Antidepressants are used to alter the concentration of neurotransmitters in the brain that is responsible for the depressed affect (feelings in response to the environment, whether positive and pleasant or negative and unpleasant).

These drugs counteract the effects of neurotransmitter deficiencies in three ways:

  • Inhibit the effects of monoamine oxidase (MAO) resulting to increased norepinephrine and serotonin or 5-hydroxytryptamine (5-HT) in the synaptic cleft;
  • Block the reuptake function of the synaptic cleft resulting to increased neurotransmitter levels in the synaptic cleft; and
  • Regulate receptor sites and breakdown of neurotransmitters resulting in accumulation of neurotransmitter in the synaptic cleft.

Antidepressants are classified into three groups: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs).

Table of Common Drugs and Generic Names


Here is a table of commonly encountered diuretic agents, their generic names, and brand names:

Classifications Generic Name Brand Name
Tricyclic Antidepressants
Amines amitriptyline
amoxapine Asendin
clomipramine Anafranil
doxepin Sinequan
imipramine Tofranil
Secondary Amines desipramine Norpramin
nortriptyline Aventyl
protriptyline Vivactil
Tetracyclic maprotiline
Monoamine Oxidase Inhibitors (MAOI) isocarboxazid Marplan
phenelzine Nardil
tranylcypromine Parnate
Selective Serotonin Reuptake Inhibitors (SSRI) citalopram Celexa
escitalopram Lexapro
fluoxetine Prozac
fluvoxamine Luvox
paroxetine Paxil
sertraline Zoloft

Manifestation Spotlight: Depression


Depression is an affective disorder characterized by a persistent and intense feeling of sadness much more severe and longer lasting than the suspected precipitating event. There may be no external causes.

  • Individuals with depression have little energy, disturbed sleep patterns, loss of appetite, and absence of motivation to perform activities of daily living. They describe overwhelming feelings of sadness, despair, hopelessness, and disorganization.
  • It can interfere with a person’s life, his family, job, and social relationships. It can lead to multiple physical problems that further depression and increase risk of suicide.
  • Researches about drugs that can effectively relieve depression lead to the formulation of biogenic amine theory which states that depression results from a deficiency of biogenic amines (NE, dopamine, and 5-HT) in key areas of the brain that regulate arousal, alertness, attention, moods, appetite, and sensory processing.

Tricyclic Antidepressants (TCAs)


Description

  • Has three sub-class namely: amines, secondary amines, and tetracyclics
  • Primarily reduce the uptake of 5HT and NE into nerves
  • The choice of TCA depends on individual response and tolerance to the drug.

Therapeutic Action

  • By inhibiting presynaptic reuptake of NE and 5-HT, there will be an accumulation of these neurotransmitters in the synaptic cleft which will increase the stimulation of the postsynaptic receptors.

Indications

  • Primarily indicated for the relief of symptoms of depression, particularly anxiety and sleep disturbances.
  • Some TCAs are indicated for enuresis in children older than 6 years.
  • Researches on its possible indications for treatment of chronic and intractable pain are currently conducted.
  • TCAs also act as anticholinergic.
  • Clomipramine is approved for use in treatment of obsessive-compulsive disorders (OCDs).

Children

  • Indication for treatment of depression in children is a challenge because children respond unpredictably.
  • Studies have not shown that antidepressants in children are effective.
  • On the other hand, it is linked to increased suicidal ideation and behavior in depressed children.
  • Only clomipramine, imipramine, nortriptyline, and trimipramine have established pediatric doses for children older than 6 years.

Adults

  • Adults must be educated that effects of drug therapy may not be seen for 4 weeks. Also, cause of depression must be ruled out before therapy begins.
  • Use cautiously for pregnant and lactating women because of potential adverse effects to fetus and baby.

Older adults

  • Older adults are more susceptible to the adverse effects of the drugs and from CNS effects (e.g. increased sedation, dizziness, etc.)
  • Doses of these drugs need to be reduced and careful monitoring for drug toxicity is a must, especially for those who have hepatic and renal impairment.

