Psychology Flashcards
Major Depressive Disorder (MDD):
-Proposed etiology
-Medical conditions that can cause secondary depression
-Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5-TR): M SIG E CAPS
-What is Ham-D or HDRS?
Proposed etiology: combination of genetic, environmental, and biologic factors
-Decreased neurotransmitters: serotonin (5-HT), norepinephrine (NE), epinephrine (EPI), dopamine (DA), glutamate, and acetylcholine (Ach)
Medical conditions: stroke, PD, dementia, MS, hypothyroidism, vitamin D deficiency, metabolic conditions (hypercalcemia), malignancy, overactive bladder, infections
DSM-5-TR: at least 5 of the following in two week period which MUST also include depressed mood or diminished interest/pleasiure:
-M: Mood (depressed) Sleep (increased/decreased) Interest/pleasure (diminished)
-G: Guilt or feelings of worthlessness Energy (decreased) Concentration (decreased)
-Apetite (increased/decreased) Psychomotor agitation or retardation Suicidial ideation
HDRS: Hamiliton Depression Rating Scale: most widely used depression assessment for medical office that rates symptoms on numerical scale and total score is added to help assess need for medication adjustment
-Score <7: no depression
-Score 7-17: mild depression
-Score 18-24: moderate depression
-Score 25 or higher: severe depression
What are drugs that can cause or worsen depression?
ADHD medications: atomoxetine (Strattera)
Analgesics: indomethacin
Antiretrovirals: NNRTIs (efavirenza, rilpivirine)
CV meds: beta-blockers (more often non-selective especiallly propranolol)
Hormones: hormonal contraceptives, anabolic steroids
Others:
-Antidepressants: BBW
-Benzodiazepines
-Systemic steroids
-Interferons
-Varenicline
-Ethanol
Major Depressive Disorder (MDD):
1. What is important to rule out before TX and why?
- What are natural products that may be used for depression? What is their evidence/considerations?
- How long does it take a typical antidepressant to truly work?
-
Bipolar disorder - to avoid inducing mania or causing rapid cycling between mania and depression
-When depression and anxiety occur together, BZDs should NOT be used alone as they can mask or worsen depression and be problematic in substance misuse disorders - St. John’s Wort, SAMe (S-adenosyl-L-methionine), and 5-HTP (5-hydroxytryptophan), valerian
-Efficacy: less evidence
-St. John’s Wort:* weak recommendation to use in pts NOT pregnant or breastfeding and prefer herbal; broad-spectrum CYP450 enzyme inducer with many DDIs; also photosensitizing*
-St. John’s Wort, SAMe, and 5-HTP: may increase risk of serotonin syndrome
-SAMe: bleeding risk -
4-8 weeks
-Physical symptoms such as low energy improve within 1-2 weeks
-Psychological symptoms: month or longer
What is the BBW all antidepressants have? What are withdrawal symptoms of D/C antidepressants abruptly?
BBW: * Increase in suicidal thoughts or actions in some children, teenagers, or young adults within first few months of TX or when dose changed
-MedGuides are REQUIRED*
Withdrawal symptoms: anxiety, agitation, insomnia, dizziness, flu-like symptoms
-Usually occurs for a week
-Can be improved when re-taking antidepressant
-Taper drugs gradually over weeks (exception of fluoxetine because of long T1/2)
Depression in Pregnancy and Postpartum Depression
1. Are antidepressants recommended during pregnancy?
- What is first line TX?
- What are antidepressant recommendations during pregnancy?
- What are antidepresssant recommendations during postpartum depression?
- YES - benefit outweighs risk; untreated depression especially in 1st and 3rd trimestere can cause adverse outcomes (premature birth, low birth weight, postnatal complications)
-
Psychotherapy
-Side note: breastfeeding can help -
Outweigh risk versus benefit
-Pt has been on antidepressant: consider continuing same medication
-Pt not currently taking antidepressant: SSRIs (escitalopram, sertraline) first-line options (paroxetine: AVOID due to cardiac effects) –> SSRIs carry warning of persistant pulmonary HTN of newborn (PPHN)
-Can taper off medication if mild depression and pt has had no symptoms for 6 months
-Avoid doxepin -
SSRIs preferred
-Alternatives: IV brexanolone (Zulresso), oral zuranolone (Zurzuvae): CIV indicated for postpartum (can cause excessive sedation)
Selective Serotonin Reuptake Inhibitors (SSRIs):
-Drugs/Brands
-MOA
-ROA
-TX
-Structure
Drugs: citalopram (Celexa), escitalopram (Lexipro), fluoxetine (Prozac), paroxetine (Paxil, Paxil CR), sertraline (Zoloft), fluvoxamine
MOA: inhibit reuptake of 5-HT, weakly affect NE and DA
ROA: PO
-ALL: available in solution (except: fluvoxamine)
TX: depression, variety of anxiety disorders
-Fluvoxamine: ONLY for OCD
-Paroxetine (Brisdelle): can be used for severe vasomotor symptoms associated w/ menopause
-Fluoxetine: can be combined w/ olanzapine for TX-resistant depression
-Fluoxetine, Paxil CR, sertraline: also approved for premenstrual dsyphoric disorder (PMDD): can be continuous or intermittent dosing
Structure: escitalopram is the S-enantiomer of citalopram
Selective Serotonin Reuptake Inhibitors (SSRIs): Dosing
-Citalopram
-Escitalopram
-What time of day should SSRIs be taken?
Citalopram: 20-40mg PO QD
-Max dose: 40mg/day
-Max dose in eldery (>60 yo): 20mg/day
Escitalopram: 10mg PO QD
-Max dose: 20mg/day
-Max dos in elderly (>60 yo): 10mg/day
Timing:
-MOST activating: FLUOXETINE (take in AM)
-MOST sedation: PAROXETINE, fluvoxamine (take in PM)
-Others: take dose in AM; if causing sedation, take in PM
Selective Serotonin Reuptake Inhibitors (SSRIs):
-AVEs
-Warnings
-CIs
AVEs:
-SEXUAL SIDE EFFECTS: decreased libido, ejaculation difficulties, anorgasmia, ED
-KNOW: somnolence, insomnia, nausea, dry mouth, diaphoresis (dose-related), weakness, tremor, dizziness, HA
-Osteopenia/osteoporosis, restless leg syndrome
Warnings:
-QT PROLONGATION: especially with citalopram > escitalopram (max dosing for elderly, liver disease, or w/ poor CYP2C19 metabolizer or on 2C19 inhibitors) –> sertraline MOST preferred in cardiac risk
-Syndrome of Inappropriate Antidiuretic Hormone (SIADH)/HYPONATREMIA, FALL RISK (Beer’s Criteria) –> caution in hx of falls/fractures or use of CNS depressants
-BLEEDING (additive risk)
CIs:
-DO NOT USE WITH MAOIs, IV methylene blue, or pimozide (increases risk for pimozide toxicity)
-Fluoxetine, paroxetine: do not use w/ thioridazine
-Fluvoxamine: do not use w/ alosetron, thioridazine, or tizanidine
-Sertraline solution: do not use w/ disulfiram
-Brisdelle (paroxetine): PREGNANCY
SSRIs: DDIs
- MOAis - 5-HT syndrome OR hypertensive crisis
-Allow 2 week interval between MAOI and SSRI (EXCEPTION: fluoxetine: 5 weeks)
-do NOT initiate in pts receiving linezolid or IV methylene blue (5-HT syndrome as well) - QT prolongation: other QT prolonging drugs, especially w/ citalopram, escitalopram
- Bleeding risk: anticoagulants, antiplatelets, NSAIDs, select natural products (gingko, garlic, ginger, ginseng, glucosamine, fish oil), thrombolytics
- Fluoxetine, paroxetine, fluvoxamine: CYP2D6 inhibitors
-Tamoxifen: requires CONVERSION via 2D6 (decreased efficacy) –> venlafaxine preferred
-Some antipsychotics (aripiprazole, olanzapine) are 2D6 substrates and may need lower dose
-do NOT use w/ thioridazine, pimozidine, or cimetidine
-Cuation in drugs that cause orthostasis or CNS depression (fall risk)
Vilazodone and Vortioxetine:
-Brand
-MOA
-ROA
-Adminsitration considerations
-AVEs
