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2 Contact Hours including 2 Advanced Pharmacology Hours
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This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN), Certified Nurse Practitioner, Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner, Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Nursing Student, Registered Nurse (RN), Registered Nurse Practitioner
This course will be updated or discontinued on or before Friday, January 30, 2026

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CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


Purpose: Schizophrenia is a severe and persistent disease that damages the lives of those it afflicts and their families and friends. Through this course, participants will explore neurobiology, clinical manifestations, therapeutic interventions, and the lived experiences of individuals grappling with schizophrenia.

≥ 92% of participants will know how to appropriately care for patients with schizophrenia.


After completing this course, the participant will be able to:

  1. Describe the neurobiology of schizophrenia.
  2. Outline the clinical manifestations of schizophrenia.
  3. Explain the diagnostic workup of the patient with schizophrenia.
  4. Identify medications used to treat schizophrenia.
  5. Describe the side effects of medications used to treat schizophrenia.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Raymond Lengel (MSN, FNP-BC, RN)


Schizophrenia affects one percent of the population, with men and women equally affected. Men, on average, present earlier (in their late teens or early twenties) with the disease than women, who usually have presenting symptoms in their late twenties or early thirties (National Institute of Mental Health, n.d.). Women tend to present with less severe symptoms, possibly because of the effect estrogen has on dopamine (Brand et al., 2021).

Schizophrenia adversely affects the lives of schizophrenic patients in many ways. About five percent of people with schizophrenia will commit suicide, and up to 50 percent will attempt suicide over their lifetime (Berardelli et al., 2021). Patients with schizophrenia marry less frequently and have higher divorce rates. It is estimated that six percent of people with schizophrenia are homeless, another six percent live in jails/prisons, ten percent live in nursing homes, and another 20 percent live in supervised housing (, n.d.). Individuals with schizophrenia have higher rates of other psychiatric conditions, including anxiety, depression, and alcohol/substance abuse.

Schizophrenia is associated with many costs to the health care system as it often presents early in life, has no cure, requires repeated interactions with the health care system, lifelong medications, and frequent hospitalizations. Medications treating the disease do not cure it; they manage the symptoms. Unfortunately, most individuals do not respond fully to the current treatments available. A 2019 analysis showed that schizophrenia costs the United States $343.2 billion (Kadakia et al., 2022). Schizophrenia is an expensive disease, and optimal management is important to reduce healthcare costs and improve the lives of patients who suffer from the disease.

Risk Factors

Many factors put one at risk for schizophrenia, with family history being the greatest risk factor. While many genetic markers are connected to schizophrenia, no specific genetic marker is directly linked. If a first-degree relative has schizophrenia, the lifetime risk is about 10 percent; if both parents are affected, the lifetime risk is 40 percent (Frankenburg, 2021).

Socioeconomic status (SES) can play a significant role in the development, course, and outcomes of schizophrenia. SES refers to an individual's or a family's social and economic position within society, often measured by factors like income, education, occupation, and wealth. SES intersects with schizophrenia in multiple ways, including:

  1. Risk factors and vulnerability: Individuals from lower socioeconomic backgrounds may face increased vulnerability to developing schizophrenia due to a combination of factors. These can include exposure to chronic stress, adverse childhood experiences, limited access to quality healthcare, and environmental factors that increase the risk of developing the disorder.
  2. Access to healthcare: Socioeconomic disparities can affect access to healthcare services, including mental health services. People with lower SES might face barriers to receiving early diagnosis, treatment, and ongoing care for schizophrenia, which can lead to delayed intervention and poorer outcomes.
  3. Quality of care: Even if individuals from lower SES backgrounds have access to healthcare, their quality of care may be compromised. Limited resources and fewer options for specialized treatment could impact the effectiveness of interventions.
  4. Medication adherence: Socioeconomic factors can influence medication adherence, a crucial aspect of managing schizophrenia. People with lower SES might struggle to afford medications or have difficulty adhering to complex treatment regimens, leading to relapses and poorer symptom control.
  5. Social support: Higher SES is often associated with more extensive social networks and access to supportive resources. Strong social support can contribute to better coping mechanisms and improved overall well-being for individuals with schizophrenia.
  6. Stigma and discrimination: Lower SES individuals with schizophrenia might face additional stigma and discrimination due to their mental health condition and socioeconomic position, which can exacerbate stress and hinder recovery.
  7. Social determinants of health: SES is closely tied to various social determinants of health, such as housing stability, education, employment opportunities, and access to nutritious food. These factors can impact overall mental health and well-being, including the severity of schizophrenia symptoms.
  8. Urban living: Lower SES individuals are more likely to live in urban areas with higher population density and less green space. Urban living has been associated with an increased risk of schizophrenia and may influence the course of the illness.
  9. Trauma and adversity: People from lower SES backgrounds are more likely to experience traumatic events and adverse life circumstances, which can contribute to developing and exacerbating schizophrenia symptoms.
  10. Recovery and rehabilitation: Functional recovery from schizophrenia often involves access to education, vocational training, and suitable employment. Lower SES individuals might encounter challenges in accessing these opportunities, impacting their ability to regain independence.

Pregnancy and birth complications are linked to schizophrenia (Frankenburg, 2021). The mother's poor nutritional status during pregnancy has been connected to schizophrenia. Certain viral illnesses, such as influenza (during certain years), contracted by the mother during pregnancy have also been coupled with schizophrenia. A healthy pregnancy is linked to a lower incidence of the disease (Ursini et al., 2018).

The relationship between drug use and schizophrenia is complex and multifaceted. While drug use is not a direct cause of schizophrenia, evidence suggests that certain substances, particularly cannabis, can interact with genetic and environmental factors to increase the risk of developing the disorder (Vaucher et al., 2018).

