromazine (Thorazine), and Atypical (SGAs) antipsychotics
(minus a few non-FDA approved SGAs) |
|
|
Term
| FDA-approved drugs for bipolar maintenance |
|
Definition
lithium (if Hx of mania)
lamotrigine (Lamictal)
quetiapine (Seroquel)
aripiprazole (Abilify)
olanzapine (Zyprexa)
valproate commonly used
risperidone (Risperdal), ziprasidone (Geodon) used. |
|
|
Term
| Used more for maintenance after Mania |
|
Definition
|
|
Term
| Used more for maintenace following depressive episode |
|
Definition
|
|
Term
|
Definition
| fine tremor, polyuria, increased thirst, diarrhea, vomiting; cognitive (impaired attention/concentration, memory, drowsiness), wt gain, muscle weakness, arrhythmias, anorexia, nausea, fatigue, blurred vision, dry mouth, dermatological (acne, rashes, psoriasis), hypothyrodism, enlarged thyroid |
|
|
Term
| Signs of Lithium toxicity (KNOW) |
|
Definition
Gross tremor, muscle fasciculations, abnormal movements, ataxia/ incoordination, muscle weakness, slurred speech, goiter, increased fatigue, confusion, psychosis, bradycardia, syncope (fainting)
Muscle rigidity, stupor, seizures, coma, renal failure, severe ventricular arrhythmias, death |
|
|
Term
| Treatement of Lithium toxicity |
|
Definition
| give saline; or hemodialysis, gastric lavage, diuretic therapy, anticonvulsant med if necessary and D/C |
|
|
Term
| Causes of elevated lithium levels |
|
Definition
Decreased salt intake (restricted salt diet or salt substitute (KCl), increased loss (sweating)
Dehydration (exercise, diarrhea, infection) |
|
|
Term
| Critical to educate pt about: |
|
Definition
Adherence to med regimen & labs (very narrow TI)
Causes of elevated lithium levels
Sxs of lithium toxicity
Risks during pregnancy (see lecture on Special Populations) |
|
|
Term
| valproate (valproic acid, divalproex, Depakote, Depakote ER, Depakene, Depacon, Stavzor) |
|
Definition
FDA-approved for acute mania & mixed episodes
FDA-approved for seizures, migraine prophylaxis
Also used for maintenance of bipolar
Blocks voltage-sensitive Na+ channels (VSSCs)
Increases GABA neurotransmission
Alters signal transduction - affecting enzymes, decreasing oxidative stress and increasing neuroprotective factors |
|
|
Term
|
Definition
headache, nausea/vomiting, asthenia, sedation (problematic), dyspepsia, dizziness, diarrhea, abdominal pain, tremor, reduced appetite, wt gain (common), constipation, alopecia (unusual), emotional lability, nervousness, depression, cognitive dysfunction, ataxia
Can cause hepatotoxicity, pancreatitis |
|
|
Term
|
Definition
| wt gain, dizziness, sedation, unsteadiness, incoordination, nausea/vomiting, blurred vision, rash, confusion, ataxia, blurred vision, headache, diarrhea, benign leukopenia |
|
|
Term
| carbamazepine (Tegretol®, Carbatrol, Equetro®) |
|
Definition
FDA-approved for acute mania/mixed mania
FDA-approved for seizures, trigeminal neuralgia
Also used for maintenance of bipolar
Blocks VSSC’s when channel is open
Inhibits release of glutamate |
|
|
Term
| Carbamazepine Rare but serious ses |
|
Definition
Aplastic anemia
Agranulocytosis
Sx’s include fever, sore throat, mouth sores, infections, unusual bleeding/bruising.