-Warnings
-CIs
-DDIs
Brand: vilazodone (Viibryd, Viibryd Starter Pack), vortioxetine (Trintellix)
MOA: “SSRI Combined Mechanism”
-Vilazodone: SSRI + 5-HT1a partial agonist
-Vortioxetine: SSRI + 5-HT3 receptor antagonist + 5-HT1a partial agonist
ROA: PO
Administration considerations (Vilazodone): take with food
AVEs: less sexual side effects than SSRIs and SNRIs, N/V/D, insomnia, decreased libido
-Vortioxetine: constipation
Warnings: avoid in pts w/ seizure hx
CI: within 14 day use of MAOI; do NOT use w/ linezolid or IV methylene blue
DDI: vortioxetine - lower dose by 50% w/ 2D6 inhibitors (ex. bupropion, fluoxetine, paroxetine, or quinidine)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs):
-Drugs/Brands
-ROA
-TX
-Dosing for venlafaxine
Drugs: venlafaxine (Effexor XR), duloxetine (Cymbalta), desvenlafaxine (Pristiq), levomilnacipran (Fetzima)
ROA: PO
TX: depression, variety of anxiety disorders
-Venlafaxine: depression, GAD, panic disorder, social anxiety disorder
-Duloxetine: depression, peripheral neuropathy, fibromyalgia, GAD, chronic musculoskeletal pain
-Desvenlafaxine: approved for depression ONLY
Venlafaxine max dose: 375mg/day (IR formula)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs):
-AVEs
-Warnings
-CIs
AVEs:
-Side effects simliar to SSRIs (sexual SEs, somnolence/insomnia, nausea, dry mouth, weakness, tremor, dizziness, HA, osteopenia/osteoporosis, restless leg snydrome)
-SEs related to NE: increased HR, dilated pupils (can lead to narrow angle glaucoma), dry mouth, excessive sweating, constipation
-Can affect uretheral resistance: caution in pts prone ot obstructive urinary disorders
-Increased BP: greatest risk w/ venlafaxine >150mg/day
-Pristiq: can leave ghost tablet in stool
Warnings:
-SIADH/hyponatremia, fall risk (Beer Criteria)
-Bleeding risk
CIs:
-Use with MAOIs
-Do NOT initiate in pt receiving linezolid or IV methylene blue
-do NOT use levomilnacipran w/ CrCl <15mL/min or duloxetine w/ CrCl <30mL/mi
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): DDIs
- MAOIs: need washout period of 2 weeks
-Do NOT initaite w/ linezolid or IV methylene blue - Additive QT prolongation risk with venlafaxine
- Caution w/ medcations that can increase BP
- Duloxetine: moderate CYP2D6 inhibitor –> tamoxifen requires 2D6 for conversion
- Bleeding risk w/ anticoagulants, antiplatelets, NSAIDs, natural products (garlic, gingko, ginger, ginseng, glucosamine, fish oils), thrombolytics
Tricyclic Antidepressants (TCAs):
-Drugs/Brand
-MOA
-ROA
-What time to day to take?
-TX
-Structure
Drugs/Brands/Structure:
-Tertriary amines (slightly more affective, but more AVEs): amitriptyline (Elavil), doxepin (Silenor, Zonalon), clomipramine, imipramine, trimipramine
-Secondary amines (relatively selective for NE, but less effective): notriptyline (Pamelor), amoxapine, desipramine, maprotiline, protripytline
MOA: inhibit NE and 5-HT reuptake
-Also inhibits: ACh and histamine receptors
ROA: PO
-Amitriptyline: QHS or divided doses
TX: depression
-Silenor: insomnia
-Zonalon cream: pruritus
Tricyclic Antidepressants (TCAs):
-AVEs
-CIs
-DDIs
AVEs:
-Cardiotoxicity:
1. QT PROLONGATION with overdose (monitor for SI as overdose can quickly cause fatal arrhythmias) –> obtain ECG baseline if cardiac risk factors or >50 yo
2. Orthostasis
3. Tachycardia
-*Anticholinergic (Beer’s Criteria): *
1. Dry mouth, blurred vision, urinary retention, constipation –> taper off to avoid cholinergic rebound
2. Vivid dreams, weight gain (varies w/ agent), sedation, sweating, myoclonus (muscle twitching - symptom of drug toxicity)
3. Risk of falls - avoid if hx of falls/fractures or use w/ CNS depressants
CIs: do NOT use w/ MAOIs, linezolid, or IV methylene blue; MI; glaucoma and urinary retention (doxepin)
DDIs:
-MAOIs and hypertensive crisis: two-week washout period
-Additive QT prolongation risk
-Metabolized by CYP2D6
Bupropion:
-Brands, ROAs, and their associated indications
-Dosing
-MOA
-AVEs
-Warnings
-CIs
Brands:
-Wellbutrin SR or XL: depression
-Wellubtrin XL and Aplenzin: seasonal affective disorder (SAD)
-Buproprion SR (Zyban): smoking cessation
-With dextromethorphan (Auvelity): ER tablet for depression
-With naltrexone (Contrave): weight management
Dosing: do NOT exceed 450mg/day due to seizure risk in IR and XL
MOA: DA and NE reuptake inhibitor
AVEs: dry mouth, CNS stimulation (insomnia, restlessness), tremors/seizures (dose-related), weight loss, HA/migraine, N/V, constipation, possible BP changes (more HTN than than hypotension)
-Sexual dysfunction: rare (no effect on 5-HT) –> can use if issues w/ other antidepressants
-Auvelity: dizziness, excessive sweating
Warnings: neuropsychiatric AVEs when used for smoking cessation (mood changes, hallucinations, paranoia, aggression, anxiety)
CI:
-Seizure disorder, hx of anorexia/bulimia (eating disorders), abrupt D/C of ethanol or sedatives
-do NOT use with MAOIs (allow 2-week washout), linezolid, or IV methylene blue or other forms of bupropion
Monoamine Oxidase Inhibitors (MOAIs):
-Drugs/Brands
-MOA
-ROA
-TX
Drugs:
-Nonselective MAOIs: isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate)
-Selective MAO-B: selegiline (Emsam, Zelepar)
MOA: inhibit monoamine oxidase that breaks down catecholamines, including 5-HT, NE, EPI, and DA
-MOA-A: 5-HT, DA, EPI, and NE
-MOA-B: DA
ROA: PO
-Emsam: transdermal patch
TX: depression
-Zelepar: ODT for Parkinson disease
Monoamine Oxidase Inhibitors (MOAIs):
-AVEs
-Warnings
-CIs
AVEs:
-Anticholinergic: taper upon D/C to avoid cholinergic rebound
-Orthostasis
-Sedation (except tranylcypromine causes stimulation)
-Sexual dysfunction, weight gain, HA, insomnia
-Selegline: constipation, gas, dry mouth, loss of appetite, sexual dysfunction
Warnings:
-NOT commonly used
-Watch for DDIs and drug-food interactions (CAN BE FATAL)
-Hypertensive crisis or serotonin syndrome with TCAs, SSRIs, SNRIs, many other drugs, and tyramine-containing foods
CIs:
-Hx of CVD, cerbrovascular defect, HA, hepatic disease, pheochromocytoma
-do NOT use w/ other sympathomimetics (hypertensive crisis)
-Severe renal disease (isocarboxazid, phenelzine)
Monoamine Oxidase Inhibitors (MOAIs): DDIs
To avoid hypertensive crisis, serotonin syndrome, or psychosis: DO NOT USE WITH drugs that increase EPI, NE, 5-HT, or DA
- Increase 5-HT: SSRIs, SNRIs, mirtazapine, trazodone, triptans, buspirone, dextromethorphan, linezolid, lithium, tramadol, opioids, St. John’s Wort
- Increase EPI: buproprion, SNRIs, levodopa, linezolid, methylene blue, stimulants for ADHD and OTC diet pills/herbal weight loss products
- Tyramine-rich foods that increase NE: aged cheese, pickled herring, yeast extract, air-dried meats, sauerkraut, soy sauce, fava beans, some red wines and beers (tap beer and any beer that has NOT been pasteurized - canned and bottle beers contain little or no tyramine)
Mirtazapine:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CIs
Brand: Remeron
MOA: central presynaptic alpha-2 adrenergic antagonist effects that increase NE and 5-HT
ROA: PO
TX: most commonly in oncology and skilled nursing facilities to help with sleep (dosed as QHS) and increase appetite in frail
AVEs: sedation, increased appetite, weight gain, dry mouth, dizziness, agranulocytosis (rare)
Warnings: anticholinergic effects, QT prolongation, blood dyscrasias, CNS depression
CIs: do NOT use w/ MAOIs, linezolid, or IV methylene blue
Trazodone:
-Brand
-MOA
-ROA
-What time of day to take?
