CNS: Psychopharm and Cannabis Flashcards
What is a common consideration across antidepressants/anxiolytics?
Do not discontinue abruptly
What is the black box warning for all antidepressants?
increases risk of SI in children, adolescents and young adults
Common contraindication across TCAs, SSRIs, SNRIs, bupropion, methylphenidate, amphetamines
Contraindicated if MAOI use within 2 weeks
What nutrient do MAOIs interact with that make it difficult to prescribe? What can that cause?
Tyramine - can cause hypertensive crisis
What is usually prescribed for panic dx?
alprazolam, clonazepam, fluoxetine, paroxetine, sertraline, Buspar (not monotherapy)
What is usually prescribed for GAD (generalized anxiety)?
alprazolam, duloxetine, escitalopram, paroxetine, venlafaxine
off-label: citalopram, desvenlafaxine, fluoxetine, fluvoxamine, mirtazapine, pregabalin, sertraline
What are the first-line agents for PTSD?
VA guidelines: sertraline, paroxetine
Canadian guidelines: paroxetine, venlafaxine, fluoxetine, sertraline
What are some medications to be aware of that affect the CYP450 system and thus interact with several antidepressants/anxiolytics?
- azole antifungals
- macrolide antibiotics
- HIV protease inhibitors
- calcium channel blockers
- SSRIs
- nefazodone
What is neuroleptic malignant syndrome?
rare but potentially fatal - extreme muscle rigidity, high fevers, coma, death
Tricyclic antidepressants
Amitriptyline, nortriptyline, imipramine, doxepin, trimipramine maleate, amoxapine, desipramine, protriptyline hydrochloride, clomipramine
Indication & MOA
Indications: depression, anxiety with sleep disturbance (doxepin, elavil), enuresis in children 6+ (imipramine), OCD (clomipramine), eating disorders
Doxepin: insomnia
MOA: Acts on serotonin, norepinephrine, histamine and acetylcholine
Tricyclic antidepressants
Amitriptyline, nortriptyline, imipramine, doxepin, trimipramine maleate, amoxapine, desipramine, protriptyline hydrochloride, clomipramine
Prescribing considerations
- Long half-life of 6-8 hours
- Metabolized by the CYP450 system
- Highly cardiotoxic; can cause life-threatening arrythmias
- narrow TI OD can be fatal OD dose isn’t that high - avoid in those with SI
Tricyclic antidepressants
Amitriptyline, nortriptyline, imipramine, doxepin, trimipramine maleate, amoxapine, desipramine, protriptyline hydrochloride, clomipramine
Avoid, caution
- Avoid: angle closure glaucoma, suicidal patients, cardiovascular disorders, glaucoma
- Caution: metabolic syndrome, seizure disorder, elderly (anticholinergic fx, hip fractures)
Tricyclic antidepressants
Amitriptyline, nortriptyline, imipramine, doxepin, trimipramine maleate, amoxapine, desipramine, protriptyline hydrochloride, clomipramine
Adverse fx (5)
- Paradoxical diaphoresis
- Anticholinergic fx
- Orthostatic hypotension
- Sedation
- drowsiness
SSRIs
Fluoxetine, olanzapine-fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
Indications & MOA
indications: depression, anxiety, panic disorders, OCD, body dysmorphic disorder, bulimia, PDD, PTSD, vasomotor symptoms in menopause
MOA: Selective inhibitory fx on presynaptic serotonin reuptake and weak fx on NE and dopamine reuptake
SSRIs
Fluoxetine, olanzapine-fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
Considerations (specific to fluoxetine, paroxtine, sertraline, citalopram, escitalopram)
- Long half-life: 26 hours
- Takes a few weeks to take effect
- Extensive first-pass metabolism
- Metabolized by the CYP450 system
- Fluoxetine: least likely to cause weight gain, increases energy can be activating (may feel like worsening anxiety), long half-life; start low and titrate slow
- Paroxetine: interacts with a lot of other medications, nasty withdrawal, stimulates appetite, significant weight gain, excessively sedating
- Sertraline: increases energy
- Citalopram: BBW for QT prolongation - max dose 40mg daily, 20mg daily if over 60
- Escitalopram: tends to be weight neutral and neither sedating nor activating
SSRIs
Fluoxetine, olanzapine-fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
BBW, pregnancy/lactation, peds, contraindications
- BBW for citalopram: QT prolongation
- Pregnancy/lactation: Eval risk vs. benefit, newborn can have withdrawal symptoms; lactation: sertraline and escitalopram have the lowest relative infant dose
- Peds: Fluoxetine is first line
- CI: hypersensitivity to SSRIs, renal or hepatic insufficiency
SSRIs
Fluoxetine, olanzapine-fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram
adverse fx
- CNS: agitation, insomnia, serotonin syndrome, blurred vision, headache, drowsiness, tremor
- GI: nausea, vomiting, diarrhea, GI bleed, hyponatremia, weight changes, dry mouth, constipation
- Other: Sexual dysfunction, rash/itching
- CV: QT prolongation (citalopram)
What is serotonin syndrome?