Fulminates very rapidly; can be fatal within 3 days
“Syndrome of inappropriate antidiuretic
hormone” (SIADH) w/ hyponatremia (low sodium)
Potentially fatal rashes, confluent, tender, purpuric,
starting in face & fulminating to whole body rapidly
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Contraindicated in Asians w/ HLA-B*1502 gene
Becoming rare if very slow titration and watched carefully for specific characteristics of these serious rashes |
|
|
Term
|
Definition
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
-confluent, tender, purpuric, starting in face & fulminating to whole body rapidly |
|
|
Term
| What drug is Contraindicated in Asians w/ HLA-B*1502 gene |
|
Definition
|
|
Term
| Why is Carbamazepine usually reserved for tx-resistant bipolar or psychosis due to: |
|
Definition
Ses
Need for regular blood tests
Multiple drug interactions
Induces all major P450 enzymes except CYP-2D6; CYP-3A4 potently
Self induction via CYP-3A4 |
|
|
Term
| oxcarbazepine (Trileptal) |
|
Definition
FDA-approved for seizures
Not proven effective for bipolar but used “off-label”
Similar actions as carbamazepine but safer
Less sedation, bone marrow suppression; fewer serious skin rashes, DDI’s (only mild induction of CYP-3A4) |
|
|
Term
|
Definition
FDA-approved for bipolar I maintenance
FDA-approved for seizures; used for pain
Used “off-label” for bipolar depression
Best for Bipolar II because of dominance of depression
Largely replaced ADs for bipolar depression
Blocks VSSC’s, inhibits release of glutamate
Alters signal transduction - affecting enzymes, decreasing oxidative stress and increasing neuroprotective factors |
|
|
Term
lamotrigine (Lamictal®)
SEs |
|
Definition
nausea/vomiting, dizziness/vertigo, blurred or double vision, sedation (daytime sedation usually avoided if taken hs), ataxia, rash, headache, rhinitus, diarrhea, fever, insomnia, tremor, abdominal pain, cough, constipation, dysmenorrhea, incoordination, anxiety, dyspepsia, irritability, anorexia, photosensitivity, fatigue
Rare but serious ses
SJS, TEN
Avoid in pts < 16 yrs of age. |
|
|
Term
|
Definition
FDA-approved for seizures, migraine prophylaxis
Apparently not effective as mood stabilizer but is being used more than it should be
Used as adjunctive to decrease wt. gain, insomnia, anxiety in pts using psychtropics
May be helpful for comorbid bipolar & binge eating, bulimia
Blocks sodium & calcium channels, potentiates GABA activity, inhibits glutamate activity |
|
|
Term
|
Definition
| metabolic acidosis (may be serious), paresthesia, sedation, dizziness, fatigue, nervousness, anorexia, cognitive dysfunction, UTI, ataxia, blurred or double vision, depression, nystagmus, nausea, fever, tremor, rhinitus/sinusitis, dyspepsia, asthenia, anxiety, abdominal pain, taste changes, psychomotor retardation, language problems, wt loss, kidney stones (may be serious) |
|
|
Term
| General ADR’s of lithium/anticonvulsants (vary w/ drug) |
|
Definition
Sedation
Decreased attention/cognition, confusion
Ataxia
Diplopia
Tremor
GI distress
Wt gain |
|
|
Term
| Mood stabilizer Rare but serious ADRs: |
|
Definition
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Birth defects (e.g., Ebstein’s anomaly, neural tube defects)
Agranulocytosis
Aplastic anemia
Pancreatitis |
|
|
Term
| gabapentin (Neurontin®) and pregabalin (Lyrica) |
|
Definition
| not efficacious for bipolar but effective for neuropathic pain, anxiety, insomnia |
|
|
Term
| Current standard for treating bipolar |
|
Definition
| Combinations of mood stabilizers |
|
|
Term
| Better to use more than one at lower doses |
|
Definition
| to get full remission w/o intolerable SEs than to use one at higher dose w/ SEs and not in remission. |
|
|
Term
| Best evidence-based combo’s include |
|
Definition
| lithium or valproate w/ an atypical antipsychotic. |
|
|
Term
| How long is Bipolar treated |
|
Definition
|
|
Term
| How is Psychotherapy valuable: |
|
Definition
Educating pt & significant others concerning:
Adherence to med regimen & labs
Extremely harmful effects of drugs of abuse on functioning and on exacerbating sxs of bipolar
Discriminating normal from abnormal mood swings
Reporting pregnancy or intention of becoming pregnant to prescriber.
Early signs of an episode, especially decreased need for sleep, and importance of adequate sleep to prevent mania (give CBT if necessary)
Sleep hygiene – regular hrs, avoiding sleep
deprivation, avoiding drugs that interfere w/ sleep
(stimulants, alcohol, BZDs, decongestants)
Avoid/limit shift work, traveling across time zones.
Keep light stable throughout year.
