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Haloperidol, the first butyrophenone neuroleptic, was created in Europe by Janssen Pharmaceuticals in 1958 and was introduced swiftly throughout the continent with great enthusiasm. On September 15, 1959, at Janssen's headquarters in Belgium, teams from around Europe praised the effectiveness of haloperidol. In the United States, on the contrary, its introduction was a tremendous failure, plagued by accusations of inefficacy and patent disputes. A clinical trial in Manhattan has been blamed for this commercial failure. The results of the Manhattan trial were seen as radically different from the results obtained in continental Europe. This divide would have considerable impact not only with regard to haloperidol's path on both sides of the Atlantic, but also possibly on the practical experience and theoretical construction of psychiatry. This article tries to reconstruct the story of that trial based mainly on published papers and interviews. Exploring how societal changes and issues of gender and race shaped this process, this investigation attempts to understand and contextualize different possible reasons for this Atlantic rift.

Tic disorders typically start in early childhood and can be classified into provisional tic disorder (tics last <12 months) and chronic tic disorders (tics last > 12 months). The widely known chronic tic disorder Tourette's syndrome is featuring multiple motor and vocal tics. Tics are typically waxing and waning in frequency and intensity. Concentration and relaxation might decrease tics, whereas stress and excitement might increase tics. Psychiatric comorbidities, like obsessive-compulsive disorder, ADHD, depression and anxiety are common. The etiology is multifactorial with genetic and environmental interactions leading to a dysregulation of cortico-striato-pallido-thalamo-cortical networks.A correct diagnosis and psychoeducation are essential for patients as well as their relatives. Additional therapies are needed for patients with severe tics that cause physical impairment or great psychosocial stress. It is crucial to also treat psychiatric comorbidities. Psychotherapeutic interventions for tics include progressive muscle relaxation, habit reversal training, exposure and response prevention and comprehensive behavioral intervention for tics. First-line psychopharmacological treatment in Europe contains aripiprazole, tiapride and risperidone, which are all used off-label for tic disorders. Haloperidol remains the only approved medication for the pharmacotherapy of tics in Germany, but is rarely used due to its side effects. Cannabinoids gain interest as a new pharmacological option, but are mainly offered within the frame of studies., Competing Interests: Dr. Richard Musil hat Vortragshonorare von Otsuka/Lundbeck erhalten. Die Autoren sind Mitglied in der Europäischen Tourette-Gesellschaft (ESSTS) und sind an klinischen Multicenterstudien im Bereich Tourette beteiligt, die von öffentlichen Trägern (DFG, BMBF, EU) oder pharmazeutischen Unternehmen gefördert werden., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality., Methods: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use., Results: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively., Conclusions: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.

When elderly Alzheimer's patients remain dangerously aggressive despite non-drug measures, there is no evidence that risperidone is safer or any more effective than haloperidol.

(1) The first-line drug for the treatment of schizophrenic disorders is a neuroleptic such as haloperidol. Amisulpride may be preferable when haloperidol causes unacceptable neurological reactions. Overall, the risk-benefit balance of more recent, so-called atypical neuroleptics is no better. (2) Sertindole, a neuroleptic, was first marketed in 1996 in several European countries before being withdrawn two years later because of numerous cardiac adverse effects. It has once again been approved and should soon be available on the French market. (3) Two comparative double-blind trials suggest that a daily sertindole dose of 24 mg is about as effective as 10 mg of haloperidol. Sertindole was no more effective than risperidone in a trial comparing these two drugs. (4) Like other 'atypical' neuroleptics, sertindole has few short-term neurological adverse effects (extrapyramidal syndrome) at the doses used in clinical trials. However, it causes weight gain. Sertindole also has alpha blocking properties, which can cause postural hypotension and reduce ejaculate volume; it also has atropinic effects (constipation, dry mouth, etc.). (5) Sertindole provokes a dose-dependent increase in the QT interval more frequently than haloperidol in comparative trials, and apparently more frequently than other 'atypical' neuroleptics such as risperidone and olanzapine. Sertindole has been suspected of increasing cardiovascular mortality but this has not been established. (6) Sertindole is metabolised by cytochrome P450 isoenzymes CYP 2D6 and CYP 3A4, hence a high risk of pharmacokinetic interactions. (7) In practice, when haloperidol has to be withdrawn because of adverse effects, especially neurological reactions, it is better to continue to resort to amisulpride, for example, with close monitoring of adverse effects, rather than expose patients to the potential dangers of sertindole.

With the goal of evaluating the available literature on the course of Tourette's disorder, we conducted a systematic literature search through electronic databases for pertinent scientific articles in English with a minimum of 20 subjects. We also examined bibliographies of papers identified in this manner for additional sources. We found only 16 articles; most consisted of retrospective reports on treated samples. Overall, the available literature suggests that Tourette's disorder follows a remitting course in a sizeable number of individuals. Little has been published regarding predictors of remission or persistence. More work is needed using longitudinal prospective studies to better define the course and outcome of Tourette's disorder.