Heavy and frequent cannabis use, especially during adolescence and in individuals with a genetic predisposition, has been associated with an increased risk of developing schizophrenia (Godin & Shehata, 2022). Cannabis contains compounds, particularly delta-9-tetrahydrocannabinol (THC), that can affect the brain's dopamine system and potentially trigger psychotic symptoms in vulnerable individuals. However, not everyone who uses cannabis will develop schizophrenia, and the relationship between cannabis use and the disorder is complex and not fully understood.

Other drugs are linked to schizophrenia but in a less direct way. The use of stimulant drugs, such as amphetamines or cocaine, can exacerbate symptoms in individuals who already have schizophrenia or trigger psychotic symptoms in those who are predisposed to the disorder. Stimulants can increase dopamine release in the brain, which may contribute to the development of psychotic symptoms.

Hallucinogenic drugs like lysergic acid diethylamide (LSD) or magic mushrooms can induce hallucinations and delusions, similar to the symptoms of schizophrenia. In individuals who are already predisposed to schizophrenia, the use of these substances might potentially trigger or worsen the disorder.

Drug use, particularly the misuse of substances like alcohol, amphetamines, and hallucinogens, can lead to a condition known as substance-induced psychosis. This condition involves the temporary appearance of psychotic symptoms that subside once the effects of the substance wear off. Substance-induced psychosis is distinct from schizophrenia, but repeated episodes of substance-induced psychosis can complicate diagnosis and potentially interact with underlying vulnerabilities.


Schizophrenia is a complex and multifaceted mental disorder that involves disruptions in thought processes, perceptions, emotions, and behaviors. While the underlying cause is not fully understood, research suggests that genetic, neurodevelopmental, neurochemical, and environmental factors contribute to its pathophysiology.

The dopamine hypothesis is a major theory in the pathophysiology of schizophrenia. It suggests that overactivity of dopamine transmission in certain brain regions, particularly the mesolimbic pathway, is linked to positive symptoms of schizophrenia, such as hallucinations and delusions (McCutcheon et al., 2019). Conversely, reduced dopamine activity in the mesocortical pathway might contribute to negative symptoms and cognitive impairments.

Dopamine is not the only neurotransmitter responsible for the symptoms of schizophrenia. Abnormalities in other neurotransmitters are likely involved in the schizophrenic brain, including norepinephrine, serotonin, glutamine, and gamma-aminobutyric acid (GABA). Dysregulation of the glutamate system, particularly the N-methyl-D-aspartate (NMDA) receptors, has also been implicated. Dysfunction in glutamate transmission is thought to underlie cognitive deficits and negative symptoms (Coyle et al., 2012).

Abnormalities in brain development during prenatal and perinatal periods can impact the structure and function of the brain. Factors such as maternal infections, malnutrition, or stress during pregnancy could increase the risk of later developing schizophrenia.

Anatomic brain changes may contribute to schizophrenia. People with schizophrenia often show enlargement of the brain's lateral and third ventricles, which could suggest reduced brain tissue volume and potential neurodevelopmental anomalies. There is evidence of reduced gray matter volume in multiple brain regions, including the prefrontal cortex, hippocampus, and thalamus (Frankenburg, 2021; Yue et al., 2016). These regions are involved in cognition, emotion regulation, and sensory processing.

The key to finding adequate treatments for schizophrenia may be finding a treatment to target the diverse chemical pathology of the disease. A medication that can target elevated dopamine levels in one section of the brain, target low levels in another, and address all other chemical abnormalities is challenging for the scientific community.

Signs and Symptoms

Chronicling the development of signs and symptoms is a useful tactic to make the diagnosis. Getting input from family members or loved ones is helpful, as schizophrenic patients often have altered perceptions.

An accurate history helps make an accurate diagnosis and rule out other diagnoses. Key information about risk factors is the first step. It includes getting a family history of schizophrenia and other mental health diseases, a history of medication and drug use, early childhood problems, and maternal health during pregnancy. It is also helpful to determine if there were problems during the teenage years, including social or academic problems.

The history should look for positive and negative symptoms. Positive symptoms are abnormal experiences or behaviors added to a person's normal mental functioning. They are called "positive" because they represent an excess or distortion of normal functioning. Common positive symptoms of schizophrenia include:

  1. Hallucinations: Hallucinations involve perceiving things that are not actually present. Auditory hallucinations, where individuals hear voices others cannot hear, are most common in schizophrenia, but visual and tactile hallucinations can also occur.
  2. Delusions: Delusions are false beliefs resistant to reasoning or contrary evidence. For example, individuals with schizophrenia may believe they have special powers, are being persecuted, or have a grandiose sense of importance.
  3. Disorganized Thinking: Disorganized thinking is evident in speech patterns. People with schizophrenia may have difficulty organizing their thoughts, resulting in incoherent or tangential speech, often called "word salad."
  4. Disorganized or Abnormal Motor Behavior: This includes various motor disturbances, such as unpredictable and erratic movements or bizarre postures. Catatonia, a state of immobility or excessive, purposeless movement, is also a possible symptom.

Negative symptoms refer to a decrease or loss of normal functioning or abilities. They reflect deficits in emotional, cognitive, and behavioral functioning and are often more challenging to treat than positive symptoms. Common negative symptoms of schizophrenia include:

  1. Affective Flattening: This refers to reduced emotional expression. Individuals with this symptom may have limited emotional responses, appearing emotionally "flat" or indifferent.
  2. Alogia: Alogia involves reduced speech fluency, manifesting as poverty of speech (reduced speech output) or poverty of content (limited meaningful information in speech).
  3. Anhedonia: Anhedonia is the inability to experience pleasure or interest in previously enjoyed activities. People with schizophrenia may lose interest in social interactions, hobbies, and everyday pleasures.
  4. Avolition: Avolition refers to a lack of motivation to initiate and sustain purposeful activities. Individuals may neglect self-care, work, and social responsibilities.
  5. Social Withdrawal: People with schizophrenia may become socially isolated and have difficulty forming and maintaining relationships.

Not all individuals with schizophrenia will experience all these symptoms, and the severity and combination of symptoms can vary widely from person to person. Other cognitive symptoms, such as impaired attention and memory, may also be present in schizophrenia.

