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Schizophrenia

2 Contact Hours - 2 Pharmacology Hours
This course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Registered Nurse (RN)
This course will be updated or discontinued on or before Friday, January 7, 2022
Course Description
This course provides information to healthcare workers on Schizophrenia and how to identify and manage the disabling disease. Upon completion of this CE, you will be able to discuss the risk factors of for Schizophrenia and describe the positive and negative related symptoms. You will also know the medications used to treat the disease and the possible side effects.
CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

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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)

Outcomes

Schizophrenia is a severe and persistent disease that damages the lives of not only those it afflicts but their families and friends. This course prepares the nurse to play a role in identifying, educating, monitoring, and referring patients to appropriate health services to get them on the road to managing this chronic, disabling disease.

Objectives

  1. List three risk factors for schizophrenia.
  2. Differentiate between positive and negative symptoms.
  3. List five medications used to treat schizophrenia.
  4. Describe five side effects of medications used to treat schizophrenia.

Introduction

Schizophrenia affects one percent of the population, with men and women being equally affected. Men, on average, present earlier (late teens or early twenties) with the disease than women (late twenties or early thirties)1. Women tend to present with less severe symptoms, possibly because of the effect estrogen has on dopamine.2

Schizophrenia adversely affects the lives of schizophrenic patients in many ways. About five percent of people with schizophrenia will commit suicide over their lifetime.3 Patients with schizophrenia marry less frequently and have higher divorce rates. It is estimated that six percent of schizophrenics are homeless and another six percent live in jails/prisons while ten percent live in nursing homes and another 20 percent live in supervised housing.4 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 interaction with the health care system, lifelong medications and frequent hospitalizations. Medications that currently treat the disease, do not cure it; they just manage the symptoms. Unfortunately, most individuals do not respond adequately to the current treatments available. An analysis showed that a patient with chronic schizophrenia has more than 15,000 dollars of health care related expenses every year.5

Risk Factors

Many factors put one at risk for schizophrenia, with family history being the greatest risk factor. While scientists have linked many genetic markers to schizophrenia, no specific genetic marker is directly linked.5 If a first-degree relative has schizophrenia, then the lifetime risk of the individual is about 10 percent; if both parents are affected the lifetime risk increases to 40 percent.6

Socioeconomic status is associated with schizophrenia. Factors that are linked include: living in a poorer residential area, lower occupational status of the father and fewer years of education of the father and mother.7

Pregnancy and birth complications may be linked to schizophrenia. Poor nutritional status of the mother during pregnancy has been connected to schizophrenia. Certain viral illness, such as influenza (during specific years), contracted by the mother during pregnancy has also been coupled to schizophrenia. Obstetric complications are linked to schizophrenia.6

Location and season of birth are correlated to schizophrenia. Being born in an urban center (compared to a rural or suburban center) confers a greater risk. Being born in February or March is also a risk factor, but that risk is not as significant as being born in an urban setting. Being born in August and September is associated with the lowest risk.8

Other factors associated with schizophrenia include:

  • Some autoimmune diseases are linked to schizophrenia, including celiac disease, bullous pemphigoid, hemolytic anemia and thyrotoxicosis. Those with antibodies to gluten are more likely to have schizophrenia.9
  • Paternal age is associated with an increased risk of schizophrenia. Age greater than 30 and younger than 25 in fathers increases the risk of schizophrenia.10
  • The environment that one is raised in is a strong predictor of future risk.11 Those with genetic risk who live with parents who communicate well and do not criticize frequently are less likely to develop the disease.12
  • A recent study showed that 108 single nucleotide polymorphisms have been linked to schizophrenia.13 This is another piece of information that links genetics to schizophrenia.

Pathophysiology

It is hypothesized that schizophrenia stems from an imbalance in the neurotransmitters in the brain because medications that effectively manage the symptoms of schizophrenia affect these neurotransmitters. Abnormalities in dopamine are one of the main contributors to the pathophysiology of schizophrenia. High dopamine activity in the mesolimbic system leads to positive symptoms, while low dopamine levels in the mesocortical system leads to negative symptoms. There are multiple dopamine receptors in the brain, with varying concentrations in different sections of the brain.