Pharmacokinetics

Route Onset Peak Duration
Oral Varies 2-4 h
T1/2: 8-16 h
Metabolism: liver
Excretion: urine

Contraindications and Cautions

  • Allergy to TCAs. Prevent severe hypersensitivity reactions.
  • Myocardial infarction. Can reoccur because of the cardiac effects of the drug
  • Myelography within previous 24 hours or in the next 48 hours. Prevent possible drug-drug interaction with dyes
  • Concurrent use of MAOIs. Potential for serious adverse effects or toxic reactions
  • Pregnancy, lactation. Potential adverse effects to the fetus and the baby
  • Preexisting cardiovascular disorders. Drug has cardiac stimulatory effect
  • Angle-closure glaucoma, urinary retention, prostate hypertrophy, GI or GU surgery. Exacerbated by the anticholinergic effects of the drug
  • History of seizures. Seizure threshold is decreased because of stimulation of receptor sites
  • Hepatorenal diseases. Interfere with drug metabolism and excretion which increase the risk of drug toxicity

Adverse Effects

Interactions

  • Cimetidine, fluoxetine, ranitidine: increased therapeutic and adverse effects of TCAs
  • Oral anticoagulants: higher serum levels of anticoagulants and increased risk of bleeding
  • Sympathomimetics or clonidine: increased risk for hypertension and arrhythmia
  • MAOIs: increased risk for severe hyperpyretic crisis with severe convulsions, hypertensive episodes, and death

Nursing Considerations

Here are important nursing considerations when administering this drug:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned cautions and contraindications (e.g. drug allergies, hepatorenal diseases, psychosis, glaucoma, etc.) to prevent any untoward complications.
  • Assess for history of seizure disorders, psychiatric problems, suicidal thoughts and myelography within the past 24 hours or in the next 48 hours to avoid potentially serious adverse reactions.
  • Perform a thorough physical assessment to establish baseline data before drug therapy begins, to determine the effectiveness of therapy, and to evaluate for the occurrence of any adverse effects associated with drug therapy.
  • Monitor results of electrocardiogram and laboratory tests (e.g. renal and liver function tests) to monitor the effectiveness of the therapy and provide prompt treatment to developing complications.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

Implementation with Rationale

These are vital nursing interventions done in patients who are taking TCAs:

  • Limit drug access if patient is suicidal to decrease the risk of overdose to cause harm.
  • Administer a major portion of dose at bedtime as ordered if drowsiness and anticholinergic effect are severe to decrease the risk of patient injury.
  • Provide comfort measures (e.g. voiding before dosing, taking food with drug, etc.) to help patient tolerate drug effects.
  • Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries.
  • Educate client on drug therapy to promote compliance.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy (e.g. alleviation of signs and symptoms of depression).
  • Monitor for adverse effects (e.g. hypotension, suicidal thoughts, cardiac arrhythmias, etc).
  • Evaluate patient understanding on drug therapy by asking the patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Monoamine Oxidase Inhibitors (MAOIs)


Description

  • Monoamine oxidase (MAO) is an enzyme found in nerves and other tissues. MAOIs exert their effect in relieving depression by inhibiting this enzyme to break down the biogenic amines NE, dopamine, and 5-HT.
  • Now used rarely because of their strict and specific dietary regimen to prevent toxicity. However, there are patients who respond only to MAOIs and so these remain to be available.

Therapeutic Action

  •  By blocking the breakdown of the biogenic amines, these drugs pave way for the accumulation of NE, dopamine, and 5-HT in the neuronal storage vesicles to cause increased stimulation of the postsynaptic receptors. This increased stimulation is thought to be the reason for the relief of depression.

Indications

  • MAOIs are generally indicated for patients who do not respond to other safer antidepressants.

Children

  • Avoided in children if at all possible because of the potential for drug-food interactions and serious adverse effects.

Adults

  • Adults must be educated that effects of drug therapy may not be seen for 4 weeks.
  • Also, the cause of depression must be ruled out before therapy begins.
  • Use cautiously for pregnant and lactating women because of potential adverse effects to fetus and baby.

Older adults

  • Older adults more susceptible to the adverse effects of the drugs and from CNS effects (e.g. increased sedation, dizziness, etc.)
  • Doses of these drugs need to be reduced and careful monitoring for drug toxicity is a must, especially for those who have hepatic and renal impairment.

Pharmacokinetics

Route Onset Peak Duration
Oral Slow 48-96 h
T1/2: unknown
Metabolism: liver
Excretion: urine

Contraindications and Cautions

  • Allergy to MAOIs. Prevent severe hypersensitivity reactions.
  • Pheochromocytoma. Sudden increase in NE can lead to severe hypertension and CV emergencies
  • CV diseases (hypertension, coronary artery disease, angina, congestive heart failure). Exacerbated by increased NE levels
  • History of headaches.
  • Abnormal CNS vessels or defects. Potential increase in blood pressure and vasoconstriction associated with higher NE levels can precipitate a stroke
  • Myelography within previous 24 hours or in the next 48 hours. Prevent possible drug-drug interaction with dyes
  • Pregnancy, lactation. Potential adverse effects to the fetus and the baby
  • Hepatorenal diseases. Interfere with drug metabolism and excretion which increase the risk of drug toxicity

