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Schizophrenia

Background of Schizophrenia

Schizophrenia is a chronic and disabling mental illness that has affected millions of people all over the world.[1] Schizophrenia is defined as a psychotic thought disorder characterized by a mixture of symptoms. These symptoms may involve alterations in perception, cognition, emotions, behavior, attention, concentration, motivation, and judgment.[1,2] They may experience difficulties relating to the people in their environment as a result of a breakdown in thought processes and a deficit in providing normal emotional responses to others.[3] The clinical features that many schizophrenics may experience can include hallucinations, delusions, loosening of associations, misinterpretations of reality, “negative” symptoms, mannerisms, and catatonia.[2] The most commonly identified positive symptoms of schizophrenia are hallucinations and delusions, with auditory hallucinations being the most identified in 74% of schizophrenics.[3] Negative symptoms can be associated with absences of normal capabilities such as emotional withdrawal, blunted affect avolition, anhedonia, or alogia, which are fundamental to understanding the functional limitations of the disorder.[4-6] The presence of these symptoms is significant enough to demonstrate a decline in social and/or occupational functioning.[7]

Proposed Etiology

While the etiology of schizophrenia still remains unclear, it is certain that there are unfavorable hereditary predispositions combined with unfavorable life experience.[8] The development of schizophrenia is not based on a single inherited predisposition but there are multiple physical, mental, inherited, and acquired dispositions that can lead to the disorder.[8] The combination of the enduring negative symptoms and the episodic displays of positive symptoms of schizophrenia can have a profound impact on activities of daily living such as social functionality and quality of life.[9]

A Brief Review of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) on Schizophrenia

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), the diagnosis of schizophrenia is based on the presence of two or more symptoms (e.g., delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms) for a significant portion of time during a one-month period.[10] Since the onset of the disturbance, there has been a significant portion of time where major areas of functioning are impaired. The signs of the disturbance last for at least 6 months, with the 6 months including at least one month of symptoms.[11,12] Also, during the prodromal (prior to the full development of symptoms) or residual periods (absence of prominent symptoms), the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms.[11] In order for a patient to receive a diagnosis of schizophrenia, other disorders must be ruled out such as schizoaffective disorder and mood disorders with psychotic features.[12] There should not be the presence of symptoms of major depressive episodes, manic episodes, or mixed episodes that have occurred with the active phase symptoms and the disturbance is not the result of a direct physiological effect of a substance.[13,14] When a diagnosis of schizophrenia is given, a patient can be categorized under the main subtypes of paranoid, disorganized, or catatonic.[15] Paranoid schizophrenia is defined as the preoccupation with one or more delusions or frequent auditory hallucinations and disorganized can consist of disorganized speech, disorganized behavior, flat, or inappropriate effect.[15,16] Catatonic type schizophrenia is the prominent motor symptoms with nonreactivity to the environment.[17] Undifferentiated is considered to be a type of schizophrenia in which symptoms of schizophrenia are present but do not meet the criteria for paranoid, disorganized, or catatonic type.[17]

Pharmacotherapy Options

The pharmacotherapy of schizophrenia is generally synonymous with the use of antipsychotic medications. Since the synthesis of the first antipsychotic medication, chlorpromazine, in the 1950s, and the drug serving as the prototype for many other antipsychotics, the current market is filled with antipsychotic medication options.[18] The development of chlorpromazine led to the creation of more first-generation antipsychotics or typical antipsychotics to be used for the general public for symptom management of schizophrenia. Subsequently, the first atypical antipsychotic, clozapine was discovered in the 1950s and introduced into the market in the 1970s to become recognized for its use in a subset of individuals with a psychotic disorder who have not benefited from conventional antipsychotic medications.[19,20] Both typical and atypical antipsychotic medications have been shown to assist with the treatment of positive symptoms (e.g., hallucination and delusion) and negative (e.g., social withdrawal and poverty of speech) and cognitive symptoms (e.g., reduction in working memory and attention) of schizophrenia.[19] Antipsychotics are considered by many to be the drugs of choice in the management and treatment of schizophrenia with efficacy being demonstrated through D2 (dopamine) antagonism for typical antipsychotics and the combination of D2 (dopamine) and 5-HT2 (serotonin) antagonism with the atypical antipsychotics.[20]

