NSC 330: Antidepressants

Study Notes for NSC 330: Antidepressants

Depression

  • Definition: Depressed mood and loss of pleasure/interest in usual activities

  • Symptoms: Must be present most of the day, nearly every day, for at least 2 weeks  

  •  -Hopelessness or sadness
      - Lack of interest in activities
      - Changes in sleep patterns (loss of sleep or excessive sleep)
      - Weight changes (loss/gain)
      - Feelings of fear/anxiousness
      - Lack of self-worth
      - Agitation
      - Unexplained physiologic symptoms
      - Suicidal ideation
      - Behavior changes
      - Anxiety
      - Panic attacks
      - Insomnia
      - Irritability
      - Hostility
      - Impulsivity
      - Mania

Pathophysiology of Depression

  • Complex Factors: Deficiency of neurotransmitters, particularly:Norepinephrine, Serotonin, Dopamine, Acetylcholine, Glutamate

Pharmacologic Treatment

  • General Note: Antidepressants are not immediately effective.

  • Mechanism of Action (MOA) of Antidepressants:
      1. Prevent reuptake of neurotransmitters, thereby increasing the concentration in CNS synapses.
        - Reuptake Inhibitors: Prevent the reuptake process
        - Alters the number and sensitivity of receptors
      2. Remaining neurotransmitters are metabolized by the enzyme monoamine oxidase (MAO).
        - MAOI Inhibitors: Prevent this metabolism, increasing neurotransmitter availability for receptor binding

General Considerations for Antidepressants

  • Response Times:Initial responses can take 1-3 weeks
      - Maximal responses may take up to 12 weeks

  • Boxed Warning: Increased risk of suicidal thoughts and behavior
      - Most likely to occur in the first 2 months, especially with dosage increase
      - Higher risk in children, adolescents, and young adults (under age 24)
      - Be vigilant for an energizing effect that may precede depressive symptom remission which could lead to suicide

Classes of Antidepressants

  • 1. Tricyclic Antidepressants (TCAs)

  • 2. Selective Serotonin Reuptake Inhibitors (SSRIs)

  • 3. Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

  • 4. Monoamine Oxidase Inhibitors (MAOIs)

  • 5. Atypical Antidepressants

Tricyclic Antidepressants (TCAs)

  • Examples:
      1. Amitriptyline
      2. Imipramine

  • MOA: Blocks reuptake of serotonin and norepinephrine; also blocks histamine and acetylcholine (causing increased adverse effects)

  • Uses:
      1. Depression
      2. Anxiety disorders
      3. OCD
      4. Panic disorder
      5. Insomnia
      6. Neuropathic pain (chronic pain)

Adverse Effects of TCAs

  • 1. Weight gain

  • 2. Sedation (due to histamine receptor blockage in CNS)

  • 3. Anticholinergic effects (blurred vision, urinary retention, dry mouth, constipation, confusion)

  • 4. Tachycardia and potential prolongation of QRS and PR/QT intervals

  • 5. Lowered seizure threshold

  • 6. Orthostatic hypotension

Nursing Implications for TCAs

  • 1. Caution with other CNS depressants or medications with anticholinergic properties

  • 2. Instruct patients that therapeutic effects may not be seen for 3-4 weeks

  • 3. An overdose is potentially fatal (8 times the average dose)

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • MOA: Inhibit serotonin reuptake, thereby increasing the availability of serotonin and prolonging the stimulatory potential of receptors

  • Uses:
      1. Depression (MDD, bipolar depression)
      2. Anxiety, OCD, panic disorder, social phobia, PTSD, PMDD (premenstrual dysphoric disorder)
      3. Bulimia

  • Examples:
      1. Fluoxetine
      2. Paroxetine
      3. Sertraline
      4. Citalopram
      5. Escitalopram
      6. Vortioxetine (newer with fewer side effects)

Adverse Effects of SSRIs

  • 1. Headache and/or nausea (initially)

  • 2. Some SSRIs are sedating (not all)

  • 3. Sexual dysfunction (up to 70% with some SSRIs)

  • 4. Early weight loss followed by potential weight gain (varies by individual)

  • 5. Withdrawal symptoms if abruptly discontinued (suggest tapering over 4 weeks)

Advantages of SSRIs

  • 1. No cardiac adverse effects

  • 2. No anticholinergic adverse effects

  • 3. Expect 3-4 weeks to observe full therapeutic effectiveness

  • 4. Monitor for suicidal thinking/behavior during the initial 2-3 weeks

SSRIs Discontinuation Syndrome

  • 1. Do not abruptly discontinue SSRIs

  • 2. Symptoms may persist for 1-3 weeks unless the drug is restarted

Serotonin Syndrome

  • Definition: A potentially serious side effect characterized by excessive serotonergic activity

  • Onset: Begins 2-72 hours after dose increase or addition

  • Resolution: Resolves spontaneously when the drug is stopped

  • Higher Risk: When used with other serotonergic drugs like MAOIs, TCAs, lithium, linezolid, and St. John's Wort

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

  • MOA: Increase both serotonin and norepinephrine at the synapse

  • Uses:
      1. Major Depressive Disorder
      2. Bipolar Disorder
      3. Anxiety Disorders
      4. PTSD
      5. Neuropathic Pain

  • Examples:
      1. Venlafaxine
      2. Duloxetine

SNRIs Considerations

  • 1. Expect a full therapeutic effect in 3-4 weeks

  • 2. Monitor for suicidal thoughts/behavior during the initial 2-3 weeks

Adverse Effects of SNRIs

    1. Same as SSRIs but with added hypertension risk

  • 2. More intense withdrawal symptoms requiring slower tapering (over 4 weeks)

Monoamine Oxidase Inhibitors (MAOIs)

  • MOA: Inhibit monoamine oxidase enzyme, increasing levels of serotonin, norepinephrine, and dopamine

  • Uses: For drug-resistant or atypical depression; less desirable due to significant drug and food interactions and poor safety profile

  • Examples:
      1. Isocarboxazid
      2. Phenelzine
      3. Tranylcypromine
      4. Selegiline patch

Dietary Considerations with MAOIs

  • Tyramine: A monoamine precursor of norepinephrine, deactivated by MAO in the GI tract and liver
      - Dietary tyramine typically doesn't reach circulation, but MAOIs prevent its metabolism

  • Avoid Foods:
      1. Aged cheeses (cheddar, Swiss, bleu)
      2. Beer
      3. Red wines
      4. Smoked meats
      5. Fermented sausages (pepperoni, salami, bologna)
      6. Soy sauce
      7. Sour cream

  • Consequences of Ingestion: May cause hypertensive crisis with symptoms such as severe headache, hypertension, tachycardia, palpitations, nausea/vomiting, confusion, profuse sweating, and potentially lead to stroke or death.

MAOIs General Considerations

  • Onset: 1-2 weeks

  • Interactions: Numerous drug-drug interactions

  • Cautions: Should not be used in impulsive patients, cognitively impaired individuals, or those unable to follow dietary restrictions

Adverse Effects of MAOIs

  • 1. Dizziness

  • 2. Orthostatic hypotension

  • 3. Insomnia

  • 4. CNS stimulation (anxiety, agitation)