Adverse Effects

  • CNS: dizziness, excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation, blurred vision
  • CV: orthostatic hypotension, arrhythmias, palpitations, angina, potentially fatal hypertensive crisis (occipital headache, palpitations, neck stiffness, nausea, vomiting, sweating, dilated pupils, photophobia, tachycardia, chest pain)
  • GI: liver toxicity, nausea, vomiting, diarrhea or constipation, anorexia, weight gain, dry mouth, abdominal pain
  • GU: urinary retention, dysuria, incontinence, changes in sexual function

Interactions

  • TCAs: hypertensive crisis, coma, severe convulsions
  • SSRIs: potentially life-threatening serotonin syndrome (a period of 6 weeks should  elapse after stopping an SSRI before beginning therapy with MAOI)
  • Sympathomimetics: increased sympathomimetic effects
  • Insulin, oral antidiabetic agents: additive hypoglycemic effects
  • Phentolamine is the treatment for hypertensive crisis.

Nursing Considerations

Here are important nursing considerations when administering this drug:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned cautions and contraindications (e.g. drug allergies, hepatorenal diseases, cardiac dysfunction, etc.) to prevent any untoward complications.
  • Perform a thorough physical assessment to establish baseline data before drug therapy begins, to determine the effectiveness of therapy, and to evaluate for the occurrence of any adverse effects associated with drug therapy.
  • Monitor results of electrocardiogram and laboratory tests (e.g. renal and liver function tests) to monitor the effectiveness of the therapy and provide prompt treatment to developing complications.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

Implementation with Rationale

These are vital nursing interventions done in patients who are taking MAOIs:

  • Limit drug access if the patient is suicidal to decrease the risk of overdose to cause harm.
  • Monitor patient for 2-4 weeks to ascertain onset of full therapeutic effect.
  • Monitor blood pressure carefully to determine the possible need for dose adjustment.
  • Secure phentolamine at the bedside as a treatment in case of hypertensive crisis.
  • Educate client on a low tyramine-containing diet. Provide a list of potential drug-food interactions that can cause severe toxicity to decrease the risk of a serious drug-food interaction.
  • Provide comfort measures (e.g. voiding before dosing, taking food with the drug, etc.) to help patient tolerate drug effects.
  • Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries.
  • Educate client on drug therapy to promote compliance.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy (e.g. alleviation of signs and symptoms of depression).
  • Monitor for adverse effects (e.g. hypotension, hypertensive crisis, cardiac arrhythmias, etc).
  • Evaluate patient understanding on drug therapy by asking the patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Selective Serotonin Reuptake Inhibitors (SSRIs)


Description

  • SSRIs is the newest group of antidepressants available in the market.
  • Only has blocking effect on the reuptake of 5-HT and has little to no effect on NE.
  • Have lesser adverse effects compared to TCAs and MAOIs. This makes them a better choice for many patients.

Therapeutic Action

  •  Blocks the reuptake of 5-HT and therefore increases its level in the synaptic cleft.
  • Realization of full therapeutic effect is up to 4 weeks.

Indications

  • Indicated for treatment of depression, OCDs, panic attacks, bulimia, premenstrual dysphoric disorder (PMDD), social phobias, and social anxiety disorders.

Children

  • Can cause serious adverse effects on children.
  • Only fluvoxamine and sertraline have established pediatric dosage guidelines for treatment of OCDs.
  • Fluoxetine is widely used to treat depression in adolescents.

Adults

  • Must be educated that effects of drug therapy may not be seen for 4 weeks.
    Also, the cause of depression must be ruled out before therapy begins.
  • Use cautiously for pregnant and lactating women because of potential adverse effects to fetus and baby.

Older adults

  • More susceptible to the adverse effects of the drugs and from CNS effects (e.g. increased sedation, dizziness, etc.)
  • Doses of these drugs need to be reduced and careful monitoring for drug toxicity is a must, especially for those who have hepatic and renal impairment.

