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Neuroleptic dysphoria: towards a new synthesis

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Abstract

Rationale

Neuroleptic dysphoria (ND) is a subtle and under-recognized side effect of antipsychotic drugs. It is an all-inclusive descriptive phrase that encompasses a variety of unpleasant subjective changes in arousal, mood, thinking and motivation induced by neuroleptic drugs. Understanding this phenomenon has wide ranging clinical and research implications.

Objective

The present review examined the themes identified in the original studies from the neuroleptic era in the light of recent findings from neuroimaging research, cumulative experience with second generation antipsychotic drugs, and new concepts such as pleasure responsivity, hedonic regulation and subjective tolerability.

Methods

Empirical studies on neuroleptic drugs involving clinical populations treated for schizophrenia, Tourette’s disorder and stuttering, studies performed on normal healthy volunteers and selected experimental studies in animals, are reviewed.

Results

Dysphoric responses occur early during treatment and typically manifest as a dislike towards medication (drug aversiveness). Dysphoria persisting over time, may lead to adverse clinical consequences such as treatment non-adherence, substance abuse, poor clinical outcome, increased suicidality and compromised quality of life. Interference with the physiological processes of hedonic capacity by the neuroleptics due to their dopaminergic blocking action in the prefrontal cortex and the shell of nucleus accumbens is the putative mediating mechanism underlying the occurrence of dysphoric responses. Second generation antipsychotic drugs with an atypical receptor blocking profile are less likely to elicit dysphoric responses.

Conclusion

Viewing neuroleptic dysphoria within a broader spectrum of disorders of subjective tolerability and exploring its neurobiological mechanisms is relevant to addressing the nuances of antipsychotic therapy, and could help unravel the questions surrounding the pathophysiology of depression, substance abuse and other dysphoric clinical states.

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Authors and Affiliations

  1. Institute of Medical Science, University of Toronto, Toronto, Canada

    L. Voruganti & A. G. Awad

  2. Schizophrenia Research Program, F-236, Research Block, 100 West 5th Street, Hamilton, Ontario, L8N 3K7, Canada

    L. Voruganti

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  1. L. Voruganti
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  2. A. G. Awad
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This paper is dedicated to the late Theodore (“Ted”) Van Putten, (1938–1993), who is fondly remembered as an elegant scholar, a gifted teacher, a pre-eminent schizophrenia researcher, an uncompromising scientist, and a warm and caring doctor. Dr. Van Putten pioneered the study of subjective responses to antipsychotic drugs, and inspired a generation of researchers to explore the phenomenon of neuroleptic dysphoria and elucidate its neurobiological basis.

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Voruganti, L., Awad, A.G. Neuroleptic dysphoria: towards a new synthesis. Psychopharmacology 171, 121–132 (2004). https://doi.org/10.1007/s00213-003-1648-y

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  • DOI: https://doi.org/10.1007/s00213-003-1648-y

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