Atypical vs. Typical Antipsychotic Effects on Quality of Life and Symptom Management in Schizophrenic Patients
Abstract
Objective: To establish the differences between atypical antipsychotics and typical antipsychotics involving quality of life and symptom management in adult patients with schizophrenia. Methods: Eligible studies were sourced from SCOPUS, PubMed, APA PsycInfo and PsychiatryOnline Premium databases. Meta-analyses and systematic reviews were used in tandem with primary sources such as case studies and cross-sectional studies that fit the criteria of involving adult patients with a schizophrenia diagnosis and no comorbidities. Results: Advantages to improving patient quality of life outcomes and symptom management were found within the use of atypical antipsychotics for treatment of schizophrenia, with specific atypical antipsychotics performing better than others. Atypical antipsychotics show significantly reduced risk of the patient developing extrapyramidal side effects. Typical antipsychotics can still be of use in personalized patient care to address symptoms that are resistant to atypical antipsychotic treatment. Conclusion: Atypical antipsychotics may prove to be more beneficial or a better first line of intervention for schizophrenia patients in terms of quality of life and management of symptoms, specifically positive symptoms. Usage of typical antipsychotics may be reserved for specific applications.
Keywords: schizophrenia, atypical antipsychotics, second generation antipsychotics, typical antipsychotics, second generation antipsychotics, quality of life, symptom management, side effects, positive symptoms, negative symptoms.
Introduction
Schizophrenia is a chronic brain disorder that severely impacts the mental, physical, and social health of the person affected. The most notable symptoms are auditory or visual hallucinations, paranoia, exaggerated beliefs, avolition (lack of motivation), and alogia (limited speech output), among many other cognitive symptoms like memory loss [1]. These symptoms are categorized into “positive” or “negative” classes. Positive symptoms are described as “things abnormally present” (e.g., hallucinations), while negative symptoms are classified as “things abnormally absent" (e.g., alogia, or lack of speech). The National Institute of Mental Health estimates that 0.25-0.64% of the United States population is affected by schizophrenia or another psychosis-related disorder, with a prevalence of 0.33-0.75% among non-institutionalized people worldwide [2]. Although affecting a small percentage of the population, schizophrenia is associated with serious health concerns, notably a very large potential loss of life on average. Those diagnosed with schizophrenia live an estimated average of 28.5 years less than a healthy individual. The leading cause of premature death in schizophrenia patients is suicide, with reported rates of anywhere between 4.9% and 10% [2, 3]. This suicide rate is an estimated 10 to 20 times higher than within the general population [3]. The elevated risk of mortality among schizophrenia patients attests to why managing symptoms and improving quality of life is of utmost urgency.
Treatment for schizophrenia is challenging due to the disputed causes of the disease. There are many hypotheses, with the most common being an imbalance of the neurotransmitters dopamine or serotonin existing in the brain. Therefore, for a person in active psychosis or at risk of a psychotic episode, treatment options begin with some dose of an antipsychotic medication. There are two types of antipsychotics: first generation (typical) antipsychotics that work on the dopamine pathways of the brain, and second generation (atypical) antipsychotics, that work on the serotonin pathways of the brain. Both medications reduce dopamine transmission in the brain by blocking dopamine receptors, disallowing dopamine from binding with its receptor; Atypical antipsychotics have an added ability to block a specific serotonin receptor named 5-HT2A, particularly in areas of the brain related to mood and cognition. These medications can be administered orally, sublingually, or by injection [4].
Selecting which antipsychotic to prescribe a patient is important due to the complexity of the disease and the antipsychotics’ health effects. While antipsychotics are essential for managing symptoms, studies have shown excessive dosages or lack of treatment altogether correlate with higher mortality [5]. There are many factors that can assist in deciding which drug to prescribe: the severity and type of the patient’s symptoms, consideration of side effects, patient clinical profile, economic status, and even body mass index [6]. The two types of antipsychotic medications can differ largely, not only in the pathways of the brain they influence, but in their efficacies on particular symptoms of schizophrenia, as well as major differences in off-target side effects. Typical antipsychotics have a strong association with nervous system dysfunction, in which these dysfunctions are known as extrapyramidal side effects. The most common of these extrapyramidal side effects is the condition tardive dyskinesia, which is classified by “stiff, jerky” uncontrollable movements of the face or body; this condition can sometimes be permanent [4]. In contrast, atypical antipsychotic medications are known to have a much lower risk of developing extrapyramidal symptoms, but still have the same potential as typical antipsychotics to cause other undesirable side effects, like drowsiness or weight gain [7].
