, Volume 182, Issue 4, pp 597–598

The effects of bupropion on cognitive functions in healthy subjects


    • Institute of Clinical Pharmacology, Medical FacultyTechnical University
  • Kathrin Werner
    • Institute of Clinical Pharmacology, Medical FacultyTechnical University
  • Christoph Schindler
    • Institute of Clinical Pharmacology, Medical FacultyTechnical University
  • Reinhard Oertel
    • Institute of Clinical Pharmacology, Medical FacultyTechnical University
  • Wilhelm Kirch
    • Institute of Clinical Pharmacology, Medical FacultyTechnical University
Letter to the Editors

DOI: 10.1007/s00213-005-0128-y

Cite this article as:
Siepmann, M., Werner, K., Schindler, C. et al. Psychopharmacology (2005) 182: 597. doi:10.1007/s00213-005-0128-y
Bupropion is an antidepressant of the aminoketone class (amfebutamone), which is structurally unrelated to the tricyclic antidepressants and is considered to be devoid of any sedative effects. In healthy volunteers, single doses of bupropion do not influence cognitive functions or quantitative EEG (qEEG; Peck et al. 1979; Hamilton et al. 1983). In a non-blind study of depressed patients comparing bupropion with drug-free controls, perceptual changes and reduced ability to ignore distractions were noted with bupropion (Becker and Dufresne 1982). Difficulties in concentration were previously reported in nicotine dependants who received cessation treatment with bupropion (Jorenby et al. 1999; Swan et al. 2003). The aim of the present study was to compare the effects of subchronic administration of bupropion with those of placebo on various cognitive functions. The design of the study and the methods used to assess cognitive functions as well as qEEG were described in detail elsewhere (Siepmann et al. 2004, 2005). Briefly, a randomized, double-blind, placebo-controlled study was conducted in 12 healthy male volunteers aged 26±3 years (mean±standard deviation). Subjects orally received 50 mg bupropion t.i.d. for 7 days and, subsequently, 100 mg t.i.d. for another 7 days. After a 14-day washout phase, placebo was administered to the subjects for 14 days under randomized crossover conditions. A liquid chromatographic–tandem mass spectrometric (LC-MS-MS) method with a rapid, simple sample preparation was developed to detect bupropion in serum. Bupropion serum concentrations were noted highest at hours 3 and 5 following last dosing with the drug (71.8±30.0 and 42.0±16.9 ng/ml respectively; mean±standard deviation). As outlined in Table 1, bupropion significantly reduced absolute alpha 2 and theta power density in the qEEG, with the subjects keeping their eyes closed 3 h after the last dose was given. Absolute power density in the alpha 1 and theta frequency bands was found attenuated under eyes-open conditions 5 h following last dosing with the drug. Bupropion did not influence power density of other frequency ranges such as the beta 1, beta 2 and delta bands nor did it have an effect on choice reaction, memory, psychomotor performance, flicker fusion frequency and subjective mood (data not shown).
Table 1

Quantitative EEG absolute power density following 14-day multiple dosing with bupropion in 12 healthy subjects (μV2/Hz; median; min–max)

Time (h)




Eyes open

Eyes closed

Eyes open

Eyes closed



3.7 (1.6–8.1)

5.3 (1.7–8.5)*

4.8 (1.5–10.0)

7.7 (1.5–19.0)

Alpha 1

6.2 (1.1–15.6)

5.3 (1.2–27.2)

7.4 (1.2–15.9)

7.1 (1.0–21.3)

Alpha 2

3.3 (1.2–4.9)

3.4 (1.2–7.3)*

3.5 (1.1–5.3)

3.8 (1.6–15.5)



3.7 (1.3–10.1)*

5.9 (1.3–11.3)

4.7 (1.7–11.1)

7.4 (1.3–13.1)

Alpha 1

5.4 (0.8–18.4)*

10.2 (0.7–27.3)

7.5 (1.1–17.0)

7.6 (0.8–17.6)

Alpha 2

3.4 (0.7–5.3)

4.6 (1.0–12.0)

3.8 (1.4–6.1)

3.8 (1.4–23.8)

*p<0.05 vs. placebo

QEEG provides one of the most sensitive pharmacodynamic measures of central drug action, and qEEG power reduction is predictive for a psychostimulant effect as previously described with amphetamine, metamphetamine, methylphenidate and caffeine (Herrmann et al. 1979; Siepmann and Kirch 2002). In the present study, reductions of absolute alpha and theta power density were observed when serum concentrations of bupropion were measured highest. In conclusion, bupropion does not improve nor deteriorate cognitive functions when given to healthy humans subchronically at daily doses of 300 mg, but qEEG changes hint at a subtle psychostimulant drug effect.


The present work was part of a thesis. The authors are sincerely thankful to Mrs. E. Hempel and Mr. J. Handel for their assistance in conducting the study.

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© Springer-Verlag 2005