Disorganized symptoms show the patient's inability to think clearly and are common in schizophrenia. Thought and speech are often disorganized and may manifest in multiple ways. Speech may use nonsense words or thoughts, shifting quickly from one thought to the next. The patient may have forgetfulness or frequently lose items. Movement may be slow. Speech is often repetitive and confusing. Schizophrenics may demonstrate repeated movements or gestures such as pacing, strange hand movements, or odd facial expressions. Patients may act like a child or have unpredictable agitation.  

Many schizophrenic patients have vague or odd symptoms such as odd dressing habits, poor personal hygiene, odd beliefs, thought blocking (having long pauses before answering questions), limited conversation, social withdrawal, and poor insight. Orientation is typically intact.  

Those with schizophrenia may also have problems with attention, working memory, processing speed, reasoning, social cognition, verbal comprehension, executive functioning, and visual learning/memory. An individual with schizophrenia typically performs 1-2 standard deviations below healthy individuals on neuropsychological testing (McCutcheon et al., 2023). Cognitive impairments typically occur prior to the presentation of positive symptoms.

It is important to note that schizophrenia is a complex and heterogeneous disorder, and not all individuals with schizophrenia will exhibit the same symptoms or at the same intensity. Additionally, the course and severity of the disorder can vary widely from person to person. Early intervention and appropriate treatment are critical for managing schizophrenia and improving the individual's quality of life.

Signs and symptoms typically occur gradually, as evidenced by a loss of interest in activities, work, or school. Hygiene and grooming get worse, and there are often more anger outbursts. Part of making the diagnosis is to rule out schizoaffective disorder, other mood disorders, and other syndromes that present similarly (Table 1). The symptoms are not related to substance abuse, a medication effect, or a general medical condition. 

The physical exam may not be helpful, but any underlying neurological conditions should be evaluated. Any movement disorder is important to document so a baseline level is known. That way, when antipsychotic medications are started, the baseline is known, and any change can be attributed to the medication and not to their baseline function.

Those with schizophrenia may present with subtle neurological signs such as impaired sensation or impaired motor coordination. Catatonia may also be seen. Many neurological signs of schizophrenia may be related to antipsychotic medications as they often block dopamine and may cause tremors, rigidity, dystonia, and bradykinesia. Metabolic abnormalities (hypertension, diabetes, and abnormal lipids) may be seen in schizophrenia.

Table 1: Other possible diagnoses that present similarly to schizophrenia
Other Potential DiagnosesCharacteristics
Substance abuseIn substance abuse, there is current use of or withdrawal from drugs or other substances.
DeliriumSchizophrenia is a chronic and enduring mental health condition with gradual onset and specific symptom patterns; delirium is an acute and reversible state of confusion and cognitive impairment often triggered by underlying medical issues or substances.
Brain lesionsBrain tumors, intracranial bleeds, or idiopathic calcification of the basal ganglia can potentially present with similar symptoms.
Brief psychotic disorderSimilar symptoms, but the duration of symptoms is less than one month.
DepressionDepression – especially if severe – can present with psychotic symptoms.
Bipolar disorderIt may be difficult to differentiate as psychotic symptoms occur during a manic or depressive state. When the patient's mood is stable, there are no psychotic symptoms.
Delusional disorderThe patient is delusional, but other symptoms of schizophrenia are not present. Typically, functioning is not impaired, and overall behavior is not bizarre.
Schizophreniform disorderSimilar symptoms, but in schizophreniform disorder, the symptoms last one to six months, while schizophrenia is a chronic mental illness with symptoms that persist for at least six months.
Schizoaffective disorderSchizophrenia primarily involves psychosis and disruptions in thought and behavior, while schizoaffective disorder includes psychosis and significant mood disturbances.
Schizotypal personality disorderThese individuals do not form close relationships and have odd behaviors and thoughts – typically, behaviors and thoughts are less severe than schizophrenia.
Seizure disorderTemporal lobe epilepsy occasionally presents with odd behavior – including memory/cognitive changes or hallucinations - before, during, or after a seizure.
Systemic lupus erythematosusSystemic lupus erythematosus can affect the central nervous system and lead to neuropsychiatric symptoms, including psychosis.
HypoglycemiaLow blood sugar levels can cause confusion, disorientation, and behavioral changes that may mimic psychotic symptoms.
Thyroid disordersBoth hyperthyroidism and hypothyroidism can lead to mood disturbances, cognitive impairment, and psychosis.
Medication-inducedDrugs that can induce schizophrenic-type symptoms include anticholinergics, phenytoin, steroids, cimetidine, and some Parkinson's medications.
InfectionsInfections that may present with similar symptoms include neurosyphilis, human immunodeficiency virus, sepsis, cerebral abscess, and Creutzfeldt-Jakob disease.
Vitamin deficiencyThiamine, vitamin B12, or folate deficiencies can cause similar signs and symptoms.
Multiple sclerosisMultiple sclerosis lesions in the brain may affect cognitive function and lead to psychiatric symptoms, including mood swings and psychosis.
(McCutcheon et al., 2023)


The diagnostic criteria for schizophrenia according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are as follows (adapted from American Psychiatric Association [APA], 2013):

  1. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated):
    • Delusions
    • Hallucinations
    • Disorganized speech (e.g., frequent derailment or incoherence)
    • Grossly disorganized or catatonic behavior
    • Negative symptoms (i.e., diminished emotional expression or avolition)
  2. Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning, such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset.
  3. Duration: Continuous signs of the disturbance persist for at least six months. This 6-month period must include at least one month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms.
  4. Schizoaffective and mood disorder exclusion: Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms or (2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.
  5. Substance/medication-induced psychotic disorder exclusion: The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.
  6. Relationship to autism spectrum disorder: If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least one month (or less if successfully treated).

Subtypes of schizophrenia (paranoid, disorganized, catatonic, undifferentiated, and residual) are no longer required due to poor reliability, no proven validity, and this classification not helping treat the disease. These subtypes were used before the last update of the Diagnostic and Statistical Manual of Mental Disorders.