Pharmacokinetics

Route Onset Peak Duration
Oral Slow 6-8 h
T1/2: 2-4 weeks
Metabolism: liver
Excretion: urine, feces

Contraindications and Cautions

  • Allergy to SSRIs. Prevent severe hypersensitivity reactions.
  • Hepatorenal diseases. Interfere with drug metabolism and excretion which increase the risk of drug toxicity
  • Severely depressed, suicidal patients. Risk of increased suicidality
  • Pregnancy, lactation. Potential adverse effects to the fetus and the baby

Adverse Effects

  • CNS: headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation, seizures
  • Respiratory: cough, dyspnea, upper respiratory infections, pharyngitis
  • GI: nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, changes in taste
  • GU: painful menstruation, cystitis, sexual dysfunction, urgency, impotence
  • Miscellaneous: sweating, rash, fever, pruritus

Interactions

  • MAOIs: increased risk of serotonin syndrome
  • TCAs: increased therapeutic and adverse effects of SSRIs

Nursing Considerations

Here are important nursing considerations when administering this drug:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

  • Assess for the mentioned cautions and contraindications (e.g. drug allergies, hepatorenal diseases, severe depression, and suicidality, etc.) to prevent any untoward complications.
  • Perform a thorough physical assessment to establish baseline data before drug therapy begins, to determine the effectiveness of therapy, and to evaluate for occurrence of any adverse effects associated with drug therapy.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for therapy:

Implementation with Rationale

These are vital nursing interventions done in patients who are taking SSRIs:

  • Arrange for lower dose in elderly patients and in those with renal or hepatic impairment because of the potential for severe adverse effects.
  • Limit drug access if patient is suicidal to decrease the risk of overdose to cause harm.
  • Monitor patient for 4 weeks to ascertain onset of full therapeutic effect.
  • Establish suicide precautions for severely depressed patients to decrease the risk of overdose to cause harm.
  • Administer drug once a day in the morning to achieve optimal therapeutic effects.
  • Suggest that the patient use barrier contraceptives to prevent pregnancy while taking this drug because serious fetal abnormalities can occur.
  • Provide comfort measures (e.g. taking food with the drug) to help patient tolerate drug effects.
  • Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries.
  • Educate client on drug therapy to promote compliance.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

  • Monitor patient response to therapy (e.g. alleviation of signs and symptoms of depression).
  • Monitor for adverse effects (e.g. sedation, dizziness, respiratory dysfunctions, GU problems, etc).
  • Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.
  • Monitor patient compliance to drug therapy.

Practice Quiz: Antidepressants


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Questions

1. Nortriptyline and protriptyline are classified as what class of TCAs?

A. Amines
B. Secondary amines
C. Tetracyclics
D. None of the above

2. The following are true about depression, except:

A. External causes always play a part in assessment and diagnosis.
B. Patients with depression have trouble sleeping and eating.
C. Depression can lead to multiple physical problems.
D. None of the above.

3. Which TCA is also approved for use in patients with OCD?

A. Imipramine
B. Clomipramine
C. Sertraline
D. Amitriptyline

4. A combination of MAOIs and TCAs will precipitate which drug adverse effect?

A. Severe hypertensive crisis
B. Severe hyperpyretic crisis
C. Severe hypnotic crisis
D. Severe amnesia

5. What is the treatment for hypertensive crisis caused by MAOI?

A. Phentolamine
B. Adenosine
C. Propanolol
D. Nifedipine

6. How many weeks will the full therapeutic effects of SSRIs be realized?

A. 2 weeks
B. 4 weeks
C. 6 weeks
D. 8 weeks

Answers and Rationale


1. Answer: B. Secondary amines.

Examples of amines include amoxapine, amitriptyline, clomipramine, doxepin, and clozapine. Example of tetracyclic include maprotiline.

2. Answer: A. External causes always play a part in assessment and diagnosis.

Depression can have no external causes.

3. Answer: B. Clomipramine.

4. Answer: B. Severe hyperpyretic crisis.

It is accompanied by convulsions, hypertensive episodes, and even death.

5. Answer: A. Phentolamine

6. Answer: B. 4 weeks.

Therefore, it is important for nurses to instruct patients that effects of the drug will not be instantly feel and experienced.

See Also


Here are other nursing pharmacology study guides:

Endocrine System Drugs

Autonomic Nervous System Drugs

Immune System Drugs

Chemotherapeutic Agents

Reproductive System Drugs

Nervous System Drugs

Cardiovascular System Drugs

Further Reading and Resources


Recommended resources and books:

  1. Focus on Nursing Pharmacology - Easy to follow guide for Pharmacology
  2. NCLEX-RN Drug Guide: 300 Medications You Need to Know for the Exam - Great if you're reviewing for the NCLEX
  3. Nursing 2017 Drug Handbook (Nursing Drug Handbook) - Reliable nursing drug handbook!
  4. Lehne's Pharmacology for Nursing Care - Provides key information on commonly used drugs in nursing
  5. Pharmacology and the Nursing Process - Learn how to administer drugs correctly and safely!
  6. Pharm Phlash Cards!: Pharmacology Flash Cards - Flash Cards for Nursing Pharmacology