-TX
-AVEs
-CIs
Brand: Desyrel, Oleptro
MOA: inhibits 5-HT reuptake; inhibits H1 and alpha-1 adrenergic receptors
ROA: PO QHS
TX: rarely for antidepressant effects –> off-label for sleep
AVEs: sedation (ER may be less sedating), orthostasis (risk of falls in elderly), sexual dysfunction and risk of priapism (go to ER for painful erection longer than 4 hours)
CIs: do NOT use w/ MAOIs, linezolid, or IV methylene blue
Nefazodone:
-MOA
-ROA
-AVEs
-CIs
-BBW
MOA: inhibits 5-HT and NE reuptake, 5-HT2, and alpha-1 adrenergic receptors
ROA: PO
AVEs: similar to trazodone, but less sedating
-Trazodone side effects: sedation, orthostasis (risk of falls in elderly), sexual dysfunction and risk of priapism (go to ER for painful erection longer than 4 hours)
CIs:
-Hepatic disease
-Concurrent use w/ MOAIs, carbamazepine, cisapride, pimozide, or triazolam
BBW: hepatotoxicty (less used due to this)
Select an antidepressant or what not to use based on the following scenarios:
1. Cardiac/QT risk
- Smoker
- Peripheral neuropathy or pain
- Seizure risk
- Cardiac:
-Sertraline is preferred
-do NOT choose a QT-prolonging drug/dose (ex. high doses of escitalopram/citalopram, venlafaxine)
-Watch for additive QT effects: SSRIs, SNRIs, TCAs, mirtazapine, or trazodone - Smoker: buproprion SR
- Peripheral neuropathy or pain: duloxetine
- Seizure risk: avoid bupropion
Select an antidepressant or what not to use based on the following scenarios:
1. Pregnancy
- Daytime sedation
- Sexual dysfunction
- Pregnancy:
-Mild-moderate depression: psychotherapy always
-Certain SSRIs (escitalopram, sertraline) are first-line for drug therapy
-Avoid: paroxetine - Daytime sedation:
-Actiavting medications in AM (fluoxetine, bupropion)
-Sedating drugs later in day (paroxetine, mirtazapine, trazodone) - Sexual dysfunction:
-High risk: SSRIs, SNRIs
-Low risk: bupropion, mirtazapine
Treatment-resistant depression:
1. American Psychiatric Association (APA): guidelines state patient should receive a ____ week trial of medication at a THERAPEUTIC dose before conclude that drug is NOT working.
- If a patient is NOT improving at this time interval, what should be considered?
- 4-8
- Consider:
-Changing to new antidepressant
-Increase antidepressant dose
-Use combination of antidepressants with different MOAs
-Augment with buspirone or a low dose of an atypical antidepressants (aripiprazole, olanzapine + fluoxetine = Symbyax, quetiapine XR, brexipiprazole, cariprazine)
-Esketamine nasal spray
-Augment with lithium, thyorid homrone, or in some cases, electroconvulse therapy (ECT)
Esketamine:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-BBW
Brand: Spravato
MOA: NMDA receptor antagonist
ROA: nasal spray
Administration Considerations:
-Must be administered under supervision of healthcare provider, monitoring for at least 2 hours following administration
-Restricted distribution under Spravato REMS program
TX: TX-resistant depression, depression with suicidality
BBW:
-Sedative and dissociative or perceptual changes, potential for abuse and misuse
-Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults
Schizophrenia:
-Pathophsyiology
-DSM-5 Diagnostic criteria
-Potent natural product for many psych conditions
Pathophysiology: altered brain structure and chemistry primarily involving increased dopamine, serotonin, and glutamate
DSM-5:
-Negative s/sx: loss of interest, lack of emotion (apathy), social withdrawl, loss of motivation (avolition), lack of speech (alogia), inability to plan or carry out activities, poor hygiene
-Positive s/sx: hallucinations (auditory, visual, or somatic), delusions, disorganized thinking/behavior, incoherent speech, difficulty paying attention
Potential Natural Product: fish oil (for inflammation often related to stress)
Drugs that can cause psychotic symptoms
-Anticholinergics (centrally-acting, high doses)
-Dextromethorphan, when used not as indicated
-Dopamine or dopamine agonists
-Inteferons
-Stimulants especially if already at risk
-Systemic steroids (typically with lack of sleep – ICU psychosis)
-Illict/recreational substances: cannabis, cocaine, lysergic acid diethylamide (LSD), methamphetamine (ice, crystal), phencyclidine (PCP), synthetic cathinons (bath salts, MDPV)
Schizophrenia:
1. General TX (cons of TX?)
- Which symptoms are usually harder to treat?
- BBW for all antipsychotics
-
General TX: antipsychotics to block dopamine (newer ones can block 5-HT)
-First line: second generation antipsychotics (SGAs) due to less extrapyramidal symptoms (EPS) unless a pt is already stabilized on a first generation antipsychotic (FGAs)
-Cons: blocking DA can affect pathways involved in focus, attention, and movement
- Negative symptoms
- BBW - NOT indicated for agitation control in elderly with dementia-related psychosis (increased mortality risk mostly due to CV conditions) –> MEDGUIDE REQUIRED
-Some also carry warning of stroke in pts with dementia
-ALL carry warning for falls
Define the types of EPS
-Dystonias
-Dyskinesias
-Akathisia
-Tardive dyskinesias (TD)
Dystonias: very painful muscle contractions (common especially in young males)
Dyskinesias: abnormal movements
Akathisia: restlessness, inability to remain still
TD: repetitive, involuntary movements (ex. grimacing and eye blinking) –> can be IRREVERSIBLE and drug should be D/C
Schizophrenia: Why is adherence to TX usually poor, and what are some ways to combat it?
Adherence poor often from pt’s inability to recognize the illness; can also have dysphagia
-Long-acting injectables (LAIs): given IM or SQ to eliminate PO QD dosing (ex. Haldol Decanoate, Risperdal Consta, Invega Sustenna, Abilify Maintena)
-ODTs: useful in dysphagia and provent cheeking (tablets hidden in cheek and spit out later) –> Abilify Discmelt, Clozapine Fazaclo, Risperidal M-Tab, Zyprexa Zydis, Saphris
-Oral solutions/suspensions: useful for children and with feeding tubes
-Acute IM injections (haloperidol, fluphenazine, Zyprexa, Geodon): provide “STAT” relief to calm down agitated pt for their safety and others –> can be given as cocktails such as with BZDs and anticholinergics to re
First Generation Antipsychotics (FGAs):
-List drugs and their brands based on: low, medium, and high potency (what are the differences regarding AVEs?)
