DRUGS USED IN SCHIZOPHRENIA AND OTHER PSYCHOTIC DISORDERS

Introduction

There are several types of drugs commonly used in the treatment of schizophrenia and other psychotic disorders. These medications are primarily aimed at reducing the symptoms of psychosis, such as hallucinations, delusions, and disorganized thinking. The specific medication prescribed can vary depending on the individual’s symptoms, medical history, and response to different medications. Here are some of the main classes of drugs used in the treatment of schizophrenia and psychotic disorders:

1. Antipsychotics (also known as neuroleptics): These medications are the cornerstone of treatment for schizophrenia and psychotic disorders. They work by blocking dopamine receptors in the brain, helping to alleviate symptoms of psychosis. There are two main types of antipsychotics: a. Typical antipsychotics: Examples include chlorpromazine, haloperidol, and fluphenazine. These medications have been in use for many years and are effective in treating positive symptoms of psychosis but may have more side effects. b. Atypical antipsychotics: Examples include risperidone, olanzapine, quetiapine, aripiprazole, and clozapine. Atypical antipsychotics are newer medications that are generally preferred due to their reduced side effects compared to typical antipsychotics. They are effective in treating both positive and negative symptoms of schizophrenia.
2. Mood stabilizers: In some cases, mood stabilizers such as lithium or valproate may be prescribed to help control mood symptoms associated with psychotic disorders, particularly bipolar disorder with psychotic features.
3. Antidepressants: Antidepressant medications may be prescribed if the individual with schizophrenia or psychotic disorder also experiences significant depressive symptoms. Selective serotonin reuptake inhibitors (SSRIs) or other antidepressants may be used cautiously, as they can sometimes worsen psychotic symptoms.
4. Benzodiazepines: These medications, such as lorazepam or clonazepam, are sometimes used in the short term to manage acute agitation, anxiety, or insomnia associated with psychosis. However, they are generally not recommended for long-term use due to the risk of dependence and sedation.

It’s important to note that medication alone is not usually sufficient for the treatment of schizophrenia and psychotic disorders. Psychotherapy, family support, and other interventions are often recommended as part of a comprehensive treatment plan. The specific medication regimen should be determined by a qualified healthcare professional who can assess the individual’s condition and monitor the effectiveness and side effects of the medication.

 

Neurotransmitter Pathways

The serotonergic, noradrenergic (norepinephrine), and dopaminergic pathways are important neurotransmitter systems in the brain that play a crucial role in regulating various physiological and psychological processes. Here is an outline of their anatomy and a summary of their known and suspected functions:

1. Serotonergic Pathway:
   • Anatomy: The serotonergic pathway is primarily composed of neurons that produce and release serotonin (5-hydroxytryptamine, or 5-HT). The cell bodies of these neurons are located in the raphe nuclei, which are found in the brainstem.
   • Function: Serotonin is involved in regulating mood, sleep, appetite, sexual behavior, and cognition. It is often associated with feelings of well-being and happiness. Dysfunction of the serotonergic system has been implicated in various psychiatric disorders, including depression, anxiety, and obsessive-compulsive disorder.
2. Noradrenergic (Norepinephrine) Pathway:
   • Anatomy: The noradrenergic pathway consists of neurons that produce and release norepinephrine (NE). These neurons are mainly located in the locus coeruleus, a nucleus located in the brainstem.
   • Function: Norepinephrine is involved in arousal, attention, alertness, and the stress response. It plays a role in regulating mood, motivation, and cognition. Dysregulation of the noradrenergic system has been implicated in conditions such as depression, attention deficit hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).
3. Dopaminergic Pathway:
   • Anatomy: The dopaminergic pathway comprises several major pathways, including the mesolimbic, mesocortical, and nigrostriatal pathways. Dopamine is synthesized by neurons located in specific brain regions, including the substantia nigra and the ventral tegmental area.
   • Function: Dopamine is involved in various functions, including reward and pleasure, motivation, movement, and reinforcement of behavior. The mesolimbic pathway, in particular, is associated with the brain’s reward system and plays a key role in addiction. Dysfunction of the dopaminergic system has been implicated in conditions such as Parkinson’s disease, schizophrenia, and addiction.

It is important to note that while the known functions of these neurotransmitter systems have been extensively studied, our understanding is still evolving, and there may be additional roles and complexities yet to be fully elucidated. Additionally, these pathways often interact and influence each other, contributing to the overall regulation of brain function and behavior.