Many of the antipsychotic medications block postsynaptic D2 receptors in the central nervous system, particularly in the mesolimbic-frontal system.[20] It has been reported that in order for an antipsychotic to be considered effective, it must exhibit a dopamine antagonism of at least 60–80%, as lower levels of dopamine antagonism are not generally associated with producing observable antipsychotic properties, and about 60–70% of schizophrenic patients may not be adequately controlled.[19] Schizophrenic patients require long-term antipsychotic maintenance treatment, hence effectiveness of the antipsychotic medication is vital to performing activities of daily living and sustaining adequate quality of life.[21] Individuals who are newly diagnosed with schizophrenia can appear to be more sensitive to antipsychotic medication therapies than those who have a longstanding diagnosis, but regardless of the selection of antipsychotic medications, despite class, have demonstrated comparable efficacy and achievement of symptom control.[21]

Clinician Awareness

Clinicians must be cognizant of the available typical and atypical antipsychotics, dosage range, relative potency, and side or adverse effect profiles.[21,22] The selection of the appropriate antipsychotic medication is at the discretion of the prescribing provider but patient preference, tolerance, and efficacy should also be considered to increase the probability of achieving optimal therapeutic results.[22]

References

  1. Gupta S, Kulhara P. What is schizophrenia: A neurodevelopmental or neurodegenerative disorder or a combination of both? A critical analysis. Indian J Psychiatry 2010;52:21-7.
  2. Hahn RK, Albers LJ, Reist C. Psychiatry. Blue Jay, California: Current Clinical Strategies Publishing; 2008.
  3. Rollins A, Bond G, Lysaker P, McGrew J, Salyers M. Coping with positive and negative symptoms of schizophrenia. Am J Psychiatry Rehabil 2010;13:208-23.
  4. Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 2006;32:214-9.
  5. Flanagan E, Solomon L, Johnson A, Ridgway P, Strauss J, Davidson L. Considering DSM-5: The personal experience of schizophrenia in relation to the DSM-IV-TR criteria. Psychiatry 2012;75:375-86.
  6. Strauss J, Bowers M, Keith S, Bleuler M. What is schizophrenia? Schizophr Bull 1984;10:8-10.
  7. Hoffmann H, Kupper Z, Kunz B. Hopelessness and its impact on rehabilitation outcome in schizophrenia—An exploratory study. Schizophr Res 2000;43:147-58.
  8. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 2013.
  9. Keller W, Fischer B, Carpenter J. Revisiting the diagnosis of schizophrenia: Where have we been and where are we going? CNS Neurosci Ther 2011;17:83-8.
  10. Idrees M, Khan I, Irfan M, Sarwar R. First rank of symptoms in the diagnosis of schizophrenia. J Postgrad Med Inst 2010;24:323-8.
  11. Suvisaari J, Perälä J, Saarni S, Juvonen H, Tuulio-Henriksson A, Lönnqvist J. The epidemiology and descriptive and predictive validity of DSM-IV delusional disorder and subtypes of schizophrenia. Clin Schizophr Relat Psychoses 2009;2:289-97.
  12. Fenton WS, McGlashan TH. Natural history of schizophrenia subtypes. I. Longitudinal study of paranoid, hebephrenic, and undifferentiated schizophrenia. Arch Gen Psychiatry 1991;48:969-77.
  13. Schatzberg AF, Cole JO, DeBattista C. Manual of clinical psychopharmacology 7th Washington, DC: American Psychiatric Association; 2010.
  14. Nisbet B, Dulmus C, Greyber L, Langa M. The spectrum clozaril clinic: A successful model for treatment of psychotic disorders. Best Pract Ment Health 2010;6:69-84.
  15. Dickson RA, Dalby JT, Williams R, Warden SJ. Hospital days in clozapine-treated patients. Can J Psychiatry 1998;43:945-8.
  16. Jafari S, Fernandez-Enright F, Huang X. Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. J Neurochem 2012;120:371-84.
  17. Gardner K, Bostwick J. Antipsychotic treatment response in schizophrenia. Am J Health Syst Pharm 2012;69:1872-9.
  18. Conley RR, Kelly DL. Current status of antipsychotic treatment. Curr Drug Targets CNS Neurol Disord 2002;1:123-8.
  19. Guo X, Fang M, Zhai J, Wang B, Wang C, Hu B, et al. Effectiveness of maintenance treatments with atypical and typical antipsychotics in stable schizophrenia with early stage: 1-year naturalistic study. Psychopharmacology (Berl) 2011;216:475-84.
  20. College of Psychiatric and Neurologic Pharmacists. 2010-2011 BCPP examination review and recertification course. Orth-McNeil Janssen Scientific Affairs, LLC, 2010.

Abimbola Farinde, PhD, PharmD
Professor, Columbia Southern University, College of Business
Orange Beach, AL

Published on 6/8/2020

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