Dealing w/ anger, denial & ambivalence; partial tx response; SEs, loss of “benefits” of hyponamia/mania; lifelong treatment; psychosocial consequences of episodes; fear of recurring episodes & subsequent inhibition of normal psychosocial interaction
Concerns about genetics
Relationships w/ others
Support groups |
|
|
Term
|
Definition
not be given for bipolar depression unless combined w/ a mood stabilizer to avoid:
“Switching” to mania
Increasing instability
Mistakenly misdiagnosing bipolar depression as unipolar depression occurs frequently. |
|
|
Term
| Gamma-aminobutyric acid (GABA) |
|
Definition
Most prevalent inhibitory neurotransmitter in CNS,
particularly forebrain, cerebellum
Synthesized from glutamate
Action terminated by:
Reuptake via GABA transporter (GAT)
GABA transaminase (GABA-T) inside presynaptic neuron |
|
|
Term
|
Definition
lorazepam (Ativan®), alprazolam (Xanax®),
diazepam (Valium®), chlordiazepoxide (Librium®),
clonazepam (Klonopin®)
Bind to GABAA receptors GABA activity
inhibition |
|
|
Term
| Alcohol & barbiturates are |
|
Definition
| GABAA PAMs w/ their own binding sites and slightly different ways of affecting the receptor. |
|
|
Term
| Alcohol, barbiturates, benzodiazepines (BZDs) & other drugs that bind to GABAA receptor should |
|
Definition
never be taken together because of additive/synergistic effects.
Can be fatal |
|
|
Term
Therapeutic effects of BZDs:
(KNOW) |
|
Definition
Decrease anxiety temporarily (breakthrough panic, while initiating or “toping up” w/ more effective drug, preoperative anxiolysis)
Induce anterograde amnesia for medical procedures
midazolam (Versed)
Induce sedation for agitation, sleep for insomnia
Relax muscles for muscles spasms
Raise seizure threshold (e.g., alcohol withdrawal) |
|
|
Term
| Side effects (SEs) of benzodiazepines |
|
Definition
Paradoxical agitation (anxiety, aggression, behavioral disinhibition)
Sedation, drowsiness, lethargy, depression (especially in elderly)
Confusion, cognitive impairments, impaired learning, amnesia (even dementia)
Ataxia, resulting in falls in elderly
Slurred speech
Dependence
Interactions with alcohol/other sedatives
Possible fetal abnormalities |
|
|
Term
|
Definition
| w/ cognitive-behavioral therapy |
|
|
Term
| BZDs should only be used for |
|
Definition
| few weeks for temporary relief until other therapy techniques can take effect. |
|
|
Term
|
Definition
| 1st-line Rx for anxiety disorders due to efficacy and to SEs of sedative-hypnotics. |
|
|
Term
| 5-HT inhibits release of DA in basal ganglia |
|
Definition
| Controls unwanted movements, obsessions, compulsions caused by excessive DA |
|
|
Term
|
Definition
| inhibits behaviors, often via action on intermediates. |
|
|
Term
|
Definition
|
|
Term
|
Definition
May increase activation of prefrontal cortex leading to increased inhibition of amygdala via GABA interneuron
5HT1A receptor may reduce excessive Glu release by neurons in prefrontal cortex & amygdala.
SSRI’s are 1st-line Rx for anxiety disorders.
But 5HT2 receptors may cause anxiety until they downregulate/desensitize. |
|
|
Term
| mirtazapine (Remeron®)used for: |
|
Definition
|
|
Term
buspirone (BuSpar®)
Partial agonist at 5-HT1A receptor |
|
Definition
Usually used as augmenting drug for anxiety
Must be used for 2-4 wks for effect
Not effective in pts who previously used BZDs
Not effective for panic attacks
Does not produce some of SEs of BZDs (sedation, disinhibition, cognitive impairment, psychomotor impairment, euphoria, dependency, withdrawal symptoms, synergy w/ alcohol/CNS depressants)
Lacks sexual SEs of SSRIs; may decrease sexual dysfunction in pts w/ GAD. |
|
|
Term
|
Definition
Bind to VSCC and closes channel
Block release of Glu when neurotransmission is excessive
Decrease anxiety, especially in social anxiety disorder and PD |
|
|
Term
|
Definition
lead to anxiety
treated with ß1 or a1 receptors antagonists.
