Psychotropic Drugs Notes

Major Depressive Disorder

  • Major Depressive Disorder (MDD) is a mood disorder. It involves changes in cognition, behavior, and physical functioning.
  • MDD includes symptoms that disrupt normal function, impacting psychological, emotional, and cognitive abilities.

Pathophysiologic Hypotheses of Depression

  • Serotonin Hypothesis:
    • A deficiency in the neurotransmitter serotonin.
  • Catecholamine Hypothesis:
    • A deficiency in norepinephrine, serotonin, or dopamine.
  • Permissive Hypothesis:
    • Reduced serotonin allows a norepinephrine deficiency to manifest as depression.
  • Beta-Adrenergic Receptor Hypothesis:
    • Depression results from increased beta-adrenergic receptor sensitivity.

Diagnostic Criteria for Major Depressive Disorder (MDD)

  • A. Symptoms: Five or more symptoms present during the same 2-week period, representing a change from previous functioning; at least one symptom must be #1 or #2:
    1. Depressed mood most of the day (irritable mood in children/adolescents).
    2. Diminished interest or pleasure in usual activities.
    3. Significant weight loss/gain or appetite decrease/increase.
    4. Insomnia or hypersomnia.
    5. Psychomotor agitation or retardation observed by others.
    6. Fatigue or loss of energy.
    7. Feelings of worthlessness or excessive/inappropriate guilt.
    8. Diminished ability to think or concentrate, indecisiveness.
    9. Recurrent thoughts of death, suicidal ideation, suicide attempt, or specific plan for suicide.
  • B. Impact: The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • C. Exclusion: The symptoms are not due to the direct physiological effects of a substance or a medical condition.

Antidepressant Drugs

  • Classes: Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase (MAO) inhibitors, and atypical agents.
  • Mechanism: These drugs affect one or more primary neurotransmitters to alleviate depression.
  • Function: Antidepressants increase the amount of neurotransmitters available in the synapse by:
    • Inhibiting metabolic degradation.
    • Decreasing the reuptake rate into the presynaptic neuron.
  • Specific Actions:
    • SSRIs: Inhibit serotonin reuptake, increasing serotonin availability.
    • SNRIs: Increase serotonin and norepinephrine concentrations; activity depends on dosage.
    • TCAs: Inhibit norepinephrine and serotonin reuptake.
    • MAO Inhibitors: Limit the metabolism of dopamine, serotonin, and norepinephrine.

DSM-5 Criteria for Generalized Anxiety Disorder (GAD)

  • A. Excessive Anxiety and Worry: Occurring more days than not for at least 6 months about a number of events or activities.
  • B. Difficulty Controlling Worry: The person finds it difficult to control the worry.
  • C. Associated Symptoms: Three or more of the following (at least some present for more days than not for the past 6 months; only one item required in children):
    1. Restlessness or feeling keyed up or on edge
    2. Being easily fatigued
    3. Difficulty concentrating or mind going blank
    4. Irritability
    5. Muscle tension
    6. Sleep disturbance
  • D. Significant Distress or Impairment: The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • E. Exclusion of Substance/Medical Condition: The disturbance is not attributable to the physiological effects of a substance or another medical condition.
  • F. Exclusion of Other Mental Disorders: The disturbance is not better explained by another mental disorder.

Treatment Algorithm for Generalized Social Anxiety Disorder

  • Initial Step: SSRI or venlafaxine for 12 weeks.
  • Response: Continue for 12 months.
  • No Response: Change to another SSRI or venlafaxine.
  • No Response Again: Switch to phenelzine. If still no response, refer to a psychiatrist. *Key:
    • Starting point for decision making (assessing, prescribing, monitoring)
    • Clinical actions
    • Decision point*

Treatment Algorithm for Anxiety (GAD)

  • Initial Assessment:
    • Is it anxiety? Yes
    • Is there any history of substance abuse?
  • Anxiety Present, No Substance Abuse History:
    • Prescribe SSRI or SNRI.
    • Evaluate at 4-6 weeks with adequate dosing.
    • Response: Continue for 4-12 months, then gradually taper off. If symptoms recur, continue for 4-12 months or keep on long-term use. Gradually taper off when possible.
    • No Response:Refer to psychiatrist or consider a TCA, addition of a BZD, AAP, or antihistamine. Also, start with BZD for time-limited anxiety.
  • Anxiety Present With Substance Abuse History:
    • Prescribe buspirone and gradually increase the dose.
    • Evaluate at 4-6 weeks with adequate dosing.

