Antidepressant Mechanisms and Effects Quiz
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Questions and Answers

Which of the following is a primary mechanism of action of nefazodone?

  • Potent agonism of 5-HT2A receptors.
  • Selective norepinephrine reuptake inhibition.
  • Inhibition of serotonin and norepinephrine reuptake, along with 5-HT2A receptor antagonism. (correct)
  • Selective serotonin reuptake inhibition.

    • What is a notable benefit of using nefazodone compared to SSRIs?

  • Reduced incidence of sexual dysfunction. (correct)
  • Quicker onset of action.
  • Increased effectiveness in the treatment of OCD.
  • Lower risk of hepatic enzyme elevation.

    • Which of the following is a potential adverse effect of nefazodone that requires careful monitoring?

  • Elevated hepatic enzyme levels and risk of liver failure. (correct)
  • Significant weight gain.
  • Reduced blood pressure.
  • Reduced appetite.

    • What is a significant consideration when transitioning a patient from an SSRI to nefazodone?

    <p>The risk of withdrawal symptoms may be exacerbated.</p> Signup and view all the answers

    What is the half-life of nefazodone?

    <p>2-4 hours.</p> Signup and view all the answers

    What is a primary therapeutic application of trazodone at low doses (e.g., 25-100mg)?

    <p>Improving sleep due to its sedative effects.</p> Signup and view all the answers

    At what dosage range is trazodone primarily used for treating Major Depressive Disorder (MDD)?

    <p>250-600 mg/day.</p> Signup and view all the answers

    Which of the following is a significant mechanism of action through which trazodone works?

    <p>Potent 5-HT2A/5-HT2C receptor antagonism combined with weak serotonin reuptake inhibition.</p> Signup and view all the answers

    Why might dividing doses of amitriptyline be preferred initially?

    <p>To reduce the likelihood of adverse effects.</p> Signup and view all the answers

    Which of the following is NOT a common side effect of tricyclic antidepressants (TCAs)?

    <p>Weight gain</p> Signup and view all the answers

    Which neurotransmitter is NOT primarily metabolized by MAO-A enzymes?

    <p>Dopamine</p> Signup and view all the answers

    A patient taking a TCA is experiencing a rapid heart rate and dizziness. Which of the following actions should be prioritized?

    <p>Monitor ECG for arrhythmias.</p> Signup and view all the answers

    What is a common side effect of MAOIs that might require increasing fluid and salt intake?

    <p>Orthostatic hypotension</p> Signup and view all the answers

    What is the primary mechanism of action for tricyclic antidepressants?

    <p>Blocking the reuptake of serotonin and norepinephrine.</p> Signup and view all the answers

    A patient on an MAOI develops paresthesia. Which vitamin supplementation would likely be indicated?

    <p>Vitamin B6 (Pyridoxine)</p> Signup and view all the answers

    A patient is experiencing severe anticholinergic effects, including confusion and delirium, after starting a TCA. Which medication might be helpful in managing these symptoms?

    <p>Physostigmine</p> Signup and view all the answers

    What is the primary mechanism behind a tyramine-induced hypertensive crisis in patients taking MAOIs?

    <p>Accumulation of tyramine in the GI tract due to inhibited breakdown</p> Signup and view all the answers

    Co-administration of MAOIs with which type of medication is most likely to induce serotonin syndrome?

    <p>SSRIs</p> Signup and view all the answers

    Which of the following is an FDA-approved TCA for the treatment of Generalized Anxiety Disorder (GAD)?

    <p>Doxepin</p> Signup and view all the answers

    A patient on a TCA reports feeling lightheaded upon standing. What is the most appropriate initial recommendation?

    <p>Increase fluid intake and salt</p> Signup and view all the answers

    What is a typical initial dose of phenelzine, an MAOI, for the treatment of depression?

    <p>15 mg/day</p> Signup and view all the answers

    Which TCA is most likely to cause parkinsonian symptoms due to its dopaminergic blocking activity?

    <p>Amoxapine</p> Signup and view all the answers

    Which best describes the mechanism of action of T3 (liothyronine) in augmenting antidepressant treatment?

    <p>It binds to intracellular receptors, influencing gene transcription.</p> Signup and view all the answers

    For patients who do not respond to antidepressants, what is the typical dose of liothyronine (T3) added to their regimen?

