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Healy, 1998 Immediate Effects of Droperidol.


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Akathisia, resulting from a single dose of this older antipsychotic, was reported by all subjects. Three of 20 subjects still felt the adverse effects of this single dose for a week.


This study is significant because the descriptions of akathisia and other adverse effects came from volunteers drawn from nursing and medical staff of a university clinic in North Wales, none of whom had a psychiatric diagnosis. It can give clinicians insight into just how adverse adverse effects from psychiatric drugs might be.


A more colorful description of this study is reported here: http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10565099&pnum=0 One of the subjects was psychologist Richard Bentall.


...Bentall, an expert on psychosis from the University of Bangor in Wales who is in New Zealand under the University of Auckland Hood Fellowship programme, developed akathisia - unpleasant sensations of inner restlessness and an inability to sit still.


"It was accompanied by a feeling that I couldn't do anything, which is really distressing. I felt profoundly depressed. They tried to persuade me to do these cognitive tests on the computer and I just started crying."


Bentall had volunteered to be in a study run by Irish psychiatrist Dr David Healy. Volunteers were given either 5mg of the antipsychotic droperidol, 1mg of lorazepam, a type of tranquillizer, or a placebo.


"The experiment completely failed," says Bentall. "Because first, it's absolutely mind-bogglingly obvious to anybody after an hour whether or not they are taking an antipsychotic or a placebo - the side effects are so marked. There is no such thing as a placebo antipsychotic in that sense."


But it was the fact that most of the healthy volunteers who took the antipsychotic became so unwell, let alone do the cognitive tests, that meant the study couldn't continue. One psychiatrist became suicidal and had to be put under observation.


In his controversial book Let Them Eat Prozac Healy wrote about what the volunteers experienced. "It was not like anything that had happened to them before... Highly personal memories of previous unhappy times - broken relationships or loneliness - seemed to be flooding back. And if they previously held themselves responsible for these unhappy times, they seemed to hold themselves responsible for feeling the way they did now as well."


Human Psychopharmacology: Clinical and Experimental Volume 13, Issue 2, pages 113–120, March 1998

Immediate effects of droperidol

David Healy, Grant Farquhar


Abstract at http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291099-1077%28199803%2913:2%3C113::AID-HUP958%3E3.0.CO;2-N/abstract Full text PDF here.


The subjective and behavioural responses of 20 healthy volunteers taking droperidol 5 mg as part of a cognitive challenge programme were catalogued. Some form of akathisia was universally experienced. Half of the subjects were dysphoric, but there appeared to be a number of different inputs to their dysphoria and a range of other effects were noted, including sedation, dissociative experiences, alterations in sensation and subtle changes in physiognomy. The duration of these effects varied from a few hours to over a week. In the acute phase, insight as to the origin of what was happening was mixed. The results have implications for the interpretation of cognitive challenge tests, the nature of akathisia, clinical therapeutics and drug development.


From the study:




None of the 20 subjects who had droperidol had a neutral or pleasant experience. None of those who had either lorazepam or placebo had an adverse experience, apart from sedation in the case of evening of the day of testing for all subjects. For lorazepam. There were both short and longer-term effects of droperidol, which will be considered together, with the issue of the mean duration of effects being discussed separately.


Droperidol, in this dose under these circumstances, induced restlessness in all 20 subjects. All subjects reported great difficulties with the completion of the tests. The tests it should be noted are boring. The levels of impatience experienced, however, were marked with some subjects remarking that they became belligerent or felt like putting a boot through the computer screen. Such reactions were out of character and were not reported in either the placebo or lorazepam groups. Fifteen of the 20 tested reported a mixture of reassurance by and irritation with the presence of the experimenter.


The restlessness had both clear motor and other components. Six of 20 subjects had what appeared to the experimenter to be visibly observable mild motor restlessness. One subject had to leave the experimental situation, although he did not attribute this at the time to the experimental compound. In contrast, all volunteers subjectively felt impatient and restless such that they wanted to get up and walk out of the testing room. When out of the room, however, either between sessions or after the testing session was over this restlessness continued for all subjects until at least that evening. The experience inhibited their ability to engage in normal social interactions. They felt there was a loss of composure in such situations, stemming in part from a sense of impatience with normal social interactions. Fifteen of the 20 found themselves to be irritable and belligerent.


Ten subjects felt that going to bed and remaining still might be a means to cope with the restlessness they were otherwise experiencing. This appeared to be an effort to manage restlessness by reducing stimulation. One of the subjects compared the predicament to that experienced by someone who might be sea-sick - in both cases there was switch to monitoring and attempting to manage internal stimuli rather the more usual focus on external stimuli. Six subjects, however, when in bed felt too restless to stay there. A feeling that a number of subjects had while snoozing or sleeping was that if they moved something would happen or would go wrong.


