Chapter 21 antidepressant agents Flashcards
Tricyclic Antidepressants (TCAs)
drug class
Amines:
Amitriptyline, Amoxapine, Clomipramine, Doxepin, Imipramine, Trimipramine
Secondary Amines:
Desipramine, Nortriptyline, Protriptyline
Tetracyclic:
Maprotiline.
MOA TCAs
Inhibits presynaptic reuptake of serotonin (5HT) and norepinephrine (NE).
Leads to an accumulation of neurotransmitters in the synaptic cleft, increasing stimulation of postsynaptic receptors.
Exact mechanism for depression treatment remains unclear but is believed to be linked to neurotransmitter accumulation.
Indications for TCAs
Relief of depressive symptoms.
Preferred for patients with depression accompanied by anxiety and sleep disturbances.
Some TCAs (e.g., Imipramine) are used for enuresis (bedwetting) in children over 6 years old.
Chronic pain management, neuropathy, fibromyalgia, anxiety disorders.
Clomipramine is approved for obsessive-compulsive disorder (OCD).
Pharmacokinetics TCAs
Well absorbed from the GI tract; peak levels in 2 to 4 hours.
Highly protein- bound, lipid-soluble, and widely distributed in tissues (including the brain).
Metabolized in the liver; excreted in urine.
Long half-life (8-46 hours).
Therapeutic effects take 10-14 days; maximum effects may take 4-8 weeks.
Crosses placenta, enters breast milk.
CI TCAs
Allergy to TCAs.
Recent myocardial infarction (MI)
due to the risk of reinfarction.
Use with monoamine oxidase inhibitors (MAOIs) (can cause serotonin syndrome, severe hypertension, convulsions, and death).
Myelography within the last 24 hours or next 48 hours (potential drug-dye interaction).
Caution in patients with:
- Cardiovascular disease (risk of arrhythmias, hypertension).
- Angle-closure glaucoma.
- Urinary retention, prostate
hypertrophy.
- GI/GU surgery.
- Seizure disorders (lowers seizure
threshold).
- Psychotic disorders (risk of
worsening paranoia, mania).
- Hepatic or renal impairment (risk of toxicity).
Boxed warning for increased suicidality risk in children, adolescents, and young adults.
AE TCAs
Central Nervous System (CNS):
- Sedation, sleep
disturbances, fatigue.
- Hallucinations,
disorientation, tremors.
- Difficulty concentrating,
weakness.
Gastrointestinal (GI):
- Dry mouth, constipation,
nausea, vomiting, anorexia.
- Decreased salivation.
Genitourinary (GU):
- Urinary retention,
hesitancy.
- Loss of libido, sexual
dysfunction.
Ocular:
- Blurred vision,
photophobia.
Cardiovascular (CV):
- Orthostatic hypotension,
hypertension.
- Tachycardia, arrhythmias,
angina, stroke, myocardial infarction.
Miscellaneous: - Weight gain/loss, flushing, chills, sweating, nasal congestion.
- Alopecia (hair loss).
Withdrawal Symptoms: Abrupt cessation can cause nausea, headache, vertigo, malaise, nightmares.
TCA DDI/food interactions
Cimetidine, Fluoxetine, Ranitidine: Increase TCA levels (risk of toxicity).
Oral anticoagulants:
Increased serum levels, risk of bleeding.
Sympathomimetics (e.g., clonidine): Risk of hypertension and arrhythmias.
MAOIs: Risk of serotonin syndrome, convulsions, hypertensive crisis, death (AVOID).
Alcohol, antihistamines, sedatives: Increased CNS depression.
TCA Care considerations
Assess contraindications (cardiac history, glaucoma, renal/hepatic impairment).
Monitor for suicidal thoughts, particularly in young adults.
Monitor for CNS effects (sedation, hallucinations, fall risk).
Educate patients:
- Effects may take 2-4 weeks to be noticeable.
- Avoid alcohol and sedatives.
- Do not abruptly stop the drug (taper gradually).
- Orthostatic hypotension precautions (rise slowly from
sitting/lying positions).
- Take at bedtime if causing drowsiness.
Monoamine Oxidase Inhibitors (MAOIs) MEDS
Isocarboxazid
(Marplan)
Phenelzine (Nardil) Tranylcypromine (Parnate)
Selegiline (Emsam – transdermal patch; Zelapar – oral form for Parkinson’s disease)
MOA: MAOIs
MAOIs block the breakdown of NE, 5HT, and dopamine, leading to increased levels of these neurotransmitters in the synaptic cleft.