Although the differences between side effects of the two classes of antipsychotics have been well established, there is still room within the realm of clinical psychiatry to further differentiate other important factors of these drugs to create more personalized plans for schizophrenia treatment [8]. Further understanding how these drugs affect quality of life and management of symptoms can lead to implementing personal treatment plans that keep mitigation of off-target effects in mind, improving overall quality of life in schizophrenia patients. A better quality of life while a patient is taking an antipsychotic increases the likelihood of continuing treatment, leading to the better control of symptoms, and therefore, lowering the risk of impacted behaviors such as suicide. Furthermore, developing a better grasp on how, where, and why these medications work can further the field of psychiatry by providing a basis for the development of even better antipsychotic medications in the future. In order to advance such understanding of both schizophrenia itself and develop better treatments for the disease, comprehensive comparisons of the two types of drugs should be created. To assist in developing a reference for customized treatment plans based on improving patient quality of life outcomes, in addition to the management of acutely-presenting symptoms, this review of literature will compare the impact on quality of life and symptom management between atypical and typical antipsychotic medications.
Methods
All studies must have been published from reputable, peer-reviewed journals. Inclusion criteria involved: adult testing groups of diagnosed schizophrenia patients, quantitative and qualitative quality of life and symptom management outcomes, and adult patients receiving any route of administration of antipsychotic medication treatment. The types of studies included were case studies, cohort studies, cross-sectional studies, systematic reviews, and meta-analyses. Studies from around the globe were selected as the diagnostic process of schizophrenia is consistent within most countries. To reflect the status of the quick moving field of psychiatry, it was attempted to select only studies within the past 5 years, however, some studies from the early 2000s were utilized as recent articles with direct comparisons between the two drugs were sparse. Studies with insufficient data or lack of apparent information were omitted from the review. Non-adult patients, patients with comorbidities, and patients with any other psychotic disorder that was not exclusively schizophrenia served as exclusion criteria for the study selections.
Searching strategies included keywords and result filters to show the most relevant studies; the used keywords were “schizophrenia”, “atypical versus typical antipsychotics”, “first generation versus second generation antipsychotics”, “quality of life”, “symptom management”, while the filters used were to find recent publications in English. All sources were critically appraised by the use of the Critical Appraisal Skills Programme checklists for their respective type of study. The process of critical appraisal involved vetting author credibility by performing background research on the author’s affiliations, and checking that bias was minimized by the use of objective measurements and reliable systems for obtaining such measurements. It was verified that all sources addressed a clear issue or research question, as well as utilized appropriate study designs, and presented their findings transparently. Outcomes of each source were compared with each other to observe consistency.
The search methodology procured five articles that involved all of the inclusion criteria and provided quantitative insight on the differences in quality of life, symptom management, and other distinctions between treatment with atypical versus typical antipsychotics. All five articles and their publishers were critically reviewed to detect bias, incompleteness, or inconsistent results, which were all undetected.
Results
Quality of Life and Symptom Management Outcomes
Four articles found a correlation between a better quality of life and symptom management in schizophrenia patients that were taking atypical antipsychotics, versus those that were taking typical antipsychotics. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis by Leucht, et al. states that in their analysis of 150 double-blind, short-term studies, 17 of which measured for quality of life, the atypical antipsychotics amisulpride, clozapine, and sertindole performed better than atypical antipsychotics. The article analyzed other sets of data that could arguably also be categorized as quality of life factors, like risk of developing extrapyramidal side effects, weight gain, and relapse rates. As for extrapyramidal side effects, all nine of the atypical antipsychotics were associated with a lower risk. Results for weight gain were mixed and dependent on the specific atypical antipsychotic; some showed a higher association of weight gain, while some showed no difference compared to low-dose typical antipsychotics. The atypical antipsychotics olanzapine, risperidone, and sertindole showed significantly less risk of relapse versus typical antipsychotics. The analysis found that four atypical antipsychotics, amisulpride, clozapine, olanzapine, and risperidone, were significantly more effective than typical antipsychotic medications for overall efficacy and treatment of both positive and negative symptoms.
