Schizophrenia antipsychotic treatment

Educate patients and families about schizophrenia, treatments, and the importance of adherence to antipsychotic treatment. 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

Kaiser, R., Konneker, M., Henneken, M. et al. (2000). Dopamine D4 receptor 48-bp repeat polymorphism no association with response to antipsychotic treatment, but association with catatonic schizophrenia. Mol. Psychiatry, 5, 418-24. 

Muller, D. J., and Kennedy, J. L. (2006) Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics. 7, 863-887. 

In cases where there is a strong family history of schizophrenia and the symptoms are particularly ominous, many clinicians will recommend antipsychotic treatment during the prodromal phase. Low doses of an atypical antipsychotic (other than clozapine) probably offer the best promise of a treatment response with a minimal risk of problematic side effects. 

Kablinger AS, Freeman AM. Prodromal schizophrenia and atypical antipsychotic treatment. J Nerv Ment Dis 2000 188(10) 642-652. 

Switching from other antipsychotics - Nh e immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, gradual discontinuation may be more appropriate for others. In all cases, minimize the period of overlapping antipsychotic administration. 

P. N. Jayakumar, B. N. Gangadhar, G. Venkatasubramanian, S. Desai, L. Velayudhan, D. Subbakrishna and M. S. Keshavan, Fligh energy phosphate abnormalities normalize after antipsychotic treatment in schizophrenia a longitudinal P MRS study of basal ganglia. Psychiatry Res., 2010,181, 237-240. 

Harvey, P.D., Keefe, R.S.E. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am. J. Psychiatry 158, 176-184, 2001. 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 2002 59(4) 337 15. 

Haro, J. M., Edgell, E. T., Novick, D., Alonso, J., Kennedy L., Jones, P. B., Ratcliffe, M., Breier, A. 2005, Effectiveness of antipsychotic treatment for schizophrenia 6-month results of the Pan-European Schizophrenia Outpatient Health Outcomes (SOHO) study, Acta Psychiatr.Scand., vol. Ill, no. 3, pp. 220-231. 

Tiihonen, J., Walhbeck, K., Lonnqvist, J., Klaukka, T., Ioannidis, J. P., Volavka, J., Haukka, J. 2006, Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder observational follow-up study, Br.Med.J., vol. 333, no. 7561, p. 224. 

Weickert, T. W., Goldberg, T. E., Marenco, S., Bigelow, L. B., Egan, M. R, Weinberger, D. R. 2003, Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia critical examination of confounds, Neuropsychopharmacology, vol. 28, no. 8, pp. 1491-1500. 

The changes in SNARE protein expression do not appear to be due to the effects of antipsychotic treatment. In rats, haloperidol and chlorpromazine increased SNAP-25 protein levels in the hippocampus (Barr et al., 2006), while in the postmortem brains of individuals with schizophrenia, SNAP-25 levels are lower in the hippocampus (Young et al., 1998 Fatemi et al., 2001 Thompson et al., 2003a). Likewise, no changes in the level of mRNA encoding SNAP-25, syntaxin or synaptobrevin were observed in the prefrontal cortex of rats chronically treated with haloperidol (Nakahara et al., 1998). 

Muller DJ, Klempan TA, De Luca V, Sicard T, Volavka J, et al. 2005. The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci Lett 379 81-89. 

McClure RK, Phillips I, Jazayerli R, Barnett A, Coppola R, et al. 2006. Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment. Psychiatry Res 148(2-3) 121-132. 

Functioning and neuronal viability of the anterior cingulate neurons following antipsychotic treatment Mr-spectroscopic imaging in chronic schizophrenia. Eur... 

Bustillo JR, Lauriello J, Rowland LM, Thomson LM, Petropoulos H, et al. 2002. Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure. Schizophr Res 58 313-321. 

Dursun SM, Deakin JF. 2001. Augmenting antipsychotic treatment with lamotragine or topiramate in patients with treatment-resistant schizophrenia A naturalistic case-series outcome study. J Psychopharmacol 15(4) 297-301. 

Schematic representation of schizophrenia phenotypes for the P50 and N100. (a) The normal pattern of P50 and N100 responses in nonaffected individuals. Note that the first response is large and the second is decreased, (b) In unmedicated schizophrenia, both the first and second responses are diminished for the P50 and N100. (c) Antipsychotic treatment results in increased amplitude of both the first and second responses for the P50 and N100 among schizophrenia patients, yielding the pattern of normal amplitude with impaired gating often described among medicated patients, (d) Nicotine reduces the amplitude of the second response among medicated schizophrenia patients (Reprinted from Umbricht et al., 2004, with permission from Elsevier)...

Bandelow B, Fritze J, Ruther E. Increased mortality in schizophrenia and the possible influence of antipsychotic treatment. Int J Psychiatry Clin Pract 1998 2(Suppl 2) S49-57. 

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