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Psychological and physiological effects of bupropion compared to methylphenidate after prolonged administration in healthy volunteers (NCT00285155)

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Abstract

Purpose

Bupropion is largely used as an antidepressant and smoking cessation therapy. The aim of this work was to compare pharmacodynamic properties of bupropion and the amphetamine-like methylphenidate after sustained administration in humans.

Methods

Twelve male volunteers completed this randomized, double-blind, placebo controlled, cross-over study. Bupropion and methylphenidate were administered separately for initial half-dose 6-day periods (150 and 10 mg respectively) followed by full-dose 8-day periods (300 and 20 mg respectively). Outcomes were subjective feelings, cognitive performances, autonomic and physiological parameters.

Results

Data are expressed as mean(SEM). After repeated administration, bupropion, like methylphenidate, decreased asthenia-fatigue [44(3.2) and 42(3.7), respectively vs. 53(4.1) for placebo; p = 0.034], despite an impairment of sleep onset [-4.3(3.32) and -1.9(3.76), respectively vs. +7.5(3.69); p = 0.016]. Both drugs increased resting diastolic blood pressure [67.9(1.23) and 65.7(0.98), respectively vs. 62.5(1.42) mm Hg; p = 0.001], body temperature [36.5(0.12) and 36.5(0.14) vs. 36.3(0.10) °C; p = 0.037] and decreased body weight [-0.7(0.23) and -0.6(0.22), respectively vs. +0.2(0.27) kg; p = 0.038]. No significant change could be observed on cognitive functions, appetite and energy consumption.

Conclusion

Although it may not share all the properties of stimulant drugs, the effect profile of bupropion presents a number of similarities with that of methylphenidate over a 2-week treatment period.

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References

  1. Preskorn SH, Othmer SC (1984) Evaluation of bupropion hydrochloride: the first of a new class of atypical antidepressants. Pharmacotherapy 4(1):20–34

    PubMed  CAS  Google Scholar 

  2. Hughes JR, Stead LF, Lancaster T (2007) Antidepressants for smoking cessation. Cochrane Database Syst Rev (1):CD000031

  3. Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E et al (1995) Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 56(9):395–401

    PubMed  CAS  Google Scholar 

  4. Cooper BR, Hester TJ, Maxwell RA (1980) Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo. J Pharmacol Exp Ther 215(1):127–134

    PubMed  CAS  Google Scholar 

  5. Arias HR (2009) Is the inhibition of nicotinic acetylcholine receptors by bupropion involved in its clinical actions? Int J Biochem Cell Biol 41(11):2098–2108

    Article  PubMed  CAS  Google Scholar 

  6. Munzar P, Goldberg SR (2000) Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology (Berl) 148(2):209–216

    Article  CAS  Google Scholar 

  7. Reichel CM, Murray JE, Grant KM, Bevins RA (2009) Bupropion attenuates methamphetamine self-administration in adult male rats. Drug Alcohol Depend 100(1–2):54–62

    Article  PubMed  CAS  Google Scholar 

  8. Lamb RJ, Griffiths RR (1990) Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine. Psychopharmacology (Berl) 102(2):183–190

    Article  CAS  Google Scholar 

  9. Bergman J, Madras BK, Johnson SE, Spealman RD (1989) Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys. J Pharmacol Exp Ther 251(1):150–155

    PubMed  CAS  Google Scholar 

  10. Bredeloux P, Dubuc I, Costentin J (2007) Comparisons between bupropion and dexamphetamine in a range of in vivo tests exploring dopaminergic transmission. Br J Pharmacol 150(6):711–719

    Article  PubMed  CAS  Google Scholar 

  11. Hamilton MJ, Smith PR, Peck AW (1983) Effects of bupropion, nomifensine and dexamphetamine on performance, subjective feelings, autonomic variables and electroencephalogram in healthy volunteers. Br J Clin Pharmacol 15(3):367–374

    Article  PubMed  CAS  Google Scholar 

  12. Peck AW, Hamilton M (1983) Psychopharmacology of bupropion in normal volunteers. J Clin Psychiatry 44(5 Pt 2):202–205

    PubMed  CAS  Google Scholar 

  13. Rush CR, Kollins SH, Pazzaglia PJ (1998) Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans. Exp Clin Psychopharmacol 6(1):32–44

    Article  PubMed  CAS  Google Scholar 

  14. Barrickman LL, Perry PJ, Allen AJ, Kuperman S, Arndt SV, Herrmann KJ, Schumacher E (1995) Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 34(5):649–657

    Article  PubMed  CAS  Google Scholar 

  15. Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J, Polisner D, Solhkhah R, Comeau S, Monuteaux MC, Parekh A (2001) A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 158(2):282–288

    Article  PubMed  CAS  Google Scholar 

  16. Kollins SH, MacDonald EK, Rush CR (2001) Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacol Biochem Behav 68(3):611–627

    Article  PubMed  CAS  Google Scholar 

  17. OMS (1993) Troubles mentaux et troubles deu comportement. Description clinique et directives pour le diagnostic. In: Classification Internationale des Maladies, Dixième révision (CIM-10). Masson, Paris

  18. Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12(2):245–258

    PubMed  CAS  Google Scholar 

  19. McNair D, Lorr M, Droppleman LF (1971/1992) Manual for the Profile of Mood States. Edits/Educational ans Industrial Testing Service, San Diego

  20. Norcross JC, Guadagnoli E, Prochaska JO (1984) Factor structure of the Profile of Mood States (POMS): two partial replications. J Clin Psychol 40(5):1270–1277