This increased stimulation of postsynaptic receptors is believed to be responsible for the antidepressant effects.
Indication: MOAIs
Used for depression in patients who do not tolerate or respond to safer antidepressants (e.g., SSRIs, SNRIs, TCAs).
Selegiline (oral form)
is also used as an adjunct in Parkinson’s disease.
Pharmacokinetics: MOAIs
Well absorbed from the GI tract; peak levels in 2 to 3 hours.
Metabolized in the liver (acetylation); excreted in urine.
Patients who are “slow acetylators” require lower doses to avoid excessive drug accumulation.
Crosses the placenta and enters breast milk.
CI : MAOIs
Allergy to MAOIs (risk of hypersensitivity).
Pheochromocytoma (increased NE levels may lead to hypertensive crisis).
Cardiovascular diseases
(hypertension, coronary artery disease, angina, heart failure).
Cerebrovascular abnormalities (risk of stroke due to vasoconstriction and high BP).
History of frequent or severe headaches (risk of hypertensive crisis).
Elective surgery (unpredictable effects on NE levels postoperatively).
Caution in pregnancy and breastfeeding (effects on the fetus and neonate unknown)
AE: MAOIs
CNS: Dizziness, excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation, blurred vision.
GI: Nausea, vomiting, diarrhea/constipation, anorexia, weight gain, dry mouth, abdominal pain.
GU: Urinary retention, dysuria, incontinence, changes in sexual function.
Cardiovascular: Orthostatic hypotension, arrhythmias, palpitations, angina.
Severe Hypertensive Crisis:
- Occipital headache,
palpitations, neck stiffness, nausea, vomiting, sweating, dilated pupils, photophobia, tachycardia, chest pain.
- Can progress to intracranial bleeding and fatal stroke.
DDI/food interactions: MAOIs
Increased risk of hypertensive crisis with tyramine-rich foods (due to MAO inhibition in the GI tract, leading to increased NE release).
Avoid: Aged cheeses, cured meats, fermented foods, beer, wine, soy products, fava beans.
Severe drug interactions:
TCAs, SSRIs, SNRIs:
Increased risk of serotonin syndrome and hypertensive crisis.
Sympathomimetic drugs (e.g., methyldopa): Exaggerated sympathomimetic effects.
Insulin and oral antidiabetic drugs: Increased risk of hypoglycemia (dose adjustments required).
Nursing considerations: MAOIs
Monitor blood pressure regularly, especially for signs of hypertensive crisis.
Limit drug access for patients at risk of suicide.
Monitor for CNS effects (mania, tremors, confusion).
Provide a detailed list of tyramine-containing foods to avoid.
Assess liver and renal function before initiation.
Educate patients about drug interactions and risks of serotonin syndrome.
Ensure slow titration of dosage due to the delayed onset of therapeutic effects.
Have phentolamine (adrenergic blocker) on standby in case of hypertensive crisis.
Selective Serotonin Reuptake Inhibitors (SSRIs) MEDS
Fluoxetine (Prozac) Citalopram (Celexa) Escitalopram (Lexapro) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft) Vilazodone (Viibryd) Vortioxetine (Brintellix)
SSRIs MOA
SSRIs block the reuptake of serotonin (5HT), increasing levels in the synapse.
Vilazodone also partially agonizes serotonin receptors to enhance antidepressant effects
Indications: SSRIs
Major depressive disorder (MDD)
Obsessive- compulsive disorder (OCD)
Panic disorders Bulimia nervosa
Premenstrual dysphoric disorder (PMDD)
Post-traumatic stress disorder (PTSD)
Social phobias & social anxiety disorders
Chronic pain, alcohol dependency, neuropathies (off- label)
- Full therapeutic
effects may take up to 4 weeks.
Pharmacokinetics: SSRIs
-Well absorbed from the GI tract
- Metabolized in the liver
- Excreted in the urine and feces
Half-life varies widely between SSRIs:
- Fluoxetine: Parent drug half- life 1-3 days, active metabolite half-life 4-16 days.
- Longer half-life in liver
dysfunction.
CI : SSRI
Allergy to SSRIs (risk of hypersensitivity)
Severe renal or hepatic dysfunction
(risk of drug accumulation)
Diabetes (SSRIs may increase blood
sugar levels)
Use with caution in:
- Children, adolescents, and young adults (risk of suicidality)
- Pregnancy and breastfeeding (risk of pulmonary and cardiac problems in newborns)
- Bipolar disorder (can induce mania or rapid cycling).