- ADR that occurs with more than one serotonergic agent taken at the same time
- Sx = altered mental status or agitation, GI distress, neuromuscular changes (clonus, tremors, hyperreflexia), VS changes, sweating, hyperthermia
SNRIs
Venlafaxine, duloxetine, milnacipran, desvenlafaxine
Indications, MOA
- MDD, GAD, neuropathy, fibromyalgia (Milnacipran), social anxiety, binge eating disorder, OCD, postmenopausal disorder, PTSD, panic disorder
- MOA: Inhibit reuptake of norepinephrine and serotonin
SNRIs
Venlafaxine, duloxetine, milnacipran, desvenlafaxine
Prescribing considerations
- Long half-life 8-17 hours
- Metabolized by CYP450
SNRIs
Venlafaxine, duloxetine, milnacipran, desvenlafaxine
Avoid, pregnancy
- Avoid: uncontrolled HTN, renal & hepatic impairment
- Pregnancy: venlafaxine & desvenlafaxine - consider tapering in 3rd trimester
SNRIs
Venlafaxine, duloxetine, milnacipran, desvenlafaxine
Interactions & Monitoring
- Interactions
- Antibiotics
- OTC medications that stimulate or cause insomnia or drowsiness
- Monitoring
- Serum transaminase levels
- SI
- Activation of hypomanic or manic symptoms
SNRIs
Venlafaxine, duloxetine, milnacipran, desvenlafaxine
Adverse fx
- CNS: Headache, somnolence, dizziness, Insomnia, Fatigue, sedation
- GI: Dry mouth, Constipation, nausea
- CV: Orthostatic hypotension
- GU: Erectile dysfunction, Ejaculation failure
- Other: sweating
Bupropion (Wellbutrin)
Indications & MOA
- indications: good with co-morbid mood dx; ADHD, MDD, smoking cessation
- MOA: inhibits reuptake of norepinephrine and dopamine
Bupropion
Contraindication & adverse fx
- CI: bupropion in seizure disorders or when tapering/withdrawing from other CNS depressants; avoid in anxiety
- ADR: insomnia
Mirtazapine/trazodone
Indications, MOA, ADRs
- Indications: Mirtazapine is an antagonist of 5HT2, 5HT3 and histamine receptors
- ADR: drowsiness at higher levels
Typical Antipsychotics
Phenothiazines: Chlorpromazine (Thorazine)
Non-phenothiazine: haloperidol (Haldol)
MOA, CI, BBW
Block dopamine receptors in the basal ganglia, hypothalamus, limbic system, medulla
CI: glaucoma, bone-marrow depression, severe liver or CVD
BBW: increased mortality in older adult patients
Typical Antipsychotics
Phenothiazines: Chlorpromazine (Thorazine)
Non-phenothiazine: haloperidol (Haldol)
Monitoring & ADRs
- Monitoring: Abnormal involuntary movement scale (AIMS)
- ADRs
- STANCE
- Sedation/sunlight sensitivity/skin effects/sexual side fx
- Tardive dyskinesia
- Anticholinergic effects and agranulocytosis
- Neuroleptic malignant syndrome
- Cardiac arrythmias
- Extrapyramidal symptoms/akathisia endocrine effects - increased prolactin
- Weight gain
- STANCE
Atypical antipsychotics
Ariprazole (Abilify),clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon)
Indications & MOA
- psychotic mania, nonpsychotic mania
- Block serotonin and dopamine receptors
Atypical antipsychotics
Ariprazole (Abilify),clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon)
Considerations, CI, ADRs
- Considerations: -pines are more sedating than the -dones, related to their antihistamine actions
- CI: hepatic or renal disease
- ADRs
- Seizures
- Weight gain
- Diabetes
- Hyperprolactinemia
- Dizziness
- Orthostatic hypotension
- Clozapine: fatal agranulocytosis
Benzodiazepines
Lorazepam (Ativan), Flurazepam (dalmane), Temazepam (restoril), Triazolam (Halcion)
Indications
- anxiety, panic disorders, alcohol withdrawal, seizures, insomnia, muscle spasms, pre-anesthesia sedation, IBS, restless leg syndrome, chemo N/V
- Flurazepam, temazepam, triazolam for insomnia
- MOA: increase the action of GABA, which decreases the effect of neuronal excitation
Benzodiazepines
Lorazepam (Ativan), Flurazepam (dalmane), Temazepam (restoril), Triazolam (Halcion)
Considerations, caution, CI, peds
- rapidly and widely distributed throughout the body following oral intake; peak 30min-8 hours
- Caution: elderly - BEERS
- CI: pregnancy, renal & hepatic impairment, hypersensitivity to benzodiazepines, acute narrow-angle glaucoma
- Peds: 6+
With which medications should you educate your patient to avoid driving while taking?
