PubMed · 9499203
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
N W Tarricone. 1998. Loxitane overdose.. https://doi.org/10.1542/peds.101.3.496
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
In 200 inpatients on regular neuroleptics, point prevalence of extrapyramidal syndromes, including Parkinson syndrome, akathisia and tardive dyskinesia (TD), was studied and found to be 20, 11 and 22%, respectively. A total of 46 patients have currently, and for a longer time, (average about 3years, median over 1year) been treated with clozapine, and 127 with typical neuroleptics (NLs). Comparing both groups, higher TD scores were found in the clozapine sample. Investigating the influence of a set of seven clinical variables on the TD score with the help of multiple regression analysis, the influence of the treatment modality disappeared, whereas the age proved to be the only significant variable. Studying the role of past clozapine therapy in patients currently on typical NLs and comparing 10 matched pairs of chronic patients with and without TD in whom a complete life-time cumulative dose of NLs was identified, a relationship between TD and length of current typical NL therapy and life-time typical NL dosage could be demonstrated. On the whole, long-term relatively extensive use of clozapine has not markedly reduced the prevalence of extrapyramidal syndromes in our psychiatric inpatient population. In particular, we failed to demonstrate a beneficial effect of clozapine on prevalence of TD. There are certainly patients who suffer from TD in spite of a long-term intensive clozapine treatment.
The placebo-controlled trial is widely regarded as the gold standard for testing the efficacy of new treatments; however, this research design is subject to ethical controversy, especially when standard treatments of proven efficacy exist. After examining regulatory standards and ethical codes relevant to placebo-controlled trials, I offer a critique of arguments against the use of placebo control groups in psychiatric research. An absolute ethical prohibition of placebo-controlled trials in psychiatric disorders for which standard, effective treatments exist is rejected because it is based on a flawed conception of research ethics, ignores important contextual factors characteristic of psychiatric research, and could lead to the approval and use of new medications that appear equivalent in efficacy to standard treatments but may be no more effective than placebos. Four standards governing the ethical use of placebos in psychiatric clinical trials are explicated: 1) placebo-controlled trials should have scientific and clinical merit; 2) risks should be minimized and justified by the anticipated benefits of generating clinically relevant scientific knowledge and the expected benefits, if any, to individual patient volunteers; 3) patient volunteers should give informed consent; and 4) investigators should offer short-term treatment optimization to patient volunteers after completion of research participation.
Because a statistical tie between standard treatment and an innovation is uninterpretable, most trials intended to demonstrate efficacy of innovations in psychopharmacology employ a placebo control group, despite the existence of standard medications for many disorders. In this review I consider the statistical issues that inform the ethics of the decision to use a placebo condition and make the following points: 1) the investigator is relying on the assumption that the effects of delayed standard treatment are neither long-lasting nor harmful; 2) the usual practice of truncating follow-up when a patient ceases to adhere to a study treatment makes it difficult to empirically test that assumption; 3) placebo control trials often suffer from methodological weaknesses (including nonrandom truncation) that reduce their inferential power; 4) these subtleties place a substantial burden on the informed consent process; 5) alternative designs are available but not well explored, due to the dominant role of "regulatory" trial methodology; and 6) researchers should consider other goals besides helping to introduce another treatment that improves on placebos but not the standard treatment.