BioMed Research International / 2017 / Article / Tab 2

Review Article

Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews

Table 2

Essential overview of the results. Overall, higher scores and letter grades would indicate more reliable content and related conclusions/perspectives/recommendations for future studies and unmet needs to be addressed. Scoring method detailed elsewhere [44].

Author, year
of publication
Country of origin (leading author)Information about the sample or coved original studies if multiple data sourcesN of covered original (RCT studies, other design)Results drawn based on the accounted evidence/adopted procedures for revision. Main conclusions and perspectives recommended by the authorsMajor biases (e.g., sponsorship bias) detected according to the R- AMSTAR methodologyScore of each 1 to 11 item assessed by R-AMSTARR-AMSTAR TOTAL SCORE
(raw)
Rank (grade letter) based on percentile of the given study

(McIntyre et al., 2013)CanadaBD-I depression; monotherapy: acute phase
1 RCT [23]FDA-approved agents should be prioritized over not (yet?) approved options. […“ Lurasidone has minimal propensity to weight gain and appears metabolically neutral, which would will be a significant advantage.”]Although systematic in nature, most of the core procedures recommended for systematic review were not documented or implemented. Covered SGAs, including lurasidone, focused only on RCT leading to FDA approval, raising concerns for selection and publication biasesI = 1
II = 1
III = 2
IV = 2
V = 1
VI = 1
VII = 3
VIII = 3
IX = 1
X = 1
XI = 2
Total score = 18
Percentile in the present set = 8.3
Quartile-derived grade letter = D

(McIntyre et al., 2012)CanadaThe review focused on the pharmacodynamics and pharmacokinetics of lurasidone rather than original RCTsStudies involving bipolar cases were underway at time of writingLurasidone would introduce simplicity of use and favorable metabolic advantages relative to several other SGAs. Outcomes in cognitive data analyses are awaited to determine if there is a key difference between lurasidone and other SGAs with respect to efficacyPublication bias with respect to RCT trials (indeed, beyond the scopes of the review)I = 1
II = 1
III = 2
IV = 2
V = 1
VI = 3
VII = 2
VIII = 3
IX = 2
X = 1
XI = 1
Total score = 19
Percentile in the present set = 16.7
Quartile-derived grade letter = D

(Franklin et al. 2015)USAThe review focused on the pharmacodynamics and pharmacokinetics
Two acute phase trials (mono- and adjunctive therapy, resp.) [23, 24]Lurasidone acts as high affinity D2 and 5-HT2A antagonist. Lurasidone, however, has somehow uniquely bind with high affinity with 5-HT7 compared to other SGAs. Lurasidone also acts as 5-HT1A partial agonist.
Lurasidone is best absorbed with 350 Kcal of food and is metabolized by CYP34A
Lack of assessment of maintenance preliminary data (publication bias)I = 1
II = 1
III = 1
IV = 1
V = 1
VI = 3
VII = 2
VIII = 3
IX = 2
X = 2
XI = 3
Total score = 20
Percentile in the present set = 25
Quartile-derived grade letter = C

(Citrome 2013)USAThe review is well-grounded with regard do evidence-based methodology and cover a broad number of SGA drugs. The review focuses on the pharmacology, efficacy and tolerability profile of lurasidone and other SGAsTwo acute phase trials (mono- and adjunctive therapy resp.) [23, 24].Although encouraging, the NNT and NNH computed about lurasidone for the acute treatment of BD-I would need additional primary research data to pool in order to allow more firm conclusionsSearch strategy and selection of the not documented in full. This is with special reference to PICO/PIPO research questionsI = 1
II = 2
III = 4
IV = 2
V = 2
VI = 3
VII = 3
VIII = 3
IX = 3
X = 3
XI = 3
Total score = 29
Percentile in the present set = 58.3
Quartile-derived grade letter = A

(De Hert et al., 2012) [46]BelgiumThe review focuses on the effects of lurasidone (and asenapine, iloperidone and paliperidone) on body weight and metabolic adverse effects in both schizophrenia and BD patientsNo RCT leading to FDA approval (extension) covered in the present piece of workBased on the evidence available at writing time, lurasidone metabolic effects would resemble those of aripiprazole, amisulpride and ziprasidone closer than the other SGAs assessed in the review at issue. Additional studies are nonetheless warrantedPublication bias with respect to RCT trials (indeed, beyond the scopes of the review)I = 3
II = 3
III = 4
IV = 2
V = 4
VI = 3
VII = 3
VIII = 2
IX = 4
X = 3
XI = 4
Total score = 34
Percentile in the present set = 83.3
Quartile-derived grade letter = A

