Antidepressant Agents

Antidepressant Agents

Affective Disorders vs Depression

  • Affective disorder
    • A person’s mood goes far beyond the normal “ups and downs”
  • Depression
    • Severe and long-lasting feelings of sadness beyond the precipitating event

Signs and Symptoms of Depression

  • Low energy level
  • Sleep disturbances
  • Lack of appetite
  • Limited libido
  • Inability to perform activities of daily living
  • Overwhelming feelings of sadness, despair, hopelessness, and disorganization

Biogenic Amine Theory of Depression

  • Depression results from a deficiency of norepinephrine (NE), dopamine, or serotonin (5HT)
    • Monoamine oxidase (MAO) may break them down to be recycled or restored in the neuron
    • Rapid fire of neurons may lead to their depletion
    • The number or sensitivity of postsynaptic receptors may increase, depleting neurotransmitter levels

Actions of Antidepressant Therapy

  • Inhibits the effects of MAO, leading to increased NE or 5HT in the synaptic cleft
  • Blocks reuptake by the releasing nerve, leading to increased neurotransmitter levels in the synaptic cleft
  • Regulates receptor sites and breakdown of neurotransmitters, leading to an accumulation of neurotransmitters in the synaptic cleft

Classifications of Antidepressants

  • Tricyclic antidepressants (TCAs)
  • MAO inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)

Sites of Action for Selected Antidepressants

Sites of Action for Selected Antidepressants

Sites of Action for Selected Antidepressants

 

 

Tricyclic Antidepressants

  • Actions
    • Reduce the reuptake of 5HT and NE into nerves
  • Use
    • All TCAs are similar
    • Choice depends on individual response to the drug and tolerance of adverse effects
  • Indications
    • Relief of symptoms of depression
    • Used for patients with sleep disorders
    • Treatment of enuresis
    • Chronic pain
  • Pharmacokinetics
    • Absorbed from the GI tract
    • Peak in 2 to 4 hours
    • Bound to plasma proteins and lipid soluble
    • Metabolized in the liver and excreted in the urine
    • T½ 8 to 46 hours
  • Contraindications
    • Known allergy, recent MI, myelography, pregnancy, and lactation
  • Cautions
    • CV disease, angle closure glaucoma, urinary retention, and manic depression
  • Adverse reactions
    • Sedation, sleep disturbances, fatigue, hallucinations, ataxia, dry mouth, constipation, nausea, and vomiting
  • Drug-to-drug interactions
    • MAOIs, cimetidine, fluoxetine, ranitidine, and oral anticoagulants

Monoamine Oxidase Inhibitors (MAOIs)

  • Isocarboxazid (Marplan)
    • Used for patients who do not respond to or cannot take newer, safer antidepressants
  • Phenelzine (Nardil)
    • Used for some patients who do not respond to newer, safer antidepressants
  • Tranylcypromine (Parnate)
    • Used for adult outpatients with reactive depression
  • Action
    • Irreversibly inhibit MAOs, allowing norepinephrine, serotonin, and dopamine to accumulate in the synaptic cleft
  • Indication
    • Treatment of patients with depression who are unresponsive to or unable to take other antidepression agents
  • Pharmacokinetics
    • Absorbed from the GI tract
    • Peak in 2 to 3 hours
    • Metabolized in the liver and excreted in the urine
    • Cross placenta and enter breast milk
  • Contraindications
    • Known allergy, pheochromocytoma, CV disease, headaches, and renal or hepatic impairment
  • Adverse reactions
    • Dizziness, excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation, liver toxicity, nausea, vomiting, diarrhea or constipation, anorexia, weight gain, dry mouth, and abdominal pain
  • Drug-to-drug interactions
    • Other antidepressants: hypertensive crisis and coma
    • Methyldopa: sympathomimetic effects increase
    • Insulin or oral antidiabetic agents: additive hypoglycemia
  • Food interactions
    • Tyramine or pressor amines: increase blood pressure

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • The newest group of antidepressant drugs
  • Specifically block the reuptake of 5HT, with little to no known effect on NE
  • Do not have the many adverse effects associated with TCAs and MAOIs
  • Action
    • Inhibit CNS neuronal reuptake of serotonin with little effect on norepinephrine and little affinity for cholinergic, histaminic, or alpha-adrenergic sites
  • Indications
    • Depression, OCD, panic attacks, bulimia, PMDD, posttraumatic stress disorders, social phobias, and social anxiety disorders
  • Pharmacokinetics
    • Absorbed from the GI tract
    • Metabolized in the liver
    • Associated with congenital abnormalities
  • Contraindications
    • Known allergy, pregnancy, lactation, and impaired renal or hepatic function
  • Adverse reactions
    • Headache, drowsiness, dizziness, insomnia, anxiety, tremor, and agitation
  • Drug-to-drug interactions
    • MAOIs
    • TCAs increase therapeutic and toxic effect

Miscellaneous Antidepressants

  • Bupropion (Wellbutrin, Zyban)
  • Mirtazapine (Remeron)
  • Nefazodone (Serzone)
  • Trazodone (Desyrel)
  • Venlafaxine (Effexor)

Use of Antidepressant Agents Across the Lifespan

Use of Antidepressant Agents Across the Lifespan

Use of Antidepressant Agents Across the Lifespan

Prototype Tricyclic Agent

Prototype Tricyclic Agent

Prototype Tricyclic Agent

Prototype MAOIs Agent

Prototype MAOIs Agent

Prototype MAOIs Agent

Prototype SSRI Agent

Prototype SSRI Agent

Prototype SSRI Agent

Nursing Considerations for Tricyclic Antidepressant Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for MAOI Antidepressant Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for SSRI Antidepressant Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation
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