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The Behavioral Side Effects of Antipsychotic Medication for Schizophrenia

Kelley Coffman

September 17, 2006

 

 

 

Introduction

            In the following article, the author hopes to show the devastating effects of the psychotic disorder – schizophrenia. The paper’s emphasis is to display the lack of treatment options or medication offered that treat the patient fully from physical and disorganization symptoms to cognitive deficits. The medication prescribed to current schizophrenic patients treats several symptoms that make them unacceptable in society, but they are incapable of promoting self-sustaining, healthy individuals. The article will discuss the current form of antipsychotic medication used, more specifically – clozapine, olanzapine, and risperidone – as well as the mechanism and side effects of each medication. Finally, the article will briefly review current or past literature of studies performed on the behavioral effects of the aforementioned medicines.

 

 

What is Schizophrenia?

            Schizophrenia is a disabling psychotic disorder, which affects over two million Americans in a given year (www.schizophrenia.com/family/sz.overview.htm). It is usually detected early in life – between late teens and early twenties. Men and women are affected by the disorder equally with men showing symptoms earlier in life. (Reported on http://health.enotes.com/medicine-encyclopedia/schizophrenia - a medical reference product designed to inform and educate readers about health disorders and treatments) The schizophrenic patient suffers from a variety to symptoms – believing others can read their mind, withdrawal from society, incoherent talk, delusions, and cognitive deficits. Some symptoms can be treated with medication, but most people suffer from the disease their entire life. www.schizophrenia.com/family/sz.overview.htm reports that it has been estimated that no more than one in five individuals recover completely.

 

 

What are the symptoms?                                                                                                                                                         

            Symptoms of schizophrenia are divided into two sections:  positive and negative. For the purpose of this article, the behavioral side effects will be discussed individually as well. The symptoms discussed were formulated from the website - http://health.enotes.com/medicine-encyclopedia/schizophrenia and http://www.schizophrenia.com/family/delusions.html.  Health.enotes.com serves as a medical reference product designed to inform and educate readers about health disorders and treatments. Schizophrenia.com is a non-profit source of information, support, and education.

 

            The positive symptoms are experiences or sensations added to the usual range of feelings, which can be caused by a variety of stresses. They include disorganized thought processes and disorganized behavior as well as delusions and hallucinations. The disorganized thought processes are seen primarily in speech such as rambling and “word salad”. The patient may babble about various different topics one after another, which to the normal person, do not appear to be connected in any way. The phrase “word salad” describes a patient’s incoherent speech, which lacks correct grammar and any obvious purpose. Disorganized behavior will be discussed in a following section. Hallucinations are false perceptions; patients believe they can hear voices others can’t and sometimes see or feel things others don’t. Delusions are misinterpretations of events and their purpose such as when patients believe the CIA is plotting against them or that their psychiatrist is involved in an assignation attempt against them. Schizophrenics cannot be reasoned with over their delusions; reasoning and discussion leads to the patient’s mistrust and anger.

 

            The negative symptoms are subtractions from the usual range of feelings such as a lack of emotional response, poor speech, and absence of will or desire. The patient appears to be devoid of emotions even when an exciting or horrific event occurs to him or her or to a loved one. The patient almost appears to be a zombie, lacking any desire or will to accomplish goals, simple tasks, or minute daily activities such as dressing or self-cleaning.

 

            The behavioral side effects include disorganized behavior and the ‘zombie effect’ previously discussed. Disorganized behavior ranges from “dressing in odd or inappropriate ways” to having trouble with goal-oriented behavior (http://health.enotes.com/medicine-encyclopedia/schizophrenia). The patient may struggle with purposeful behavior such as self-care, cooking, and dressing. The patient may participate in “sexual self-stimulation in public or agitated shouting or cursing” (http://health.enotes.com/medicine-encyclopedia/schizophrenia). The zombie effect follows closely to disorganized behavior but consists more of an ‘I-don’t-care’ or an ‘I-can’t’ attitude.

 

Schizophrenia is associated with cognitive function deficits including memory, attention, executive function, and working memory. The cognitive deficits hurt patients in retaining information or skills. Executive function is described on an educational resource website for parents concerned with their student’s learning abilities (http://www.schoolbehavior.com/conditions_edfoverview.htm). It is described as the central processes that are involved in giving organization and order to our actions and behavior such as planning for the future and strategic thinking, prioritizing and organizing, and initiating behavior. Another site describes executive function as “the processes that enable us to plan, sequence, initiate, and sustain our behavior towards some goal, incorporating feedback and making adjustments along the way” (http://www.tourettesyndrome.net/ef.htm - a website intended to inform parents and educators about various childhood-onset disorders including executive dysfunction). Without these cognitive abilities, schizophrenics have difficultly maintaining jobs because of their inability to retain skills and to work towards a goal using higher-order brain processes.