In A Systematic Review on the Effectiveness of Antipsychotic Drugs on the Quality of Life of Patients with Schizophrenia by Sampogna, et al., 110 articles were analyzed, with the authors concluding that, when an atypical antipsychotic is used in the treatment of a patient with schizophrenia, quality of life improves more than it would if a typical antipsychotic were used. The atypical antipsychotics aripiprazole and lurasidone were among the top medications showing the best outcomes. Quality of life was assessed by the use of the Quality-of-Life Scale (QLS), which is a “semi-structured interview aimed at rating the deficit derived from schizophrenia by exploring social relations, roles at home/work/school, motivation, and daily activities.” Other scales, like the World Health Organization’s scale (WHOQOL-BREF), were also utilized to measure patient outcomes. The authors state that route of administration also has an effect, with long-lasting injectable medications leading to a more stable blood concentration of the drug, increasing the drug’s tolerability within the patient, ultimately lessening side effects, and increasing long-term patient compliance with treatment.
The cross-sectional study Association of Typical versus Atypical Antipsychotics with Symptoms and Quality of Life in Schizophrenia by Fujimaki, et al. observed quality of life and other symptoms of long-stay inpatients with schizophrenia on both atypical and typical antipsychotic treatments at a hospital in Mihara, Japan. 144 patients, hospitalized at some point between the years 2000 and 2009, were observed. Quantitative results for this study were obtained by the use of the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), a scale that rates 30 quality of life factors on a scale of 0 to 4, with the higher number denoting a worse quality of life. The scale “yields measures on three subscales that address 1) dysfunction of psycho-social activity, 2) dysfunction of motivation and energy, 3) level of symptoms and side effects”, and also “has been shown to have substantial sensitivity to subtle changes and treatment effects.” The JSQLS scores were found to be significantly higher in patients that were being treated with typical antipsychotics, indicating a worse quality of life. In one of their scales, the Brief Psychiatric Rating Scale (BPRS), atypical antipsychotics were more efficacious in treating positive symptoms, but had no significant effect on increasing cognitive function. Additionally, Fujimaki et al. found that psycho-social dysfunction was more apparent in individuals treated with typical antipsychotics.
The study The influence of antipsychotic type (typical vs. atypical) on quality of life among individuals with schizophrenia by Nistor, et al. was conducted to analyze quality of life differences in patients receiving treatment with first-generation antipsychotics (typical antipsychotics) versus second-generation antipsychotics (atypical antipsychotics) in order to provide insight into the pharmacological approach to schizophrenia treatment with emphasis on patient wellbeing. The cross-sectional study was conducted in a psychiatry hospital in Romania and included 109 patients that met the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) or ICD-10 (International Classification of Diseases) criteria for schizophrenia. Patients with a history of other psychiatric disorders were disqualified. The study used the Positive and Negative Syndrome Scale (PANSS) to assess schizophrenia symptoms, and The European Quality of Life Quality of Life Scale – 5 Dimensions (EQ-5D) to assess patient quality of life. The results of the study showed that patients treated with atypical antipsychotics showed much better scores in regards to quality of social relationships and lower levels of functional impairment. The study did show that there was no significant difference in the severity of patient symptom outcomes between the two classes of drugs.
Additional Findings
The case report Can typical and atypical antipsychotics show differential effectiveness in treating paranoia and hallucinations in schizophrenia? by Osimo, et al. describes the clinical case of a 35-year old schizophrenic male presenting hallucinatory symptoms, who was resistant to the atypical antipsychotic olanzapine. When the clinicians switched the subject to a typical antipsychotic, his hallucinatory symptoms were reduced, but a large increase in paranoia occurred. This led the subject’s treatment team to simultaneously prescribe both a typical and atypical antipsychotic as a part of his treatment plan to observe the different effects the drugs have on specific schizophrenia symptoms. The authors argue that combination treatments can provide insight into the function of typical versus atypical antipsychotics on symptoms. Quality of life is found to increase when symptoms are appropriately managed, and for some patients, such an effective treatment may not be done without the usage of both kinds of drugs.
