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Editor—Until the Committee on the Safety of Medicines restricted the use of thioridazine in 2000, it was the most widely used antipsychotic drug in the United Kingdom, with 50 million years of safe use by patients worldwide. In Scotland in 1999, were 250 808 were prescriptions dispensed in primary care (hospital data not available, but the safety committee reports that it was the most widely used antipsychotic drug in hospitals too). This dropped to 39 177 in 2001, according to information from the Primary Care Information Unit in Edinburgh.
Is thioridazine safer, cheaper, and more effective than alternative antipsychotic drug treatments for anxiety, agitation, mania, and hypomania? We do not have enough evidence to answer this because thioridazine has been widely used for 30 years—before the days of rigorous randomised controlled trials. Lack of evidence is not evidence of no benefit. Conversely, there is only evidence of a handful of adverse cardiac events, some of which may not have been directly caused by thioridazine or may have been due to combination with other drugs. Although the reported cardiac deaths are lamentable, it seems that thioridazine is much safer than other effective drugs such as aspirin, which continues to be sold over the counter. Even if adverse events are under-reported, there is far more practical evidence of long term safety for thioridazine compared with much more expensive and much less tried and tested drugs. A recent study noted that many new drugs have a high rate of serious side effects which go undetected until late in postmarketing surveillance.2 The Committee for the Safety of Medicines needs to balance these relative risks.
The manufacturers of thioridazine have raised few objections to the restricted use of thioridazine because it is an extremely cheap drug, costing only a few pence compared with newer antipsychotics that may be up to a hundred times more expensive, as well as having different and sometimes distressing side effects. The prescription costs of antipsychotic drugs has risen sharply in Scotland in the past two years.
Anecdotally, considerable numbers of patients with hypomania, anxiety, and agitation are having considerable problems in adjusting to a change of drugs, and, as Davies et al point out, informed consent may be a problem.1 It would be very helpful if the National Institute for Clinical Excellence or Health Technology Board for Scotland reviewed the evidence, risks, and benefits of thioridazine, and considered more humane guidelines for its future use. It seems quite wrong to deprive so many patients of a well tried drug.
Footnotes
Competing interests: None declared.
References
1.Davies SJC, Cooke LB, Moore AG, Potokar J. Discontinuation of thioridazine in patients with learning disabilities: balancing cardiovascular toxicity with adverse consequences of changing drugs. BMJ. 2002;324:1519–1521. doi: 10.1136/bmj.324.7352.1519. . (22 June.) [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215–2220. doi: 10.1001/jama.287.17.2215. [DOI] [PubMed] [Google Scholar]
Editor—The article by Davies raised some important issues on discontinuation of thioridazine in populations with learning disability.1-1 We had successful withdrawal of thioridazine in our services in Salford district.
We looked at the following issues before withdrawal of thioridazine:
(1) Initial diagnosis before thioridazine was prescribed
(2) Duration and dose of treatment
(3) Review of previous psychiatric treatment including attempts to reduce or stop thioridazine.
Results indicated that 28 out of 175 patients under the care of a psychiatrist specialising in learning disability received thioridazine. Twenty three patients received small doses (50-100 mg) for many years. The main indication for use was marked challenging behaviour (12 patients). Based on the above information, a decision was made to gradually reduce (12 patients) or suddenly stop thioridazine (16 patients).
As an alternative, a tranquilliser was prescribed for all 28 patients. Risperidone was the most commonly used atypical antipsychotic drug because of some evidence of its effectiveness in challenging behaviour.1-2 A review of patients' mental state three months after the substitution of tranquillisers indicated that twenty one patients either remained stable or improved, and seven patients deteriorated. These seven patients subsequently improved, either by a change to a different psychotropic drug or by adjusting the dose of existing drugs. No patient needed to restart taking thioridazine.
Review of previous psychiatric treatment helped us to identify instances of rebound increase in behavioural problems when thioridazine was stopped. It also prompted us to avoid using neuroleptics that were either ineffective or caused unacceptable side effects. Evidence of rebound aggression on stopping neuroleptics was also observed by Mos et al.1-3 This lead us to withdraw thioridazine gradually in most cases.
In our opinion risk associated with the withdrawal of thioridazine was managed carefully and minimised by taking into account the diagnosis, the dose and duration, and consequences of previous reduction in medication followed by a careful strategy of either gradual reduction or sudden stoppage with replacement of alternative tranquillisers in appropriate doses.
Footnotes
Competing interests: None declared.
References
1-1.Davies SJC, Cooke LB, Moore AG, Potokar J. Discontinuation of thioridazine in patients with learning disabilities: balancing cardiovascular toxicity with adverse consequences of changing drugs. BMJ. 2002;324:1519–1521. doi: 10.1136/bmj.324.7352.1519. . (22 June.) [DOI] [PMC free article] [PubMed] [Google Scholar]
1-2.Vander Ben Borre R. Risperidone as add-on therapy in behavioural disturbances in mental retardation: a double blind placebo-controlled cross-over study. Acta Psychiatrica Scandinavica. 1993;87:167–171. doi: 10.1111/j.1600-0447.1993.tb03350.x. [DOI] [PubMed] [Google Scholar]
1-3.Mos J, Van Aken HH, Van Oorschot R, Olivier B. Chronic treatment with eltoprazine does not lead to tolerance in its anti-aggressive actions, in contrast to haloperidol. Eur Neuropsychopharmacol. 1996;6:1–7. doi: 10.1016/0924-977x(95)00051-p. [DOI] [PubMed] [Google Scholar]