In the lab settings, researchers were able to stimulate the release of dopamine and showed that psychotic symptoms worsened. Those with acute schizophrenia release higher levels of dopamine than in healthy subjects and this is likely a large contributor to the acute psychosis.14

Dopamine is not the only neurotransmitter responsible for the symptoms of schizophrenia. Other neurotransmitters are likely involved in the schizophrenic brain, and they may include norepinephrine, serotonin, glutamine and gamma-aminobutyric acid (GABA). The NMDA receptor, which is a key target for glutamine on the neuron, is another abnormality in schizophrenia.

The key to finding adequate treatments in 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 section, and address all of the other chemical abnormalities is a challenge for the scientific community.

When compared to the healthy brain, neuroimaging has shown bilateral ventriculomegaly and decreased brain volume in the medial temporal lobes, particularly in the superior temporal gyrus in the schizophrenic brain.6 While this is an interesting finding, it provides little in the way of diagnostic clues or treatment options.

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 will help make an accurate diagnosis and rule out other diagnoses. Critical information about risk factors is the first step and includes getting a family history of schizophrenia and other mental diseases, 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 with social or academic issues.

The history should look for positive and negative symptoms. Positive symptoms refer to obvious symptoms, typically psychotic symptoms, and include hallucinations and delusions. Auditory hallucinations (e.g., voices, music, and machinery) are the most common type of hallucinations. Positive symptoms are most responsive to medications. Delusions may be bizarre or non-bizarre, and the content may be paranoid, grandiose, nihilistic or erotomanic (falsely thinks that they have a special relationship with another person).

Negative symptoms refer to a loss or decrease of normal functioning and include symptoms such as flat affect, social withdrawal, loss of pleasure, poor grooming, poor social skills, catatonia, poverty of speech and lack of motivation or energy. These symptoms often present earlier than the positive symptoms. The presence of negative symptoms is highly correlated to occupational function and quality of life. Those with high levels of negative symptoms often have poor work performance, inadequate self-care or problems with interpersonal relationships.

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 make use of 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. The patients may demonstrate repeated movements or gestures such as pacing, strange hand movements or odd facial expressions. The 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, strange 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 about 1-2 standard deviations below healthy individuals on neuropsychological testing.15 Cognitive impairments usually occur prior to the presentation of positive symptoms.16

While multiple symptoms may define schizophrenia, when the symptoms are taken together, they must be present for a significant portion of one month to make the diagnosis. This interval may be less if successfully treated. Some symptoms must be present for at least six months.17

Signs and symptoms typically come on gradually, as evidenced by loss of interest in activities, work or school. Hygiene and grooming get decline and there is often an increasing number of 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 is typically not helpful, but any underlying neurological conditions should be evaluated. Any movement disorder is important to document, so a baseline level is known. This 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. Many of the neurological problems seen in schizophrenia may be related to antipsychotic medications as they often block dopamine and may cause tremor, rigidity, dystonias and bradykinesia. Catatonia may also be seen. Metabolic abnormalities (hypertension, diabetes and abnormal lipids) may be seen in schizophrenia.

Table 1: Other possible diagnoses that present similarly to schizophrenia

Differential diagnosis

Differentiating characteristics

Substance abuse

There is current use of or withdrawal from drugs or other substances.

Delirium

Similar features but a shorter course of illness; delirium symptoms typically come on faster.

Brain lesions

Brain tumors, intracranial bleeds or idiopathic calcification of the basal ganglia can potentially present with similar symptoms.

Brief psychotic disorder

Similar symptoms but duration of symptoms is less than 1 month.

Depression

Depression – especially if severe – can present with psychotic symptoms.