 

Schizophrenia Symptoms Overview

Schizophrenia is a complex mental disorder characterized by a range of symptoms that affect a person’s thoughts, emotions, perceptions, and behavior. The symptoms can vary in intensity and presentation among individuals, but they typically fall into three broad categories: positive symptoms, negative symptoms, and cognitive symptoms. It’s important to note that schizophrenia symptoms can be chronic or episodic, meaning they may come and go over time. Here’s an overview of the major symptoms and signs of schizophrenia:

1. Positive Symptoms:
   • Hallucinations: Hearing, seeing, smelling, or feeling things that are not present in reality. Auditory hallucinations (hearing voices) are the most common.
   • Delusions: Holding false beliefs that are not based in reality. Delusions of persecution, grandeur, or reference (believing that random events or actions have significant meaning) are common.
   • Disorganized thinking and speech: Incoherent or illogical thought processes that manifest as disorganized speech patterns, difficulty staying on topic, or making loose associations.
2. Negative Symptoms:
   • Reduced emotional expression: Restricted range of emotions, appearing emotionally flat or lacking in enthusiasm.
   • Social withdrawal: Avoiding social interactions, preferring to be alone, and having difficulty forming and maintaining relationships.
   • Anhedonia: Loss of interest or pleasure in activities previously enjoyed.
   • Lack of motivation: Decreased drive, energy, and initiative, leading to difficulties in completing tasks and achieving goals.
   • Diminished speech: Decreased amount or quality of speech, characterized by brief or monotonous responses.
3. Cognitive Symptoms:
   • Impaired memory and attention: Difficulties in sustaining attention, remembering information, and organizing thoughts.
   • Poor executive functioning: Struggles with planning, decision-making, problem-solving, and managing time.
   • Reduced working memory: Challenges in holding and manipulating information in mind.
   • Trouble with learning and processing information: Difficulty understanding and integrating new information.

 

Dopamine Hypothesis of Schizophrenia

 

Receptors Blocked by Antipsychotics

 

Antipsychotic Drug Classifications

There are two main classifications of antipsychotic drugs: first-generation (typical) antipsychotics and second-generation (atypical) antipsychotics.

1. First-generation (Typical) Antipsychotics: First-generation antipsychotics were developed in the mid-20th century and were the first class of drugs used to treat psychotic symptoms. They primarily block dopamine receptors in the brain, which helps reduce the activity of dopamine, a neurotransmitter associated with psychosis. These drugs are often referred to as “typical” because they were the first to be introduced and have been used for several decades.Some commonly prescribed first-generation antipsychotics include:
   • Chlorpromazine (Thorazine)
   • Haloperidol (Haldol)
   • Fluphenazine (Prolixin)
   • Perphenazine (Trilafon)

   First-generation antipsychotics tend to be effective in treating positive symptoms of schizophrenia, such as hallucinations and delusions. However, they have a higher risk of causing side effects, particularly movement disorders known as extrapyramidal symptoms (EPS). These include muscle stiffness, tremors, and involuntary movements.

2. Second-generation (Atypical) Antipsychotics: Second-generation antipsychotics, also known as atypical antipsychotics, were introduced in the 1990s and became a significant advancement in the treatment of psychotic disorders. These medications also target dopamine receptors but have a broader mechanism of action by affecting other neurotransmitters, including serotonin.Some commonly prescribed second-generation antipsychotics include:
   • Risperidone (Risperdal)
   • Olanzapine (Zyprexa)
   • Quetiapine (Seroquel)
   • Aripiprazole (Abilify)
   • Clozapine (Clozaril)

   Atypical antipsychotics are generally effective in treating both positive and negative symptoms of schizophrenia. They have a lower risk of causing movement disorders compared to typical antipsychotics. However, they can still cause side effects such as weight gain, metabolic changes, and increased risk of diabetes.

It’s important to note that while these classifications provide a general framework, each individual antipsychotic drug may have unique characteristics and varying levels of efficacy and side effects. The choice of antipsychotic medication depends on the specific needs of the patient, their medical history, and the judgment of the prescribing healthcare professional.

 

Antipsychotic Pharmacodynamics and Clinical Uses

The pharmacodynamics of antipsychotic drugs refers to their mechanism of action and how they interact with specific receptors in the brain to produce therapeutic effects. Antipsychotics primarily target dopamine, serotonin, and other neurotransmitter receptors, influencing their activity to alleviate symptoms of psychosis and related psychiatric disorders.

Dopamine receptor blockade is a central aspect of the pharmacodynamics of antipsychotics. These drugs can be broadly classified into two categories based on their effects on dopamine receptors: typical (first-generation) antipsychotics and atypical (second-generation) antipsychotics.