    Article  PubMed  CAS  Google Scholar 

  21. Norris H (1971) The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology 10(21):181–191

    Article  PubMed  CAS  Google Scholar 

  22. Bond A, Lader M (1974) Use Of Analog Scales In Rating Subjective Feelings. British Journal Of Medical Psychology 47:211–218

    Article  Google Scholar 

  23. Parrott AC, Hindmarch I (1980) The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review. Psychopharmacology (Berl) 71(2):173–179

    Article  CAS  Google Scholar 

  24. Hindmarch I (1980) Psychomotor function and psychoactive drugs. Br J Clin Pharmacol 10(3):189–209

    Article  PubMed  CAS  Google Scholar 

  25. Ridout F, Shamsi Z, Meadows R, Johnson S, Hindmarch I (2003) A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180 mg alone and with alcohol, with hydroxyzine hydrochloride 50 mg as a positive internal control, on aspects of cognitive and psychomotor function related to driving a car. Clin Ther 25(5):1518–1538

    Article  PubMed  CAS  Google Scholar 

  26. Sherwood N (1995) Comparative Behavioural Toxicity of the Selective Serotonin Reuptake Inhibitors. Human Psychopharmacology 10:S159–S162

    Article  CAS  Google Scholar 

  27. Smith JM, Misiak H (1976) Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects-a review. Psychopharmacologia 47(2):175–182

    Article  PubMed  CAS  Google Scholar 

  28. Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18(6):643–662

    Article  Google Scholar 

  29. Wechsler D (1955) A manual for the Wechsler Adult Intelligence Scale. The Psychological Corporation, New York

    Google Scholar 

  30. Simard M, van Reekum R (1999) Memory assessment in studies of cognition-enhancing drugs for Alzheimer’s disease. Drugs Aging 14(3):197–230

    Article  PubMed  CAS  Google Scholar 

  31. Raben A, Tagliabue A, Astrup A (1995) The reproducibility of subjective appetite scores. Br J Nutr 73(4):517–530

    Article  PubMed  CAS  Google Scholar 

  32. Gobbi G, Slater S, Boucher N, Debonnel G, Blier P (2003) Neurochemical and psychotropic effects of bupropion in healthy male subjects. J Clin Psychopharmacol 23(3):233–239

    PubMed  CAS  Google Scholar 

  33. Siepmann M, Werner K, Schindler C, Oertel R, Kirch W (2005) The effects of bupropion on cognitive functions in healthy subjects. Psychopharmacology (Berl) 182(4):597–598

    Article  CAS  Google Scholar 

  34. Carvalho AF, Kohler CA, Cruz EP, Sturmer PL, Reichman BP, Barea BM, Izquierdo I, Chaves ML (2006) Acute treatment with the antidepressants bupropion and sertraline do not influence memory retrieval in man. Eur Arch Psychiatry Clin Neurosci 256(5):320–325

    Article  PubMed  Google Scholar 

  35. Griffith JD, Carranza J, Griffith C, Miller LL (1983) Bupropion: clinical assay for amphetamine-like abuse potential. J Clin Psychiatry 44(5 Pt 2):206–208

    PubMed  CAS  Google Scholar 

  36. Miller L, Griffith J (1983) A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers. Psychopharmacology (Berl) 80(3):199–205

    Article  CAS  Google Scholar 

  37. Newton TF, Roache JD, De La Garza R 2nd, Fong T, Wallace CL, Li SH, Elkashef A, Chiang N, Kahn R (2006) Bupropion reduces methamphetamine-induced subjective effects and cue-induced craving. Neuropsychopharmacology 31(7):1537–1544

    Article  PubMed  CAS  Google Scholar 

  38. Heil SH, Holmes HW, Bickel WK, Higgins ST, Badger GJ, Laws HF, Faries DE (2002) Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users. Drug Alcohol Depend 67(2):149–156

    Article  PubMed  CAS  Google Scholar 

  39. Bishop C, Roehrs T, Rosenthal L, Roth T (1997) Alerting effects of methylphenidate under basal and sleep-deprived conditions. Exp Clin Psychopharmacol 5(4):344–352

    Article  PubMed  CAS  Google Scholar 

  40. Newton TF, Roache JD, De La Garza R 2nd, Fong T, Wallace CL, Li SH, Elkashef A, Chiang N, Kahn R (2005) Safety of intravenous methamphetamine administration during treatment with bupropion. Psychopharmacology (Berl) 182(3):426–435

    Article  CAS  Google Scholar 

  41. Wilens TE, Hammerness PG, Biederman J, Kwon A, Spencer TJ, Clark S, Scott M, Podolski A, Ditterline JW, Morris MC, Moore H (2005) Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry 66(2):253–259

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was successfully carried out thanks to the expert scientific, medical, pharmaceutical and logistic assistance of JL Allaz, AM Barbanel, F Barnay, R Blanc, B Bories-Azeau, A Cadène, F Collado, P Dumas, J Foppolo, I Gabillaud, A Massebiau, P Rambourg, D Robert and I Roch-Torreilles.

Funding

This work was supported by the French Ministry of Health [PHRC régional 2003].

Conflict of Interest Statement

The authors declare that they have no conflict of interest.

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Correspondence to Hugues Chevassus.

Additional information

This study was sponsored by the University Hospital of Montpellier (UF7759). This work was supported by the French Ministry of Health [PHRC régional 2003].

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Chevassus, H., Farret, A., Gagnol, JP. et al. Psychological and physiological effects of bupropion compared to methylphenidate after prolonged administration in healthy volunteers (NCT00285155). Eur J Clin Pharmacol 69, 779–787 (2013). https://doi.org/10.1007/s00228-012-1418-z

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  • DOI: https://doi.org/10.1007/s00228-012-1418-z

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