 

 

What are the treatment options?                                                                                                                             

            The primary treatment option for schizophrenic patients is antipsychotic medication. Other options exist such as therapy and alternative medicine; however, they are normally used in conjunction with antipsychotic medications.  Antipsychotic drugs typically control the positive symptoms but have little effect on disorganized behavior and other negative symptoms. As reported on http://health.enotes.com/medicine-encyclopedia/schizophrenia (a website serving as a medical reference product designed to inform and educate readers about disorders and treatments), only 60-70% of schizophrenic patients will respond to antipsychotic drugs, and it is normal for patients to take their medication indefinitely to prevent relapse.

 

            Antipsychotic medication falls into two categories:  Dopamine Receptor Antagonist (Conventional antipsychotics) and Seratonin Dopanine Antagonists (Atypical antipsychotics). The exact mechanism for both categories is unknown; however, researchers believe that it is the lowering of sensitivity to sensory stimuli that allows the patient to better interact with others.

 

            Dopamine receptor antagonists, or conventional antipsychotics, are the older form of antipsychotic drugs. Physicians have difficulty finding the best dosage level of conventional antipsychotics for patients. Another main concern of these older antipsychotics is that extrapyramidal side effects are frequently produced when the dosage level is high enough to control psychotic symptoms. Extrapyramidal side effects are discussed on the website - http://www.hubin.org/publicfamilyinfo/treatment/side_effects/side_effects_6_en.html. (Hubin is a site dedicated to accelerate research and development to find new solutions for human brain disease. They store data from research projects to be analyzed.) Extrapyramidal symptoms (EPS) can include involuntary movements, tremors and rigidity, body restlessness, muscle contractions, and changes in breathing and heart rate. The most common side effect is the involuntary movements of the body – mouth, lips and tongue; this side effect is called tardive dyskinesia and is most common when treatment has occurred for long periods as discussed on the website http://www.emedicine.com/NEURO/topic362.htm. (emedicine is a byproduct of WebMD and serves to carry the largest and most current Clinical Knowledge Base for physicians and healthcare professionals.) EPS can also include Parkinsson’s disease, which involves temporary paralysis and slowness of movement. EPS side effects occur in over 60% of patients taking conventional antipsychotics, and it can cause great stress and pain to the patient. Conventional antipsychotics may relieve the patient of schizopherenic symptoms, but the medication also tends to induce other devastating symptoms. (Dopamine receptor antagonists include the drugs haloperidol, chlorpromazine, and fluphenazine.)

 

            Seratonin dopamine antagonists, or atypical antipsychotics, are the newer form of antipsychotic drugs. Atypical antipsychotics have a smaller tendency to induce EPS and are more likely to help control the negative symptoms of schizophrenia. The downside of the newer drugs is their expense. The drugs can reduce long-term costs by preventing the need for hospitalization, but the short-term cost may discourage patients from using the medication. Atypical antipsychotics are not currently available in intramuscular injection form, which presents an obstacle for patients who struggle to take their medication daily. The newer antipsychotics are beginning to be first choice for physicians, but it is more common for seratonin dopamine antagonists to be prescribed when the dopamine receptor antagonists are not providing the desired results. (Seratonin dopamine antagonists include the drugs clozapine, risperidone, and olanzapine.)

 

 

Clozapine (Clozaril)                                                                                                                                             

            The information contained in this section was found on the website http://www.medicinenet.com/clozapine/article.htm.  MedicineNet.com is a website devoted to bringing knowledge to the general public. It claims to be written by pharmacists and reviewed by doctors.

 

Mechanism:  Clozapine blocks receptors in the brain for several neurotransmitters, which are chemicals that nerves use to communicate with each other. The receptors that clozapine blocks includes dopamine type 4 receptors, serotonin type 2 receptors, norepinephrine receptors, acetylcholine receptors, and histamine receptors. Clozapine is the only drug to weakly block the dopamine type 2 receptors. 

 

Side Effects:  Clozapine’s main side effect is the development of a condition called agranulocytosis, which is a severe reduction in white blood cell count. The disease occurs in approximately 1 in 100 patients who are taking the medication for a year or more.

Death for unclear reasons can result if clozapine is used on patients with dementia-related psychosis.

