Pharmacotherapeutic treatment for schizophrenia – new approaches to develop schizophrenia medications

New approaches for developing schizophrenia medications target glutamatergic neurons due to their suggested positive effect on negative symptoms and cognitive deficit that arise in schizophrenia (Tiihonen & Wahlbeck 2012). Examples of such drugs are D-cycloserine and GSK729327, whose trials were completed in 2005 and 2010 respectively, and Ampakine, whose trial was terminated in 2007 through a sponsor’s request (Clinicaltrials.gov 2012). A review of studies that carried out an intervention comprising a combination therapy of such glutamatergic drugs and other antipsychotics did not find significant evidence to recommend the use of glutamatergic agents in clinical practice (Tiihonen & Wahlbeck 2012).

In Australia, a trial sponsored by The Afred, is investigating the efficacy of Raloxifene, an oestrogen, in treatment of schizophrenia in women (ClinicalTrials.gov 2012). Other clinical trials being conducted in Australia are aimed at elucidating potential benefits of various antipsychotic enhancements (e.g. Quetiapine fumarate, and paliperidone palmitate) with regard to safety, tolerability and increased duration of action (ClinicalTrials.gov 2012).

Conclusion

Schizophrenia is a debilitating mental illness whose victims experience disruptions in cognitive, affect and behavioural functions. This paper evaluates the pharmacotherapeutic approaches for managing schizophrenia. Although, an absolute cure for the ailment is yet to be discovered, antipsychotic medications have been used successively to achieve symptom remission. Such antipsychotic drugs are thought to work principally by blocking D2-receptors, with the adverse effects associated with D2-receptor blockade leading to the development of atypical (second-generation) antipsychotics that exhibit D2/5HT affinity thus reducing the extrapyramidal side effects of typical antipsychotics. Antipsychotics exhibit drug interactions with such drugs as enzyme inducers and other drugs with which they compete for metabolic enzymes. Their contraindications relate to individual hypersensitivity and presence of disease conditions that heighten development of adverse effects of antipsychotics. New approaches to schizophrenia medication include medications targeting glutamate receptors and those seeking to reduce adverse effects of existing antipsychotics.

References

Aleman, A, Kahn, RS & Selten, JP 2003, ‘Sex differences in the risk of schizophrenia’, Arch Gen Psychiatry, vol. 60, no. 6, pp. 565 – 571.

American Psychiatric Association – APA 2012, DSM, Arlington, VA, viewed 19 April 2012 < http://www.psychiatry.org/practice/dsm>.

Andreasen NC 2011, ‘Concept of schizophrenia: past, present, and future’, in Schizophrenia, eds DR Weinberger & P Harrison, John Wiley & Sons, pp. 1905 – 1913.

Arango, C & Carpenter, WT 2011, ‘The schizophrenia construct: symptomatic presentation’, in Schizophrenia, eds DR Weinberger & P Harrison, John Wiley & Sons, pp. 1914 – 1936.

Breier, A 1995, ‘ Serotonin, schizophrenia and antipsychotic drug action’, Schizophrenia Research, vol. 14, pp. 187 – 202.

Collier, DA & Li, T 2003, ‘The genetics of schizophrenia: glutamate not dopamine? European Journal of Pharmacology, vol. 480, no. 1-3, pp. 177 – 184, doi:10.1016/j.ejphar.2003.08.105.

ClinicalTrials.gov 2012, Search results for Schizophrenia AND Australia, viewed 12 April 2012 < http://clinicaltrials.gov/ct2/results?term=schizophrenia+AND+Australia>

Davies, MA, Conley, Y & Puskar, K 2010, ‘Incorporating Evidence From Pharmacologic

and Pharmacogenetic Studies of Atypical Antipsychotic Drugs Into Advanced Psychiatric Nursing Practice’, Perspectives in Psychiatric Care, vol. 46, no. 2, pp. 98 – 107, doi: 10.1111/j.1744-6163.2010.00245.x

De Leon, J, Greenlee, B, Barber, J, Sabaawi, M & Singh, NN 2009, ‘Practical guidelines for the use of new generation antipsychotic drugs (except clozapine) in adult individuals with intellectual disabilities’, Research in Developmental Disabilities, vol. 30, pp. 613 – 669, doi:10.1016/j.ridd.2008.10.010

Farde, L 1997, ‘Brain imaging of schizophrenia – the dopamine hypothesis’, Schizophrenia Research, vol. 28, no. 2-3, pp. 157 – 162.

Hafner, H & Heiden, W 1997, ‘Epidemiology of schizophrenia’, Can J Psychiatry, vol. 42, pp. 139 – 151.

Hodgkinson, CA, Goldman, D, Jaeger, J, Persaud, S, Kane, JM, Lipsky, RH, & Malhotra, AK 2004, ‘Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder’ Am. J. Hum. Genet., vol. 75, pp. 862 – 872.