-Structure
-MOA
Low potency: chlorpromazine, thioridazine
-Increased sedation and lower EPS risk
Medium potency: loxapine (Adasuve), perphenazine
High potency: decreased sedation and higher EPS risk
-haloperidol (Haldol, Haldol Decanoate)
-fluphenazine
-thiothixene
-trifluoperazine
Structure:
-Many are in phenothiazine class (end in -azine)
-Haloperidol: in butyrophenone class
MOA: mainly block dopamine-2 (D2) receptors with minimal 5-HT2A blockade
First Generation Antipsychotics (FGAs):
-AVEs
-Warnings
-BBW
AVEs:
-Sedation, dizziness, anticholinergic effects, increased prolactin
-EPS: can give anticholinergic (ex. benztropine or Benadryl) to limit/avoid painful dystonic reactions
-Adasuve (loxapine): dysgeusia (bad, bitter, or metallic taste in mouth)
-Injections (haloperidol, fluphenazine): injection site pain/redness
Warnings:
-CV: QT prolongation (especially w/ thioridazine, haloperidol, chlorpromazine, orthostasis/falls, tachycardia)
-Anticholinergic: constipation, xerostomia, blurred vision, urinary retention
-CNS depression
-EPS: including Parkinsonims, dystonic rxns, akathisia, TD (increased EPS with injections)
-Hyperprolactinemia: infertility, oligomenorrhea/amenorrhea (fewer or no menstrual periods), galactorrhea (abnormal breast discharge), ED/decreased libido
-Neuroleptic maligant syndrome (NMS): monitor for mental status changes, fever, muscle rigidity, autonomic instability
-Blood dyscrasisa (leukopenia, neutropenia, agranulocytosis), ocular effects
BBW: elderly pts w/ dementia-related psychosis (increased mortality risk)
-Thioridazine: QT prolongation
-Adasuve (loxapine): bronchospasm (REMS program)
Aripiprazole:
-Brand
-MOA
-ROA
-AVEs
Brand: Abilify
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
-Unique MOA: D2 and 5-HT1a partial AGONIST
ROA: PO or IM
-Abilify MyCite: tablets embedded w/ ingestible sensor to track drug compliance
-IM: Ability Maintena, Aristada, Abilify Asimtufii
-Aristada Initio: one-time IM LD along with PO abilify when starting or restarting Aristada
AVEs: akathisia, activation or sedating, HA, anxiety, constipation
-Lower risk of weight gain, some QT prolongation, ESP more in children
Clozapine:
-Brand
-MOA
-ROA
-TX
Brand: Clozaril
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO
TX: NO sooner than 3rd-line for schizophrenia (very effective and decreased risk of EPS/TD, BUT serious other side effects related to metabolic and neutropenia)
Clozapine:
-AVEs
-BBW
-Monitoring
AVEs: agranulocytosis, seizures, constipation, somnolence, metabolic syndrome (increased weight, BG< lipids), sialorrhea (hypersalivation), hypotension
BBW:
-Significant risk of life-threatening neutropenia/agranulocytosis (REMS program)
-Bradycardia, orthostatic hypotension, syncope and cardiac arrest (risk highest in initial titration period, especially w/ rapid dose increases –> titrate slowly)
-Myocarditis and cardiomyopathy –> D/C if suspected
-Seizures (dose-related): start at no higher than 12.5mg QD or BID, titrate slowly using divided doses (use in caution w/ hx of seizure, head trauma, alcoholism, or takine medications that lower seizure threshold)
Monitoring:
-REMS: prescribers and pharmacies must be certified and pts must enroll
-To start TX: baseline ANC must be >/=1500/mm3; check ANC weekly x6 months then Q2 weeks x6 months then Qmonth –> stop therapy if ANC <1000/mm3
Lurasidone:
-Brand
-MOA
-ROA
-Administartion considerations
-AVEs
-CI
Brand: Latuda
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO
Administration Considerations: take CF (at least 350 kcal)
AVEs: somolence, EPS (dystonias), nausea
-Decreased risk of metabolic syndrome compared to other SGAs
CI: use w/ CYP450 3A4 inducers and inhibitors
Olanzapine:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-BBW
Brand: Zyprexa
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO, IM
Administration: take QHs (due to sedation)
AVEs: somnolence, metabolic syndrome (increased weight, BG, lipids), orthostasis
BBW (Zyprexa Relprevv): sedation (including coma) and delirium (agitation, anxiety, confusion, disorientation) following injection; must administer in registered healthcare facility and pts to be monitored 3 hours post-injection (Zyprexa RElprevv REMS program requirements)
What medications may you see combined with olanzapine?
Olanzapine should NOT be combined with ________ due to excessive risk of sedation and breathing difficulty.
Drugs Combos:
-Fluoxetine + Olanzapine = Symbyax: TX-resistant depression
-Samidorphan + Olanzapine = Lybalvi: schizophrenia, bipolar disorder –> samidorphan is an opioid recepotr antagonist that can help mitigate weight gain from olanzapine (CI in pts taking opioids or undergoing acute opioid withdrawl)
Sedation and breathing difficulty risk: combined w/ BZDs
Paliperidone:
-Brand
-MOA
-ROA/Dosing frequency
-TX considerations
-AVEs
Brand: Invega
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
-Very similar to risperidone, just lasts longer
ROA: PO or IM
-Invega Trinza: IM Q3 months
-Invega Hafyera: IM Q6 months
TX considerations: adequate TX w/ IM must be established before starting Invega Trinza or Invega Hafyera
-Osmotic release oral system (OROS) enables once daily dosing -do NOT break or crush
AVEs:
-Increased prolactin: sexual dysfunction, galactorrhea, irregular/missed periods
-EPS, especially at higher doses
-Tachycardia, QT prolongation
-Metabolic syndrome (increased weight, BG, lipids)
-Somnolence
-Invega can have ghost tablet (empty shell) in stool
Quetiapine:
-Brand
-MOA
-ROA
-Adminstration considerations
-AVEs
Brand: Seroquel
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO
Administration considerations: take XR at night WITHOUT food or with light meal
-IR can take w/ or w/o food
AVEs: somnolence, metabolic syndrome (increased weight, BG, lipids), orthostasis, possible occular effects (cataracts)
-LOW EPS risk (often used for psychosis in PD)
Risperidone:
-Brand
-MOA
-ROA
-AVEs
Brand: Risperdal
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO, IM, SQ
AVEs:
-Increased prolactin: sexual dysfunction, galactorrhea, irregular/missed periods
-ESP, especially at higher doses
-Tachycardia, QT prolongation
-Metabolic syndrome (increased weight, BG, and lipids)
-Somnolence
Ziprasidone:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-CI
Brand: Geodon
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO, IM
Administration considerations: PO –> CF
AVEs: somnolence, EPS, dizziness, nausea
CI: QT prolongation (do NOT use w/ QT risk)
Asenapine:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-CI
Brand: Saphris, Secuado
MOA: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
ROA: PO, patch
Administration considerations: no food/drink for 10 minutes after dose
AVEs: somnolence, tongue numbness (SL), EPS, QT prolongation
CI: severe hepatic impairment
Mischellaneous Antipsychotics: cariprazine, brexipiprazole, iloperidone, lumateperone
-MOA
ALL: second generation antipsychotic (SGA) that blocks D2 and 5-HT2A receptors
Unique MOAs:
-D2 and 5-HT1a partial agonists: brexipiprazole, cariprazine
-5-HT2a antagonist: brexipiprazole
Antipsychotics: treatment considerations
1. How long is an adequate trial?
- What drugs to avoid if/preferred options:
-Cardiac risk/QT prolongation risk
-History of movement disorder (ex. PD)
-Overweight/metabolic risk - What are options for failure with 2 or more antipsychotics?
- 6 weeks at least including adequate dose and adherence
- AVOID if:
-Cardiac risk/QT prolongation (especially w/ low K and Mg; D/C if QT >500msec): ziprasidone > haloperidol > thioridazine; chlorpromazine
-Hx of movement disorder: FGAs, risperidone, paliperidone (at higher doses) –> quetiapine preferred
-Overweight/metabolic risk: olanzapine, quetiapine –> lower risk: aripiprazole, ziprasidone, lurasidone, asenapine
- clozapine (tablets: Clozaril, suspension: Versacloz)
Antipsychotics: treatment considerations
1. List SGAs highest to lowest for metabolic AVes.
- List SGAs with highest increased prolactin risk.
- -Highest: clozapine, olanzapine, quetiapine
-Moderate: risperidone, paliperidone
-Lower risk: aripiprazole, ziprasidone, lurasidone, osenapine
- Risperidone, paliperidone
What drug is approved for psychosis in Parkinson disease? What is its AVEs, warnings, and MOA?