No lab test can diagnose schizophrenia, but a battery of tests should be run to rule out conditions that may be causing the presenting symptoms. A comprehensive drug screen should be done on anyone who presents with psychosis. Other important tests include a complete blood count, electrolytes, liver and renal function, thyroid studies, glucose level, vitamin B-12, folate, and calcium levels.

Other tests to be considered on an individual basis include human immunodeficiency virus (HIV) serology, serology for hepatitis C, syphilis serology, ceruloplasmin, urinalysis and culture, an anti-nuclear antibody (ANA), 24-hour urine for porphyrins, and copper and heavy metal levels (Frankenburg, 2021). A pregnancy test should be done on females. An electrocardiogram (EKG) should be done for those on antipsychotics that prolong the QT interval (e.g., clozapine, iloperidone, thioridazine, and ziprasidone).

Imaging exams – computed tomography (CT) scan or magnetic resonance imaging (MRI) - will help rule out other conditions (subdural hematoma, tumors, vasculitis, and cerebral abscess) that may mimic the disease. A chest x-ray (CXR) may be done if there is suspicion of a malignancy. Electroencephalography (EEG) may be indicated as it may assist in the diagnosis and may help with treatment options.


Schizophrenia is a chronic illness that affects every aspect of life. Treatment goals include the following:

  • Optimize quality of life
  • Reduce or eliminate symptoms
  • Aid in recovery 

Treating schizophrenia is a process, and with each healthcare encounter, treatment plans and diagnoses need to be reevaluated and adjusted if needed. Acute phase treatment should prevent harm, reduce psychosis, determine causes of the acute episode, control disturbing behaviors, reduce symptoms, and develop a treatment plan with the patient and family. Any other medical conditions need to be evaluated and stabilized.  

Evaluating for suicide and any aggressive behaviors is a critical part of the initial evaluation. Any risk for suicide or aggressive behaviors that would put others or the patient at risk should lead to hospitalization of the patient.

photo of files labeled schizophrenia treatment

Schizophrenia Treatment


Antipsychotic medications are the mainstay of treatment for schizophrenia. During the acute phase, these medications must be titrated to target quickly, and then the patient should be monitored. Treatment typically reduces agitation quickly, but psychosis lingers and may take weeks to resolve.

During stabilization, the main goal is to prevent relapse. In addition, the patient should be adapted back into the community; symptoms need to be controlled and stress reduced. Second-generation antipsychotic (SGA) medications are typically the drug of choice in schizophrenia. Risperidone, olanzapine, and aripiprazole are often used first-line due to their favorable side effect profile (Gómez-Revuelta et al., 2020; Marder, 2023).

Antipsychotic medications are a cornerstone in treating schizophrenia and related psychotic disorders but have drawbacks. Antipsychotics treat positive symptoms, but negative symptoms are not managed as well (Correll & Schooler, 2020; Marder, 2023). Antipsychotics effectively prevent relapse when taken, but those who stop the medication relapse about 80 percent of the time within one year (Frankenburg, 2021).

Atypical and typical antipsychotics are two broad categories of medications used to treat various psychiatric disorders, particularly schizophrenia and bipolar disorder. They differ in their mechanisms of action, side effect profiles, and therapeutic uses.

Typical Antipsychotics (First-generation)

First-generation antipsychotics (FGAs) primarily block dopamine receptors in the brain, particularly the D2 receptors, which help reduce the positive symptoms of schizophrenia (e.g., hallucinations and delusions). While they are effective in treating positive symptoms, they have limited effectiveness in managing negative symptoms and cognitive impairments associated with schizophrenia (Marder, 2023).

Common side effects of FGAs include extrapyramidal symptoms (EPS), such as dystonia, akathisia, and parkinsonism. Tardive dyskinesia (involuntary repetitive movements) can also occur with long-term use. They may also cause sedation and anticholinergic side effects (e.g., constipation, urinary retention, dry mouth, and blurred vision). FGAs have a higher risk of causing movement disorders and EPS than atypical antipsychotics.

Atypical Antipsychotics (Second-generation)

SGAs, also known as atypical antipsychotics, are a class of medications used to treat psychiatric disorders, particularly schizophrenia and bipolar disorder. Each SGA may have unique pharmacological properties, but they generally share some common mechanisms of action. It is important to note that the exact mechanisms of action may vary among individual drugs within this class.

  1. Dopamine receptor modulation:
    • SGAs primarily exert their effects by antagonizing dopamine receptors in the brain. Unlike first-generation antipsychotics (primarily targeting D2 receptors), SGAs have a lower affinity for D2 receptors, and some have a more balanced or greater affinity for other dopamine receptor subtypes, such as D1, D3, D4, and D5.
  2. Serotonin (5-HT2A) receptor antagonism:
    • Most SGAs block serotonin receptors, particularly the 5-HT2A subtype. This serotonin-dopamine antagonism is believed to contribute to the lower risk of EPS compared to first-generation antipsychotics.
  3. Noradrenergic and histaminergic receptor blockade:
    • Some SGAs also block alpha-adrenergic receptors and histamine receptors. This activity may contribute to various side effects, including sedation and weight gain.
  4. Neurotransmitter receptor affinities:
    • SGAs often have varied affinities for a range of neurotransmitter receptors, including dopamine, serotonin, norepinephrine, histamine, and acetylcholine receptors. The unique receptor profile of each SGA contributes to its specific side effect profile and efficacy.
  5. Partial agonism:
    • Some SGAs, like aripiprazole, act as partial agonists at dopamine receptors. This partial agonism is believed to provide a stabilizing effect on dopaminergic activity, potentially reducing both excessive and insufficient dopamine transmission.

SGAs generally have a lower risk of causing extrapyramidal symptoms compared to FGAs. Some individuals may also experience anticholinergic side effects. SGAs are associated with a higher risk of metabolic side effects, including weight gain, diabetes, and dyslipidemia, compared to FGAs.