Bipolar disorder

May be difficult to differentiate as psychotic symptoms may be present during a manic or depressive state. When the patient’s mood is stable, there are no psychotic symptoms.

Delusional disorder

Other symptoms of schizophrenia are not present. Typically, no impairment in functioning and overall behavior is not bizarre.

Schizophreniform disorder

Similar symptoms; it lasts one to six months.

Schizoaffective disorder

A combination of thought disorder and mood disorder.

Schizotypal personality disorder

These individuals do not form close relationships, and they have odd behaviors and thoughts – typically, behaviors and thoughts are not as severe as in schizophrenia.

Seizure disorder

Temporal lobe epilepsy occasionally present with odd behavior – including memory/cognitive changes or hallucinations - before, during, or after a seizure.

Systemic lupus erythematosus

May present with fever, joint pain, cognitive changes or psychosis.

Hypoglycemia

Similar symptoms at times but accompanied by low blood sugar and symptoms correct when sugar is treated.

Wilson disease

Disorder of copper metabolism; initial symptoms are vague; changes in behavior during the teenage years.

Endocrine disorders

Hyper/hypothyroidism may present with psychosis; parathyroid disease can lead to mental status change.

Medication-induced

Drugs that can induce schizophrenic type symptoms include anticholinergics, phenytoin, steroids, cimetidine and some Parkinson’s medications.

Infections

Infections that may present with similar symptoms include neurosyphilis, human immunodeficiency virus, sepsis, cerebral abscess and Creutzfeldt-Jakob disease.

Vitamin deficiency

Thiamine, vitamin B12 or folate deficiencies can cause similar signs and symptoms.

Electrolyte disorder

Hyponatremia, hypo/hypercalcemia can present with similar symptoms.

Diagnosis

Patients with schizophrenia must have at least two of the following symptoms: delusions, hallucinations, disorganized speech, catatonic or disorganized behavior or negative symptoms. For full criteria see table 2.

Table 2: Diagnostic Criteria for Schizophrenia (adapted from the American Psychiatric Association, 2013)
  1. Two or more of the following symptoms present for a significant portion of the time during a one-month period:
    1. Delusions
    2. Hallucinations
    3. Disorganized speech
    4. Disorganized behavior or catatonia
    5. Negative symptoms
  2. Work, interpersonal relationships, and/or self-care are below prior level of function.
  3. Signs and symptoms must be present most of the time during a one-month period, with some level of disturbance being present over six months.
  4. Major depression, schizoaffective disorder, mania and bipolar disease - have been ruled out.
  5. The symptoms are not associated with a medication, substance or another medical condition.
  6. If autism or a communication disorder of childhood is present, the diagnosis is made only if prominent delusions or hallucinations are present for at least one month.

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 the treatment of the disease. These subtypes were used prior to the last update of the Diagnostic and Statistical Manual of Mental Disorders.

Work up

No lab test is able to 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 to obtain include a complete blood count, electrolytes, liver and renal function, thyroid studies, glucose level, vitamin B-12, folate and a calcium level.

Other tests to be considered on an individual basis include human immunodeficiency virus serology, serology for hepatitis C, syphilis serology, ceruloplasmin, urinalysis and culture, an anti-nuclear antibody (ANA), and 24-hour urine for porphyrins, copper or heavy metals.6 A pregnancy test should be done on females. An EKG should be done for those on antipsychotics that prolong the QT interval (e.g., clozapine, iloperidone, thioridazine, and ziprasidone).

Imaging exams – computed tomography scan or magnetic resonance imaging - will rule out other conditions (subdural hematoma, tumors, vasculitis and cerebral abscess) that may mimic the disease. Chest x-ray may be done if there is suspicion of malignancy. Electroencephalography (EEG) may be indicated as it may assist in the diagnosis and may help with treatment options.18

Treatment

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

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

Treatment of schizophrenia is a process and with each health care encounter, treatment plans and diagnosis needs to be reevaluated and adjusted if required. Acute phase treatment should prevent harm, reduce psychosis, determine causes of the acute episode, control disturbing behaviors, reduce symptoms, and develop a plan with the patient and family for treatment. 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.