Discussion
The results gathered from the literature suggest that there are some advantages to the use of atypical antipsychotic medications over their typical counterparts involving quality of life outcomes and symptom management. Management of symptoms increases the chance that the patient pertains to their medicinal regimen. When a high quality of life is also considered in the treatment plan, the capability of reentry into society and the ability to form and maintain interpersonal relationships is increased. Combined, these two factors decrease the chance of relapse and premature mortality. In four out of the five selected studies, atypical antipsychotics outperformed typical antipsychotics in quality of life and symptom management categories. The Leucht et al. meta-analysis highlighted specific atypical antipsychotic medications (olanzapine, risperidone, and sertindole) that reduced both positive and negative symptoms more effectively as well as reduced risk of relapse. The class of atypical antipsychotics in their entirety have a significantly lower risk of causing the development of extrapyramidal side effects that can drastically and negatively affect patient quality of life, making atypical antipsychotics very advantageous in this regard. However, the Leucht et al. article also established an indifference in quality of life and symptom management with some other atypical antipsychotic medications in comparison to low-dose typical antipsychotics, as well as the prevalence of other side effects, like weight gain. The studies by Nistor et al. and Fujimaki et al. also contained similar reports of quality of life improvement and less psycho-social dysfunction in patients taking an atypical antipsychotic. The systematic review by Sampogna et al. reinforces the evidence that atypical antipsychotics do generally perform better in the betterment of patient quality of life, as well as adding the component of the difference that route of administration can make on patient outcomes. Additionally, the articles suggest that quality of life should be one of the most important determinants of schizophrenia treatment options, other than the management of symptoms.
Despite the apparent advantage of atypical antipsychotics, the case report by Osimo et al. includes an additional factor of patients that may become resistant to or are less affected by atypical antipsychotics. Consequently, while typical antipsychotics are possibly less advantageous or may cause severe side effects, there is still a utilization for them in the treatment of schizophrenia. The case report highlights the differences in the mechanism of action each drug utilizes, where typical antipsychotics are most likely to target negative symptoms, while atypical antipsychotics are most proficient at lessening positive symptoms. Osimo et al. uses this as a call for physicians to consider creating treatment plans that are personalized to the patient to ensure the most beneficial treatment possible.
There are some limitations to consider within the review; the mixed results in Nistor et al. with the indifference of atypical antipsychotics in certain areas of treatment and the case study by Osimo et al. may lead to the results not being decisive enough to declare that atypical antipsychotics are entirely advantageous over typical antipsychotics. Further studies on how different atypical antipsychotics treat individual schizophrenia symptoms may prove valuable in designing a reactive and personalized treatment plan. Additionally, the results showing that atypical antipsychotics are more effective were focused on short-term patient outcomes; the results may not be the same over a longer period of study. As a remedy to this, long-term studies comparing atypical and typical antipsychotics in symptom management and quality of life areas would be valuable. The Fujimaki et al. study did establish that spending long periods of time on any kind of antipsychotic medication, typical or atypical, leads to decreased social functioning, exacerbating the need to establish more efficacious, individualized treatment plans. Finally, the age of some of the articles in an ever-changing field like psychiatric medicine is also a significant limitation. However, the main strength of this review is that it is well established across all sources that the use of atypical antipsychotics greatly reduces the risk of developing certain side effects, namely extrapyramidal symptoms. Extrapyramidal symptoms like tardive dyskinesia dramatically decrease quality of life, resulting in a cascade of potential negatives, beginning with discontinuation of treatment.
Conclusion
Atypical antipsychotics are less likely to cause severe side effects like tardive dyskinesia and are generally better at blanket symptom management, making them slightly more advantageous, and possibly a better first line of intervention. While atypical antipsychotics do possess these advantages, it is not to discredit or remove typical antipsychotic medications from their place in the realm of psychiatric treatments. In terms of quality of life, atypical antipsychotics are associated with a better chance of readaptation into society as well as the ability to form and maintain interpersonal relationships. A suggestion for the future of schizophrenia treatment and antipsychotic prescription would be personalized intervention plans made specifically for the patient’s symptoms, with an emphasis on improving quality of life, and adjustments in response to the patient’s symptomatology, as displayed in the Osimo et al. article. Further explorations into how atypical and typical antipsychotics differ in symptom assessment and quality of life will help with understanding the disease better, as well as with creating more efficient treatment plans that may involve one or both of the classes of antipsychotics. Additional research on long-term effects of atypical versus typical antipsychotics may prove to have a more decisive result on how these medications affect quality of life and symptom management differently. The rates of severe side effect development, relapse, or mortality in those affected by schizophrenia can be reduced in obtaining a more detailed understanding of the specific applications of both medications to form personalized treatment plans.