    <p>25-50 mcg/day</p> Signup and view all the answers

    Which of the following increases the risk of seizures when taking a TCA?

    <p>Rapid dose escalation or high doses</p> Signup and view all the answers

    What is a rare but serious adverse effect associated with the long-term use of thyroid hormones?

    <p>Osteoporosis</p> Signup and view all the answers

    Which statement regarding TCAs and pregnancy is most accurate?

    <p>TCAs cross the placenta and can lead to neonatal withdrawal syndrome.</p> Signup and view all the answers

    A patient is prescribed a TCA but has a history of narrow-angle glaucoma. What is the recommended adjustment to their treatment plan?

    <p>Switch to a different category such as SSRIs</p> Signup and view all the answers

    Which medication used with thyroid hormones can enhance its anticoagulant effects?

    <p>Warfarin</p> Signup and view all the answers

    A patient is started on a TCA and exhibits a sore throat and fever within the first month of therapy? What is the most important next step?

    <p>Perform a complete blood count (CBC)</p> Signup and view all the answers

    Which of the following is a contraindication for using thyroid hormones?

    <p>Cardiac disease</p> Signup and view all the answers

    Which of the following is a common ECG change seen with tricyclic antidepressant use?

    <p>Prolonged QT interval</p> Signup and view all the answers

    How does the TRH stimulation test help in diagnosing thyroid conditions in psychiatric patients?

    <p>It assesses the pituitary's response to thyroid-releasing hormones.</p> Signup and view all the answers

    What is the initial starting dose for most TCAs in the initial phase of treatment?

    <p>25 mg/day</p> Signup and view all the answers

    In the context of using thyroid hormones, what is the significance of monitoring TSH and Free T4 levels?

    <p>To check for signs of hyperthyroidism, or hypothyroidism</p> Signup and view all the answers

    Which of the following medications, when taken concurrently with a tricyclic antidepressant, may increase the risk of hypotension?

    <p>Antihypertensives</p> Signup and view all the answers

    A patient with symptoms of depression is undergoing a TRH stimulation test, and there is a blunted TSH response. What might this indicate?

    <p>Subclinical hypothyroidism or lithium-induced hypothyroidism.</p> Signup and view all the answers

    Which of the following statements best describes why TCAs are not recommended for patients with bipolar depression?

    <p>TCAs can induce mania or hypomania in susceptible individuals with bipolar disorder.</p> Signup and view all the answers

    Study Notes

    Nefazodone

    • Pharmacologic Action: Half-life 2-4 hours, steady state in 4-5 days.
    • Active Metabolites: Hydroxynefazodone and mCPP (serotonergic effects: migraine, anxiety, weight loss).
    • Mechanism of Action: Inhibits serotonin and norepinephrine uptake; antagonizes 5-HT2A receptors (antidepressant/anxiolytic). Mild alpha-1 adrenergic antagonism may cause orthostatic hypotension.
    • Therapeutic Indications: Major depression (300-600 mg/day), panic disorder, GAD, PMDD, PTSD, chronic pain, chronic fatigue syndrome.
    • Advantages: Less sexual dysfunction than SSRIs. Improves REM sleep and sleep continuity, potential help in treatment-resistant depression.
    • Limitations: Ineffective for OCD.
    • Precautions and Adverse Reactions:
      • Common Adverse Effects: Sedation, nausea, dizziness, insomnia, weakness, agitation, visual trails.
      • Hepatic Risks: Potential for severe hepatic enzyme elevation and liver failure; serial liver function tests are crucial.
      • Cardiovascular Caution: Risk of postural hypotension; use cautiously in cardiac conditions, dehydration, or with antihypertensives.
      • Switching from SSRIs: May exacerbate withdrawal symptoms.
      • Overdose: Survivable above 10 g, but fatal with alcohol; symptoms include nausea, vomiting, somnolence.
    • Elderly Considerations: Slower metabolism, especially in women; lower doses recommended.
    • Dosage and Clinical Guidelines:
      • Initial Dosage: General population: 100 mg twice daily; Elderly or sensitive: 50 mg twice daily.
      • Maintenance Dosage: Optimal: 300-600 mg/day in two divided doses. Once-daily dosing (e.g., bedtime) might be suitable.