Example:
propranolol (Inderal)
prazosin (Minipress) |
|
|
Term
|
Definition
| usually not used for anxiety, but some pts do respond, presumably due to ability to desensitize/down regulate these receptors over time. |
|
|
Term
|
Definition
Memory/learning, reasoning, reaction time, executive function
Memory is 40% poorer with one night of < 7-8 hrs
People are not aware of deficits and think they have “adapted” |
|
|
Term
| Many children and adolescents are sleep-deprived |
|
Definition
getting < 7 hrs
Should get 9-10 hrs (brain reorganization is taking place) |
|
|
Term
| Most adults are sleep-deprived secondary mainly to lifestyle |
|
Definition
Getting only 6.7 hrs
Should get 7.5-8 hrs |
|
|
Term
|
Definition
| < 7-8 hrs will impair mental acuity |
|
|
Term
| sleep-deprivation effects |
|
Definition
| accumulative; cannot be compensated for |
|
|
Term
| Sleep Deprivation Consequences |
|
Definition
Irritability and emotional lability
Amygdala becomes hyperactive; prefrontal hypoactive (seen in subjects deprived for 35 hrs.)
Depression
Monoamines (5-HT, NE, DA) synthesized during deep-stage sleep
Serotonin levels lower in night-shift workers
Critical for mood stability, especially countering depression
Bipolar spectrum disorder
Sleep deprivation is major precipitant and hallmark of manic episode.
Night-shift disruption in circadian rhythms may be factor in bipolar.
Postpartum depression
Highest risk at 4-6 wks postpartum
No prior depression -- 8-10%
Hx of depression -- 25%
Hx of postpartum depression -- 50%
Sleep deprivation is a major factor.
Take naps if necessary.
Metabolic and hormonal abnormalities
After 6 nights of only 4 hrs of sleep or w/o deep-stage sleep:
Hyperglycemia, pre-diabetic (Type II), increased appetite, obesity
Abnormal insulin levels in sleep-deprived & night-shift workers
May increase risk of Alzheimer’s
Insulin may reduce inflammation in brain & may promote learning/memory, but insulin resistance interferes with this. |
|
|
Term
|
Definition
increased risk for chronic illness:
40-50% for heart disease
50% for obesity (same for sleep-deprived)
Miscarriage, pre-term birth, low birth-weight |
|
|
Term
| Sleep deprivation: decreased melatonin production |
|
Definition
Breast (50%) and colon (35%) cancers
This hormone inhibits tumor growth possibly through effect on genes |
|
|
Term
|
Definition
Difficulty initiating or maintaining sleep or having nonrestorative sleep for at least one month
Causes clinically significant distress or impairment in functioning
No clear underlying cause and not due to another sleep disorder, psychiatric disorder, medical condition, medications, or other substances |
|
|
Term
|
Definition
| Underlying medical or psychiatric condition causing or significantly contributing to insomnia (e.g., psychiatric disorder, pain, medications, obstructive sleep apnea) |
|
|
Term
|
Definition
most common sleep disorder.
Over 10% of population experience persistent insomnia.
Over 30% of primary care patients experience persistent insomnia.
Societal burdens include functional impairments, accidents, QOL (quality of life), risks of depression and higher healthcare costs. |
|
|
Term
| majority of professional treatments |
|
Definition
|
|
Term
| OTCs (over the counter drugs) and hypnotics (KNOW) |
|
Definition
| do not address the most important factors affecting chronic insomnia- behavioral and psychological factors. |
|
|
Term
|
Definition
slow-wave, delta sleep
Deepest, restorative level, 10-20% of sleep
Usually occurs in the first 1/3 to 1/2 of night and increases in duration in response to sleep deprivation
NE, 5-HT, DA synthesized during delta sleep
Decreases with age
Age 20: 100 minutes
Age 50: 20 minutes |
|
|
Term
| factors interfere with slow-wave sleep |
|
Definition
Apnea
Periodic leg movement disorder
Chronic pain
Corticotropic-releasing hormone (CRH), cortisol (stress) prevent slow-wave sleep
Lack of exercise |
|
|
Term
| Drugs that interfere with NREM sleep |
|
Definition
Most sedatives/hypnotics except zolpidem (Ambien), zaleplon (Sonata), eszopliclone (Lunesta), ramelteon (Rozerem), melatonin supplement
All benzodiazepines including ones used for sleep
