Antidepressant augmentation: Good news, limitations, and stumbling blocks

Classified as probably not a substantial claim.

It is unclear whether any of the 45 studies in Zhou et al.'s efficacy analysis focused on partial responders to an initial agent.

“Strikingly, it is unclear to me whether any of the 45 studies included in the efficacy analysis of the current article focused on partial responders to an initial agent, which, according to expert consensus, should be the target population for augmentation studies.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The available copy contains a repository record (no section or page), not the study methods or efficacy analysis. Searches for the 45-study count, partial responders, and inclusion criteria found no passage that establishes whether any included study focused on partial responders. The copy therefore cannot verify the citing author's stated uncertainty. (LLM, conf=0.74)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Zhou et al.'s analysis covered only pharmacologic augmentation and excluded psychotherapy and neuromodulation.

“The analysis is restricted to pharmacologic approaches and does not deal with psychotherapy or neuromodulation options for augmentation.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The available indexed passage is a title and repository page text, with no methods or eligibility criteria. Searches for pharmacologic augmentation, psychotherapy, and neuromodulation found no passage establishing which approaches the analysis included or excluded. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Zhou et al. identified bipolar spectrum disorder, family history of bipolar disorder, rejection sensitivity, nonpsychotic paranoia, and low-normal thyroid hormone level as important potential moderators of augmentation response.

“I absolutely agree with the potential moderators they have identified in the discussion as important-bipolar spectrum disorder, family history of bipolar disorder, rejection sensitivity, nonpsychotic paranoia, and thyroid hormone level in the low-normal range.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The supplied passage is a repository listing, not the paper’s Discussion, and has no section or page number. Searches for the named moderators, including bipolar-spectrum features, rejection sensitivity, and low-normal thyroid hormone, found no relevant passage in our copy, so it cannot verify what Zhou et al. identified. (LLM, conf=0.77)

  Experimental — accuracy not yet measured

May combine two claims.

Applying Thase and Rush staging to the 48 eligible TRD trials, Zhou et al. found 35 trials with stage I or greater, 12 with stage II or greater, and 1 with stage III or greater.

“Using the criteria developed by Thase and Rush 5 for staging treatment resistance in the 48 eligible trials of participants with treatment-resistant depression (TRD), Zhou and colleagues 1 found 35 trials with TRD patients of stage I or greater, 12 trials of stage II or greater, and 1 trial of stage III or greater.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The available passage (unlabeled repository page, no page number) contains the paper’s title and site navigation, not its trial results. Searches for Thase and Rush, 48 eligible trials, and the stage counts found no passage addressing the claim, so the counts cannot be checked against our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [5]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

In the reviewed evidence, buspirone, bupropion, and methylphenidate each had at least one adequately powered trial that failed to show efficacy as augmentation.

“Noteworthy among the failures having at least 1 adequately powered trial were buspirone, bupropion, and methylphenidate.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The available copy contains an IRIS repository listing and a link to a PDF, but no passage from the paper’s findings. Searches for the three agents, trial power, and augmentation efficacy returned no relevant passage, so the claim cannot be checked against this copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Zhou and colleagues conducted a review and analysis of global evidence on how well and how acceptably drugs work when added to antidepressants for treatment-resistant unipolar major depression.

“D r Zhou and colleagues 1 have done an excellent job of reviewing and analyzing the world's literature on the efficacy and tolerability of pharmacologic agents used to augment antidepressants in treatment-resistant unipolar major depression.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourcePartly supported

  The indexed title identifies the work as a systematic review and network meta-analysis of augmentation agents in treatment-resistant depression, comparing efficacy, acceptability, and tolerability. The available copy contains only a title and webpage navigation; it does not establish the claim's narrower description of pharmacologic agents added to antidepressants for unipolar major depression or the scope of the literature reviewed. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

In Zhou et al.'s analysis, four augmentation agents showed significant response efficacy and six showed significant remission efficacy compared with placebo.

“The good news is that several agents were found to have significant efficacy in terms of response (4 agents) and remission (6 agents) in comparison to placebo.”

• Also stated in: § The Problem of Differential Moderators of Response · hedged

  “The results reported by Zhou et al 1 found least 4 agents based on response rates and 6 agents based on remission rates that had better results than placebo, but they had a lack of data to study potential moderators of response.”

• cites [1] 1. Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-e498. sourceCould not verify

  The available copy is an IRIS repository listing, not the paper’s results; it contains no response or remission findings. Searches for the reported counts and for significant efficacy versus placebo returned no relevant passage, so the claim cannot be checked against this copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

The APA Practice Guideline identified anxiety as a potential moderator for buspirone and fatigue/hypersomnolence for modafinil.

“The Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition, 6 identified other potential moderators, such as anxiety (buspirone) or fatigue and hypersomnolence (modafinil).”

• cites [6]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

In STAR*D phase I, citalopram nonremitters who were intolerant or less responsive were more likely to choose a medication switch, while those with some improvement were more likely to choose augmentation randomization.

“Nonremitters to citalopram in phase I of STAR*D were more likely to choose a switch of medication if they were either intolerant or less responsive, whereas those who had some improvement in phase I were more likely to choose to be randomized to augmentation.”

• cites [3] 3. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. Am J Psychiatry. 2010;167(suppl):1-152.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [4]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

STAR*D's decisions used equipoise randomization (patient choice) and were not blinded or randomized, so they did not provide a true prospective test of the recommendations' validity.

“Unfortunately, these decisions were based on equipoise randomization (patient choice) and were not blinded or randomized, so they did not provide a true prospective test of the validity of the recommendations.”

• cites [3] 3. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. Am J Psychiatry. 2010;167(suppl):1-152.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [4]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

According to expert consensus, partial responders to an initial antidepressant are the target population for augmentation studies.

“which, according to expert consensus, should be the target population for augmentation studies.”

• cites [2] 2. Crismon ML, Trivedi MH, Pigott TA, et al. The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder. J Clin Psychiatry. 1999;60(3):142-156. d o i : 1 0 . 4 0 8 8 / J C P . v 6 0 n 0 3 0 2 P u b M e d 3. Trivedi MH, Fava M, Wisniewski SR, et al; STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243-1252. d o i : 1 0 . 1 0 5 6 / N E J M o a 0 5 2 9 6 4 P u b M e d 4. Rush AJ, Trivedi MH, Wisniewski SR, et al; STAR*D Study Team. Bupropion- SR, sertra sourceNot checked — no full text of the source

May combine two claims.

1990s expert consensus guidelines, such as the Texas Medication Algorithm Project, recommended adding a second agent for partial responders and switching antidepressants for nonresponders.

“Expert consensus guidelines developed in the 1990s, such as the Texas Medication Algorithm Project, 2 recommended augmentation with a second agent for partial responders and switching to a new antidepressant for nonresponders.”

• cites [2] 2. Crismon ML, Trivedi MH, Pigott TA, et al. The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder. J Clin Psychiatry. 1999;60(3):142-156. d o i : 1 0 . 4 0 8 8 / J C P . v 6 0 n 0 3 0 2 P u b M e d 3. Trivedi MH, Fava M, Wisniewski SR, et al; STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243-1252. d o i : 1 0 . 1 0 5 6 / N E J M o a 0 5 2 9 6 4 P u b M e d 4. Rush AJ, Trivedi MH, Wisniewski SR, et al; STAR*D Study Team. Bupropion- SR, sertra sourceNot checked — no full text of the source