The choice between FGAs and SGAs depends on various factors, including the specific psychiatric diagnosis, the individual's response to the medication, and the side effect profile. Recently, SGAs have become more commonly prescribed due to their broader effectiveness and potentially lower risk of causing movement disorders.

It is important to note that individual responses to antipsychotic medications can vary, and the choice between SGAs and FGAs should be made on a case-by-case basis, considering the patient's specific needs and tolerability. In some cases, FGAs may still be preferred or used with SGAs for certain patients, depending on the clinical presentation and response to treatment. Additionally, SGAs are not without their own side effects, and monitoring and managing side effects should always be a part of schizophrenia treatment.

While first and second-generation medications are effective at treating positive symptoms, they are less effective at treating negative symptoms. Negative symptoms can be challenging to treat. Generally, antipsychotics do not manage negative symptoms (Correll & Schooler, 2020), but a newer medication, cariprazine, may have some benefit, particularly with social functioning (Nemeth et al., 2017).

While negative symptoms are not treated as well with traditional therapies, negative symptoms caused by something else can be treated. For example, if depression is causing a flat affect, then antidepressants may be effective. Treatment of the cause of the negative symptoms is the goal, and if negative symptoms continue, they are probably primary negative symptoms and will likely not be amenable to treatment.

Table 2: Antipsychotic Medications
First-generation antipsychoticsSecond-generation antipsychotics
High PotencyZiprasidone (Geodon®)
Thiothixene (Navane®)Aripiprazole (Abilify®)
Fluphenazine (Prolixin®)Risperidone (Risperdal®)
Perphenazine (Trilafon®)Quetiapine (Seroquel®)
Haloperidol (Haldol®)Olanzapine (Zyprexa®)
Low PotencyClozapine (Clozaril®)
Thioridazine (Mellaril®)Lurasidone (Latuda®)
Chlorpromazine (Thorazine®)Paliperidone (Invega®)
 Asenapine (Saphris®)
 Cariprazine (Vraylar®)
 Brexpiprazole (Rexulti®)
 Iloperidone (Fanapt®)
(Marder, 2023; Nemeth et al., 2017)

When medications are started, the psychosis may take time to resolve, but the patient may quickly demonstrate less agitation (Frankenburg, 2021). Medications that acutely control symptoms are often continued to help maintain patient stability. When there is a partial response, the prescriber should ensure patient adherence, and if compliant, the dose should be titrated into the therapeutic range (see Table 3). Higher doses are associated with an increased risk of side effects. After a partial response, typically after at least six weeks of treatment at a therapeutic dose, the next course of action is less well-defined. Options at this point may include switching medications or adding another medication, although less evidence supports this option (Frankenburg, 2021).

Adverse Effects and Dosages

Recognizing and treating side effects is a key component of pharmacotherapy in schizophrenia. Those afflicted with too many side effects will discontinue therapy and likely relapse.

FGAs are associated with more neurological side effects than SGAs. The degree of side effects is related to the potency of the medication. Generally, high-potency first-generation antipsychotics have a high risk of EPS and a medium risk of sedation. Low-potency first-generation medications are associated with a lower risk of EPS side effects and a high risk of sedation and anticholinergic effects. As a class, these medications are associated with weight gain and sexual side effects (breast tenderness, lack of sexual interest, or erectile dysfunction). The selection of antipsychotics may be based on side effect profile.

The next few paragraphs will discuss the neurological side effects associated with antipsychotics. Extrapyramidal neurological effects include tardive dyskinesia (TD), dystonia, parkinsonism, and akathisia. The most severe neurological side effect is neuroleptic malignant syndrome.

The most permanent of these side effects is TD, which is associated with repetitive and involuntary movements of the face and mouth. It may look like the patient is grimacing, chewing, or sucking. The risk of TD is higher in older adults and females. It often occurs after months or years of treatment and has no reliable remedy. TD is more common with FGAs. Treatment includes reducing the medication dose or switching to a second-generation medication. Symptoms may persist despite stopping medications. Regularly performing the Abnormal Involuntary Movement Scale (AIMS) is a reliable method to evaluate side effects. The test takes about ten minutes and looks at seven body areas using a 5-point scale, which looks for abnormal movements.

Dystonic reactions entail involuntary back, face, and neck muscle contractions. It may also include torticollis, a twisting, or abnormal neck positioning. Oculogyric crisis is an involuntary and sustained upward deviation of the eyes, and facial grimacing with uncontrolled facial movements is often seen. Dystonic reactions typically occur within one to five days and can be treated with antiparkinsonian medications, diphenhydramine, or benztropine.

A set of symptoms that mimics Parkinson's disease, which, if present, typically occurs within one month of starting the medication, includes the symptoms of bradykinesia, tremor, and rigidity. Parkinsonism is a common side effect of FGAs. Discontinuing or reducing the medication is the best treatment, but anti-Parkinson's medications can treat the symptoms (Wisidagama et al., 2021). Second-generation medications can also be used in the management of schizophrenic symptoms in those who are unable to tolerate first-generation medications.

Akathisia, a sense of restlessness, mental unease, irritability, and inability to sit still, is another side effect that may occur up to two months after starting the medication. It is treated with antiparkinsonian medications, benzodiazepines, propranolol, or by decreasing or changing the antipsychotic medication (Patel & Marwaha, 2023).

Neuroleptic malignant syndrome is a life-threatening syndrome associated with antipsychotic use. It is characterized by fever, rigidity, labile blood pressure, catatonia, stupor, and myoglobinemia—the risk peaks from four days to two weeks after starting the medication. Treatment involves stopping the medication, supportive treatment, and using dantrolene (Dantrium®), amantadine (Symmetrel®), or bromocriptine (Parlodel®). Patients with this condition are hospitalized.

Sedation commonly occurs with most first-generation medications and some second-generation medications. The body tends to develop some tolerance to this side effect, so the symptoms lessen the longer the patient is on the medication. The degree of sedation can vary among individuals, and some people may experience more sedation than others, even when taking the same medication.