Seizures occur in 1 of every 20 to 30 persons, and dizziness occurs in 1 of 5 persons. Drowsiness is the most common side effect but others include headaches, tremor, and fever. It can cause extrapyramidal symptoms and tardive dyskinesia; however, because of the weakened block of the dopamine type 2 receptors, the risk is smaller compared to older anti-psychotics.

 

 

Olanzapine (Zyprexa, Zydis)                                                                                                                        

            The information contained in this section was found on the website http://www.medicinenet.com/olanzapine/article.htm.  MedicineNet.com is a website devoted to bringing knowledge to the general public. It claims to be written by pharmacists and reviewed by doctors. Olanzapine is used to treat agitation due to schizophrenia.

Mechanism:  Olanzapine’s exact mechanism is not known but is thought to work similarly to clozapine by blocking receptors for several neurotransmitters in the brain. Olanzapine is thought to block the receptors: alpha-1, dopamine, histamine H-1, muscarinic, and serotonin type 2 (5-HT2) receptors. 

Side Effects:  Akathisia – an inability to sit still, constipation, dizziness, drowsiness, and weight gain. Extrapyramidal effects may occur. Tardive dyskinesia may occur in 1 of 100 persons taking olanzapine, which can be irreversible. The risk of getting tardive dyskinesia increases with the length of treatment.

 

Risperidone (Risperdal)                                                                                                            

            The information contained in this section was found on the website http://www.medicinenet.com/risperidone/article.htm.  MedicineNet.com is a website devoted to bringing knowledge to the general public. It claims to be written by pharmacists and reviewed by doctors.

Mechanism:  Risperidone works similarly to the other atypical antipsychotics. The drug interferes with communication between brain nerves by blocking neurotransmitter receptors such as dopamine type 2, serotonin type 2, and alpha 2 adrenergic.

Side Effects:  The most common side effect is extrapyramidal effects, dizziness, hyperactivity, tiredness, and nausea. Orthostatic hypotension, a drop in blood pressure upon rising from lying down, can occur from the medication.

 

 

 

 

What does the research say about the behavioral effects of atypical antipsychotics?           

 

            Stip (2006) concluded in his review “…that cognitive impairments are as important as positive and negative symptoms in the clinical assessment and management of patients with schizophrenia” (p. 341). Stip discusses a study performed by his group – three groups were formed according to the medication each patient was taking (haloperidol, clozapine, and risperidone) and were compared to normal controls. The comparison was based upon two procedural learning tasks – a visuomotor learning task (mirror drawing) and a problem solving learning task (Tower of Toronto). Stip found that patients receiving clozapine had no deficits, but patients receiving haloperidol underwent deleterious effects. For patients receiving risperidone, the effect depended on the task. Stip discusses the behavioral effects of cognitive deficits – how they affect planning and the patient’s aptitude to initiate and regulate goal-oriented situations. This idea is explored in a study conducted in Montreal concerning the relationship between executive function impairments and difficulties in planning daily activities. To measure executive function, treatment and control groups were subjected to memory and script productions tasks. The groups were required to recite 10-20 actions that would typically occur during daily life activity. The results indicated that sequencing errors, repetitions, and omissions were higher in the patient group than the control. The study concluded that executive function impairment hinders basic daily activities in schizophrenic patients, especially those with negative symptoms. Stip ends his review with the suggestion that cognitive deficits should integrate clinical practice by becoming a standardized assessment approach (Stip, 2006). 

 

            Hori et. al. (2006) performed an experiment on 67 patients with chronic schizophrenia and 92 controls. Four hours of neurocognitive tests were administered including the Wechsler Memory Scale-Revised (measures verbal memory, visual memory, attention, and delayed recall), the Wechsler Adult Intelligence Scale-Revised (Verbal, Performance and full-scale IQ test), the Wisconsin Card Sorting Test (assesses executive function including cognitive flexibility in response to feedback), and the Advanced Trail Making Test (measures spatial working memory). Patients were divided up into two groups containing subgroups – a “standard” versus “nonstandard” group and a “atypical” versus “conventional” group. The first group was divided depending on the amount of medication they were taking, and the type of medication the patients were using determined the second group. The second group of Hori et. al.’s study will be discussed in this section. The design was to examine whether differences of cognitive deficits existed between patients treated with atypical antipsychotics and with conventional antipsychotics. The results of the various neuropsychological tests indicated that verbal memory, information, arithmetic, and digit symbol was favorable to the atypical antipsychotics group. The group also performed better on visual memory and delayed recall. The study concluded that a wide range of cognitive domains is impaired in patients with chronic schizophrenia. It also showed that the differences of medication and of cognitive function are associated and may be due to differential illness severity, but conclusions could not be indisputably drawn (Hori et. al. 2006).