    Trazodone

    • Pharmacological Actions: Weak serotonin reuptake inhibitor; potent 5-HT2A/5-HT2C receptor antagonist. Metabolized by the liver.
    • Therapeutic Indications: Depressive disorders (250-600 mg/day); improves sleep quality without influencing stage 4 sleep. Insomnia (first-line treatment due to sedative effects; 25-100 mg at bedtime). Erectile dysfunction (can enhance erections but may cause priapism). Other uses: low doses (50 mg/day) for agitation in dementia; >250 mg/day for GAD; PTSD-related insomnia and nightmares.
    • Precautions and Adverse Reactions:
      • Common Side Effects: Sedation, dizziness, orthostatic hypotension, headache, nausea.
      • Serious Concerns: Priapism, arrhythmias (in predisposed individuals), orthostatic hypotension (especially with food or high doses).
      • Overdose: Symptoms include lethargy, dizziness, tachycardia, coma; supportive treatment (possible gastric lavage).
    • Contraindications: Pregnancy, breastfeeding, hepatic/renal impairment.
    • Drug Interactions:
      • CNS Depression: Potentiates effects of alcohol and other CNS depressants.
      • Hypotension: Increased risk with antihypertensives.
      • No Hypertensive Crisis: Safe with MAOI-associated insomnia.
      • Increased Drug Levels: May elevate digoxin, phenytoin, and warfarin.
      • CYP3A4 Inhibitors: Raise mCPP levels, increasing side effects.
    • Laboratory Interference: No known lab test interferences.

    Tricyclics and Tetracyclines (TCAs)

    • Pharmacologic Actions: Increase serotonin and norepinephrine levels by blocking reuptake, affecting histamine and acetylcholine receptors.
    • Side Effects: Anticholinergic effects (constipation, sedation, dry mouth) vary by drug; less sexual dysfunction and weight gain than SSRIs. Common: orthostatic hypotension, sedation, lightheadedness.
    • Therapeutic Indications: Major depressive disorder (melancholic features, recurrent depression); not for bipolar depression; Panic disorder with agoraphobia, GAD (Doxepin, Imipramine potentially helpful*); OCD (Clomipramine is most effective); Chronic pain and migraines (Amitriptyline); Other disorders (childhood enuresis, PTSD, ADHD, narcolepsy, sleep disorders).
    • Clinical Considerations: Alternative for SSRI-intolerant patients; dosage adjustments for genetic factors and interactions. Monitor for orthostatic hypotension and sedation.
    • Precautions and Adverse Reactions:
      • Psychiatric Effects: May induce mania/hypomania; worsen psychotic symptoms; high plasma levels can cause confusion/delirium (especially elderly/dementia).
      • Anticholinergic Effects: Dry mouth, constipation, blurred vision, delirium, urinary retention; severe effects may lead to CNS anticholinergic syndrome. Management: sugarless gum/lozenges, bethanechol, avoid in narrow-angle glaucoma.
      • Cardiac Effects: ECG changes (tachycardia, flattened T waves, prolonged QT interval, depressed ST segments). Contraindicated in conduction defects/heart conditions unless necessary; persistent tachycardia may lead to discontinuation; overdose can cause life-threatening arrhythmias.
      • Other Autonomic Effects: Orthostatic hypotension (most common; management includes hydration, salt in diet, reducing antihypertensive meds if possible; Nortriptyline has the lowest risk). Stop TCAs days before elective surgery.
      • Sedation: Frequent effect due to anticholinergic and antihistaminergic properties.
      • Neurologic Effects: Tremors, myoclonic twitches, tremors of tongue/extremities. Rare: speech blockage, paresthesia, peroneal palsies, ataxia.
      • Drug-Specific Effects: Amoxapine (Parkinsonian symptoms, akathisia, dyskinesia, neuroleptic malignant syndrome). Maprotiline (increases seizure risk, especially with rapid dose increases). Clomipramine & amoxapine (lower seizure threshold than other TCAs).
      • Allergic and Hematologic Effects: Rashes, agranulocytosis, leukocytosis, leukopenia, eosinophilia; sore throat/fever warranting CBC testing.
      • Hepatic Effects: Mild, self-limiting increases in serum transaminases. Rare but severe: fulminant hepatitis (0.1-1%). Discontinue immediately if acute hepatitis suspected.
    • Teratogenicity/Pregnancy: Crosses placenta; neonatal withdrawal syndrome (tachypnea, cyanosis, irritability, poor sucking reflex); discontinue 1 week before delivery. Breastfeeding: present in low levels (usually undetectable).
    • Dosage Initiation and Titration: Starting dose 25 mg/day, gradual increase. Initial divided doses can reduce side effects, but entire dose at bedtime is possible.