Pimavanseron (Nuplazid)
-MOA: inverse agonist and antagonist at 5-HT2A receptors and lesser extent at 5-HT2C receptors (NO impact on DA receptors, thus does NOT worsen PD)
-AVEs: peripheral edema, confusion
-Warnings: NOT appropriate for dementia-related psychosis; QT prolongation (avoid in pts w/ risk factors or drugs that increase QT interval)
Antipsychotics: DDIs
ALL:
-Can prolong QT interval (high risk FGA: thioridazine, chlorpromazine; high risk SGAs: ziprasidone, haloperidol, droperidol): caution w/ other QT-prolonging drugs
-BZDs: monitor respiratory depression and hypotension (do NOT use w/ olanzapine)
-DA blocking drugs (ex. metoclopramide): EPS and TD risk further increased
Smoking: can reduce plasma levels of olanzapine and clozapine (may need higher doses)
Clozapine: avoid concurrent drugs that lower seizure threshold
Risperidone, paliperdone: caution w/ CYP2D6 inhibitors (including fluoxetine and paroxetine) –> can increase prolactin and cause EPS
Tardive Dyskinesia (TD): medications approved for TD TX
-Drugs/Brands
-MOA
-Warnings
-CIs
-DDIs
Drugs: valbenazine (Ingrezza), deutetrabenazine (Austedo, Austedo XR)
MOA: reversibly inhibit vesicular monoamine transporter 2 (VMAT2) that regulates momamine uptake from cytoplasm to synpatic vesicle for storage and release
Warnings: somnolence, QT prolongation
CI (deutretrabenazine): hepatic impairment, use with tetrabenazine or valbenazine, use with MAOI within 14 days
DDIs:
-Avoid use w/ MAOIs
-Substrates of CYP3A4 and 2D6: dose reduction required w/ CYP3A4 inhibitors or 2D6 (paroxetine, fluoxetine)
-Valbenazine: P-gp inhibitor that can increase digoxin concentrations
Neuroleptic Maligant Syndrome (NMS):
-Define
-S/Sx
-TX
NMS: rare, but highly lethal condition where usually starting within 2 weeks or immediately following high dose increase of dopamine antagonist causing intese muscle contractions that can lead to renal injury due to rhabdomylosis, suffocation, and death
S/Sx:
-Hyperthermia (high fever, profuse sweating), extreme muscle rigidity (called “lead pipe” rigidity) that can lead to respiratory failure, mental status changes, tachycardia, tachypnea, blood pressure changes
-Increased creatinine phosphokinase
-Increased WBCs
TX:
-STOP ANTIPSYCHOTIC
-Supportive care: cardiorespiratory and hemodynamic support, manage electrolytes
-Control pt’s temperature: cooling bed, antipyretics, cooled IV fluids
-Relax muscles: BZDs, dantrolene (Ryanodex, Dantrium, Revonto) or potentially a dopamine agonist (bromocriptine)
-After resolution, consider different antipsychotic
Bipolar Disorder (BP):
-Define
-S/Sx
-DSM-5
BP: fluctuations in mood from depression (extremely sad or hopeless states) to abnormally elevated, overexcited, or irritable moods (mania or hypomania - milder form of mania) for at least a week in duration (or any duration if hospitalization needed); some states can be mixed
S/Sx:
-Inflated self-esteem; high-risk, pleasurable activities (ex. shopping sprees, sexual indiscretions, gambling)
-More talkative than normal
-Jumping from topic to topic, easily distracted
-Increased in goal-directed activity
-Needs less sleep
DSM-5: exhibits 3 or more symptoms (if mood is only irritable, exhibits 4 or more)
Bipolar Disorder (BP):
-Classifications
-What is cyclothymia?
Classifications:
-Bipolar I: at least one episode of mania and usually bouts of intense depression (depressive episodes NOT required) –> mania associated with significant impairment in social/work functioning, psychosis/delusions, or requires hospitalization
-Bipolar II: at least one episode of hypomania (lasting 4 or more consecutive days) and at least one depressive episode (leasting 2 weeks or more) –> hypomania does NOT affect social/work functioning, does NOT cause psychosis, and does NOT require hospitalization
Cyclothymia: related disorder consisting of periods of hypomanic and depressive symptoms w/o meeting defined criteria for major depressive, manic, or hypomanic episode
Bipolar Disorder (BP): General TX
Goal is to stabilize moods without inducing a depressive or manic state
-Mood stabilizers: lithium, antiepileptic drugs (valproate, lamotrigine, carbamazepine)
-Antipsychotics: NOT traditional mood stabilizers, but can stabilize mood when mania occurs w/ psychosis; SGAs preferred due to less EPS (options: aripiprazole, olanzapine, quetipaine, risperidone, ziprasidone, lurasidone, olanzapine/fluoxetine)
-Antidepressants: can incude or exacerbate manic episode as MONOTHERAPY –> use in combination with mood stabilizer
Bipolar Disorder (BP): Acute TX
Manic episode: first line = antipsychotic (olanzarpine, risperidone), lithium, or valproate (severe: antipsychotic + lithium or valproate)
Depressive episode: first line = antipsychotic (quetiapine, lurasidone); alternatives or add ons: lithium, valproate, or lamotrigine (lamotrigine: longer titration, not helpful in acute mania)
Bipolar Disorder (BP): TX considerations in pregnancy
Preferred safer options: lamotrigine most favorable sfaety profile; SGAs safer than valproate, carbamazepine, or lithium
-Valproate: increases risk of fetal anomalies including long-term adverse cognitive effects (decreased IQ), neural tube defects, and fetal valproate syndrome (avoid especially in first trimester, worst of all BP drugs)
-Carbamazepine: can cause fetal carbamazepine syndrome resulting in facial abnormalities and incomplete organ development, including cardiac effects (especially avoid in first trimester)
-Lithium: can increase congenital cardiac malformations
Lithium:
-Brand
-MOA
-ROA
-TX
-Therapeutic range
Brand: Lithobid
MOA: proprosed mechanism is influencing of reputake of 5-HT and/or NE or by moderating gluatamate levels in brain
-Glutatamte is primary excitatory neutransmitter that could cause mania
ROA: PO
TX: Bipolar disorder
-Off-label: refractory depression as augment
Therapeutic range: 0.6-1.2 mEq/L (trough level); acute mania may require 1.5mEq/L initially
-NTI drug
Lithium:
-AVEs within therapeutic range
-AVEs within toxic ranges
-Warnings
-BBW
-CIs
-Monitoring
AVEs within therapeutic range: GI upset (N/D), cognitive effects, cogwheel rigidity, fine hand tremor, thirst, polyuria/polydipsia, weight gain, hypothyroidism, hypercalcemia, cardiac abnormalities, edema, anorexia, worsening psoriasis, blue-gray skin pigmentation, impotence
AVES within toxic ranges:
->1.5mEq/L: ataxia (lack of muscle coordination/balance), coarse hand tremor, vomiting, persistent diarrhea, confusion, sedation
->2.5mEq/L: CNS depression, arrhythmias, seizure, coma
Warnings: renal impairment, hyponatremia, dehydration (increased lithium toxicity), serotonin syndrome
BBW: serum lithium levels should be monitored to avoid toxicity
CI: avoid in pregnancy (cardiac malformations in first trimester), avoid in breastfeeding
Monitoring: serum levels, renal function, thyroid function (TSH, T4), electrolytes (Ca, Phos, Na). ECG (pt >40yo)
-Lithium is 100% renally cleared
Lithium: DDIs
Lithium levels increase with:
-Reduced salt intake, sodium loss (ex. ACEIs, ARBs, thaizide diuretics)
-NSAIDs: ASA and sulindac are safer options
Lithium levels decrease with: increased salt intake, caffeine, theophylline
Risk of 5-HT syndrome: * SSRIs, SNRIs, triptans, linezolid, etc.*
Increased risk of neurotoxicity (ataxia, tremors, nausea): verapamil, diltiazem, phenytoin, carbamazepine
***Lithium changes with Na intake because the kidneys cannot tell the difference between Na and Li. Therefore, increasing Na, the kidney will try to clear Na and also Li
Lithium: main counseling points
- Take with food or at end of meal to reduce nausea
- Maintain consistent salt intake
- Maintain adequate hydration with NON-caffeinate beverages
- Notify healthcare provider immediately for worsening nausea or diarrhea, slurred speech, shakiness, or confusion
- Can cause impaired alterness: caution when driving or during tasks that require alertness
Attention Deficit Hyperactivity Disorder (ADHD):
-Pathophysiology
-DSM-5
Pathophysiology: NOT well understood –> imbalance of catecholamine metabolism with subsequent decreased DA
DSM-5:
-Primary symptoms: inattention, hyperactivity, and impulsivity
-Inattention or hyperactivity/impulsivity: >/=6 symptoms of intattention for children up to age 16 (>/= 5 symptoms for 17 yo and older) that are present for at least 6 months and inappropriate for developmental level
-Several inattentive or hyperactive-impulsive symptoms present before age 12
-Symptoms must have been present in 2 or more settings (ex. home, work, school, friends)
-Symptoms intefere w/ functioning and NOT caused by another disorder
Attention Deficit Hyperactivity Disorder (ADHD):
-General TX
-Supplements in ADHD
General TX:
-Age 4-5yo: first line is parent training in behavior management and/or behavior classroom intervention
-6 yo and older: behavioral interventions + medications (first line = stimulants)
-Non-stimulants in ADHD: atomoxetine, viloxazine –> after trial of 2-3 stimulants (or first line in concern of abuse or diversion)
-Add-on medications: guanfacine ER (Intuniv), clonidine ER (Kapvay)
-To help sleep at night: clonidine IR, diphenhydramine, melatonin
Supplements: data for efficacy LIMITED and not routinely recommended (fish oil was studied with limited evidence, some limited data on combined omega-3 and omega-6 supplementation)
-Melatonin may be helpful for sleep onset insomnia in pts taking stimulants
Stimulants: what are patient friendly options for children and others that cannot swallow capsules or tablets?