Typical antipsychotics, such as haloperidol and chlorpromazine, primarily block dopamine D2 receptors in the brain. This blockade leads to a reduction in dopamine transmission in the mesolimbic pathway, which is associated with positive symptoms of psychosis, such as hallucinations and delusions. By antagonizing D2 receptors, typical antipsychotics help alleviate these symptoms, but they are also associated with a higher risk of extrapyramidal side effects, such as parkinsonism and tardive dyskinesia.

Atypical antipsychotics, including drugs like risperidone, olanzapine, and clozapine, have a broader receptor profile, affecting both dopamine and serotonin receptors. They exhibit high affinity for serotonin 5-HT2A receptors, and they also block dopamine D2 receptors, albeit to a lesser extent than typical antipsychotics. By antagonizing both these receptors, atypical antipsychotics can effectively target positive symptoms of psychosis while potentially having a lower risk of extrapyramidal side effects.

Furthermore, atypical antipsychotics often have additional effects on other receptors, such as partial agonism at serotonin 5-HT1A receptors and antagonism at various adrenergic, histaminergic, and cholinergic receptors. These additional receptor interactions contribute to the complex pharmacodynamic profile of atypical antipsychotics and may contribute to their broader efficacy and different side effect profiles compared to typical antipsychotics.

The clinical uses of antipsychotic drugs are primarily aimed at managing psychotic disorders, including schizophrenia and bipolar disorder with psychotic features. Both typical and atypical antipsychotics are effective in reducing positive symptoms like hallucinations, delusions, and thought disorders. However, atypical antipsychotics are often preferred as they also address negative symptoms (such as social withdrawal, blunted affect, and reduced motivation) and cognitive impairments associated with schizophrenia.

Atypical antipsychotics are also used in other psychiatric conditions like major depressive disorder, where they may be combined with an antidepressant to enhance efficacy. Additionally, some atypical antipsychotics, such as aripiprazole, have FDA approval for the treatment of autism spectrum disorders, irritability associated with autistic disorder, and Tourette’s disorder.

In summary, antipsychotic drugs exert their therapeutic effects by modulating dopamine and serotonin receptors in the brain. The specific receptor profile of each drug, whether typical or atypical, contributes to its clinical use and potential side effect profile. Atypical antipsychotics, with their broader receptor interactions, offer advantages in terms of addressing both positive and negative symptoms of psychosis and are often preferred in clinical practice.

 

Adverse effects and the behavior effects of the major antipsychotic drugs

Here is a general overview of some of the common adverse and behavioral effects associated with major antipsychotic drugs:

1. Adverse Effects: a. Extrapyramidal symptoms (EPS): These are movement-related side effects that can include:
   • Parkinsonism: Symptoms similar to Parkinson’s disease, such as tremors, rigidity, and bradykinesia (slowness of movement).
   • Akathisia: Restlessness, an intense urge to move, and difficulty sitting still.
   • Dystonia: Involuntary muscle contractions causing abnormal postures or movements.
   • Tardive dyskinesia (TD): Involuntary repetitive movements, such as lip smacking, tongue protrusion, or facial grimacing.

   b. Metabolic side effects:

   • Weight gain: Antipsychotics can cause significant weight gain, potentially leading to obesity and related health issues.
   • Hyperglycemia: Increased blood sugar levels, which can contribute to the development of diabetes.
   • Dyslipidemia: Abnormal lipid (fat) levels in the blood, including increased cholesterol and triglycerides.

   c. Cardiovascular effects:

   • Orthostatic hypotension: A drop in blood pressure upon standing, leading to dizziness or fainting.
   • QT prolongation: An alteration in the heart’s electrical activity, which can increase the risk of irregular heart rhythms.

   d. Endocrine effects:

   • Hyperprolactinemia: Increased levels of the hormone prolactin, which can cause menstrual irregularities, breast enlargement, and sexual dysfunction.
   • Sexual dysfunction: Antipsychotics can lead to decreased libido, erectile dysfunction, or difficulties achieving orgasm.
2. Behavioral Effects: a. Sedation: Many antipsychotics have a sedating effect and can cause drowsiness and reduced alertness. b. Cognitive effects: Some individuals may experience cognitive impairment, including difficulties with concentration, memory, and problem-solving. c. Emotional blunting: Antipsychotics can reduce the intensity of emotions, making individuals feel less emotionally reactive or expressive. d. Dysphoria or depression: In some cases, antipsychotics may contribute to feelings of sadness, low mood, or even depressive symptoms. e. Anticholinergic effects: These can include dry mouth, blurred vision, constipation, and urinary retention.

It’s essential to discuss any concerns about medication side effects with a healthcare professional. They can provide specific information regarding individual antipsychotic medications and help weigh the benefits against the potential risks for each individual patient.

 

Pharmacokinetics and pharmacodynamic of lithium