Antipsychotic medications are the mainstay of treatment in schizophrenia. During the acute phase, these medications need to be titrated to target quickly and then the patient should be monitored.

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. Medication is typically continued for at least 6 months, but many are left on therapy for longer periods of time.

Antipsychotics treat positive symptoms, but negative symptoms are not managed as well. They are effective at preventing relapse when taken, but those who stop mediations relapse about 80% of the time within one year.6

Antipsychotics can be classified as typical (first-generation) or atypical (second-generation). Typical antipsychotics have been available since the 1950s. They include the drugs: Thioridazine (Mellaril®), Molindone (Moban®), Fluphenazine (Prolixin®), Haloperidol (Haldol®), and Perphenazine (Trilafon®). Typical antipsychotics are associated with more neurological side effects. Prescribers often dose these medications at the EPS threshold, which is the dose that will induce minimal rigidity on exam. This is a dose that is found most effective, and higher doses are no more effective and are typically associated with poor compliance due to side effects.

Atypical antipsychotics have been around since the late 1980s. These medications are less likely to cause neurological side effects, which results in better compliance. This class of medication is associated other side effects such as weight gain, diabetes and elevated cholesterol.

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, but a newer medication, cariprazine, may have some benefit, particularly with social functioning.19

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 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 antipsychotics

Second-generation antipsychotics

High Potency

Ziprasidone (Geodon®)

Thiothixene (Navane®)

Aripiprazole (Abilify®)

Fluphenazine (Prolixin®)

Risperidone (Risperdal®)

Perphenazine (Trilafon®)

Quetiapine (Seroquel®)

Haloperidol (Haldol®)

Olanzapine (Zyprexa®)

Low potency

Clozapine (Clozaril®)

Thioridazine (Mellaril®)

Lurasidone (Latuda®)

Chlorpromazine (Thorazine®)

Paliperidone (Invega®)

 

Asenapine (Saphris®)

 

Cariprazine (Vraylar®)

 

Brexpiprazole (Rexulti®)

 

Iloperidone (Fanapt®)

When medications are initiated, the psychosis typically resolves over several days but may take up to six weeks. When the dose is at the therapeutic range (see table 3), it should be used for a few days with no improvement before the dose is increased as higher doses are associated with increased risk of side effects. If the patient only has a minimal response to the antipsychotic agent in the first two weeks, it is not likely that they will have a strong response.20 Patients should be trialed on antipsychotics for 2-6 weeks before concluding that the medication is ineffective. Iloperidone and quetiapine require longer titration and may require longer trials.21

Adverse Effects

Being able to recognize and treat side effects is a key component of pharmacotherapy in schizophrenia. Those who are afflicted with too many side effects will discontinue therapy and likely relapse.    

The first-generation antipsychotic medications, known as typical antipsychotics, are associated with a higher degree of neurological side effects than second-generation antipsychotics. The degree of side effects is related to the potency of the medication. High potency first-generation antipsychotics (Table 2) have a high risk of extrapyramidal side effects (EPS) and 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.22 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, dystonia, Parkinsonism and akathisia. The most severe neurological side effect is neuroleptic malignant syndrome.

The most permanent of these side effects is tardive dyskinesia (TD) and 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 the elderly and females. It often occurs after months or years of treatment and has no reliable remedy. This is a permanent side effect and is much more common in first-generation agents. 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 muscle spasms of the back, face and neck with neck twisting and an upward gaze. They come on within one to five days and can be treated with antiparkinsonian medications, diphenhydramine (Benadryl®), or benztropine (Cogentin®).  