    Monoamine oxidase inhibitors (MAOIs)

    • Pharmacologic Actions: MAO enzymes break down monoamine neurotransmitters (norepinephrine, serotonin, dopamine, tyramine).
    • Mechanism: Inhibit MAO enzymes, increasing neurotransmitter levels.
    • Therapeutic Indications: Depression (especially atypical depression).
    • Adverse Effects and Precautions:
      • Common Side Effects: Orthostatic hypotension (manage hydration/salt, stockings, fludrocortisone), insomnia (divide doses, avoid evening dosing, benzodiazepines if necessary).
      • Neurological Effects: Paresthesias (pyridoxine deficiency), myoclonus, muscle pain, or confusion (require dosage adjustments).
    • Tyramine-Induced Hypertensive Crisis: MAOIs prevent tyramine breakdown, causing severe hypertension. Symptoms: headache, stiff neck, diaphoresis, nausea, vomiting. Management: immediate medical attention, dietary restrictions for 2 weeks and avoid tyramine-rich foods and sympathomimetics.
    • Overdose: Symptoms (agitation to coma with hyperthermia, hypertension, tachypnea, tachycardia, dilated pupils) emerge 1-6 hours after overdose.
    • Drug interactions: CNS depressants (potentiated), serotonergic drugs (serotonin syndrome risk), opioids (fatal reactions).
    • Dosage and Clinical Guidelines:
      • Phenelzine: Start 15 mg/day, gradual weekly increase to 90 mg/day.
      • Tranylcypromine & Isocarboxazid: Start 10 mg/day, increase to 10 mg TID within a week.
    • Clinical Considerations: Refractory depression (combinations with other drugs possible, use cautiously).

    Transdermal Selegiline

    • Low doses selectively inhibit MAO-B, providing antidepressant effects. At higher doses, selectivity decreases requiring monitoring.

    Thyroid Hormones

    • Pharmacologic Action: T3 binds to intracellular receptors, affecting gene transcription (including neurotransmitter receptors); exact antidepressant augmentation mechanism is unknown.
    • Therapeutic Indications: Adjuvant therapy in psychiatry, especially for non-responders after 6 weeks of antidepressant therapy.
    • Dosage: Liothyronine (T3) 25-50 µg/day added to antidepressants.
    • Precautions and Adverse Effects:
      • Adverse Effects (at 25-50 µg/day): Headache, weight loss, palpitations, nervousness, diarrhea, tremors, insomnia.
      • Serious: Osteoporosis (long-term), cardiac failure, death in overdose.
    • Contraindications: Cardiac disease, angina, hypertension, thyrotoxicosis, uncorrected adrenal insufficiency, acute MI.
    • Drug Interactions: Warfarin increased anticoagulant effects, Insulin & Digitalis can increase dosage requirements, Sympathomimetics, ketamine, and maprotiline can endanger cardiac function. Other antidepressants (SSRIs, tricyclics, lithium, carbamazepine) can mildly alter thyroid function (e.g., lower T4, raise TSH); regular monitoring needed.
    • Thyroid Function and Diagnostic Tests: T4, TSH, FT4I; hypothyroidism common in depression patients (10%); Lithium can induce hypothyroidism or hyperthyroidism; TRH stimulation test diagnoses subclinical hypothyroidism/lithium-induced hypothyroidism (normal response is 5–25 mIU/mL TSH increase).

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    Test your knowledge on the pharmacology of nefazodone, trazodone, and tricyclic antidepressants. This quiz covers their mechanisms of action, benefits, potential adverse effects, and important clinical considerations. Understand how these medications differ from SSRIs and their therapeutic applications.

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