AE: SSRIs
Central Nervous System (CNS):
- Headache, dizziness,
insomnia, anxiety,
agitation, tremor
- Mania/hypomania
activation, seizures
Gastrointestinal (GI): Nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, taste changes
Genitourinary (GU): Painful menstruation, cystitis, urinary urgency, sexual dysfunction, impotence
Respiratory: Cough, dyspnea, upper respiratory infections, pharyngitis
Miscellaneous: Sweating, rash, fever, pruritus
Serotonin Syndrome (Potentially Fatal) Symptoms: - Confusion, agitation,
disorientation, hallucinations, delirium, tachycardia, unstable BP, diaphoresis, fever, hyperreflexia, tremors, nausea, vomiting, diarrhea, coma
DDI/food interactions : SSRIs
MAOIs: Risk of serotonin syndrome (6-week washout period needed before switching to an MAOI).
TCAs and other antidepressants: Increased risk of serotonin syndrome.
St. John’s Wort, triptans, SNRIs: Risk of serotonin syndrome.
Aspirin, NSAIDs, anticoagulants: Increased risk of bleeding.
Evening primrose, ginkgo, ginseng, valerian: Increased risk of seizures or interactions
nursing considerations : SSRIs
Monitor for suicidal ideation (especially in young adults).
Educate patients that full effects may take 4 weeks.
Monitor for signs of serotonin syndrome.
Advise patients to avoid St. John’s Wort and NSAIDs. Take in the morning to reduce insomnia.
Encourage small, frequent meals for GI upset.
Assess for sexual dysfunction and weight changes.
Caution with driving until effects are known.
Indications SNRIs
All SNRIs are indicated for the treatment of major depressive disorder (MDD).
Milnacipran is specifically approved for fibromyalgia in adults.
Serotonin- Norepinephrine Reuptake Inhibitors (SNRIs) MEDS
Desvenlafaxine
(Pristiq)
Duloxetine
(Cymbalta)
Levomilnacipran
(Fetzima) Milnacipran (Savella) Venlafaxine (Effexor, Effexor XR)
SNRIs MOA
SNRIs increase levels of serotonin and norepinephrine in the synaptic cleft.
Some may weakly inhibit dopamine reuptake.
Do not inhibit monoamine oxidase (MAO).
Therapeutic effects take 4-6 weeks to become apparent.
Pharmacokinetics SNRIs
Readily absorbed from the GI tract.
Metabolized in the liver.
Excreted in the urine.
Half-lives vary, so
dosing can range from once to twice daily.
CI SNRIs
Allergy to any SNRI.
Do not use with MAOIs (risk of hypertensive crisis and serotonin syndrome).
Caution in patients who are severely depressed or suicidal, especially children, adolescents, and young adults, due to the increased risk of suicidality.
Screen for bipolar disorder and seizure risk before initiating therapy.
Pregnancy/Breastfeeding: Unclear safety profile; risk of pulmonary and cardiac problems in newborns exposed in the third trimester.
SNRIs are excreted in human milk, so alternative feeding methods may be necessary.
AE SNRIs
Most common effects due to increased serotonin and norepinephrine:
- Nausea, constipation,
dizziness, headache.
- Higher heart rates,
hyperhidrosis (excessive
sweating).
- Erectile dysfunction,
decreased libido.
- Tachycardia, vomiting,
palpitations.
Serious risks:
- Serotonin syndrome
- Hypertension
- Abnormal bleeding
- Angle-closure glaucoma
- Urinary retention.
DDI SNRIs
Increased risk of serotonin syndrome when combined with:
- MAOIs, SSRIs, TCAs.
- Triptans, fentanyl,
lithium, tramadol, tryptophan, buspirone, amphetamines, St. John’s Wort.
Increased bleeding risk with:
- Aspirin, NSAIDs,
antiplatelet drugs, anticoagulants.
Nursing interventions SNRIs
Assess for suicidality before and during treatment.
Monitor for serotonin syndrome, especially in drug
interactions.
Monitor blood pressure due to risk of hypertension. Caution in patients with glaucoma (angle-closure risk). Evaluate for urinary retention.
Educate patients:
- Therapeutic effects take up to 6 weeks.
- Avoid alcohol and St. John’s Wort.
- Report severe headache, rash, worsening depression, or
suicidal thoughts.
Dose adjustments may be needed for elderly patients and those with hepatic impairment.