A set of symptoms that mimics Parkinson’s disease typically occurs within one month of starting the medication and includes the symptoms of bradykinesia, tremor and rigidity. This is the most common side effect of first-generation antipsychotics. Discontinuing or reducing the medication is the best treatment, but anti-Parkinson’s medications can be used to treat the symptoms. Second-generation medications can also be used in the management of schizophrenic symptoms in those who are unable tolerate the 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 2 months after starting the medication. It is treated with antiparkinsonian medications, benzodiazepines, propranolol or by decreasing or changing the antipsychotic medication.   

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 mediation, 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. 

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.6

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.6,21   

The atypical antipsychotic medications have less risk of neurological side effects, but they 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.23  

Metabolic syndrome is a contributing factor to cardiovascular disease and the use of atypical antipsychotics contributes to metabolic syndrome. Metabolic syndrome involves increased blood pressure, elevated body weight, insulin resistance and dyslipidemia. Metabolic syndrome needs to be assessed and monitored for in those taking atypical antipsychotics.

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, second generation antipsychotic medication developed, is considered the most efficacious second-generation antipsychotic 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 6 months, then every 2 weeks, and then every 4 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 compared with other second-generation antipsychotics, 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 level.6

Olanzapine (Zyprexa®) is effective and is dosed once a day. It is more effective than risperidone at the treatment of negative symptoms.24 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 risk of orthostatic hypotension, weight gain, and the development of diabetes is possible. The risks of sexual side effects are low. Eye exams need to be done every 6 months on those on this medication as it was associated with cataracts in animals.25

Ziprasidone (Geodon®) is associated with a low risk of EPS, orthostatic hypotension, anticholinergic effects, weight gain and sexual side effects. This drug may lead to sedation and prolong the QT interval and theoretically, may increase the risk of cardiac arrhythmia.6,25

Aripiprazole (Abilify®) is pharmacologically different from other second-generation antipsychotics. It is associated with a risk of cardiac conduction abnormalities and other side effects include nausea, vomiting, tremor, headache, constipation and insomnia.6

Lurasidone (Latuda®) has a larger affinity for receptors other than dopamine and serotonin and may be better able to manage the symptoms of mood, memory and cognition.26 Significant drug-to-drug interactions include ketoconazole (contraindication), rifampin (contraindication) and diltiazem (reduce dose of lurasidone). It should be taken with food (at least 350 calories).

Paliperidone (Invega®, Invega® Sustenna) was approved in 2006 and is approved for schizophrenia and schizoaffective disorder. It is a major active metabolite of risperidone but is thought to lead to fewer EPS symptoms.27 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 a day. It is also available as an intramuscular injection, with tolerability being 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 5 mg two times a day with a maximum dose of 20 mg a day. 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 1 mg two times a day. 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 a day. The advantages of this medication are that it has minimal metabolic, histaminergic, anticholinergic and adrenergic side effects. Common side effects include extrapyramidal symptoms, headache, insomnia, parkinsonism and akathisia.28 This medication has been shown to be most effective in treating negative symptoms in schizophrenia.21

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

Table 3: Medication Doses
MedicationStaring dose
(per day) in mg
Typical dose
(per day) in mg
Typical max dose
(per day) in mg
First-Generation Agents

Chlorpromazine

25-75200-600

800

Fluphenazine

2-102-10

12

Haloperidol

1-42-20

30

Loxapine

2020-80

100

Perphenazine

8-1612-24

24

Thiothixene

5-1010-20

30

Thioridazine

150200-800

800

Second-Generation Agents

Aripiprazole

10-1510-15

30

Asenapine

1010-20

20

Clozapine

12.5300-450

600-900

Iloperidone

212-24

24

Lurasidone

20-4040-80

160

Olanzapine

5-1010-20

20

Paliperidone

66-12

12

Quetiapine

50150-750 (IR); 400-800 (ER)

750 (IR); 800 (ER)

Risperidone

1-22-6

8

Ziprasidone

4040-160

160

Cariprazine

1.51.5-6

6

Brexpiprazole

1.01-4

4

Medication issues

Antipsychotics treat aggression, hallucinations, delusions, irritability and sleep disturbances. They work well for those who have good function prior to taking these medications. Improper escalation of the dosage and non-compliance are common causes of drug failure.