Some antipsychotic medications are associated with anticholinergic symptoms such as dry mouth, urinary retention, constipation, confusion, and blurred vision. Risperidone, aripiprazole, and ziprasidone are the least likely medications to cause these symptoms (Frankenburg, 2021).

Cardiovascular side effects are a risk with antipsychotic medications. Orthostatic hypotension can occur, especially in risperidone, clozapine, and quetiapine. Abnormal heart rhythms, including the often fatal Torsades de Pointes, may be caused by a prolonged QT interval in patients on antipsychotic medications. Some antipsychotics – clozapine being the most significant – increase the risk of venous thromboembolism (Frankenburg, 2021).

SGAs have less risk of neurological side effects but are not without risk. These agents are associated with an increased risk of weight gain, diabetes, and abnormal cholesterol levels. Antipsychotics may cause weight gain and diabetes, but they are independent of one another, and diabetes may be reversed when the medication is stopped. Together, these effects are even more concerning as they are components of the metabolic syndrome and are linked to a 6-fold increase in the risk of type 2 diabetes and death from coronary heart disease (Bostwick & Murphy, 2017).

Metabolic syndrome contributes to cardiovascular disease, and the use of SGAs contributes to metabolic syndrome. Metabolic syndrome involves increased blood pressure, elevated body weight, insulin resistance, and dyslipidemia. Metabolic syndrome must be assessed and monitored in those taking SGAs. It is unclear how to monitor for these side effects, but most clinicians recommend regularly monitoring blood pressure, weight, blood sugar, and cholesterol.

Clozapine (Clozaril®), the first SGA developed, is considered the most efficacious SGA at treating positive symptoms, but it is associated with the most severe side effects of the class. Agranulocytosis, seizures, and rarely cardiomyopathy may occur with this drug. It requires intensive monitoring by checking the white blood cell and absolute neutrophil count every week for six months, every two weeks, and then every four weeks. It is also associated with sedation, anticholinergic effects, deep vein thrombosis, weight gain, drooling, and orthostatic hypotension.

Risperidone (Risperdal®) has a higher risk of EPS than other SGAs, especially with higher doses (greater than 6 mg). It is also associated with a risk of orthostatic hypotension, sexual side effects, weight gain, and elevated prolactin levels (Frankenburg, 2021).

Olanzapine (Zyprexa®) is effective and is dosed once a day. It is more effective than risperidone in treating negative symptoms (Suresh Kumar et al., 2014). It is associated with a low risk of EPS, sedation, and orthostatic hypotension. It is linked to sexual side effects, weight gain, and diabetes.

Quetiapine (Seroquel®) is sedating and associated with the risk of orthostatic hypotension, weight gain, and the development of diabetes is possible. The risks of sexual side effects are low.

Ziprasidone (Geodon®) is associated with a low risk of EPS, orthostatic hypotension, anticholinergic effects, weight gain, and sexual side effects. Ziprasidone may lead to sedation, prolong the QT interval, and theoretically increase the risk of cardiac arrhythmia (Jibson, 2023).

Aripiprazole (Abilify®) is pharmacologically different from other SGAs, and some classify this agent as a third-generation antipsychotic (Vasiliu, 2022). It is associated with low rates of motor side effects, metabolic adverse effects, akathisia, and tremor compared to other antipsychotics. It is associated with a risk of cardiac conduction abnormalities, and other side effects include nausea, vomiting, tremors, headache, constipation, and insomnia (Frankenburg, 2021; Preda & Shapiro, 2020).

Lurasidone (Latuda®), an SGA, is believed to have a high affinity for serotonin receptors (5-HT2A). It is effective in managing the symptoms of mood, memory, and cognition (Sumiyoshi, 2013). Significant drug-to-drug interactions include ketoconazole (contraindication), rifampin (contraindication), and diltiazem (reduced dose of lurasidone). It should be taken with food, at least 350 calories (Azhar & Shaban, 2023).

Paliperidone (Invega®, Invega Sustenna®) was approved in 2006 for schizophrenia and schizoaffective disorder. It is a major active metabolite of risperidone but is thought to lead to fewer EPS symptoms (Scarff & Casey, 2011). For schizophrenia, it is dosed 6 mg in the morning, and it may be increased by 3 mg, no sooner than every five days, to a maximum of 12 mg daily. It is also available as an intramuscular injection, with tolerability established with oral paliperidone or oral risperidone prior to initiation.

Asenapine (Saphris®) is indicated for schizophrenia and is formulated as a sublingual tablet. It is initially dosed at 5 mg twice daily with a maximum dose of 20 mg daily. Patients should not eat or drink for 10 minutes after taking the sublingual form of this medication as it reduces absorption.

Iloperidone (Fanapt®) is initially dosed at 1 mg twice daily. A dose reduction of iloperidone should occur in those on paroxetine, fluoxetine, ketoconazole, or clarithromycin.

Cariprazine (Vraylar®), approved in 2015, is used in schizophrenia for adults and is typically started at 1.5 mg once a day and may be increased in 1.5 to 3 mg increments to a maximum dose of 6 mg daily. Cariprazine's advantages are minimal metabolic, histaminergic, anticholinergic, and adrenergic side effects. Common side effects include extrapyramidal symptoms, headache, insomnia, parkinsonism, and akathisia. This medication is effective in treating negative symptoms of schizophrenia (Pappa et al., 2023).

Brexpiprazole (Rexulti®) is indicated for schizophrenia and is typically started at 1 mg for the first four days and then titrated upwards to a maximum of 4 mg daily. Common side effects include akathisia, headache, weight gain, and extrapyramidal symptoms.

