antipsychotics

Selection of Symptoms in Psychosis

Overview of Symptoms
  • Symptoms in Psychosis: Generally categorized as positive and negative symptoms.
    • Positive Symptoms: Features added to the individual's experience, such as agitation, delusions, hallucinations.
    • Negative Symptoms: The absence of traits that should be present, including a lack of motivation, pleasure, and apathy.
  • Cognitive Symptoms: Associated with chronic pain psychosis but minimally addressed by pharmacological treatment.
Understanding Positive and Negative Symptoms
  • Positive Symptoms:
    • Defined as symptoms that are added to the normal psychological profile of an individual.
    • Examples:
    • Agitation
    • Delusions
    • Hallucinations
  • Negative Symptoms:
    • Defined as the lack of normal emotional responses and behaviors.
    • Examples:
    • Lack of motivation
    • Lack of pleasure
    • Apathy
  • Connection to Pharmacology: Understand which medications effectively target positive versus negative symptoms. Some patients may experience a combination of both.
Neurotransmitter Involvement
  • Dopamine Dysregulation:
    • Prefrontal Cortical Pathway: Decreased dopamine leads to negative symptoms.
    • Mesolimbic Pathway: Increased dopamine leads to positive symptoms.
  • Other Neurotransmitters:
    • Serotonin and Glutamate contribute to symptoms and treatment responses, although traditionally the focus has been on dopamine.
    • Recent developments include drugs affecting serotonin and glutamate pathways alongside dopamine.

Antipsychotic Medications

First Generation Antipsychotics (FGAs)
  • Overview:
    • Established primarily for the treatment of psychosis, but less favored currently due to side effects.
    • Categories:
    • High Potency: e.g., Haloperidol (Haldol), Fluphenazine, Parfemazine.
    • Low Potency: e.g., Chlorpromazine (Thorazine).
  • Common Side Effects: Extrapyramidal symptoms (EPS) due to dopamine receptor antagonism, especially with high-potency FGAs.
Extrapyramidal Symptoms (EPS)
  • Definition: A range of movement disorders caused by dopamine antagonism. Common manifestations include:
    • Bradykinesia
    • Rigidity
    • Dystonia
    • Akathisia
Mechanisms of Action
  • High Potency FGAs: Strong D2 receptor antagonism primarily to alleviate positive symptoms leading to EPSs as side effects.
  • Low Potency FGAs: Generally less likely to cause EPS but still have anticholinergic and antihistaminergic effects resulting in sedation.
Second Generation Antipsychotics (SGAs)
  • Overview: Offer a broader spectrum of effects with a lower risk for EPS compared to FGAs. Common SGAs include:
    • Clozapine (noted for neutropenia).
    • Olanzapine (risk of metabolic syndromes).
    • Risperidone (URL for hyperprolactinemia).
    • Quetiapine (notable for weight gain).
    • Aripiprazole (partially works as agonist/antagonist).
  • Mechanism of Action: Involve D2 antagonism and influence serotonin receptors (5-HT2A) alongside additional receptor interactions (D3, D4, alpha-adrenergic, H1).
  • Indications: Treatment for schizophrenia, bipolar disorder, acute psychosis, and other conditions.
Side Effects of Antipsychotics
  • EPS: More common with FGAs, but can occur with SGAs.
  • Hyperprolactinemia: Mainly a concern with risperidone. Symptoms may manifest in abnormal lactation and menstrual irregularities.
  • QT Prolongation: Notable in ziprasidone; an important consideration when prescribing.
  • Metabolic Risks: Weight gain and diabetes risks associated with clozapine and olanzapine. Monitor pre-treatment and during therapy.
Management of Extrapyramidal Symptoms
  • General Approach: First review the current dose and response; consider up-titration. If EPS develops:
    • Dystonia Treatment: Use of anticholinergics like diphenhydramine, trihexphenidyl, or benztropine.
    • Akathisia Management: Consider beta-blockers such as propranolol or benzodiazepines (with caution).
Neuroleptic Malignant Syndrome (NMS)
  • Overview: Rare but life-threatening condition characterized by:
    • Muscle rigidity
    • Elevated temperature
    • Autonomic dysfunction.
  • Management Steps:
    • Stop the offending agent.
    • Consider administering dantrolene to manage muscle rigidity.
    • Monitor patient and provide supportive care without restraining them unnecessarily.
Differences Between NMS and Serotonin Syndrome
  • Key Differences:
    • NMS: More rigid muscle tone, elevated creatine kinase (CK) levels indicative of muscle damage.
    • Serotonin Syndrome: Hyperreflexia and clonus prevalent, typically presents with different medications (SSRIs).
Management of Acute Symptoms
  • Drug Options for Management: Ensure evaluation of jerk and not prescribe antipsychotics with other CNS acting drugs and manage carefully switching between medications.
  • Use of Long-acting Injectables: Consider for patients requiring ongoing treatment once stability is established on oral doses.
Summary and Insights
  • Individualized Treatment: Tailoring selections based on symptom types and patient history. Consider the anxiety levels when switching antipsychotics.
  • Monitoring: Vital in managing ongoing treatment and preventing adverse effects with particular attention to EPS, metabolic symptoms, and QT prolongation.
Long-acting Options.
  • A variety of long-acting injectable options available for patients with chronic conditions who miss oral doses due to cognitive impairments.
  • Transition only to injectables after establishing tolerance to oral formulations.
Conclusion
  • Understanding the pharmacological actions and managing the side effects are key components in treating patients with psychotic disorders, especially when discussing antipsychotic medications. Precise management strategies are critical for optimizing patient outcomes, balancing symptom control with side effect profiles.