NSC 330: Antipsychotics & Mood Stabilizers

Antipsychotics

Uses

• Antipsychotics are primarily used for:
    1. Schizophrenia
    2. Psychotic symptoms associated with:
       - Head injury / CVA (Cerebrovascular Accident)
       - ETOH W/D (Alcohol Withdrawal)
    3. Severe agitation and delusions associated with dementia

Mechanism of Action (MOA)

• Antipsychotics primarily decrease dopamine activity.

• They also impact other neurotransmitters including:
    - Acetylcholine
    - Histamine
    - Norepinephrine

Categories

1. Typical Antipsychotics (First Generation)

2. Atypical Antipsychotics (Second Generation)

Symptoms

Positive Symptoms

• Indicate the presence of abnormal behaviors:
    1. Delusions
    2. Agitation / Combative behavior
    3. Hallucinations
    4. Insomnia
    5. Paranoia
    6. Disordered thinking
    7. Disorganized speech

Negative Symptoms

• Reflect a decrease in normal functions:
    1. Social withdrawal
    2. Emotional withdrawal
    3. Lack of motivation
    4. Blunted affect
    5. Poor insight
    6. Poor judgment
    7. Poor self-care

Typical Antipsychotics (First Generation)

Examples

• Phenothiazines:
    1. Chlorpromazine
    2. Fluphenazine

• Nonphenothiazines:
    1. Haloperidol

Adverse Effects (AEs)

1. Higher risk of EPS (Extrapyramidal Symptoms)

2. Increased sedation

3. Anticholinergic effects

4. Orthostatic hypotension

5. Lower seizure threshold

6. Sexual dysfunction

7. Fatal cardiac dysrhythmias

Atypical Antipsychotics (Second Generation)

Examples

1. Clozapine

2. Olanzapine

3. Risperidone

Adverse Effects (AEs)

1. More prominent metabolic effects:
      - Weight gain
      - Diabetes
      - Dyslipidemia

Extrapyramidal Symptoms (EPS)

Types of EPS

1. Acute Dystonia:
      - Muscle spasms of tongue, face, neck, and back

2. Parkinsonism:
      - Bradykinesia
      - Tremor
      - Rigidity
      - Shuffling gait
      - Drooling
      - Stooped posture

3. Akathisia:
      - Compulsive, restless movement (e.g., pacing, squirming)
      - Anxiety
      - Agitation

4. Tardive Dyskinesia:
      - Oral-facial dyskinesias
      - Twisting and writhing movements
      - Hyperkinetic movements (e.g., lip smacking, tongue protrusion)

Treatment for EPS

• Treat with an anticholinergic or antiparkinson drug to mitigate symptoms.

General Concepts

1. Both typical and atypical antipsychotics are considered equally effective.

2. The selection of medication should be based on:
      - Efficacy
      - Safety
      - Cost

3. Acute psychotic episodes may require:
      - Higher doses
      - IM (intramuscular) administration
      - Hospitalization

4. Adherence Issues:
      - Address medications by potentially using a single HS (at bedtime) dose when able, which can help:
        - Increase compliance
        - Allow for better sleep
        - Decrease orthostatic hypotension
        - Decrease daytime sedation

5. Improvement in symptoms generally observed:
      - Possible improvement in 1-2 days
      - Significant improvement seen after 1-2 weeks
      - Full response may take several months

Mood Stabilizers

Uses

• Mood stabilizers are used for:

1. Bipolar Disorder

2. To treat and prevent manic episodes

Lithium

Mechanism of Action (MOA)

• The exact mechanism of action of lithium is unclear, but it is suspected to:
     - Increase glutamate levels
     - Increase serotonin levels

Pharmacokinetics

1. Lithium has a short half-life and a narrow therapeutic index.

2. The elimination of lithium is significantly affected by serum sodium levels:
      - Kidneys process lithium and sodium in a similar manner
      - Lower sodium levels lead to reduced elimination of lithium.

Importance of Sodium Levels

1. Low serum sodium = Higher lithium levels within the body.

2. Key focus: Maintain normal sodium levels through:
      - Consistent sodium intake
      - Adequate hydration
      - Caution needed during scenarios such as diarrhea or dehydration, and avoidance of diuretics.

Narrow Therapeutic Index

• Lithium has a therapeutic range of:
    $0.4 - 1.5 ext{ mEq/L}$

1. Requires frequent monitoring at initial stages and every three months once stable.

2. Draw trough levels by taking samples in the morning, 12 hours after the last PM dose and before the AM dose.

Lithium Adverse Effects

Common Adverse Effects

1. Gastrointestinal issues:
      - Nausea
      - Vomiting
      - Diarrhea

2. Hypothyroidism

3. Nephrotoxicity

4. Fine hand tremors

5. Drowsiness

6. Polyuria (increased urination)

7. Polydipsia (increased thirst)

Signs and Symptoms of Lithium Toxicity

1. Persistent nausea, vomiting, and diarrhea

2. Course hand tremors

3. Blurred vision

4. Tinnitus (ringing in the ears)

5. Confusion

6. Impaired muscle coordination, including clonus

7. Severe hypotension

8. Dysrhythmias

9. Seizures

10. Coma or death

Summary of Essential Lithium Monitoring Parameters

• Lithium levels should be monitored as they have an inverse relationship with sodium levels.

• Symptoms to be vigilant for include:
     - Tremors
     - Thirst
     - Hypotension
     - Increased urination
     - Upset stomach
     - Mania