What are the treatment durations of these medications?
- Flurazepam, temazepam, triazolam: Should not be used more than 3x a week for less than 3 months
- Zolpidem not to be used longer than 8 weeks; females take half-dose
- Zaleplon should not be used longer than 5 weeks
Benzodiazepines
Lorazepam (Ativan), Flurazepam (dalmane), Temazepam (restoril), Triazolam (Halcion)
Interactions, Monitoring, ADRs
- Interactions
- digoxin, TCAs: benzo increases level
- barbiturates, nefazodone, fluoxetine, fluvoxamine, MAOIs, sertraline, antihistamines: increased CNS depression
- Clozapine: increased sedation, salivation, hypotension, delirium, respiratory arrest
- Monitoring if long term use: LFTs, CBC, TCA and digoxin levels
- ADRs
- CNS depression
- Sedation
- Physical dependence
Buspirone (BuSpar)
MOA, considerations
- partial agonist for serotonin 5-HT1a receptors in the brain
- May take up to 6 weeks to see fx
- No physical dependence/withdrawal/abuse potential
- Less sedating and limited psychomotor impairment
- Lack of interaction with alcohol
Buspirone (BuSpar)
Interactions, ADRs
- Interactions
- MAOIS, SSRIs may cause serotonin syndrome
- Atypical antipsychotics
- ADRs
- Dizziness
- Drowsiness
- nausea
Benzodiazepine receptor agonist
Zolpidem (ambien), zaleplon (sonata), eszopiclone (Lunesta)
Indication, MOA, CI, Interactions, monitoring, ADRs
- Indication: Insomnia
- MOA: agonists on the benzodiazepine site of the GABAa receptor
- CI: pregnancy, elderly, children, long-term use
- Interactions: Avoid with alcohol, other CNS depressants
- Monitoring: LFTs
- ADRs: CNS depression, sedation, abnormal behaviors
Lithium (Lithobid, eskalith)
Indications, considerations
- Indications: Mood stabilizer: manic episodes, maintenance treatment of manic depressive patients with hx of mania; off-label maintenance for bipolar depression and adjunct for MDD, dementia
- Considerations
- Not metabolized by the liver, excreted by kidneys
- Long half-life: 15-36 hours
- Maintain adequate salt intake
Lithium (Lithobid, eskalith)
CI, Monitoring
- CI: pregnancy
- Monitoring
- Narrow TI - monitor every 10-14 days after initiating then every 2-3 months after
- TSH, kidney function, EKG
Lithium (Lithobid, eskalith)
ADRs
- Toxicity
- ECG changes
- LMNOP: Lithium can cause movement issues (tremors); nephrotoxicity; hypothyroidism; pregnancy problems
Valproic acid
Indications, MOA, consideration, CI, monitoring
- Indications - Mood stabilizer: acute mania and mixed episodes; off-label: maintenance tx of bipolar disorder, bipolar depression, psychosis, schizophrenia
- MOA: Block GABA
- Considerations: Metabolized by the CYP450 system
- CI: pregnancy
- Monitoring
- Plasma levels every 3 months
- Platelets, LFTs, coagulation studes
Lamotrigine, gabapentin, topiramate
Indications, monitoring, ADRs
- Indications: Mood stabilizer: maintenance of bipolar I; off-label: bipolar depression, bipolar mania, neuropathic/chronic pain, MDD
- Monitoring: ophthalmological checks required, baseline kidney/liver function tests
- ADRs
- Somnolence
- Dizziness
- Weight changes
- Topiramate has 1% chance of renal calculi
Carbamazepine (Tegretol)
Indications, considerations, monitoring
- Indications: off-label - bipolar depression, bipolar maintenance, psychoses, schizophrenia adjunct
- Considerations: Ancestry across broad areas of asia should consider screening for HLA-B1502 allele - can increase risk of Stevens-Johnson syndrome
- Monitoring: CBCs, LFTs, kidney function, TSH
Stimulants
Methylphenidate, dexamphetamine, amphetamine
Indications, MOA
- First line ADHD, narcolepsy
- increase neurotransmission of dopamine and norepinephrine
Stimulants