When putting capsule contents in food, use a small amount of food (do NOT warm the food). Eat the food right away, without chewing.
-If beads are chewed, drug can become IR
Capsules that can be opened:
-Many long-acting capsules (ex. Adderall XR, Ritalin LA, Aptension XR, Folacin XR): can sprinkle on applesauce
-Vyvanse capsules: can be mixed in water, orange juice, or yogurt (unique because most stimulant levels decreased with acid - aka orange juice) –> take right away, do NOT let sit
Other options:
-Chewable tablets: Vyvanse, QuilliChew ER (only ER that can be crushed)
-ODTs
-Patches: Daytrana
-Suspensions
Stimulants:
1. All stimulants are control schedule ___ that must be dispensed with _________.
- What is the BBW for all stimulants?
- What is the CI for all stimulants?
- What is general administration for all stimulants?
- CII; medguide
- High potential for abuse and dependence
-Can contribute to development of substance use disorder
-Misuse can lead to overdose and death
-Symptoms of misuse: dilated pupils, increased HR/BP, sweating, tremor, anxiety - Use with MAOI within 14 days –> hypertensive crisis
- Administration: Qam, titrated up Q7 days PRN
-Do NOT need to be tapered off when used as directed (aka NOT abused)
What are warnings for all stimulants?
-Stimulant abuse and misuse can lead to drug diversion
-Increased DA and NE can increase HR and BP, causing serious CV events w/ or w/o pre-existing disease
-Other vascular problems: priapism, Raynaud’s disease: may require dose reduction or D/C
-New-onset psychosis or mania or exacerabtion of pre-existing psychosis
-Loss of appetite very common: can decrease child’s growth trajectory
-Risk of serotonin syndrome w/ other serotonergic drugs
-Some can lower seizure threshold
-Visual disturbances: difficulty w/ accomodation and blurry vision
Methylphenidate ROAs: for each brand, explain what ROA and any administration considerations
1. Ritalin
2. Ritalin LA
3. Concerta
Ritalin (IR tablet): start at 5mg BID, taking 30 minutes before breakfast and lunch
Ritalin LA (ER capsule): take Qam
Concerta (ER tablet w/ OROS delivery): start at 18-36mg Qam
-OROS delivery: outer coat dissolves fast for immediate action, but rest released slowly and harder to crush which decreases drug abuse potential
-Can see ghost tablet in stool
Methylphenidate ROAs: for each brand, explain what ROA and any administration considerations
1. Jornay PM
2. Daytrana
3. QuilliChew ER
Jornay PM (ER capsule): take Qpm
-Outer coating delays intial drug release 10 hours to allow for evening dosing
-Inner coating controls slow release of drug during the day
Daytrana (transdermal patch): apply to hip (alternating) Qam
-Apply 2 hours before desired effect (or as soon as child awakens to deliver prior to school)
-Remove after 9 hours
-Discard used patches by flushing down the toilet
QuilliChew ER (chewable tablet): Qam
-Contain phenylalanine (avoid with PKU)
Methylphenidate:
-Brands
-MOA
-AVEs
-Warnings
-Monitoring
Brands: Riltain, Ritalin LA, Jornay PM, QuilliChew ER, Concerta, Daytrana, Relexxii
MOA: stimulant that blocks reuptake of NE and DA
AVEs: insomnia, decreased appetite/weight loss, HA, irritability, N/V, blurry vision, dry mouth
Warnings:
-Daytrana (transdermal patch): loss of skin pigmentation at appllication site and areas distant from site (can resemble vitiligo); allergic contact dermatitis wth local rxns (edema, papules)
-Concerta, Relexxii (both OROS delivery): do NOT use w/ GI narrowing conditions (ex. motility issues, small bowel disease)
Monitoring:
-Consider ECG prior
-Monitor BP and HR, cardiac symptoms, CNS effects, and abuse potential
-Children: monitor height and weight
Stimulants:
1. _____________(generic and brand) is the active isomer of methylphenidate. How would you convert dosing?
- _____________ is the prodrug to dexmethylphenidate. It comes combined with dexmethylphenidate under the brand __________.
- _____________(generic and brand) is a prodrug of L-lysine bonded to dextroamphetamine and hydrolyzed in blood to active dextroamphetamine. It has low drug abuse potential since if its injected or snorted, the fast effect is muted.
- The brand name for methamphetamine is _________.
- Dexmethylphenidate (Folacin, Folacin XR)
- Serdexmethylphenidate; Azstarys
- Lisdexamphetamine (Vyvanse)
- Desoxyn
Amphetamine, Dextroamphetamine, and Combinations:
-Brands for dextroamphetamine/amphetamine, amphetamine, and dextroamphetamine
-MOA
-IR prdocuts are approved for children >/= ____ yo except ________ brand
-AAP guidelines do NOT recomend dextroamphetamine in children ____ </= yo
-Administration considerations
Brands:
-Combination = Adderall, Adderall XR, Mydavis
-Amphetamine = Adzenys XR-ODT, Dyanavel XR, Evekeo, Evekeo ODT
-Dextroamphetamine = Dexedrine, ProCentra, Zenzedi, Xelstrym
MOA: stimulant that blocks reuptake of NE and DA
IR products: children 3 yo or older EXCEPT Evekeo ODT
-Dextroamphetamine: NOT recommended in children 5 yo or younger
Administration considerations:
-ER formulations: CANNOT be substituted for other products on a mg-per-mg basis –> follow dosing schedule per manufacturer
-Dyanavel XR: shake suspension prior to use
-do NOT take w/ acidic foods such as juice or vitamin C (decrease absorption)
Selective Norephinephrine Reuptake Inhibitors:
-Drugs/Brands
-ROA
-Administration considerations
-TX
Drugs: atomoxetine (Strattera), viloxazine (Qelbree)
ROA: PO
Administration Considerations:
-Atomoxetine: do NOT open capsules (ocular irritant)
-Viloxazine: capsule can be opened and contents sprinkled on 1 tsp of pudding or applesauce (swallow without chewing)
TX: ADHD (non-stimulants)
Selective Norephinephrine Reuptake Inhibitors:
-AVes
-Warnings
-CI
-BBW
-Monitoring
-DDIs
AVEs: decreased appetite, insomnia, somnolence, dry mouth, increased BP/HR, HA, nausea, abdominal pain
Warnings:
-CV events, psychosis, mania: assess at baseline and PRN
-Atomoxetine: aggressive behavior, hepatotoxicity, priapism, urinary hesistancy/retention, growth delays
CI: MAOI use within past 14 days
-Atomoxetine: glaucoma, pheochromocytoma, severe CVDs
-Viloxazine: concurrent use of CYP1A2 substrates (or substrates w/ NTI)
BBW: risk of suicidial ideation
Monitoring: BP, HR, ECG, mood, weight
DDIs:
-Volxazine: strong CYPA1A2 inhibitor and weak CYP2D6/3A4 inhibitor
-Atomoxetine: CYP2D6 substrate
Centrally-Acting Alpha-2 Adrenergic Receptor Agonists for ADHD:
-Drugs/Brands
-ROA/Dosing frequencies/Adminsitration Considerations
-AVEs
-Warnings
-Monitoring
-DDIs
Drugs: clonidine ER (Kapvay), guanfacine ER (Intuniv)
ROA: PO
-Take QHS
-Must be tapered off due to increased risk of rebound HTN (decreased dose Q3-7 days; clonidine: </=0.1mg/day; guanfacine: </=1mg/day)
-do NOT substitute IR clonidine or guanfacine for ER formulations
AVEs: dry mouth, somnolence, fatigue, dizziness, constipation, decreased HR, hypotension, HA, nausea, abdominal pain
Warnings:
-Dose-dependent CV events (bradycardia, hypotension, orthostasis, syncope), sedation, drowsiness
-do NOT D/C abruptly: rebound HTN
-Guanfacine: skin rash (rare, D/C if occurs); dose adjustments w/ CYP3A4 inducers and inhibitors
Monitoring: BP, HR
DDIs:
-Additive sedation w/ other CNS depressants
-Caution with drugs that decrease BP and HR
-Guanfacine: double the dose if w/ strong CYP3A4 inducers; decrease dose by 50% if w/ strong CYP3A4 inhibitors
Drugs that can cause anxiety
Pscyhiatric Medications: antipsychotics (ex. aripiprazole, haloperidol), bupropion, stimulants
Others:
1. Albuterol: if used too frequently or incorrectly
- Caffeine, in high doses
- Decongestants (ex. pseudophedrine)
- Illict drugs
- Levothyroxine, if therapeutic overdose occurs
- Steroids
- Theophylline - converted to caffeine
Anxiety Disorders:
1. What are some of the common types of anxiety disorders? What are disorders with symptoms of anxiety?
- Non-pharmacological TX
- What are natural products that may be used?
1.
-Common: generalized anxiety disorder (GAD), panic disoder (PD), social anxiety disorder (SAD)
-Disorders w/ anxiety: obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD)
- Non-pharmacological TX:
-Cognitive behavioral therapy (CBT): trained clinicians help explore patterns of thinking that lead to problem-solving, relaxation techniques, and worry exposure
-Treat comorbid conditions (ex. hyperthyroidism)
-Lifestyle changes: increased physical activity, community involvement, meditation
What are natural products that may be used for anxiety?
Natural Products: generally limited by safety issues
-Kava: relaxant, but severe liver damage (NOT recommended)
-Valerian: for anxiety/sleep, but may be contaminated w/ liver toxins
-Passionflower: appears to be safe and listed as possibly effective via NatMed
-5-HTP, L-typtophan: eosinophilia mylagia syndrome
-St John’s Wort: strong CYP3A4 inducer, photosensitivity, serotonin snydrome
Anxiety: general TX
First line: SSRIs and SNRIs
-FDA approved: escitalopram, fluoxetine, paroxetine, stetraline, duloxetine, venlafaxine
-Start low and titrate slowly to avoid jitteriness or exacerbation of anxiety
-Takes at least 4 weeks to see benefit
Second line:
-Buspirone: takes 2-3 weeks to see benefit, can use in combo w/ antidepressants (more favorable in elderly than BZDs)
-TCAs: anticholinergic AVEs, NOT FDA approved
-Hydroxyzine: sedating antihistamine, used only as short term, does NOT treat underlying condition
-Pregabalin, Gabapentin: for anxiety (NOT FDA approved) and neuropathic pain
Stage Fright: Propranolol
-NOT FDA approved, but can reduce symptoms of stage fright or performance anxiety (ex. tremors, tachycardia)
-Can cause CNS AVEs (dizziness, confusion)
-Dose 10-40mg one hour prior to event
Short term only: benzodiazepines (BZDs)
Buspirone:
-Brand
-MOA
-ROA
-Administration considerations
-TX and considerations
Brand: BuSpar
MOA: not fully known, but may have affinity for 5-HT1A and 5-HT2 receptors
ROA: PO
Administration: tablets scored to easily break into half or two thirds
TX: anxiety
-NO potential for abuse, tolerance, or psychological dependence
-Takes 2-4 weeks for optimal effect
-When switching from BZD to buspirone, BZD should be tapered slowly
Buspirone:
-AVEs
-Warnings
-CI
-DDIs
AVEs: dizziness, drowsiness, HA, lightheadedness, nausea, excitement
Warnings: risk of serotonin syndrome
CI:
-MAOI use within 14 days or with linezolid or IV methylene blue
-Avoid in severe kidney or liver impairment
DDIs: CYP3A4 substrate
-Avoid grapefruit, grapefruit juice (may increase levels of buspirone)
-Decrease dose w/ strong inhibitors or increase w/ strong inducers
-Avoid alcohol: CNS depression
-Avoid opioids: profound sedation, respiratory depression, coma, and death
Benzodiazepines (BZDs):
-Drugs/Brands
-MOA
-ROA
-Considerations for TX in anxiety
-Other uses
Drugs: alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorezapam (Ativan), chlordiazepoxide, clorazepate (Tranxene), oxazepam
MOA: enhance gamma-aminobutyric acid (GABA), an inhibitory neutrotransmitter that causes CNS depression resulting in anxiolytic, anticonvulsant, sedative, and/or muscle relaxant properties
ROA: PO, injection, intranasal
Considerations in Anxiety TX:
-Provide fast relief of symptoms, but do NOT treat underlying cause
-Useful in short-term of acute anxiety preventing restful sleep and disrupting life
-Taken long-term: risk of developing tolerance (recommended to use for only 1-2 weeks then D/C and if used longer, taper off slowly to prevent withdrawl symptoms)
-Consider BZD w/ longer T1/2 to reduce risk of abuse (clonazepam, lorazepam, diazepam)
Others Uses:
-Sleep: lorazepam, temazepam
-Seizures: diazepam rectal gel (Diastat AcuDial)
Benzodiazepines (BZDs):
-AVEs
-Warnings
-CI
-BBW
-DDIs
AVEs: somnolence, dizziness, ataxia, weakness, lightheadedness
Warnings:
-CNS depression
-Anterograde amnesia
-Potential for abuse
-Safety risks in 65 yo and older: imapired cognition, delirium, falls/fractures
-Extravasation w/ IV use
-Paradoxical rxns
-Severe renal or liver impairment
-Pregnancy: crossess placenta and can cause birth defects or neonatal withdrawl syndrome
CI:
-Acute narrow-angle galucoma
-Sleep apnea, severe respiratory insufficiency
-Severe liver disease (clonazepam, diazepam)
-Myasthenia gravis (diazepam)
-NOT for infants <6 months (diazepam) or premature infants (lorazepam)
BBW:
-Use w/ opioids: sedation, respiratory depression, coma, death
-Risk for abuse, misuse, and addition leading to overdose and death (less in clonezpam since longer T1/2)
-Continued use leads to physical dependence and abrupt D/C can cause withdrawl symptoms (taper off slowly when using >10 days)
DDIs:
-Additive CNS depression (most pain meds, alcohol, skeletal muscle relaxants, etc)
-Diazepam, clonazepam, chlordiazepoxide, and clorazepate: caution w/ CYP3A4 inhibitors
-Alprazolam: CI with strong CYP3A4 inhibitors
-Valproate increases levels of lorazepam
BZDs: Specifics
1. Which BZDs are safer in elderly patients?
- Which BZDs are often used for alcohol withdrawl syndrome?
- _________ is a lipophilic and fast BZD with high drug abuse potential despite its long T1/2.
- LOT drugs: Lorazepam, Oxazepam, Temazepam
- Lorazepam, diazepam, chlordiazepoxide
- Diazepam
BZDs: Specifics:
1. ________ is a fast onset BZD often abused from its quick action.
- _________ is a BZD used more in acute care.
- _________ is the reversal for BZDs.