Iqbal, N, & van Praag, HM 1995, ‘The role of serotonin in schizophrenia’, European Neuropsychopharmacology Supplement, vol. 5, suppl., pp. 11 – 23.

Johnsen, E, Kroken, RA, Wentzel-Larsen, T & Jorgensen, HA 2010, ‘Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quaetiapine, risperidone and ziprasidone’, BMC Psychiatry, vol. 10, doi:10.1186/1471-244X-10-26.

Lehninger, AL, Nelson, DL & Cox, MM 2005, Lehninger principles of biochemistry, 4th edn, W.H. Freeman, New York.

Leucht, S, Pitschel-Walz, G, Abraham, D & Kissling, AW 1999, Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials’, Schizophrenia Research, vol. 35, pp. 51 – 68.

Lindenmayer J, Khan A, Eerdekens M, Hove IL, & Kushner S 2007, ‘Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder’, Eur Neuropsychopharmacol, vol. 17, no. 2, pp.138-144, doi:10.1016/j.euroneuro.2006.08.004,

McGrath, J, Saha, S, Welham, J, El Saadi O, MacCauley, C & Chant, D 2004, ‘A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology’, BMC Medicine, vol. 2, no. 13, viewed 10 April 2012, < http://www.biomedcentral.com/1741-7015/2/13/abstract>

Meltzer, HY 2002, ‘Mechanism of action of atypical antipsychotic drugs’, in Neuropsychopharmacology: the fifth generation of progress, eds KL Davis, D Charney, JT Coyle & C Nemernoff, Amerixan College of Neuropsychopharmacology, Brentwood, TN, pp. 819 – 831.

Meltzer, HY, Li, Z, Kaneda, Y & Ichikawa, J 2003, ‘Serotonin receptors: their key role in drugs to treat schizophrenia’, Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 27, no. 7, pp. 1159 – 1172, doi:10.1016/j.pnpbp.2003.09.010.

Murray, RM, Lappin, J & Di Forti, M 2008, ‘Schizophrenia: from developmental deviance to dopamine dysregulation’, European Neuropscyhopharmacology, vol. 18, pp. s129 – s134, doi:10.1016/j.euroneuro.2008.04.002

Prior, TI, Chue, PS, Tibbo, P & Baker, GB 1998, ‘Drug metabolism and atypical antipsychotics’, European Neuropsychopharmacology, vol. 9, pp. 301 – 309.

Ryan, MCM & Thakore, JH 2002, ‘Physical consequences of schizophrenia and its treatment: the metabolic syndrome’, Life Sciences, vol. 71, pp. 239 – 257.

Saha, S, Chant, D, Welham, J & McGrath, J 2005, ‘A systematic review of the prevalence of schizophrenia, PLoS Medicine, vol. 2, no. 5, e141, pp. 0413 – 0433, doi:10.1371/journal.pmed.0020141

Schizophrenia Research Institute 2010, The key facts, Schizophrenia Research Institute, viewed 10 April 2012, < http://www.schizophreniaresearch.org.au/index.php?r=3&menu=About>

Sporn, A, Addington, A, Reiss, AL, Dean, M, Gogtay, N, Potocnik, U, Greenstein, D, Hallmayer, J, Gochman, P, Lenane, M, Baker, N, Tossell, J & Rapoport, JL 2004, ‘22q11 deletion syndrome in childhood onset schizophrenia: an update’, Molecular Psychiatry, vol. 9, pp. 225 – 226, doi:10.1038/sj.mp.4001477

Tandon, R, Keshavan, MS & Nasrallah, HA 2008, ‘Schizophrenia, “just the facts” what we know in 2008. Epidemiology and etiology’, Schizophrenia Research, vol. 102, no. 1 – 3, pp. 1 – 18, doi:10.1016/j.schres.2008.04.011

Tiihonen, J, & Wahlbeck, K 2012, ‘Glutamatergic drugs for schizophrenia (edited)’, Cochrane Database of Systematic Reviews, Issue. 2, Art. No. CD003730, doi:10.1002/14651858.CD003730.pub2.

Van Os, J & Kapur, S 2009, ‘ Schizophrenia’, Lancet, vol. 374, no. 9690, pp. 635 – 645, doi:10.1016/S0140-6736(09)60995-8

Weiden, PJ 2012, ‘Iloperidone for the treatment of schizophrenia: an updated clinical review’, Clinical Schizophrenia & Related Psychoses, vol. 6, no. 1, pp. 34 – 44.

World Health Organization (WHO) 1993, The ICD-10 classification of mental and behavioural disorders, WHO, Geneva, viewed 10 April 2012 <http://www.who.int/classifications/icd/en/GRNBOOK.pdf>.

Zhou Z, Li X, Peng H, Yu X, Yang M, Su F, et al. 2006, ‘Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia’, Acta Pharmacol Sin, vol. 27, no. 3, pp. 381-386, viewed 10 April 2012 http://www.nature.com/aps/journal/v27/n3/pdf/aps200649a.pdf

find the cost of your paper