Neuroleptics, also known as antipsychotic medications, supress various symptoms of psychosis and, hence, are used as treatment for Schizophrenia––a psychological disorder whose primary symptom is psychosis (Ameer & Saadabadi, 2022). Two types of antipsychotics include first generation––dopamine receptor antagonists––and second generation––seratonin-dopamine receptor antagonists (Ameer & Saadabadi, 2022). Both classes of antipsychotics work to block receptors for dopamine, serotonin or both; their efficacy follows from the discovery that dopaminergic abnormalities are linked to psychosis (Howes et al., 2009). Since the 1950s, antipsychotics have been considered the savior of individuals with Schizophrenia (Moncrieff, 2015).
A meta-analysis of three randomized controlled trials analyzes treatment using Olanzapine, Risperidone, Amisulpride, and placebo for each (Furukawa et al., 2015). Participants were of two types: having predominantly positive symptoms––change in behavior with hallucinations or delusions––or negative symptoms––withdrawn and emotionless (NHS, 2019). The results suggest that for both types of patients, the antipsychotics made statiscally signficant, p value of 0.01, improvements in patients’ symptoms (Furukawa et al., 2015). Severity of Schizophrenia directly correlates with efficacy of the treatment, so the study concludes that for for people with severe cases of Schizophrenia, antipsychotics should be prescribed for better quality of life. With less severe cases, placebo remains an option that may help; nevertheless, this is patient-dependent. Although there is mention of lower effectiveness for the mildest cases of Schizophrenia and possibly adverse effects due to antipsychotics, one could argue that this meta-analysis limits itself in exploring range of severity. Furthermore, myriad antipsychotic medications unaccounted for in this meta-analysis are still prescribed today (NYU Langone Health, 2022). Consequentially, neuroleptics’ efficacy is limited to these drugs and cannot be generalized to all prescribed drugs. Nevertheless, while considering short-term measures, antipsychotics prove to be effective.
However, recent research elucidates that long-term exposure to antipsychotics results in relapse: the reemergence of psychotic symptoms (Moncrieff, 2015). Wunderink et al. performed a study on one hundred and twenty eight participants with Schizophrenia, post-remission, who were randomly assigned to a dose reduction/discontinuation group or a maintenance treatment group. In the former, participants would substantially decrease dosage or fully discontinue anti-psychotics, and in the latter, participants would consistently maintain their antipsychotics treatment plan. This clinical trial took place for two years, after which patients were under the care of their respective psychiatrists (Wunderink et al., 2013). Eventually, after seven years, a follow-up confirmed that recovery rates were twice as much in the dose reduction/discontinuation group (Wunderink et al., 2013). This substantive variance highlights the potential reversal effects of antipsychotics due to long-term high-dosage exposure. However, one must account for the period of seven years where the patients are left under the case of their psychiatrists there must have been numerous confouding variables that could not have been controlled for in such a prospective study. Regardless, the difference is unusually vast such that the confounding variables could not only have attributed to these results.
Whitaker (2004) showcases, through critical systematic review using a fifty-year period of data, that at least forty percent of patients’ conditions would ameliorate quicker if not for the heavy medication, reiterating adverse reversal effects of psychotic symptoms due to antipsychotics. The study reccommends that psychiatrists should refrain from immediate neuroleptization within early stages of Schizophrenia, and that all patients should at least be given the opportunity, if not encouraged to, gradually withdraw from antipsychotics (Whitaker, 2004). With this approach, the study claims to increase the recovery rates and the efficacy of antipsychotics. Ergo, both studies explored support the conclusion that long-term antipsychotics use may entail slower recovery rates and possible aggravation of psychotic symptoms.
An alternate perspective propagated by another research exploration quantifies this matter by deducing a risk to benefit ratio for long-term antipsychotic treatment (Correll et al., 2018). Researchers consider side effects on morbidity, mortality, metabolic disturbance, and tardive dyskinesia––a neurological disorder involving involuntary movements of the jaw and face––and long-term effectiveness (Cornett et al., 2017). This study concludes that the ratio is favorable, implying that the benefits of antipsychotics outweigh the potential disadvantages (Correll et al., 2018). However, one could argue that this study’s limitation is in its primary consideration of side effects as opposed to reversal of symptoms many years later, which aforementioned studies have considered in depth.
In effect, the pharmaceutical industry pursues rigorous research to mitigate potential adverse effects of antipsychotic medications, as they are commonly prescribed for Schizophrenia and many neurological disorders apart from it as well. Latent replacements for neuroleptics encompass phytochemicals derived from plants and various types of therapies––aroma, acupuncture, cognitive-behavioral, and social skills (Saleem et al., 2022). This exploration deems long-term efficacy of antipsychotics and replacements to be imperative areas of study in treating patients with Schizophrenia and moderating medication for other neurological disorders.
References
Ameer, M. A., & Saadabadi, A. (2022, August 29). Neuroleptic Medications. Retrieved November 20, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK459150/
Cornett, E. M., Novitch, M., Kaye, A. D., Kata, V., & Kaye, A. M. (2017). Medication-Induced Tardive Dyskinesia: A Review and Update. The Ochsner journal, 17(2), 162–174.
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018). What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry, 17(2), 149–160. https://doi.org/10.1002/wps.20516
Furukawa, T. A., Levine, S. Z., Tanaka, S., Goldberg, Y., Samara, M., Davis, J. M., Cipriani, A., & Leucht, S. (2015). Initial severity of schizophrenia and efficacy of antipsychotics. JAMA Psychiatry, 72(1), 14–21. https://doi.org/10.1001/jamapsychiatry.2014.2127
Howes, O., Egerton, A., Allan, V., McGuire, P., Stokes, P., & Kapur, S. (2009). Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: Insights from PET and SPECT imaging. Current Pharmaceutical Design, 15(22), 2550–2559. https://doi.org/10.2174/138161209788957528
Moncrieff, J. (2015). Long-term effects of antipsychotics. BJPsych Advances, 21(2), 78–79. https://doi.org/10.1192/apt.bp.114.012591
NHS. (2019, November 11). Symptoms - Schizophrenia. Retrieved November 20, 2022, from https://www.nhs.uk/mental-health/conditions/schizophrenia/symptoms/
NYU Langone Health. (2022). Medication for Schizophrenia. Patient Care. Retrieved November 20, 2022, from https://nyulangone.org/conditions/schizophrenia/treatments/medication-for-schizophrenia
Saleem, A., Qurat-ul-Ain, & Akhtar, M. F. (2022). Alternative therapy of psychosis: Potential phytochemicals and drug targets in the management of schizophrenia. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.895668
Whitaker, R. (2004). The case against antipsychotic drugs: A 50-year record of doing more harm than good. Medical Hypotheses, 62(1), 5–13. https://doi.org/10.1016/s0306-9877(03)00293-7
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy. JAMA Psychiatry, 70(9), 913–920. https://doi.org/10.1001/jamapsychiatry.2013.19
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