Methylphenidate, dexamphetamine, amphetamine
Considerations
- Methylphenidate: food slows absorption and onset of action
- Amphetamines - Vyvanse is the least likely to cause addiction
Stimulants
Methylphenidate, dexamphetamine, amphetamine
General CI & caution, then specific to methylphenidate vs. other amphetamines
- CI: CVD, HTN, pregnancy
- Caution: glaucoma, other mental health conditions, personal/family hx of Tourette’s or tics, seizure dx, Anxious/agitated/tense patient
- Methylphenidate: circulation issues in fingers or toes
- Amphetamines: hyperthyroidism, history of drug misuse, hx of issues with stimulants, liver or kidney issues, thyroid issues
Stimulants
Methylphenidate, dexamphetamine, amphetamine
ADRs
- Insomnia
- Weight loss
- Palpitations
- HA
- HTN
Non-stimulants
Atomoxetine, guanfacine, clonidine
Indications, MOA, considerations
- Indications: 2nd line ADHD
- Guanfacine, clonidine: best if hyperactivity and impulsivity poorly controlled
- MOA: inhibits presynaptic norepinephrine transport
- Consideration: Potential for patients with hx of substance abuse, tics or severe adverse fx to stimulants
Cannabis
Indications, MOA
- Indications
- THC: analgesia, anti-inflammatory fx, antiemetic
- CBD: analgesic, anti-inflammatory and anti-seizure
- CB1: cannabinoid receptors in the CNS modulate cognition, memory, motor function and analgesia
- CB2: cannabinoid receptors found in tissues related to immune fxn such as WBC, bone marrow, tonsils, thymus and spleen
Cannabis
Types
- Sativa: uplifting, energetic, anti-depressive fx, preferred for daytime use
- Indica: relaxing, calming, sedating, preferred for nighttime use
- CBD/THC: can be used day or night - CBD mitigates the psychoactive component of THC
Cannabis
ADRs
- Xerostomia, nausea, vomiting with excessive use, drowsiness, somnolence, vertigo/dizziness
- Cannabinoid hyperemesis syndrome may occur with people who smoke excess of marijuana daily and long term - once stopped this should go away but can return if use resumes
Clonidine
MOA & Indications
- MOA: centrally acting alpha-2 agonist
- Indications: approved for HTN and ADHD; off-label for PTSD, social anxiety, Tourette’s, substance withdrawal, menopausal flushing, severe pain not relieved by opiates alone
Propranolol (Inderal)
Indications & MOA
- Indication: off-label: PTSD, GAD, violence/aggressive behavior
- MOA:
- Helps to prevent the development of PTSD: blocks beta-1 adrenergic receptors and may prevent fear conditioning and reconsolidation of fear
- Violence/aggression: presumed to be related to central actions at beta adrenergic and serotonin receptors
Pediatric considerations for the following:
Lithium, olanzapine, risperidone, ariprazole, ziprasidone, asenapine
- Lithium: approved for acute mania/mixed mania and bipolar maintenance 7+
- Olanzapine: approved 13+ for schizophrenia and acute mania; 10+ in combo with fluoxetine for bipolar depression
- Risperidone: approved 13+ for schizophrenia; 10+ acute mania/mixed mania; 5-16 for autism-related irritability
- Ariprazole: approved 13+ schizophrenia; 10+ acute mania/mixed mania; 6-17 autism related irritability; 6-18 Tourette’s
- Ziprasidone: clinical trials have demonstrated efficacy for behavioral disturbances in children and adolescents
- Asenapine: approved 10-17
Pregnancy considerations for the following:
Lithium, valproates, carbamazepine, lamotrigine
- Lithium: associated with increased neonatal readmissions, first-trimester exposure has major risk for malformation in infant
- Valproate: avoid as it can cause fetal abnormalities
- Carbamazepine: avoid as it can cause fetal carbamazepine syndrome
- Lamotrigine: potential option for maintenance therapy
