The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index; 2 of the 26 sources its claims cite were checked for support.
Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis
Open accessAbstract
Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.
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Claims the paper makes
50 Own result · 12 No basis given · 9 No full text of the sources · 8 Own interpretation · 6 Own method · 1 Partly supported · 1 Not supported · 1 Sources not found · 1 Not checked yet · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Currently, atypical antipsychotics are only considered by treatment guidelines as second-or third-line therapy in the management of bipolar depression”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
What the sources say
- Disputedcites Fountoulakis et al. 2007 sourceExperimental — accuracy not yet measured
Table 1 in the Background section lists olanzapine, an atypical antipsychotic, as a first-step treatment for acute bipolar depression under the 2002 TMAP guideline. That contradicts the claim that guidelines consider atypical antipsychotics only as second- or third-line therapy. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects regarding remission also showed a high degree of heterogeneity on global assessment (p=0.0010).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quetiapine and olanzapine trials (3/5, 60 %) demonstrated superiority over placebo (p<0.001).”
- Also stated in: § Assessment of the MADRS scale · boosted
“All quetiapine and olanzapine trials demonstrated significant superiority over placebo at week 8 (i.e.all CIs in the pooled analysis excluded zero).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Assessment of the MADRS scale · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when assessing the estimates within each drug, the heterogeneity was substantially reduced [quetiapine : p=0.803 ; olanzapine : p non-estimable (one study) ; aripiprazole : p=0.813].”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of the MADRS scale
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when assessing the estimates within each drug, the heterogeneity was substantially reduced [quetiapine : p=0.266 ; olanzapine : p non-estimable (one study) ; aripiprazole : p=0.5930].”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects exhibited a high degree of heterogeneity on the global assessment (p=0.013).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of the MADRS scale
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Random-effects analysis were pooled, estimated with an overall effect size of 0.67 (95 % CI 0.45-0.98)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when assessing the estimates within each drug, the heterogeneity was substantially reduced [quetiapine : p=0.119 ; olanzapine : p nonestimable (one study) ; aripiprazole : p=0.415].”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Random-effects analysis were pooled, estimated with an overall effect size (OR 0.66, 95 % CI 0.49-0.89)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects regarding response exhibited a high degree of heterogeneity on the global assessment (p=0.018).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 21
- It may state two separate claims as one. 20
- The quote only partly states this claim. 3
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Atypical antipsychotics have not traditionally been considered as a major option in depression guidelines, unless psychotic features were present during the acute depressive episode”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Introduction
What the sources say
- Not matchedcites APA, 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Grunze et al. 2002 sourceExperimental — accuracy not yet measured
The Recommendations (page unavailable) discuss atypical-antipsychotic augmentation in the context of severe and psychotic depression, while the Conclusions identify a mood stabiliser plus antidepressant as the emerging first-line approach. But the paper does not establish a historical rule across depression guidelines that atypical antipsychotics were a major option only when psychotic features were present; it also notes possible antidepressant effects from atypicals themselves. (LLM, conf=0.80)
- Not matchedcites Yatham et al. 2005b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The aripiprazole trials (Thase et al. 2008) excluded patients with psychotic features and bipolar II patients were only enrolled in the quetiapine studies (32-34 %) ; no trials excluded patients with rapid cycling, which represented 18-40 % of patients in the studies reporting such data”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Included studies
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Medline search identified 15 studies.Only three of these met the inclusion criteria.Two additional studies were identified from a review of meeting proceedings or consultation with study investigators.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, when performing the sensitivity analysis excluding the aripiprazole group, the heterogeneity was smaller (p=0.052), and the pooled OR was 0.51 (95 % CI 0.35-0.74,p<0.001)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further, when performing the sensitivity analysis excluding the aripiprazole group, the heterogeneity was smaller (p=0.1280), and the pooled OR was 0.55 (95 % CI 0.41-0.74,p<0.001)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of response and remission
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A total of five studies were included.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The overall mean estimate was x3.91 (95 % CI x5.55 to x2.26, p<0.001).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of the MADRS scale
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, when performing the sensitivity analysis excluding the aripiprazole group, the heterogeneity was then negligible (p=0.302), and the pooled mean was x4.90 (95 % CI x6.21 to x3.59, p<0.001)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Assessment of the MADRS scale
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The baseline depression scores were similar in all the studies with moderate to severely depressed patients at inclusion (score range from 28.49 to 32.6).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All of the atypical antipsychotics demonstrated significant efficacy from week 1 and throughout the first 6 wk, which was the time with the maximal effect size reported by all of the studies.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Pooled data for each antipsychotic by week