Recommended Order of Treatment for Anxiety

  • First Line: SSRI or SNRI
    • Useful for anxiety and coexisting comorbidity.
  • Second Line: Buspirone or imipramine
    • Takes 1-2 weeks for effect.
  • Third Line: Adjunctive therapy with pregabalin, buspirone
    • Do not use if the patient is alcohol or drug dependent. May be first-line drug in motivated patients with acute anxiety to a time-limited stress.

Mechanism of Action of Antidepressant Agents

  • Neurotransmitters: Norepinephrine (NE), serotonin (S), and dopamine (D) are released from the presynaptic neuron into the synaptic space.
  • Interaction: They interact with the postsynaptic receptors to continue neuronal transmission.
  • Post-Release: After release from the postsynaptic neuron, these agents are broken down by monoamine oxidase (MAO) and recycled into the presynaptic neuron, or reuptaken.
  • Antidepressant Action: Antidepressants can:
    1. Block MAO enzymes (MAO inhibitors).
    2. Inhibit neurotransmitter reuptake (TCAs, SSRIs).
    3. Agonize or antagonize an associated receptor.

Recommended Order of Treatment in Antidepressant Therapy

  • First Line: SSRIs
    • Fluoxetine and sertraline may be good for patients with somnolence.
    • Paroxetine may be good for patients with insomnia.
  • Second Line: TCA (desipramine or nortriptyline) or atypical antidepressant
    • Selection of agent should be based on patient's past experiences with medications and drug interactions.
    • Cost may be a consideration.
  • Third Line: Atypical antidepressant or TCA
    • These agents have the better side effect profile of the class and should be considered as agents of choice for the TCA class.
    • Depending on past response to other agents and side effect profile

Treatment Algorithm

  • Stage 1: Monotherapy (SSRI, bupropion, nefazodone, or venlafaxine)

  • Stage 2: Alternate Monotherapy (SSRI, bupropion, nefazodone, TCA, or venlafaxine)
    *Partial response or nonresponse: Change drugs.

  • Stage 3: Alternate Monotherapy (SSRI, bupropion, nefazodone, TCA, venlafaxine, MAOI drug from a class other than used in Stage 1 or 2) or Combination antidepressants: TCA + SSRI
    *Partial response or nonresponse: Change drugs.

  • Stage 4: Partial response or nonresponse goes to Stage 5.

  • Stage 5: ECT or Other
    Abbreviations: EC = electroconvulsive therapy, MAOI = monoamine oxidase inhibitor, SSRI =selective serotonin reuptake inhibitor, TCA = tricyclic antidepressant.

    • aa SSRIs preferred.
    • bb Consider TCA or venlafaxine if not tried.
      Remission each step: go to continuation, then Maintenance

Benzodiazepines

  • Used for sedative or hypnotic effects.
  • Examples: Alprazolam, Estazolam, Flurazepam, Lorazepam, Temazepam, Triazolam.
  • Induce a state resembling natural sleep in large doses increasing total sleep time and decreasing awakenings.

Benzodiazepines: Alprazolam

  • Actions:
    • Enhances GABA, an inhibitory neurotransmitter in the CNS.
    • Acts at the limbic, thalamic, and hypothalamic levels of the CNS.
    • Produces anxiolytic, sedative, hypnotic, skeletal muscle relaxant, and anticonvulsant effects.
  • Indications:
    • Anxiety.
    • Panic disorders.
  • NP Considerations:
    • Monitor for adverse reactions like drowsiness, dry mouth, diarrhea, and constipation.
    • Not recommended for long-term use.
    • Avoid abrupt discontinuation; seizures may occur.

Benzodiazepines - Important Considerations

  • Lethal Combination:
    • Taking benzodiazepines with other CNS depressants (alcohol, anticonvulsants) enhances sedative and CNS depressant effects, potentially causing reduced level of consciousness, reduced muscle coordination, respiratory depression, and death.
      *Hormonal contraceptives may reduce the metabolism of flurazepam and lorazepam, increasing the risk of toxicity.

Nonbenzodiazepines-Nonbarbiturates

  • Use: Short-term only.
  • Patient Education: Work with healthcare provider for best sleep solutions.
  • Examples:
    • Eszopiclone.
    • Zaleplon.
    • Zolpidem.

Antianxiety Drugs (Anxiolytics)

  • Commonly prescribed in the United States.
  • Used to treat anxiety disorders.
  • Main Types:
    • Benzodiazepines.
    • Barbiturates.
      *Buspirone (ineffective for quick relief due to slow onset).