- Alprazolam
- Midazolam (Versed)
- Flumazenil
Chronic Insomnia:
-Define
-Non-pharmacological TX
-Natural Products
Insomnia: symptoms at least three times per week for at least 3 months despite adequate opportunity to sleep:
-Difficulty falling asleep (sleep initiation or sleep latency)
-Reduced sleep duration
-Poor sleep quality (ex. awakenings after sleep onset)
Non-pharmacological TX:
-Cognitive behavioral threapy (CBT-I): PREFERRED
-Address underlying medical conditions (ex. pain, SOB from HF, anxiety, BP, depression, alcohol use disorder)
-D/C medications that cause insomnia
Natural Products:
-Melatonin 1-5mg Qpm: substrate of CYP1A2 and prolonged effects can occur w/ 1A2 inhibitors (ex. ciprofloxacin, fluvoxamine); can help w/ jet lag (adjusting to different sleep time)
-Valerian, Kava: NOT recommended due to hepatotoxicity
-Chamomile tea: can help pt to feel calmer
Drugs that cause insomnia
Psychiatric/Neurologic Medications: acetylcholinesterase inhibitors, aripiprazole, atomoxetine, buproprion, stimulants, fluoxetine (if taken late in day)
Others:
1. Alcohol - can help induce sleep, BUT reduces QUALITY of sleep
- Caffeine
- Decongestants (ex. pseudophedrine)
- Diuretics (from nocturia)
- Nicotine (including NRT)
- INSTIs
- Steroids
- Varenicline
Chronic Insomnia: General TX
First line: NON-PHARM
-Keep bedroom dark, comfortable, and quiet
-Keep regular sleep schedule
-Avoid daytime naps, even after poor night of sleep or limit to 30 minutes
-Reserve bedroom for sleep and other appropriate activities (NO TV or other stimulants)
-Turn face of clock aside to minimize anxiety
-If unable to sleep, get up and do something to take mind off sleeping
-Extablishe pre-bedtime ritual to condition body (ex. soft music, mild stretching, yoga, pleasurable reading)
-Avoid exercising right before bed
-Do NOT eat heavy meals before bedtime
-Do NOT consume caffeine in afternoon
Second Line:
-Trouble falling asleep: Z drugs (eszopiclone, zolpidem, zaleplon), Ramelteon
-Trouble staying asleep: eszopiclone, zolpidem, doxepin, suvorexant
-BOTH: eszopiclone, zolpidem
Short-term: benzodiazepines, OTC first-generation antihistamines
Z Drugs:
-Drugs/Brands
-MOA
-ROA
Drugs: eszopiclone (Lunesta), zolpidem (Ambien, Edluar), zaleplon (Sonata)
MOA: non-BZD hypnotics that act selectively at the BZD receptor to increase GABA, an inhibitor neurotransmitter to induce CNS depression
ROA: PO
-Edluar: SL tablet
Z Drugs:
-AVEs
-Warnings
-CI
-BBW
-DDIs
AVEs: somnolence, dizziness, ataxia, HA, lightheadedness, “pins and needles” feeling on skin
-Eszopiclone: dysgeusia (altereted sense of taste)
Warnings:
-CNS depression and next-day impairment with <7-8 hours of sleep (especially at high doses or coadministration w/ other CNS depressants including alcohol)
-Abnormal thinking, behavioral changes, worsening depression, respiratory depression
-Potential for abuse and dependence (can cause withdrawl if used longer than 2 weeks)
CI: hx of complex sleep disorder
BBW: complex sleep behavior (ex. sleep-walking, sleep-driving, engaging in other activities while NOT fully awake)
DDIs:
-Caution w/ potent CYP3A4 inhibiotrs
-Additive CNS depression
-do NOT take w/ fatty foods, a heavy metal, or alcohol
Orexin Receptor Antagonists:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-AVEs
-Warnings
-CI
-DDIs
Drugs: daridorexant (Quviviq), lemborexant (DayVigo), suvorexant (Belsomra)
MOA: orexin receptor antagonist that inhibits orexin neuropeptide signaling system that promotes wakefulness
ROA: PO
Administration:
-do NOT take if <7 hours of sleep remaining
-Onset of action delayed if taken with meal
AVEs: somnolence, HA, dizziness, abnormal dreams
Warnings: worsening depression/SI, sleep paralysis, hallucinations, cataplexy-like symptoms (sudden loss of muscle tone), complex sleep behavior, daytime impairment (risk when use w/ other CNS depressants)
-NOT recommended in severe hepatic impairment
CI: narcolepsy
DDIs: caution with CYP3A4 inhibitors
Melatonin Receptor Antagonists:
-Drugs/Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-Warnings
-DDIs
Drugs: ramelteon (Rozerem), tasimelteon (Hetlioz)
MOA: agonists at MT1 and MT2 melatonin receptors that promote sleepiness and regulate circadian rhythm to coordinate sleep-wake cycle
ROA: PO
Administration: do NOT take with fatty food
-NOT a controlled substance among the other sleep drugs
TX (tasimelteon): specifically for NON-24 hour sleep-wake disorder (do NOT have normal cycle - ex. blind pt)
AVEs: somnolence, dizziness
Warnings:
-Ramelteon: complex sleep behavior
DDIs: do NOT take w/ fluvoxamine (strong CYP1A2 inhibitor that increases concentrations of this drug class)
Doxepin:
-Brand
-MOA
-ROA
-Considerations for insomnia usage
Brand: Silenor
MOA: tricyclic antidepressant that inhibits NE and 5-HT reuptake along with inhibition of ACh and histamine
ROA: PO
Considerations for sleep:
-For insomnia, use ER version to stay asleep
-Warning of complex sleep disorder
-AVEs: seizures, somnolence, anticholinergic effects
-Increase in SI in young pts
First-generation antihistamines for sleep:
-Drugs/Brands
-MOA
-AVes
-Considerations
Drugs: diphenhydramine (Benadryl), doxylamine (Unisom, SleepTabs)
MOA: inhibits H1 receptor
AVEs:
-Sedation: tolerance to sedative effects that can develop after 10 days of usage
-Confusion, seizures (high dose, older adults)
-Paradoxical excitation in young children (do NOT use in children <12 yo)
-Peripheral anticholinergic AVes: dry mouth, urinary retnetion, dry eyes/blurry vision, constipation
Considerations:
-Avoid use in BPH (can worsen symptoms) and glaucoma (can elevate IOP)
-Avoid in older adults (Beers Criteria): confusion, dizziness, risk of falls, hypotension
-Risk of mix-up: some OTX Unisom branded-products contain diphenhydramine
Narcolepsy:
-Define
-General TX
-Drug considerations
Narcolepsy: excessive daytime sleepiness with cataplexy (sudden loss of muscle tone) and sleep paralysis which can last from a few seconds to several minutes
General TX:
-Stimulants: armodafinil, modafinil
-Sodium oxybate (Xyrem)
-Others: pitolisant (histamine-3 receptor antagonist/inverse agonist), solriamfetol (DA and NE reuptake inhibitor)
Stimulants (armodafinil, modafinil):
-AVEs: HA, insomnia, anxiety, nause
-Warnings: caution in pre-existing cardiac, hepatic, renal, or psychiatric conditions; severe rash that can be life-threatening (ex. SJS)
-C-IV
Sodium oxybate (Xyrem):
-MOA: active moiety of oxybate salts in sedative GHB (derived from GABA)
-AVEs: dizziness, confusion, nausea
-Warnings: depression, suicide, psychosis, anxiety, sleepwalking
-CI: use w/ sedative-hypnotics, alcohol
-BBW: STRONG CNS DEPRESSANTS –> respiratory depression, coma, and death risk; drug can be used illicitly and sometime to facilitate sexual assault (“date rape” drug –> REMS PROGRAM)
-C-III
Restless Leg Syndrome (RLS):
-Define
-Pathophysiology
-General TX
RLS: urge to move lower legs sometimes described as a “creeping sensation” that is worse at night and relieved w/ movement
Pathophysiology: thought to be from dysfunction of dopamine
General TX:
-Primarily dopamine agonists (pramipexole, ropinirole –> though taken for PD, taken IR 1-3 hours before bed for RLS; ritigotine: patch applied daily)
-Gabapentin enacarbil (Horizant): for RLS or postherepetic neuralgia –> taken at 5pm daily (XR version of gabapentin); take w/ food and swallow whole