About the Author: Olivia Zepeda
Olivia Zepeda graduated with a degree in pharmaceutical chemistry with a personal emphasis on antipsychotics in the treatment of schizophrenia. In 2024, Olivia studied abroad at Academia Sinica, Taipei, Taiwan doing a biochemistry program involving anxiety and depressive biological responses of zebrafish. She hopes to work on the betterment of medicine and treatment options in the field of psychiatry after graduation.
Author's Note
This is a review of literature that was assigned as a final project for UWP 104. I chose this topic because I lost a close friend to complications with schizophrenia in 2023, and since then, have decided that all of my work will be dedicated to related sciences to hopefully improve treatment options and clear the stigma of schizophrenia. I would like readers to understand that while these disorders may be difficult to treat, they are still approachable medicinally via antipsychotics. While there is room to improve such medications, understanding how these medications work and the options available can help those impacted by these disorders by increasing accessibility to a tailored treatment plan that works best for the patient.
References
van Os, J., & Kapur, S. 2009. Schizophrenia. Lancet (London, England) [Internet]. 374(9690), 635–645. https://doi.org/10.1016/S0140-6736(09)60995-8
Schizophrenia—National Institute of Mental Health (NIMH). n.d. Accessed September 10, 2024. Available from https://www.nimh.nih.gov/health/topics/schizophrenia
Murray, R. 2003. The epidemiology of schizophrenia (1st ed.). Netw Sci (Camb Univ Press). Pages 273-277.
Meltzer, H. Y., & Gadaleta, E. 2021. Contrasting Typical and Atypical Antipsychotic Drugs. Focus (Am Psychiatr Publ) [Internet]. 19(1), 3–13. https://doi.org/10.1176/appi.focus.20200051
Weinmann, S., Read, J., & Aderhold, V. 2009. Influence of antipsychotics on mortality in schizophrenia: Systematic review. Schizophrenia Research [Internet]. 113(1), 1–11. https://doi.org/10.1016/j.schres.2009.05.018
Edlinger, M., Hofer, A., Rettenbacher, M. A., Baumgartner, S., Widschwendter, C. G., Kemmler, G., Neco, N. A., & Fleischhacker, W. W. 2009. Factors influencing the choice of new generation antipsychotic medication in the treatment of patients with schizophrenia. Schizophrenia Research [Internet]. 113(2), 246–251. https://doi.org/10.1016/j.schres.2009.06.008
Leucht, S., Corves, C., Arbter, D., Engel, R. R., Li, C., & Davis, J. M. 2009. Second-generation versus first-generation antipsychotic drugs for schizophrenia: A meta-analysis. The Lancet [Internet]. 373(9657), 31–41. https://doi.org/10.1016/S0140-6736(08)61764-X
Osimo, E. F., Goujon, M. J., Perez, J., & Murray, G. K. 2019. Can typical and atypical antipsychotics show differential effectiveness in treating paranoia and hallucinations in schizophrenia? BMJ Case Rep [Internet]. 12(3), e228573. https://doi.org/10.1136/bcr-2018-228573
Sampogna, G., Di Vincenzo, M., Giuliani, L., Menculini, G., Mancuso, E., Arsenio, E., Cipolla, S., Della Rocca, B., Martiadis, V., Signorelli, M. S., & Fiorillo, A. 2023. A Systematic Review on the Effectiveness of Antipsychotic Drugs on the Quality of Life of Patients with Schizophrenia. Brain Sciences [Internet]. 13(11), Article 11. https://doi.org/10.3390/brainsci13111577
Fujimaki, K., Takahashi, T., & Morinobu, S. 2012. Association of Typical versus Atypical Antipsychotics with Symptoms and Quality of Life in Schizophrenia. PLoS ONE [Internet]. 7(5), e37087. https://doi.org/10.1371/journal.pone.0037087
Nistor, D.-E., Horosan, L., Saftencu, M., Rosca, A. 2021. The influence of antipsychotic type (typical vs. Atypical) on quality of life among individuals with schizophrenia. Rom J Neurol Psychiatry [Internet]. 23(1), 5–12. https://doi.org/10.37897/RJPP.2021.1.1