Medication will not work if they are not taken. As with many mental diseases, compliance with mediation regimes is a real challenge for schizophrenic patients. One study suggested that 41.9 percent of patients with schizophrenia were non-compliant with medications.29 Non-compliance with medication regimes is made worse by paranoia which results in a lack of trust of health care 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 not necessary.29 Not taking medications leads to reoccurrence of symptoms. Managing the medications so side effects are minimized and providing education to the family and patient are the two important strategies in improving compliance.

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 a specialized formulation that allows injection of the medication that lasts for two to four weeks. In the United States, haloperidol, fluphenazine, risperidone, olanzapine, paliperidone and aripiprazole are all available in depot form. This form of 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 who have a long history of medication non-adherence. It is not clear if long-acting injectable medications are more effective than oral medications in regard to compliance.6 One study showed that long-acting injectable risperidone was no better than oral antipsychotics in the treatment of schizophrenia and the injectable form was associated with more side effects.30

Adjunct medications are often needed to manage the disease properly. Antidepressants for co-morbid depression, 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 have negative effects on symptoms and social adjustment.6

Case study 1

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 soda 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 has no interest in pursuing a college degree anymore. His mom reports that he just sits around the house all day and only bathes about two times a week.

Upon further evaluation, the patient’s mother reports that the patient has always enjoyed playing by himself and was an anxious child. About 18 months prior the presentation to the doctor 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, some looseness of associations and he is noted to speak tangentially (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 one mg two times a day. He is brought back to the clinic two days later, and he is 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 the next day 2 mg twice a day. Four mg a day is considered a therapeutic dose and is therefore 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 his thinking appears much less delusional, and his grooming is much improved. He still is showing no motivation to go back to college or to 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 is not increased as doses above 8 mg a day are associated with 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 with information regarding his disease and medications. He was also educated about the effect stress and over-stimulation may have on 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.

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

Family therapy educates the family and provides training in how to communicate, solve problems, and provides coping methods. A recent study that looked at the effects of education and regular follow up on the phone after an inpatient stay over a six month period showed that caregivers in a group of individuals who received education had less depression and family burden when compared to those who did not have the education.31 Involved and engaged families improve the treatment of the patient.32

Skills training help the schizophrenic patient enter the workforce. Supportive employment can help patients find jobs and maintain steady employment.

The use of other health care professionals can significantly aide 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 are unable to 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

Schizophrenic patients smoke cigarettes more than the general population. This may be one reason that their rates of heart disease are two to three times higher. Helping to get the patients to cease smoking is an important job of the health care system.

Schizophrenics have a 5 percent lifetime prevalence of suicide. Those at highest risk are male, young, those with previous attempts, family history of suicide, active hallucinations and delusions, drug use, co-morbid depression, poor adherence to treatment or recent loss.3 Health care professionals and families need to recognize these risk factors and monitor patients appropriately. Adequate treatment and adherence to treatment are critical in the prevention of suicide.

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

Case Study 2

KL is a 22-year-old male who is studying accounting at a community college. His roommate and family have been concerned because over the last month he has been acting bizarre. He has been talking to himself in an agitated voice. He recently got rid of his computer because he is concerned that the government is tracking all of his activities 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 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 ER. At the ER he continues to make comments 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 exam, he is 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 ER, he is seen by psychiatry. When the psychiatrist sees him, he becomes very defensive and begins to raise his voice and thrash around. When the nursing staff comes in to assist the physician, the patient attempts to choke the nurse. The patient is placed in 4-point restraints and given haloperidol 10 mg intramuscularly. He calms down over the next thirty minutes.

He is admitted to the mental health unit and is stabilized on olanzapine over a period of 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 with information regarding his disease and medications.

Conclusion

Nurses 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. The patient needs to be taught to take medications as prescribed. Patients 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 rates of disease. Nurses have vital roles in the management of schizophrenia.

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