The experience of akathisia lasted until the evening of the day of testing for all subjects. For seven it had cleared up by the following morning or was only mildly present. Five subjects took procyclidine but none found that it substantially alleviated the experience. Seven took alcohol and these seven reported what appeared to be better effects from the alcohol than procyclidine. Two subjects took both procyclidine and alcohol and both claimed that the alcohol was more helpful. For the remaining 13 subjects the experience lasted at least through the following day and for eight, although waxing and waning during subsequent days, the problem lasted even longer regardless of the measures taken to alleviate it.




Seventeen of the 20 subjects felt, in their words, sedated.....



Eleven subjects reported dysphoria while the other nine were quite sure that although akathisic, they were not dysphoric in any meaningful sense of that word. The onset of dysphoria in most cases was relatively immediate with one subject breaking down in tears within an hour of having droperidol. In part dysphoria appeared to mean an experience during the testing session that personal horizons were closing in. Another component appeared to stem from an anxiety that the state was likely to go on forever. Yet another component seemed to stem from the effort they were now having to make even to do the most simple things; they found this tremendously dispiriting and worried that every- thing would take a comparable effort in the future. Some of these subjects found themselves remember- ing some of the unhappiest moments in their life, perhaps owing to state dependent effects. There was a feeling of the return of mood-dependent memories, of having fallen back into traps they had been in the past. This, in some instances, was accompanied by an evocation of imagery from the past, on others it simply appeared to be an evocation of feelings. Suicidal feelings emerged acutely in two subjects and were entertained in two more subjects whose reactions continued over succeeding days.


There was a growing element of anxiety for a number of subjects when the condition appeared to persist. Some had expected that when they got home and back into their normal routine that they would feel well and they were alarmed when they did not feel well. Others wondered whether they had done some irreversible damage to their brains - this was particularly the case for those subjects for whom the effects lasted more than 24 h. Even when the condition began to ameliorate, four of the subjects with longer lasting reactions described feeling vulnerable as though they were standing on the edge of a possible relapse.


Other experiences reported

Among other experiences reported were skin hypersensitivity, which was reported by five subjects. This was an odd feeling of either fleeting tingling or painful sensations in arms or legs or in the trunk....It can be noted that sensations of this sort are a commonly unrecognised, but not infrequent, occurrence in neuroleptic induced extrapyramidal syndromes (Decina et al., 1992).



There were subtle changes in physiognomy in some subjects, noticeable to the observing experi- menter, which in some cases were later remarked on independently by relatives of the participants. These appeared to involve changes to skin and hair as well as a 'shrunken' appearance, that to the observing experimenter had the appearances of an incipient influenzal infection. Changes of this sort led to one of the participants being later described, by a team member unaware of their participation in the study, as looking like a chronic schizophrenic.




....When challenged on the discrepancy between their reports of no undue discomfort at the time of testing and subsequent reports of extreme distress all subjects recognised a paradox. The 18 subjects who had not reported distress at the time of testing subsequently reported that even when they were denying discomfort they had been acutely restless, impatient or dysphoric. One explanation for this dissociation was an unwillingness to report these subjective effects in case they indicated they had been taken in by the experimental protocol. There was also a feeling that they didn't want to be affected and that not acknowledging a problem might help it to go away. There was a disbelief that a small dose of a psychotropic agent in common use not noted to produce severe problems could be causing such discomfort. Thus there appeared to be some awareness of an altered state, but an unwill- ingness or inability to admit to this altered state, owing in part to the rapidity of its onset and in part to a more general difficulty in pinpointing the distinctive features of an unusual experience....




....Another unexpected and interesting finding was that a number of behaviours that are associated with individuals with schizophrenia, that have ordinarily been seen as part of the illness or otherwise problematic, appeared in a new light following this study. Some could be seen as adaptive strategies to manage side effects. A number of individuals found that the best way to handle their side effects was to disengage from company and take to bed. A number of others found that the most effective antidote to their restlessness was alcohol. This finding has not been reported in the literature. It emerged quite independently from several different volunteers who had been advised as part of the experimental protocol not to take alcohol that evening. Future studies might explore this effect more systematically.



While the volunteers involved underwent con- siderable discomfort, those working in the mental health services all found the cxperience illumin- ating. They expected it to influcnce their clinical practice and despite their discomfort felt further studies should be undertaken to explore the phenomena further....


This experiment clearly illustrates what the cost in terms of quality of life of some of the older neuroleptics may be. Antipsychotic drugs that do not induce comparable levels of dysphoria or akathisia would seem to be clearly preferable, even if their cost is substantially greater. Unfortunately, at present, the kinds of studies that would establish such findings are not being conducted. In order to tease apart the contribution of the different active principles in any of these cocktail compounds and the interaction of those principles with personality and constitutional profiles as well as the context in which such compounds are given, an ideal experiment would require the availability of several hundred healthy volunteers.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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