Buspirone

  • Advantages:
    • Less sedation.
    • No increased CNS depressant effects with alcohol or sedative-hypnotics.
    • Lower abuse potential.
  • Common Reactions:
    • Dizziness.
    • Light-headedness.
    • Insomnia.
    • Rapid heart rate.
    • Palpitations.
    • Headache.

Antidepressant and Mood Stabilizer Drugs

  • Treat affective disorders (mood disturbances like depression or elation).
  • Types:
    • Selective serotonin reuptake inhibitors (SSRIs).
    • MAO inhibitors.
    • TCAs.
      *Other antidepressants.

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Developed for depression with fewer adverse effects.
  • Examples:
    • Citalopram.
    • Escitalopram.
    • Fluoxetine.
    • Fluvoxamine.
    • Paroxetine.
    • Sertraline.

Selective Serotonin Reuptake Inhibitors: Fluoxetine

  • Actions:
    • Inhibits CNS neuronal uptake of serotonin.
  • Indications:
    • Depression.
    • Bulimia nervosa (binge eating and vomiting).
    • Premenstrual dysphoric disorder.
    • Anorexia nervosa.
    • Panic disorder.
    • Alcohol dependence.
  • Nursing Considerations:
    • Monitor for anxiety, insomnia, drowsiness, nausea, diarrhea, and dry mouth.
    • Give in the morning to prevent insomnia.
    • Suicide watch: Linked with increased suicidal ideation and aggression.
    • Avoid hazardous activities until CNS effects are known.

SSRI Discontinuation Syndrome

  • Cause: Abrupt discontinuation of SSRIs.
  • Symptoms: Dizziness, vertigo, ataxia, nausea, vomiting, muscle pains, fatigue, tremor, headache, anxiety, crying spells, irritability, sad feelings, memory problems, and vivid dreams.
  • Occurrence: Up to one third of patients.
  • Risk Factors: SSRIs with short half-life (e.g., paroxetine); less likely with fluoxetine due to its long half-life.
  • Management: Self-limited (resolves in 2-3 weeks with treatment). Tapering the drug dosage slowly helps prevent it.

MAO Inhibitors

  • Examples: Rasagiline, Selegiline, Isocarboxazid, Phenelzine, and Tranylcypromine.
  • Switching Medications:
    • Discontinue MAO inhibitors 2 weeks before starting an alternative antidepressant.
    • When switching from another antidepressant to an MAO inhibitor, wait 2 weeks (5 weeks for fluoxetine).
  • Food Interactions: Tyramine-rich foods (chocolate, red wine, aged cheese, smoked or processed meats, and fava beans) can cause severe reactions.
    Caffeine may also interact, but to a lesser extent.

MAO Inhibitors - Important Considerations

  • Dietary Restrictions:
    • Patients must avoid tyramine-rich foods to prevent hypertensive crisis.
  • Overdose Signs:
    • Palpitations, severe hypotension, and frequent headaches.

Foods with High Tyramine Content

  • Aged cheese (cheddar, blue, Gouda, Swiss).
  • Yeast products.
  • Aged meats, processed meats, nonfresh meat.
  • Beef liver or chicken liver.
  • Sauerkraut.
  • Licorice.
    *Tap beer.

Teachings: MAO Inhibitors

  • Avoid tyramine-rich foods and large amounts of caffeine.
  • Sit up for 1 minute before getting out of bed to avoid dizziness.
  • Avoid overexertion.
  • Consult the prescriber before taking other drugs.
  • Don’t stop taking the drug suddenly.

Tricyclic Antidepressants (TCAs)

  • Treat depression.
  • Examples: Amitriptyline hydrochloride, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine hydrochloride, Imipramine pamoate, Nortriptyline, Protriptyline, Trimipramine.

TCAs - Use and Considerations

  • Used to treat major depression, especially with weight loss, anorexia, or insomnia.
  • Response time varies (1-4 weeks).
  • Concurrent use with MAO inhibitors may cause extremely elevated body temperature, excitation, and seizures.
    *Increased anticholinergic effects are seen when taken with anticholinergic drugs.

Tricyclic Antidepressants: Imipramine

  • Actions:
    • Inhibits the reuptake of norepinephrine and serotonin in CNS nerve terminals, enhancing neurotransmitter concentration and activity in the synaptic cleft.
    • Exerts antihistaminic, sedative, anticholinergic, vasodilatory, and quinidine-like effects.
  • Indications:
    • Depression.
    • Enuresis in children older than age 6.
  • Nursing Considerations:
    • Monitor for sedation, anticholinergic effects, and orthostatic hypotension.
    • Don’t withdraw the drug abruptly; gradually reduce the dosage over several weeks.
    • Avoid hazardous activities until CNS effects are known.

