On 2017 Apr 12, Konstantinos Fountoulakis commented:

None

On 2017 Apr 12, Konstantinos Fountoulakis commented:

This is a study on 70 patients suggesting that depressed people exposed to high early life stress (ELS) had a greater likelihood of remission when their amygdala showed hyperreactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, amygdala hyporeactivity to both rewarding and threat-related stimuli predicted remission (1) The main problem with this study is that the data are uncontrolled. It is important to note that depressed patients have a high placebo response rate (up to 40%) in the short term (2) We also know that acute response to placebo is equal to up to 80% or more to the response to active drugs (3, 4), meaning that if we accept the additivity hypothesis (this is of course a matter of debate) (5, 6), most patient who acutely responded to active drug might be in reality placebo responders. Therefore the results of the study under discussion should not be accepted without caution. Adding to the above concerns is the report the STAR-D study, that one third of patients who remitted after step 1 will relapse within 4-5 months, while up to 50% will relapse from later steps (7). It is unknown what these patients stand for, however one could argue that at least some of them are patients unresponsive to antidepressants who however manifested a placebo response. Additional problems are that the patients included had low depression severity (mean HDRS=21) and low dosages of antidepressants used (on average 10 mg of escitalopram, 50-62.5 mg of sertraline and 87.5-90.8 mg of venlafaxine). Also, of prime importance is that the determining of early life stress (ELF) with the use of a self-report questionnaire alone could be misleading, since many depressed patients especially with character pathology might tend to over-report such events.<br> These problems exist mainly because the study under discussion tries to elucidate an issue concerning a mechanism of action without using an adequately controlling methodology. What that study suggests is that patients who acutely remit (no matter the reason) might present with the characteristics reported, but any inference concerning the role of pharmacotherapy per se is problematic.

References

1. Goldstein-Piekarski A, et al. (2016) Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. PNAS.
2. Furukawa TA, et al. (2016) Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies. The lancet. Psychiatry.
3. Khan A, Leventhal RM, Khan SR, & Brown WA (2002) Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. Journal of clinical psychopharmacology 22(1):40-45.
4. Gibbons RD, Hur K, Brown CH, Davis JM, & Mann JJ (2012) Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Archives of general psychiatry 69(6):572-579.
5. Yang H, Novick SJ, & Zhao W (2015) Testing drug additivity based on monotherapies. Pharmaceutical statistics 14(4):332-340.
6. Lund K, Vase L, Petersen GL, Jensen TS, & Finnerup NB (2014) Randomised controlled trials may underestimate drug effects: balanced placebo trial design. PloS one 9(1):e84104.
7. Rush AJ, et al. (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American journal of psychiatry 163(11):1905-1917.

On 2017 Apr 12, Konstantinos Fountoulakis commented:

This is a study on 70 patients suggesting that depressed people exposed to high early life stress (ELS) had a greater likelihood of remission when their amygdala showed hyperreactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, amygdala hyporeactivity to both rewarding and threat-related stimuli predicted remission (1) The main problem with this study is that the data are uncontrolled. It is important to note that depressed patients have a high placebo response rate (up to 40%) in the short term (2) We also know that acute response to placebo is equal to up to 80% or more to the response to active drugs (3, 4), meaning that if we accept the additivity hypothesis (this is of course a matter of debate) (5, 6), most patient who acutely responded to active drug might be in reality placebo responders. Therefore the results of the study under discussion should not be accepted without caution. Adding to the above concerns is the report the STAR-D study, that one third of patients who remitted after step 1 will relapse within 4-5 months, while up to 50% will relapse from later steps (7). It is unknown what these patients stand for, however one could argue that at least some of them are patients unresponsive to antidepressants who however manifested a placebo response. Additional problems are that the patients included had low depression severity (mean HDRS=21) and low dosages of antidepressants used (on average 10 mg of escitalopram, 50-62.5 mg of sertraline and 87.5-90.8 mg of venlafaxine). Also, of prime importance is that the determining of early life stress (ELF) with the use of a self-report questionnaire alone could be misleading, since many depressed patients especially with character pathology might tend to over-report such events.<br> These problems exist mainly because the study under discussion tries to elucidate an issue concerning a mechanism of action without using an adequately controlling methodology. What that study suggests is that patients who acutely remit (no matter the reason) might present with the characteristics reported, but any inference concerning the role of pharmacotherapy per se is problematic.

References

1. Goldstein-Piekarski A, et al. (2016) Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. PNAS.
2. Furukawa TA, et al. (2016) Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies. The lancet. Psychiatry.
3. Khan A, Leventhal RM, Khan SR, & Brown WA (2002) Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. Journal of clinical psychopharmacology 22(1):40-45.
4. Gibbons RD, Hur K, Brown CH, Davis JM, & Mann JJ (2012) Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Archives of general psychiatry 69(6):572-579.
5. Yang H, Novick SJ, & Zhao W (2015) Testing drug additivity based on monotherapies. Pharmaceutical statistics 14(4):332-340.
6. Lund K, Vase L, Petersen GL, Jensen TS, & Finnerup NB (2014) Randomised controlled trials may underestimate drug effects: balanced placebo trial design. PloS one 9(1):e84104.
7. Rush AJ, et al. (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American journal of psychiatry 163(11):1905-1917.

On 2017 Apr 12, Konstantinos Fountoulakis commented:

None