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only 2/5 (40 %) (both aripiprazole trials) failed in”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In fact, weight gain associated to quetiapine administration was mild and dose-related, with <9 % of patients gaining o7% from baseline as a clinical meaningfully measurement.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The studies also differed in whether they included rapid-cycling patients or those in mixed states and also in the proportion of bipolar I or II patients with psychotic features.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The olanzapine adverse-event profile was consistent with previously reported findings whereas the OFC profile was similar to that of olanzapine, except for higher rates of nausea and diarrhoea.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“except for aripiprazole trials which have shown a 6-wk limited superiority compared to placebo, decreasing its effect size at endpoint (Thase et al. 2008).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
What the sources say
- Not checked — no full text of the sourcecites Thase et al. 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The superiority of quetiapine and olanzapine monotherapy by week is emphasized by higher response and remission rates and, except for aripiprazole, lower drop-out rates due to adverse events.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The studies also differed in whether they included rapid-cycling patients or those in mixed states and also in the proportion of bipolar I or II patients with psychotic features.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most common adverse effects reported in y30 % of patients were not severe, mostly somnolence and sedation leading to withdrawal from the study, with most discontinuations occurring within the first week.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The olanzapine adverse-event profile was consistent with previously reported findings whereas the OFC profile was similar to that of olanzapine, except for higher rates of nausea and diarrhoea.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The homogeneity across the trials' design and also in their study sample characteristics were the rule.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, atypical antipsychotics, are generally classified as a class, despite their marked differences in pharmacodynamic properties”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Introduction
What the sources say
- Not checked — no full text of the sourcecites Brugue & Vieta, 2007 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Currently available data suggest that combining atypical antipsychotics and mood stabilizers is the most efficacious treatment in acute mania, reinforced after a systematic review and meta-analysis of pooled data conducted by Perlis and Scherk”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Introduction
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Abstract
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Meta-analytical procedures allow us to answer questions about overall magnitude of effect and relative effect by week with greater statistical power than individual trials.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder.”
- Also stated in: § Introduction · boosted
“Randomized, placebo-controlled trials (RCTs) have demonstrated efficacy for atypical antipsychotics in the treatment of acute mania in bipolar disorder, either as monotherapy or adjunctive treatment”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Abstract
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Introduction · boosted
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“while evidence suggests some atypical antipsychotics may have antidepressant (Yatham et al. 2005a) and stabilizing effects (Vieta et al. 2008a).”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Introduction
What the sources say
- Not matchedcites Yatham et al. 2005a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Vieta et al. 2008a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To avoid publication bias, we checked the web (www. clinicaltrials.gov)and contacted all industry sponsors for finalized studies.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results raise questions on the current approach by most treatment guidelines and on the potential mechanism of the action involved in the improvement of depressive symptoms in bipolar depression by means of drugs traditionally considered as antipsychotics.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In the only olanzapine trial which included an olanzapinefluoxetine combination (OFC) treatment, we only considered the olanzapine monotherapy arm for the analysis in order to obtain homogeneous comparative results.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Data analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Bipolar disorders present initially with a depressive episode in >50 % of patients, which is considered the major burden of bipolar disorder in terms of disability and suicide risk”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since it was considered likely a priori that not all trials would produce exactly equal underlying effect sizes, a random-effects model was considered preferable to a fixed-effects models.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Data analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The question of their class effect seems to be answered positively regarding its early onset of action but with differences in the magnitude and maintenance of effect.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This fact suggests one potential reason for failed results in the aripiprazole trials (tolerability issues, especially akathisia perhaps related to dosing), leading to drop-outs and also related to differences in its mechanism of action such as too high D 2 affinity and low H 1 affinity compared to quetiapine and olanzapine.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We also performed a sensitivity analysis to assess the source of heterogeneity by excluding the aripiprazole studies, as they were negative on the primary outcome.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Data analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The very early onset of action of all tested atypical antipsychotics in the treatment of bipolar depression, even as monotherapy, may highlight an overlapping mechanism of action of these drugs as a potential class effect with independence of the monoaminergic pathways.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary our results suggest some atypical antipsychotics (quetiapine and olanzapine) may be considered as a first-line management option in acute bipolar I and/or II depression, even for poor responder subgroups such as rapid cyclers and patients with psychotic features.”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Study
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
No published systematic reviews or meta-analyses evaluating the efficacy of modern atypical antipsychotics in bipolar depression existed at the time of the study.
“Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression.”
