G I Papakostas


Affiliation: Massachusetts General Hospital
Country: USA


  1. Papakostas G, Stahl S, Krishen A, Seifert C, Tucker V, Goodale E, et al. Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression): a pooled analysis of 10 studies. J Clin Psychiatry. 2008;69:1287-92 pubmed
    ..Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety. ..
  2. Papakostas G, Miller K, Petersen T, Sklarsky K, Hilliker S, Klibanski A, et al. Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine. J Clin Psychiatry. 2006;67:952-7 pubmed
    ..05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment. ..
  3. Papakostas G, Johe K, Hand H, Drouillard A, Russo P, Kay G, et al. A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. Mol Psychiatry. 2019;: pubmed publisher
    ..Both doses were well tolerated. These findings replicate those of phase 1b study, and warrant further exploration of the antidepressant and pro-cognitive effects of NSI-189. ..
  4. Papakostas G, Petersen T, Homberger C, Green C, Smith J, Alpert J, et al. Hopelessness as a predictor of non-response to fluoxetine in major depressive disorder. Ann Clin Psychiatry. 2007;19:5-8 pubmed
    ..Similar studies involving treatment with higher doses of fluoxetine and for greater duration as well as a placebo comparator arm are needed to further explore the relationship between hopelessness, placebo response and drug response. ..
  5. Papakostas G, Østergaard S, Iovieno N. The nature of placebo response in clinical studies of major depressive disorder. J Clin Psychiatry. 2015;76:456-66 pubmed publisher
    ..Several elements have emerged that seem to play a critical role in trial success, gradually reshaping the design of clinical, translational, as well as mechanistic studies in depression. ..
  6. Papakostas G, Fan H, Tedeschini E. Severe and anxious depression: combining definitions of clinical sub-types to identify patients differentially responsive to selective serotonin reuptake inhibitors. Eur Neuropsychopharmacol. 2012;22:347-55 pubmed publisher
    ..These findings are preliminary, of yet undetermined clinical relevance, and warrant replication and further exploration. ..
  7. Papakostas G, Chuzi S, Sousa J, Fava M. 5HT1A-mediated stimulation of cortisol release in major depression: use of non-invasive cortisol measurements to predict clinical response. Eur Arch Psychiatry Clin Neurosci. 2010;260:175-80 pubmed publisher
    ..Although the 5HT1A-desensitization hypothesis is still a valid one, the results of the present study could not provide any evidence in support. ..
  8. Papakostas G, Ionescu D. Updates and trends in the treatment of major depressive disorder. J Clin Psychiatry. 2014;75:1419-21 pubmed publisher
  9. Papakostas G, Shelton R, Zajecka J, Etemad B, Rickels K, Clain A, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012;169:1267-74 pubmed publisher
    ..Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs. ..

More Information


  1. Papakostas G, Charles D, Fava M. Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies in major depressive disorder. World J Biol Psychiatry. 2010;11:300-7 pubmed publisher
    ..Developing treatment strategies allowing clinicians to deliver higher initial SSRI doses while enhancing the tolerability of treatment may represent an alternative approach to improving the efficacy of treatment of MDD. ..
  2. Papakostas G. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009;70 Suppl 6:16-25 pubmed publisher
  3. Papakostas G, Petersen T, Iosifescu D, Burns A, Nierenberg A, Alpert J, et al. Obesity among outpatients with major depressive disorder. Int J Neuropsychopharmacol. 2005;8:59-63 pubmed
    ..Greater relative body weight, but not obesity, predicted non-response. In conclusion, greater relative body weight was found to place MDD outpatients at risk for fluoxetine resistance. ..
  4. Papakostas G, Petersen T, Denninger J, Tossani E, Pava J, Alpert J, et al. Psychosocial functioning during the treatment of major depressive disorder with fluoxetine. J Clin Psychopharmacol. 2004;24:507-11 pubmed
  5. Papakostas G, Petersen T, Farabaugh A, Murakami J, Pava J, Alpert J, et al. Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder. J Clin Psychiatry. 2003;64:1357-61 pubmed
    ..The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with nortriptyline. ..
  6. Papakostas G, Petersen T, Iosifescu D, Roffi P, Alpert J, Rosenbaum J, et al. Axis III disorders in treatment-resistant major depressive disorder. Psychiatry Res. 2003;118:183-8 pubmed
    ..Thus, the present results cannot be generalized to such populations. ..
  7. Papakostas G, Fava M. A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Eur Psychiatry. 2007;22:444-7 pubmed
  8. Papakostas G. Tolerability of modern antidepressants. J Clin Psychiatry. 2008;69 Suppl E1:8-13 pubmed
  9. Papakostas G, Petersen T, Sonawalla S, Merens W, Iosifescu D, Alpert J, et al. Serum cholesterol in treatment-resistant depression. Neuropsychobiology. 2003;47:146-51 pubmed
    ..The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD. ..
  10. Papakostas G, Nutt D, Hallett L, Tucker V, Krishen A, Fava M. Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry. 2006;60:1350-5 pubmed
    ..Although preliminary, these results warrant prospectively designed studies examining potential differences between bupropion and the SSRIs on these specific depressive symptoms. ..
  11. Papakostas G, Petersen T, Burns A, Fava M. Adjunctive atomoxetine for residual fatigue in major depressive disorder. J Psychiatr Res. 2006;40:370-3 pubmed
    ..Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD. ..
  12. Papakostas G, Nielsen R, Dragheim M, Tonnoir B. Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response. J Psychiatr Res. 2018;101:72-79 pubmed publisher
    ..This study has the ClinicalTrials.gov identifier NCT01488071. ..
  13. Papakostas G, Mischoulon D, Shyu I, Alpert J, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167:942-8 pubmed publisher
    ..1% versus 11.7%, respectively). These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication. ..
  14. Papakostas G. Identifying patients with depression who require a change in treatment and implementing that change. J Clin Psychiatry. 2016;77 Suppl 1:16-21 pubmed publisher
    ..Timely and appropriate treatment adjustment is necessary to help patients with MDD achieve recovery. ..
  15. Papakostas G, Martinson M, Fava M, Iovieno N. Demographic variables, design characteristics, and effect sizes of randomized, placebo-controlled, monotherapy trials of major depressive disorder and bipolar depression. J Clin Psychiatry. 2016;77:e619-24 pubmed publisher
    ..Therefore, the present study suggests no clinically significant differences in the overall short-term efficacy of pharmacologic monotherapies for MDD and bipolar depression. ..
  16. Papakostas G, Cassiello C, Iovieno N. Folates and S-adenosylmethionine for major depressive disorder. Can J Psychiatry. 2012;57:406-13 pubmed
    ..Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium. ..
  17. Papakostas G, Fava M. A metaanalysis of clinical trials comparing moclobemide with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Can J Psychiatry. 2006;51:783-90 pubmed