 

            Meltzer and McGurk (1999) reviewed numerous studies on the atypical antipsychotics: clozapine, risperidone, and olanzapine. Their goal was to determine the effect of these medicines on cognitive function in schizophrenic patients. After reviewing 12 studies on clozapine, Meltzer and McGurk concluded that the drug had a great effect on verbal fluency and attention. Some studies revealed improvement in some type of executive function and verbal learning and memory. However, “no study found improvement in every cognitive domain” (Meltzer and McGurk, 1999, p. 242). Upon reviewing six studies on risperidone, Meltzer and McGurk concluded that the drug effects perceptual/motor processing, reaction time, executive function, working memory, verbal learning and memory, and motor function. They found that the drug was not effective with verbal fluency or motor learning. Meltzer and McGurk formulated a conclusion on olanzapine as a result of their own testing of 20 schizophrenic patients since no studies were to be found. They concluded that the drug affected some measures of reaction time, executive function, verbal learning and memory, and verbal fluency. They reported that the magnitude of the effects were greater than in the other two drugs; however, this opinion was drawn from only one study. Finally, Meltzer and McGurk concluded that each drug was able to help several of the cognitive deficits caused by schizophrenia but not all of the deficits. The importance of the behavioral effects of the medicine is seen in the text, “There is evidence that verbal learning and memory, in particular, is important for occupational and community functioning, as summarized by Green (1996)” (Meltzer and McGurk, 1999, p. 248). They suggest that further research be conducted to improve the medication to treat more cognitive symptoms as well as to determine the individual factors that affect the ability of the drugs to improve cognition (Meltzer and McGurk, 1999). 

 

 

Conclusion

            Schizophrenia is a devastating psychotic disorder, which is becoming more prevalent. The treatment options available for patients do not fully treat the disorder. Generally, the antipsychotics available are more efficient at treating the positive symptoms then the negative symptoms. The newer atypical antipsychotics are beginning to address some of the negative symptoms, but their expense discourages many psychiatrists from prescribing them and many patients from taking them. The medicines discussed in this essay – Clozapine, Risperidone, and Olanzapin – are effective in some areas of cognitive deficits as shown in Meltzer and McGurk’s review. However, not one proved to be effective in treating all cognitive deficits. Three independent researchers came to the conclusion that studies and clinical approaches must be redirected towards treating cognitive deficits if patients are to be transformed into self-sustaining individuals. Medication for the physical symptoms may trick the average person into believing a schizophrenic patient is cured, but without treating the cognitive deficits, patients suffering from the disorder will not be able to lead a normal life. In conclusion, for any improvement in patient care to be seen, it is imperative that research and treatments be redirected to include cognitive deficits.  

 

 

References

 

H. Hori et al. (2006). Antipsychotic medication and cognitive function in schizophrenia. Schizophrenia Research, 86, 138-146.

 

Meltzer, H.Y., and McGurk, S.R. (1999). The Effects of Clozapine, Risperidone, and Olanzapine on Cognitive Function in Schizophrenia. Schizophrenia Bulletin, 25 (2), 233-255.

 

Stip. E. (2006, May-Jun). Cognition, Schizophrenia and the Effect of Antipsychotics. Encephale, 32 (3 Pt 1), 341-50.

 

http://www.medicinenet.com/risperidone/article.htm

http://www.medicinenet.com/olanzapine/article.htm

http://www.medicinenet.com/clozapine/article.htm

http://www.emedicine.com/NEURO/topic362.htm

http://www.hubin.org/publicfamilyinfo/treatment/side_effects/side_effects_6_en.html

http://health.enotes.com/medicine-encyclopedia/schizophrenia

http://www.tourettesyndrome.net/ef.htm

http://www.schoolbehavior.com/conditions_edfoverview.htm

www.schizophrenia.com/family/sz.overview.htm

http://www.schizophrenia.com/family/delusions.html

 

Images (in order used in essay):

www.mental-health-abuse.org/schizophrenia.html

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Microsoft Word Clip Art

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http://images.google.com/imgres?imgurl=http://www.oup.com/uk/booksites/content/0199275009/student/2d/ch05/ch05_fig24olanzapine.jpg&imgrefurl=http://www.oup.com/uk/booksites/content/0199275009/student/2d/ch05/&h=518&w=475&sz=27&hl=en&start=35&tbnid=QYDpvbUym9OF3M:&tbnh=131&tbnw=120&prev=/images%3Fq%3Dolanzapine%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26rls%3DGGLG,GGLG:2006-21,GGLG:en%26sa%3DN

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