“meta-analyses addressing the efficacy and effectiveness of atypical antipsychotics in bipolar depression are lacking.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Abstract
“Data were combined through meta-analysis using risk ratio as an effect size with a 95 % confidence interval (95 % CI)”
§ Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis > Data analysis
“The between-treatment comparisons were estimated by means of the odds ratio (OR) and 95 % confidence intervals (95 % CI) for the binary variables (remission and response)”
Citations
Cites
Journal of Clinical Psychiatry
(2018) · Journal of Clinical Psychiatry · doi:10.5505/kpd · Cited by 13,703
Extending Indications for Long-Term Pharmacotherapy: Opportunities and Challenges
Kane, J. M. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.1.1 · Cited by 989
Tohen, M., Vieta, E., Calabrese, J., Ketter, T. A., Sachs, G., Bowden, C., Mitchell, P. B., Centorrino, F., Risser, R., Baker, R. W., et al. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.11.1079 · Cited by 908
Self-citationCalabrese, J. R., Keck, P. E., Macfadden, W., Minkwitz, M., Ketter, T. A., Weisler, R. H., Cutler, A. J., McCoy, R., Wilson, E., Mullen, J., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.7.1351 · Cited by 883
Olanzapine versus placebo in the treatment of acute mania
Tohen, M., Sanger, T. M., McElroy, S. L., Tollefson, G. D., Chengappa, K. N. R., Daniel, D. G., Petty, F., Centorrino, F., Wang, R., Grundy, S. L., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.5.702 · Cited by 585
Thase, M. E., Macfadden, W., Weisler, R. H., Chang, W., Paulsson, B., Khan, A., & Calabrese, J. R. (2006) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000248603.76231.b7 · Cited by 559
Efficacy of Olanzapine in Acute Bipolar Mania A Double-blind, Placebo-Controlled Study
Tohen, M. F. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.9.841 · Cited by 539
Keck, P. E., Marcus, R. N., Tourkodimitris, S., Ali, M. W., Liebeskind, A., Saha, A. R., Ingenito, G. G., & Aripiprazole Study Group (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.9.1651 · Cited by 501
Bauer, M., Bschor, T., Pfennig, A., Whybrow, P. C., Angst, J., Versiani, M., Möller, H., & WFSBP Task Force on Unipolar Depres (2007) · The World Journal of Biological Psychiatry · doi:10.1080/15622970701227829 · Cited by 483
Tohen, M. F., Chengappa, K. N. R., Suppes, T. M., Zarate, C. A., Calabrese, J. R., Bowden, C. L., Sachs, G. S., Kupfer, D. J., Baker, R. W., Risser, R. C., et al. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.1.62 · Cited by 464
Research works printed but not linked: 1
- Vieta, Journal of Psychopharmacology
Cited by
Sorted by citations
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Beaulieu, S., Alda, M., O’Donovan, C., MacQUEEN, G. M., McIntyre, R. S., Sharma, V., et al. (2012) · Bipolar Disorders · doi:10.1111/bdi.12025 · Cited by 1,230
“Several meta-analyses have assessed the efficacy of atypical antipsychotic agents and other medications for the treatment of bipolar depression (81, 82).”
BackgroundAngst, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.87 · Cited by 414
“We chose 15 characteristics known to be associated with a diagnosis of bipolar disorder.(13,17,23-28) Each item was required to assess avariable relatively independentof all others.”
BackgroundMethodDurgam, S., Earley, W., Lipschitz, A., Guo, H., Laszlovszky, I., Németh, G., Vieta, E., Calabrese, J. R., & Yatham, L. N. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020164 · Cited by 209
Self-citationOstacher, M. J., Ng‐Mak, D., Patel, P., Ntais, D., Schlueter, M., & Loebel, A. D. (2017) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1285050 · Cited by 201
“…examined acute treatments for bipolar depression, and also reported that quetiapine and olanzapine were significantly more efficacious than placebo (Cruz et al. 2010; Vieta et al. 2010), while aripiprazole (Cruz et al. 2010; Vieta et al. 2010; NICE 2014; Taylor et al. 2014; Franklin et al. 2015)…”
BackgroundResultInfluentialBipolar Depression: Overview and Commentary
Baldessarini, R. J., Vieta, E., Calabrese, J. R., Tohen, M. F., & Bowden, C. L. (2010) · Harvard Review of Psychiatry · doi:10.3109/10673221003747955 · Cited by 161
Self-citation
Metadata
- Authors
- Cruz, N., Sanchez-Moreno, J., Torres, F., Goikolea, J. M., Valentí, M., & Vieta, E.
- Affiliations
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Harvard University (US)
- Corresponding author
- Vieta, Eduard
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-29
- Volume
- 13
- Issue
- 01
- Pages
- 5
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2142698669
- Cited by
- 121
- References
- 45
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 12 · 2013: 17 · 2012: 15
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, public-domain)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red de Salud Mental
- Servier
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar depression, atypical antipsychotics, quetiapine, olanzapine, aripiprazole, antipsychotic monotherapy, antidepressant combination therapy, rapid onset of action, Montgomery-Asberg Depression Rating Scale
- MeSH terms
- Aripiprazole, Quetiapine Fumarate, Olanzapine, Antidepressive Agents, Benzodiazepines, Bipolar Disorder, Dibenzothiazepines, Drug Combinations, Drug Therapy, Combination, Fluoxetine, Humans, Piperazines, Placebos, Antipsychotic Agents, Quinolones, Randomized Controlled Trials as Topic, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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