Atypical Antidepressants

  • Examples:
    • Bupropion
    • Duloxetine
    • Venlafaxine
    • Trazodone
    • Mirtazapine

Adverse Reactions - Atypical Antidepressants

  • Bupropion: Headache, confusion, tremor, agitation, tachycardia, anorexia, nausea, and vomiting.
  • Venlafaxine and Duloxetine: Headache, somnolence, dizziness, and nausea.
  • Trazodone: Drowsiness and dizziness.

Lithium

  • Use: Mood stabilizer to prevent or treat mania.
  • Discovery: A milestone in treating mania and bipolar disorders.

Lithium - Important Considerations

  • Salt Restriction:
    • Patients on severe salt-restricted diets are susceptible to lithium toxicity.
    • Increased sodium intake may reduce therapeutic effects.
  • Common Adverse Reactions:
    • Reversible ECG changes.
    • Thirst.
    • Polyuria.
      *Elevated WBC count.

Lithium Toxicity

  • Symptoms: Confusion, lethargy, slurred speech, increased reflex reactions, and seizures.

Teachings: Lithium

  • Take with plenty of water and after meals.
  • Has a narrow therapeutic margin of safety.
  • Watch for signs and symptoms of toxicity.
  • Avoid activities that require alertness and good psychomotor coordination until the drug’s CNS effects are known.
  • Don’t switch brands or take other prescription or over-the-counter drugs without the prescriber’s approval.
    *Wear or carry medical identification.

Antipsychotic Drugs

  • Control psychotic symptoms such as delusions, hallucinations, and thought disorders in schizophrenia, mania, and other psychoses.
  • Major Groups:
    1. Atypical antipsychotics.
    2. Typical antipsychotics.

Atypical Antipsychotics

  • Treat numerous psychiatric conditions.
  • Examples: Clozapine, Lurasidone, Olanzapine, Risperidone, Quetiapine, Ziprasidone, Brexpiprazole, Aripiprazole.

Atypical Antipsychotics - Important Considerations

  • Olanzapine: Minimal risk for extrapyramidal effects; weight gain is common.
  • Risperidone: Higher risk for extrapyramidal effects at doses > 6 mg/day.
  • Quetiapine and aripiprazole: Associated with sedation.
    *Ziprasidone: Not recommended for patients with heart problems due to potential ECG changes (prolonged QT interval and heart block).

Typical Antipsychotics

  • Include phenothiazines and nonphenothiazines.
  • Examples: Chlorpromazine, Fluphenazine decanoate, Fluphenazine hydrochloride, Perphenazine, Trifluoperazine, Mesoridazine besylate, Thioridazine, Haloperidol and haloperidol decanoate, Molindone

Phenothiazines: Chlorpromazine

  • Actions:
    • Dopamine antagonist, blocking postsynaptic dopamine receptors in the CNS.
    • Produces antiemetic effects by blocking the chemoreceptor trigger zone.
    • Produces varying degrees of anticholinergic and alpha-adrenergic receptor blocking actions.
  • Indications:
    • Agitated psychotic state, hallucinations, bipolar disorder, excessive motor and autonomic activity.
    • Severe nausea and vomiting induced by CNS disturbances.
    • Moderate anxiety, behavioral problems caused by chronic organic mental syndrome, tetanus, acute intermittent porphyria, intractable hiccups, itching, and symptomatic rhinitis.
  • Nursing Considerations:
    • Monitor for adverse reactions and extrapyramidal symptoms.
    • Neuroleptic malignant syndrome may occur.
    • Elevated liver enzyme levels may indicate an allergic reaction.
    • Don’t withdraw the drug abruptly; gradually reduce the dosage over several weeks.
    • Avoid hazardous activities until CNS effects are known.

Teachings: Antipsychotic Drugs

  • Take as prescribed.
  • Take the full dose at bedtime if daytime sedation occurs.
  • Watch for adverse reactions and report unusual effects, especially involuntary movements.
  • Avoid alcohol while taking this drug.
  • Avoid hazardous tasks until the drug’s full effects are established.
  • Excessive exposure to sunlight, heat lamps, or tanning beds may cause photosensitivity reactions.
  • Avoid exposure to extreme heat or cold.
    *Phenothiazines may cause pink or brown discoloration of urine.

Warning Signs of Suicidal Ideation

  • Pacing, agitated behavior, frequent mood changes, and chronic episodes of sleeplessness.
  • Actions or threats of assault, physical harm, or violence.
  • Delusions or hallucinations.
  • Threats or talk of death.
  • Putting affairs in order.
    *Unusually risky behavior.