Table 3: Medication Doses
MedicationStarting Dose
(per day) in mg
Typical Dose
(per day) in mg
Typical Max Dose
(per day) in mg
First-Generation Agents
Second-Generation Agents
Asenapine (oral)1010-2020
Asenapine (patch)3.8 mg per 24 hours5.7 mg per 24 hours7.6 mg per 24 hours
Quetiapine50 (IR); 300 (ER)400-800800
Risperidone (oral)1-22-68
*IR= Immediate release; ER= Extended release
(Frankenburg, 2021; Jibson, 2023; Suresh Kumar et al., 2014; Preda & Shapiro, 2020; Scarff & Casey, 2011; Vasiliu, 2022)

Medication Issues

Treating schizophrenia involves medications to manage symptoms and improve the individual's quality of life. However, not all individuals respond well to the same medications, and some may experience what is referred to as "medication failure" or "treatment-resistant schizophrenia." Here are some reasons why medication may fail in the treatment of schizophrenia:

  • Non-adherence: One of the most common reasons for treatment failure is non-adherence to prescribed medications. Individuals with schizophrenia may sometimes stop taking their medications due to side effects, lack of insight into their illness, or other reasons. One study suggested that 20-89 percent of patients with schizophrenia were non-compliant with medications (Guo et al., 2023). Paranoia worsens non-compliance with medication regimes, stemming from a lack of trust in healthcare professionals. Other factors associated with non-compliance include poor illness insight, younger age, early-onset age of disease, unemployment, finances, lack of access to health care, substance abuse, denial of illness, side effects, and feeling the medication is unnecessary (Chandra et al., 2014). Not taking medications leads to a reoccurrence of symptoms. Managing the medications, minimizing side effects, and educating the family and patient are important strategies for improving compliance.
  • Inadequate dosage or duration: Sometimes, the prescribed dosage of the medication may be insufficient to manage symptoms effectively. Additionally, some individuals may not continue with the medication for a long enough period to see its full benefits.
  • Side effects: Antipsychotic medications, which are commonly used to treat schizophrenia, can have significant side effects. If the side effects are intolerable, individuals may discontinue the medication, leading to treatment failure.
  • Wrong medication or combination: Finding the right medication or combination of medications can be a process of trial and error. Not all individuals respond to the same medications, and it may take time to identify the most effective treatment.
  • Polypharmacy issues: Some individuals with schizophrenia may be prescribed multiple medications simultaneously, known as polypharmacy. This can increase the risk of side effects and interactions, contributing to treatment failure.
  • Comorbid conditions: Individuals with schizophrenia may have co-occurring mental health or medical conditions. If these conditions are not adequately addressed, it can impact the overall success of treatment.
  • Genetic factors: Response to medications can be influenced by genetic factors. Some individuals may have a genetic predisposition that affects how they metabolize certain medications, leading to treatment resistance.
  • Substance abuse: Substance abuse is common among individuals with schizophrenia. Substance use can interfere with the effectiveness of medications and exacerbate symptoms, contributing to treatment failure.
  • Psychosocial factors: Social and environmental factors, such as a lack of social support, housing instability, or high stress levels, can impact treatment success.
  • Lack of access to care: Limited access to mental health care services, including a lack of consistent follow-up and monitoring, can contribute to treatment failure.

Determining how to manage medications is a challenging task for the treating prescriber. It is necessary to determine which medication, at which dose, is most likely to provide a benefit without excessive side effects.

Depot injections are specialized formulations that allow an injection of the medication that lasts two to four weeks. In the United States, haloperidol, fluphenazine, risperidone, olanzapine, paliperidone, and aripiprazole are all available in depot form. Depot medication is theoretically helpful for those who do not comply with medications. It provides a reliable method to deliver medication and is often used in those with a long history of medication non-adherence. Long-acting injectable antipsychotics in the treatment of schizophrenia are associated with almost 50 percent fewer psychiatric and overall hospitalizations and 44 percent fewer suicide attempts without an increased risk of side effects (Wei et al., 2022).

Adjunct medications are often needed to manage the disease properly. Antidepressants for comorbid depression and anti-anxiety medications for anxiety or agitation can be helpful. Adding lithium, valproic acid, or carbamazepine may be necessary in resistant cases.

Medications should be started right away during the acute phase of schizophrenia. If they are delayed, it may negatively affect symptoms and social adjustment (Frankenburg, 2021). In most cases, antipsychotic medications are titrated to the therapeutic range as quickly as possible to optimize control of symptoms.

Case Study One

A 19-year-old male patient presents to the clinic with his mother, and it is reported that he frequently hears his brother (who lives 500 miles away) and father (who does not live in the same home as his mother) talking in the other room of the house where he and his mother live. He reports that they are plotting against him, and he collects pop cans and places them in front of his door to prevent his father and brother from going into the closet to spy on him. He also recently dropped out of school as he is no longer interested in pursuing a college degree. His mom reports that he sits around the house all day and only showers twice weekly.

Upon further evaluation, the patient's mother reports that he has always enjoyed playing alone and was an anxious child. About 18 months prior to the presentation, the patient had some vague symptoms, including social withdrawal and a flattened affect. In the early part of his senior year of high school, he was noted to have a significant reduction in the quality of his schoolwork. He went from being an A and B student to a C student.

The physical exam is generally unremarkable, except the mental status exam suggests that the patient is suspicious of the doctor, has a flat affect, has some looseness of associations, and is noted to speak tangential (speaks at length but never answers the question). The neurological exam is unremarkable.

The laboratory workup, including a serum/urine toxicology, complete blood count, electrolytes, glucose, liver, renal, and thyroid function tests, HIV test, hepatitis screen, and a syphilis test, is unremarkable.

The patient was assessed to be at low risk for suicide or aggressive behaviors, and it was determined that he could be managed as an outpatient.

He is started on risperidone 1 mg two times a day. He was brought back to the clinic two days later and noted to be free of significant sedation, akathisia, or hypotension. On the third day, the dose is increased to 1 mg in the morning and 2 mg in the evening, then 2 mg twice daily the next day. Four mgs daily is considered a therapeutic dose and is maintained for two weeks.

After two weeks, the patient shows significant improvement as he reports he no longer hears his brother and father talking in the other room. His mother reports that his thinking appears less delusional, and his grooming has improved a lot. He still shows no motivation to return to college or get a job.

