The Experience of Antipsychotics III: “Normal” (Non-patient) Subjects

(NB:  More “effects on normal subjects” postings to come.)

Moncrieff et al.’s (2009) intro (an overview):

Antipsychotic drugs are being prescribed with increasing frequency to people with an expanding variety of diagnoses (1). Although, their physical effects have been well characterized, their subjective effects, in particular the mental alterations they produce, are less well recognised. Their mechanism of action has also not been clarified. Early investigators noted the striking ability of the first such drugs to produce a subjective state characterized by mental slowing, apathy and emotional indifference (2, 3). Subsequent studies with volunteers and first person accounts by patients also emphasize the emotional detachment, reduced initiative, dysphoria and akathisia produced by these drugs (4–7). Over the years, various labels have been used to describe these effects, including  “neuroleptics induced dysphoria” (8), “akinetic depression” (9),”neuroleptic induced deficit syndrome” (10), and “behavioural toxicity” (11, 12).


The Israeli researchers Belmaker and Wald’s (1977) letter to the editor of the British Journal of Psychiatry reporting their personal experiences of haloperidol:

“Haloperidol is an effective antipsychotic agent which is a relatively specific blocker of dopamine transmission in the brain (Anden et al, 1970). As part of the preliminary trials in a study of possible dopaminergic mechanism in affective disorder, the two authors each were given haloperidol 5 mg intravenously in a two-minute push. The effect was marked and very similar in both of us: within ten minutes a marked slowing of thinking and movement developed, along with profound inner restlessness. Neither subject could continue work, and each left work for over 36 hours. Each subject complained of a paralysis of volition, a lack of physical and psychic energy. The subjects felt unable to read, telephone or perform household tasks of their own will, but could perform these tasks if demanded to do so. There was no sleepiness or sedation; on the contrary, both subjects complained of severe anxiety.

The present experience was similar to that previously reported of neuroleptic effects in normal subjects (DiMascio et al, 1963; Heninger at al, 1965), though previous studies used neuroleptics which block both dopamine and noradrenaline receptors (Anden et al, 1970).We used a relatively specific dopamine blocker, haloperidol, and experienced profound cognitive and emotional restriction. Dopamine blocking by neuroleptics may function to restrict cognitive and emotional processes in normals as well as in schizophrenics and thus it is possible that it does not specifically antagonize schizophrenic pathology. In the presence of psychotic anxiety or delusions, such cognitive or emotional restriction may be desirable and therapeutic. However, the restrictive effect may be a general one…”


Excerpts from Healy and Farquhar’s (1998) study of droperidol (a dopamine antagonist) in normal subjects:


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.


Seventeen of the 20 subjects felt, in their words, sedated. Seven snoozed during the breaks between testing sessions, some feeling unable not to. Ten went to bed immediately on returning home that afternoon or early evening. Some slept successfully at that point, but others, owing to restlessness, did not. It was difficult to tease apart a proper sedative effect of the droperidol from the feeling of boredom in the test situation, but also from the feeling that things had become more effortful. Some subjects felt tired at the prospect of doing things and felt that they might not have been feeling sedated if the sense of effortfulness were lifted. There is a question, therefore, about the nature of this ‘sedative’ effect or the number of its component parts.


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 everything would take a comparable effort in the future. Some of these subjects found themselves remembering some of the unhappiest moments in their life, perhaps owing to state dependent effects.


Six subjects had very obvious ‘freezing’ responses during the course of the testing sessions. Images would flash up on the computer screen that required a response, but the subject was left looking at the screen and did not respond. This immobility was experienced by subjects as a lack of caring about the outcome. There was a general feeling common to all subjects to some extent of disengagement – a feeling of uninvolvement with tasks in hand. While feeling disengaged and uninterested, a number of subjects reported what appeared to be a paradoxical heightening of visual or auditory perceptions.

Mental effort appeared to be difficult, with all subjects reporting some problems with concentration. Apparently simple tasks, such as obtaining a sandwich from a sandwich machine, proved too difficult for some people, which contributed in turn to the dysphoria mentioned above.


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