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. 2018 Apr 27:14:1125-1138.
doi: 10.2147/NDT.S148557. eCollection 2018.

Antidopaminergic medication in healthy subjects provokes subjective and objective mental impairments tightly correlated with perturbation of biogenic monoamine metabolism and prolactin secretion

Tanja Veselinović  1   2 , Ingo Vernaleken  1   2 , Paul Cumming  3   4 , Uwe Henning  5 , Lina Winkler  1   2 , Peter Kaleta  1   2 , Michael Paulzen  1   2 , Christian Luckhaus  6 , Gerhard Gründer  1   2   7
Affiliations

Antidopaminergic medication in healthy subjects provokes subjective and objective mental impairments tightly correlated with perturbation of biogenic monoamine metabolism and prolactin secretion

Tanja Veselinović et al. Neuropsychiatr Dis Treat. .

Abstract

Objectives: Off-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals.

Methods: In this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject's mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial.

Results: Of the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well.

Conclusion: We found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week's treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk-benefit evaluation in cases of off-label prescription of antipsychotic medications.

Keywords: HVA; aripiprazole; catecholamine metabolites; dopamine; halo-peridol; off-label prescription; prolactin; reserpine.

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Conflict of interest statement

Disclosure TV has received grant support from Bristol-Myers Squibb. IV has served on the speakers’ bureaux of Bristol-Myers Squibb (New York, NY), Eli Lilly (Indianapolis, IN), and GlaxoSmithKline (London, UK). GG has served as a consultant for Allergan, Boehringer Ingelheim, Eli Lilly, Janssen-Cilag, Lundbeck, Ono Pharmaceuticals, Otsuka, Recordati, Roche, Servier, and Takeda, and served on the speakers’ bureaux of Eli Lilly, Janssen Cilag, Lundbeck, Neuraxpharm, Otsuka, Roche, Servier, and Trommsdorff. He has received grant support from Boehringer Ingelheim and Roche, and is cofounder of Pharma Image and Brainfoods GmbH. The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Changes in monoamine metabolite concentrations after the 7-day medication period. Notes: (A) P=0.001; (B) P=0.009; (C) P=0.006. Abbreviations: HVA, homovanillic acid; MHPG, 3-methoxy-4-hydroxyphenylglycol; VMA, vanillylmandelic acid.
Figure 2
Figure 2
Prolactin (Prl) changes versus scales for third-party and subjective assessment. Abbreviations: PANSS, Positive and Negative Syndrome Scale; HRSD, Hamilton Rating Scale for Depression; BDI, Beck Depression Inventory; VAS, visual analogue scale.
See this image and copyright information in PMC

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