lorazepam (Ativan), flurazepam (Dalmane), triazolam (Halcion), temazepam (Restoril), estalozam (ProSom)
Barbiturates
alcohol
Antihistamines
diphenhydramine
Benadryl, Nytol, Simply Sleep, Sominex
doxylamine [Unisom-2]
hydroxyzine [Vistaril, Atarax])
caffeine
Even if don’t drink after noon, enough stays in system to interfere
At risk, if 250 mg/day (2 cups)
Very likely to have problem if > 550 mg/day
Half-life goes from 3 hrs to 31 hrs if taking 1A2 inhibitors (fluvoxamine [Luvox],ciprofloxacin [“cipro”]) |
|
|
Term
| Drugs that interfere with sleep |
|
Definition
alcohol
Short half-life leads to rebound insomnia
Interferes with REM & NREM
Agents with stimulating effects
Amphetamines
lisdexamfetamine (Vivanse)
d-amphetamine (Dexedrine)
Mixed amphetamine salts (e.g., Adderall XR)
d,l-methylphenidate (e.g., [Ritalin LA], [Concerta XR], [Metadate XR])
atomoxetine (Strattera)
Agents with stimulating effects (cont’d)
modafinil (Provigil)
Appetite suppressants
caffeine
cocaine
nicotine
theophylline
Decongestants (phenylephrine)
Dopamine agonists (L-dopa, bromocriptine [Parlodel])
Antidepressants
bupropion (Wellbutrin), SSRI’s (except luvoxamine [Luvox]), SNRI’s, MAOI’s
But most ADD’s are potent REM suppressors NREM & monoamine synthesis
Hypnotics (chronic use) due to rebound when D/C
Corticosteroids (e.g., prednisone) can provoke insomnia, depression, agitation, mania, anxiety
Diuretics
Thyroid medications
guarana, ginseng
BZDs are commonly used but have problems and are not 1st-line Rx.
They bind to GABAA receptor in such a way as to change its shape so that tolerance, dependence and withdrawal/rebound occur.
Their half-lives are either too short or too long.
They are more likely to be abused.
They interfere w/ slow-wave sleep. |
|
|
Term
| Hypnotics that do not interfere w/ sleep |
|
Definition
The “z” drugs
zolpidem (Ambien, Ambien CR, Edluar, Zolpimist), zaleplon (Sonata), eszopliclone (Lunesta) |
|
|
Term
| Why some hypnotics do not interfere w/ sleep |
|
Definition
| Enhance action of GABAA receptor but bind in such a way as to not interfere w/ deep sleep or cause tolerance, dependence or withdrawal/rebound. |
|
|
Term
| commonly used drug for sleep, but have problems and are not 1st-line Rx |
|
Definition
|
|
Term
|
Definition
Headache, drowsiness, dizziness, lethargy, “drugged feeling”
Complex sleep-related behaviors (e.g., sleep walking, sleep driving)
Should not to be taken with alcohol.
Caution is needed with other CNS depressant drugs. |
|
|
Term
|
Definition
Agonist at M1/M2 (melatonin) receptors
Melatonin from pineal reinforces circadian & seasonal rhythms
M2 may reset normal circadian rhythms in pts w/ shift-work disorder or jet lag |
|
|
Term
| melatonin supplement (synthetic melatonin) |
|
Definition
Best for initial insomnia
Evening for pts w/ phase-delay
Morning for pts w/ phase-advance
Inconsistent doses in OTC supplements
SEs of dizziness, headache, transient depression |
|
|
Term
| trazodone and mirtazapine (Remeron) |
|
Definition
| Antagonize H1 receptor when used at low doses |
|
|
Term
| Best tx for sleep problems |
|
Definition
| cognitive and behavioral treatments, collectively called cognitive-behavioral therapy (CBT) are more efficacious than hypnotics - both in the short and long term |
|
|
Term
| CBT targets the following: |
|
Definition
Cognitive and psychological factors
Beliefs, expectations, appraisal, worry
Behaviorally based factors that perpetuate insomnia
Maladaptive sleep habits, irregular sleep schedule
Arousal reduction-
Relaxation, meditation, biofeedback
Didactic sleep hygiene education-
Targeting factors interfering and promoting sleep
Sleep restriction
Stimulus-control therapy
Reduce anxiety or conditioned arousal pts may feel when attempting to go to bed and give a set of instructions designed to re-associate bed/bedroom w/ sleep
Relaxation-based therapy
Cognitive therapy
Sleep hygiene education
CBT combined with medications |
|
|
Term
|
Definition
FDA-approved for reducing sleepiness in pts w/ narcolepsy, shift-work sleep disorder, or obstructive sleep apnea
Promotes wakefullness by inhibiting DA reuptake, leading to downstream increase of histamine from hypothalamus.
SEs include headache, anxiety, insomnia (treate wakefulness) |
|
|