It was decided to continue with intensive therapy and not increase the medication dose. If no improvement is seen in a few weeks, increasing the dose to 4 mg twice a day with careful assessment of side effects will be considered. If no improvement is seen with this dose, the dose will not be increased as doses above 8 mg a day are associated with a significant risk of EPS, and the risk is more than the slight benefit that may be noticed with the increase in the dose.

The patient was provided information regarding his disease and medications. He was also educated about how stress and overstimulation may affect the disease. Patients need to understand the importance of recognizing the signs and symptoms of early decompensation, which may lead to relapse, such as irritability or insomnia.

His family was referred to the National Alliance for the Mentally Ill.

Other Treatments

The stable schizophrenic patient needs multiple interventions above medications to maximize the quality of life and minimize the effects of the disease. Interventions include cognitive and behavioral therapy, family intervention, skill and vocational training, and community support groups. These interventions can help with coping, insight, and awareness and enhance relapse prevention.

Effective coping strategies help manage stress, anxiety, and other emotional challenges associated with the illness. Coping strategies include relaxation techniques, mindfulness, and problem-solving skills. Insight and awareness training fosters insight into the illness and awareness of symptoms to empower individuals in managing their condition, which can contribute to better self-care and decision-making. Relapse prevention training helps develop strategies to identify early signs of relapse and implement preventive measures, including creating a relapse prevention plan and building a support network.

Psychotherapy, including individual, group, or family, is helpful for the schizophrenic patient. These sessions offer education, improve coping skills, and provide support. The goals are to improve quality of life and reduce symptoms and hospitalizations.

Family therapy educates the family and provides training in communicating, solving problems, and coping methods. An analysis looked at the effects of education and regular follow-up on the phone after an inpatient stay over six months. It showed that caregivers who received education had less depression and family burden when compared to those who did not have the education (Ozkan et al., 2013). Involved and engaged families improve the treatment of the patient.

Skills training helps schizophrenic patients enter the workforce. Supportive employment can help patients find jobs and maintain steady employment. Social skills training will help develop and enhance social skills to improve interpersonal relationships and increase social integration, which may involve role-playing, social cue interpretation, and communication skills training. Daily living skill training assists individuals in acquiring and maintaining daily living skills, such as personal hygiene, cooking, and managing finances, to promote independence.

Other healthcare professionals can significantly aid the schizophrenic patient and their families in managing this disease. Social workers can help work with the family and set up services such as vocational training, support groups, and living arrangements if necessary. Many schizophrenic patients live in specialized housing, as many cannot live alone. Dietitians can help the patient manage dietary issues. Schizophrenic patients often have poor diets. The use of antipsychotic medications increases the risk of weight gain, diabetes, and hypercholesterolemia. Dietitians can help improve diets to minimize the risk of these conditions.

Referring patients to the National Alliance for the Mentally Ill is helpful. They can provide information and support to schizophrenic patients and their families.

Health Habits

Smoking leads to many negative health outcomes. Schizophrenic patients smoke cigarettes more than the general population, which may be one reason their heart disease rates are two to three times higher (Ding & Hu, 2021). Helping patients to cease smoking is an important job of the health care system.

Suicide is a leading cause of death in patients with mental illness. People with schizophrenia have a five percent lifetime prevalence of suicide (Frankenburg, 2021). Risk factors for suicide in schizophrenia include male gender, young age, history of previous attempts, family history of suicide, active hallucinations and delusions, drug use, comorbid depression, poor adherence to treatment, or recent loss. Healthcare professionals and families must recognize these risk factors and monitor patients appropriately. Adequate treatment and adherence to treatment are critical in the prevention of suicide.

Healthcare follow-up is poor in the schizophrenic population. Patients often neglect to take medications, attend follow-up appointments, or attain necessary medical care. The healthcare system has to work with these patients to help ensure that they have good medical follow-up.

Case Study Two

KL is a 22-year-old male who is studying accounting at a community college. His roommate and family have been concerned because he has acted bizarrely over the last month. He has been talking to himself in an agitated voice. He has recently got rid of his computer because he is concerned that the government is tracking all of his activity and reading his emails. He will not go to the psychiatrist as he believes this is a plot by his father, a postal worker who is a government employee. He has no medical, surgical, or psychiatric history.

One evening, he presents to the emergency department (ED) because he punched his father at a local restaurant when he suspected his father was going to "take him in." When the police came, he was yelling at the police and accusing them of being part of the government plot to control him. The police eventually transported him to the local ED. At the ED, he continues to comment about a government plot to destroy him; he is noted to be talking to the wall. Even though it is summer and over 80 degrees, he is wearing long pants, a sweater, and a jacket.

Upon examination, he was noted to be confused and unable to provide information about his medical or surgical history. He knows his name but is unable to recite the date or place. While he is in the ED, he is seen by a psychiatrist. When the psychiatrist sees him, he becomes defensive, raises his voice, and thrashes around. When the nursing staff comes in to assist the physician, the patient attempts to choke the nurse. The patient is temporarily restrained and given haloperidol 5 mg intramuscularly. He calms down over the next thirty minutes.

He was admitted to the mental health unit and has been stabilized on olanzapine for over a week. The social worker gets involved with his case to help him connect with a community psychiatrist and develop short and long-term treatment plans. The patient was provided information regarding his disease and medications.


Nurses and other healthcare providers have key roles in the management of the schizophrenic patient. Teaching the patient about the disease and the importance of compliance with the treatment plan is essential. Patients need to be taught to take medications as prescribed and should be encouraged to participate in social skills training, including vocational training. Nurses need to perform regular screening for abnormal movements utilizing tests such as the AIMS test. Nurses should encourage a healthy lifestyle such as smoking cessation, regular exercise, good nutrition, and maintenance of regular health care appointments, not just for their mental disease but also for medical conditions, as schizophrenic patients have higher cardiac disease rates.

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Implicit Bias Statement

CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.


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