First Generation Antipsychotics

First Generation Antipsychotics


First generation antipsychotics (FGAs) are called such because they were the first class of antipsychotic medications to be developed and introduced for the treatment of psychiatric disorders. These medications emerged in the mid-20th century, starting with the discovery of chlorpromazine (Thorazine) in the 1950s.
First generation antipsychotics (FGAs) have played a significant role in the treatment of various mental health conditions. Here, we’ll delve into the world of first generation antipsychotics, discussing their uses, potential side effects, and their effectiveness in managing psychiatric disorders.

Understanding First Generation Antipsychotics

  1. Definition and Development: Provide an overview of FGAs, explaining their classification as the first generation of antipsychotic medications and the historical context of their development.
  2. Mechanism of Action: Describe how FGAs work in the brain by blocking dopamine receptors, specifically the D2 receptors, to alleviate symptoms of psychosis.

Uses of First Generation Antipsychotics

  1. Treatment of Psychosis: Highlight the primary indication of FGAs in the management of psychotic disorders, including schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features.
  2. Off-label Uses: Discuss additional uses of FGAs, such as controlling severe nausea and vomiting, managing agitation in dementia, and adjunctive treatment in certain mood disorders.

Potential Side Effects of First Generation Antipsychotics

However, FGAs can also cause some serious side effects that affect the movement of your muscles and nerves, as well as other organs and systems in your body. These include:

  • Extrapyramidal side effects (EPS): These are involuntary movements or muscle spasms that can affect your face, neck, trunk, or limbs. They can be painful and interfere with your breathing, swallowing, speech, or daily activities. EPS can occur within the first few days of taking FGAs and may last for hours or days. They include dystonia, akathisia, parkinsonism, and tardive dyskinesia.
  • Neuroleptic malignant syndrome (NMS): This is a rare but life-threatening reaction that can occur due to FGAs’ interference with dopamine. Symptoms may include fever, rigid or stiff muscles, altered mental status, irregular pulse or blood pressure, fast or irregular heartbeat, and excessive sweating. If you experience these symptoms, stop taking FGAs right away and get medical help. NMS can damage your muscles and kidneys.
  • Anticholinergic effects: These are effects that result from FGAs’ blocking of acetylcholine receptors in the brain and body. They include dry mouth, blurred vision, constipation, urinary retention, confusion, and memory impairment. They can occur at any time during FGA treatment and may last for weeks or months.
  • Cardiovascular effects: These are effects that result from FGAs’ interference with the electrical activity of the heart. They include low blood pressure, irregular heartbeat, and prolonged QT interval. They can occur after weeks or months of taking FGAs and may increase the risk of sudden cardiac death.
  • Metabolic effects: These are effects that result from FGAs’ interference with the metabolism of glucose and lipids. They include weight gain, diabetes mellitus, and dyslipidemia. They can occur after long-term use of FGAs (months or years) and may increase the risk of cardiovascular disease.

FGAs are effective in treating positive symptoms of schizophrenia, such as hallucinations, delusions, and paranoia. However, they are less effective in treating negative symptoms of schizophrenia, such as withdrawal, apathy, and lack of motivation. They also do not improve cognitive function or social functioning.

Effectiveness and Limitations of First Generation Antipsychotics

  1. Efficacy: Explore the effectiveness of FGAs in managing symptoms of psychosis, emphasizing their ability to reduce positive symptoms like hallucinations and delusions.
  2. Limitations and Challenges: Discuss the limitations of FGAs, including a higher risk of side effects compared to second-generation antipsychotics (SGAs) and their limited impact on negative symptoms and cognitive impairments.

How to Use FGAs Safely and Effectively

The best way to use FGAs safely and effectively is to follow your doctor’s instructions on how to take them. Your doctor will prescribe the lowest effective dose of FGA for the shortest possible time. Your doctor will also monitor your response and adjust your dose accordingly.

You should also inform your doctor if you have any risk factors for FGA side effects, such as:

  • Being young or male
  • Having a history of EPS or NMS with other medications
  • Having low levels of potassium or magnesium in your blood
  • Having low thyroid function or a family history of long QT syndrome
  • Taking other medications that can interact with FGAs, such as antiemetics (metoclopramide, droperidol), lithium, SSRIs (fluoxetine), stimulants (methylphenidate), TCAs (amitriptyline) or antivirals (ribavirin).

If you develop any signs of FGA side effects while taking them, you should contact your doctor immediately. Do not stop taking FGAs without consulting your doctor first, as this may worsen your symptoms or cause a rebound effect.

Depending on the type and severity of your FGA side effects, your doctor may:

  • Reduce your dose of FGA
  • Switch you to another antipsychotic medication that has a lower risk of side effects (such as a second-generation antipsychotic)
  • Add another medication that can counteract the effects of FGA on your muscles and nerves (such as benztropine or trihexyphenidyl)
  • Refer you to a specialist for further evaluation and treatment

First Generation Antipsychotics Vs Second Generation Antipsychotics

AspectFirst Generation Antipsychotics (FGAs)Second Generation Antipsychotics (SGAs)
Discovery and DevelopmentDeveloped in the 1950s and 1960sDeveloped in the 1990s and onwards
Mechanism of ActionPrimarily block dopamine D2 receptorsBlock both dopamine and serotonin receptors, with varying affinities
EfficacyEffective in reducing positive symptoms of psychosis, such as hallucinations and delusionsEffective in addressing both positive and negative symptoms of psychosis, and may have better outcomes for negative symptoms
Side EffectsHigher risk of extrapyramidal side effects (EPS) including Parkinsonism, akathisia, dystonia, and tardive dyskinesiaLower risk of EPS, but may be associated with metabolic side effects such as weight gain, diabetes, and dyslipidemia
SedationMore sedatingGenerally less sedating
Anticholinergic EffectsMore likely to cause anticholinergic effects such as dry mouth, blurred vision, and constipationLess likely to cause anticholinergic effects
Treatment OptionsA broader range of options available, providing more choices for individualized treatmentA broader range of options is available, providing more choices for individualized treatment
Use in Clinical PracticeStill prescribed in certain cases, especially when cost or specific side effect profile is a considerationOften considered as a first-line choice due to a better side effect profile and efficacy for both positive and negative symptoms

Conclusion and Future Perspectives

Summarize the key points discussed in the article, highlighting the historical significance and continued use of first generation antipsychotics. Mention the advancements in second-generation antipsychotics while acknowledging the ongoing relevance of FGAs in certain clinical scenarios.