Elsevier

Biological Psychiatry

Volume 57, Issue 3, 1 February 2005, Pages 220-228
Biological Psychiatry

Original articles
Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression

https://doi.org/10.1016/j.biopsych.2004.10.033Get rights and content

Background

Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy.

Methods

Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans. For each medication PET data from patients compared with control subjects was analyzed as a function of treatment response (defined as moderate to marked improvement on the Clinical Global Impression Scale).

Results

Treatment response rates were similar for buproprion (32%) and venlafaxine (33%). Compared with control subjects, responders but not nonresponders, to both drugs demonstrated frontal and left temporal hypometabolism. Selectively, compared with control subjects bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders (n = 7) showed bilateral temporal and basal ganglia hypometabolism.

Conclusions

These data suggest that pretreatment frontal and left temporal hypometabolism in never-hospitalized depressed outpatients compared with control subjects is linked to positive antidepressant response and that additional alterations in regional metabolism may be linked to differential responsivity to bupropion and venlafaxine monotherapy.

Section snippets

Subjects

Through local newspaper advertisements in the Washington, D.C., metropolitan area, the study recruited 23 outpatients with unipolar depression (11 women, 12 men; mean age 46.3 ± 12.9 SD) and no history of psychiatric hospitalization and 20 healthy control subjects (11 women, 9 men; mean age 46.6 ± 13.1 SD) without personal or first-degree relative history of psychiatric illness. After a complete description and discussion of the study including the possible risks and benefits of participation,

Clinical data

Of 23 patients, 17 were crossed over to the other drug (phase 2) because of suboptimal treatment response or side effects on the first treatment phase (phase 1). Based on CGI determinations, overall treatment responses (defined as moderate to marked improvement) were similar for buproprion (32%) and venlafaxine (33%). With bupropion 25% of patients responded in phase 1, and 43% of patients responded in phase 2. With venlafaxine 36% of patients responded in phase 1 and 30% of patients responded

Discussion

Among 20 never-hospitalized outpatients with unipolar depression compared with control subjects, responders but not nonresponders to monotherapy with either bupropion or venlafaxine showed baseline bilateral frontal and left temporal hypometabolism. Selectively, only bupropion responders also showed cerebellar hypermetabolism, whereas only venlafaxine responders additionally showed right temporal and basal ganglia hypometabolism. To our knowledge, this is the first functional brain imaging

References (51)

  • G.S. Leverich et al.

    The Stanley Foundation Bipolar Treatment Outcome Network: I. Longitudinal methodology

    J Affect Disord

    (2001)
  • J.T. Little et al.

    Venlafaxine but not bupropion decreases cerebrospinal fluid 5-hydroxyindoleacetic acid in unipolar depression

    Biol Psychiatry

    (1999)
  • E.A. Osuch et al.

    Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder

    Biol Psychiatry

    (2001)
  • J.D. Schmahmann et al.

    Cerebellar cognitive affective syndrome

    Int Rev Neurobiol

    (1997)
  • M.E. Schmidt et al.

    Gender differences in brain metabolic and plasma catecholamine responses to alpha2-adrenoceptor blockade

    Neuropsychopharmacology

    (1997)
  • M.K. Spearing et al.

    Modification of the clinical global impressions (CGI) scale for use in bipolar illness (BP)The CGI-BP

    Psychiatry Res

    (1997)
  • A.M. Speer et al.

    Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients

    Biol Psychiatry

    (2000)
  • J.A. Sweeney et al.

    Prefrontal and cerebellar abnormalities in major depressionevidence from oculomotor studies

    Biol Psychiatry

    (1998)
  • W.W. Zung

    A rating instrument for anxiety disorders

    Psychosomatics

    (1971)
  • Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • A. Anand et al.

    Norepinephrine dysfunction in depression

    J Clin Psychiatry

    (2000)
  • J.A. Ascher et al.

    BupropionA review of its mechanism of antidepressant activity

    J Clin Psychiatry

    (1995)
  • J.J. Bartko et al.

    On the methods and theory of reliability

    J Nerv Ment Dis

    (1976)
  • A.T. Beck et al.

    An inventory for measuring depression

    Arch Gen Psychiatry

    (1961)
  • R.A. Brooks

    Alternate formula for glucose utilization using labeled deoxyglucose

    J Nucl Med

    (1982)
  • Cited by (84)

    • How brain single photon emission computed topography imaging informs the diagnosis and treatment of mood disorders

      2021, The Neuroscience of Depression: Genetics, Cell Biology, Neurology, Behavior, and Diet
    • Measuring brain glucose metabolism in order to predict response to antidepressant or placebo: A randomized clinical trial

      2021, NeuroImage: Clinical
      Citation Excerpt :

      We hypothesize that the predictive insula metabolism signal in the SSRI group determined in McGrath et al 2013 will be enhanced through application of dynamic PET imaging technique with blood as a reference. In combination with results from previous FDG-PET investigations, we also hypothesize that pretreatment MRGlu in the left vPFC (Buchsbaum et al., 1997; Little et al., 2005; Mayberg et al., 1997) and the RN (Milak et al., 2009) will be associated with post-treatment depression severity decrease (referred to as prediction study). While these regions were primarily chosen because of the confluence of data from previous studies indicating their predictive potential, there is also evidence to suggest that these regions are biologically relevant to depression severity decrease.

    View all citing articles on Scopus
    View full text