Antipsychotic drugs in schizophrenia

Jones PB, Barnes TE, Davies L, Duim G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW. Cost utility of the latest antipsychotic drugs in schizophrenia smdy (CUTLASS 1). Arch Gen Psychiatry 2006 63 1079-87. 

Jones, P. B., Barnes, T. R., Davies, L., Dunn, G., Lloyd, H., Hayhurst, K. P., Murray, R. M., Markwick, A., Lewis, S. W. 2006, Randomized controlled trial of the effect on quality of Life of second- vs first-generation antipsychotic dmgs in schizophrenia Cost utility of the latest antipsychotic drugs in schizophrenia study (Cutlass 1), Arch.Gen.Psychiatry, vol. 63, no. 10, pp. 1079-1087. 

Abi-Dargham A, Laruelle M. 2005. Mechanisms of action of second generation antipsychotic drugs in schizophrenia Insights from brain imaging studies. Eur Psychiatry 20 15-27. 

Jain AK, Kelwala S, and Gershon S (1988) Antipsychotic drugs in schizophrenia Gurrent issues. International Clinical Psychopharmacology 3(1) 1-30. 

Lieberman JA, Stroup TS, McEvoy JP, et al. Clinical antipsychotic trials of intervention effectiveness (CATIE) investigators. Effectiveness of antipsychotic drugs in people with chronic schizophrenia. N Engl J Med 2005 353 1209-1223. 

Lee, C. et al. (2006). Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia. Aust. N. Z. J. Psychiatry, 40, 437-45. 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

All of the above trials were conducted in adults and, to the best of our knowledge, there are no trials of antipsychotic medication in children with psychoses and MR. To date there have been two double-blind trials of antipsychotic drugs in normal-IQ children and adolescents with schizophrenia, as well as several open-label trials (Ernst et al., 1999). The majority of these studies and case reports have demonstrated substantial reductions in schizophrenic symptoms. Given the lack of data on children and adolescents having both MR and schizophrenia, it seems that clinicians have little choice but to follow the standard of care applied with normal-IQ schizophrenic children, namely to use anti-... 

Atypical Antipsychotic Effects in Schizophrenia. Molecular Psychiatry 12 (2007) 934-945. Kaddurah-Daouk and colleagues sampled the blood of 50 schizophrenia patients before and after drug treatment and found differences in metabolites that depended on the drug the patient received. 

FIG. 5-3. Effects of neuroleptics on thought disorder and behavioral symptoms of schizophrenia. BPRS, Brief Psychiatric Rating Scale TDI, Thought Disorder Index. (From Davis JM, Barter JT, Kane JM. Antipsychotic drugs. In Kaplan HI, Sadock BJ, eds. Comprehensive textbook of psychiatry, 5th ed. Baltimore Williams Wilkins, 1989 1604, with permission.)... 

Cannabinoid antagonists. Cannabinoid receptors are discussed in further detail in Chapter 13 on drug abuse. An antagonist to cannabinoid 1 (CB1) receptors, SR141716A, reduces the activity of mesolimbic dopamine neurons in animal models, suggesting possible antipsychotic actions in schizophrenia and leading to testing in schizophrenic patients. 

YamashitaH, Mori K, Nagao M, Okamoto Y, Morinobu S, Yamawaki S (2005) Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia comparison of middle-aged and older adults. Am J Geriatr Psychiatry 13 377-384... 

Lieberman, J., Stroup, T., McEvoy, J., Swartz, M., Rosenheck, R., Perkins, D., et al. (2005a). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine, 353, 1209-1223. 

Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, et al. 1999. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci USA 96 13432-13437. 

SSRIs are often prescribed with antipsychotic drugs, and some SSRIs inhibit CYP2D6, which can lead to increased blood concentrations of the antipsychotic drug. In 13 patients aged 26-56 years with schizophrenia, stabilized on risperidone 4-6 mg/day who took sertraline 50 mg/day for 4 weeks, plasma concentrations of risperidone and its major metabolite, 9-OH-risperidone, did not change... 

The discovery that the first antipsychotic drugs in the early 1950s, such as chlorpromazine, work in vitro by blocking dopamine receptors led to the hypothesis that schizophrenia was the result of excessive dopaminergic neurotransmission (54, 55). Supporting this hypothesis, dmgs that enhance dopamine action (e.g., cocaine, amphetamines, and L-DOPA) worsen the symptoms of schizophrenia. However, it is clear that 1) not all patients respond to neuroleptic treatment and 2) not all symptoms are reversed by the medication. 

In another analysis of prescribing data from the US Department of Veterans Affairs, 60% of 279779 individuals without schizophrenia or bipolar disorder who received at least one prescription for an antipsychotic drug in 2007 had no record of a diagnosis for an FDA-approved indication [105]. 

Systematic reviews First-generation and second-generation antipsychotic drugs in patients with schizophrenia have been compared in a meta-analysis [14= ] (for an in-depth review, see SEDA-27, 50). The study included 150 double-blind, mostly shortterm, randomized clinical trials with 21 533 participants. Four second-generation antipsychotic drugs (amisulpride, clozapine, olanzapine, and risperidone) were better than first-generation ones for overall... 

EUFEST study group. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder an open randomised clinical trial. Lancet 2008 371(9618) 1085-97. 

Bufotenine has been detected in the urines of schizophrenics Methysergide (1-methyl-D-lysergic acid butanolamide), which attenuates or prevents the adverse effects of bufotenine, was evaluated as an antipsychotic drug. In one study it was reported ineffective, in another it was said to have a deleterious effect In 1966, diphosphopyridine nucleotide was publicized in the lay press as an effective drug for short term treatment of schizophrenia. This prompted further studies which found DPN to be of no therapeutic value to acute or chronic schizophrenics ... 

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