(Greenberg and Citrome, 2016)USAThe review focused on the pharmacodynamics and pharmacokineticsNo RCT leading to FDA approval (extension) covered in the present piece of workThe review provides a very comprehensive and updated synthesis of lurasidone pharmacological properties. Distinguishing features of lurasidone against alternative SGA are also outlined, with a special emphasis towards the very potent 5-HT7 activity excreted by lurasidone and its complex interactions with 5-HT1A partial agonist activityPublication bias with respect to RCT trials (indeed, beyond the scopes of the review)I = 1
II = 2
III = 4
IV = 3
V = 2
VI = 4
VII = 3
VIII = 4
IX = 4
X = 3
XI = 3
Total score = 33
Percentile in the present set = 75
Quartile-derived grade letter = A

(Tarazi and Stahl, 2012) [47]USAThe review covers the preclinical and clinical data available about lurasidone, asenapine and iloperidone until writing timeNo RCT leading to FDA approval (extension) covered in the present piece of workThe review provides an expert opinion perspective about titration, dosing and management of most common side effects eventually experienced by patients with BD in receipt of lurasidone. This allows making inference about some of the clinical unmet needs to be address by forthcoming studiesPublication biasI = 1
II = 3
III = 4
IV = 2
V = 4
VI = 3
VII = 3
VIII = 4
IX = 3
X = 3
XI = 4
Total score = 36
Percentile in the present set = 100
Quartile-derived grade letter = A

(Gao et al., 2015) [48]USAThe review focuses on the NNT and NNH computed for the essential SGAs approved by the FDA for the treatment of acute bipolar depression in adults, including lurasidoneTwo acute phase trials (mono- and adjunctive therapy resp.) [23, 24]Staining the relatively favorable profile of lurasidone, the authors recommend that the selection of an FDA-approved SGAs for bipolar
depression should be based upon priority given to safety and tolerability issues
Publication biasI = 1
II = 2
III = 3
IV = 2
V = 2
VI = 3
VII = 4
VIII = 2
IX = 3
X = 2
XI = 4
Total score = 26
Percentile in the present set = 50
Quartile-derived grade letter = A

(Sanford and Dhillon, 2015) [49]New ZealandThe review provides a synthesis about the use of lurasidone in adults with bipolar depressionTwo acute phase trials (mono- and adjunctive therapy, resp.) [23, 24].
Maintenance open-trial is likewise critically accounted. [28]
The review stresses out the relatively favorable profile of lurasidone in terms of both acute and potentially long-term tolerability in the treatment of BD-I depression, either as mono- or as adjunctive treatmentPublication bias, tough the present review is among the most updated and concise available at writing timeI = 2
II = 2
III = 3
IV = 2
V = 3
VI = 4
VII = 2
VIII = 3
IX = 3
X = 3
XI = 3
Total score = 30
Percentile in the present set = 66.7
Quartile-derived grade letter = A

(Jaeschke et al., 2016) [50]PolandThe present review covers both the 2016 updates about the use of lurasidone in BD and schizophrenia, including synthesis of the pharmacological profile and essential reference to both animal and human studiesTwo acute phase trials (mono- and adjunctive therapy, resp.) [23, 24].
Maintenance open-trial is likewise critically accounted. [28]
This is a very accurate, yet concise, update of the evidence up to early 2016. Nonetheless, the authors failed to expand any conclusive sections about recommendations and the unmet needs for future clinical use and research developmentPublication bias but no suspiciousness of sponsorship biasI = 1
II = 3
III = 3
IV = 2
V = 4
VI = 4
VII = 3
VIII = 4
IX = 4
X = 4
XI = 4
Total score = 36
Percentile in the present set = 100
Quartile-derived grade letter = A

(Woo et al. 2013) [51]South KoreaThis is a “preliminary” review about the potential use of lurasidone in the treatment of bipolar depression associated with BD-I in adultsNo RCT leading to FDA approval (extension) could be covered in the present piece of work at writing timeDespite the publication bias and intrinsic limitation of lack of evidence, the review is formulated in a critical manner, which would contribute to providing useful clinical recommendation for the actual use of the drug and its further developmentPublication biasI = 2
II = 2
III = 2
IV = 1
V = 2
VI = 3
VII = 2
VIII = 2
IX = 2
X = 2
XI = 3
Total score = 24
Percentile in the present set = 41.7
Quartile-derived grade letter = A

(Findlay et al. 2015) [52]USAThe review focuses on the tolerability and efficacy profile of lurasidone in the treatment of BD-I depression in adultsTwo acute phase trials (mono- and adjunctive therapy, resp.) [23, 24].
Maintenance open-trial is likewise critically accounted. [28]
Tough very concise and only partially “systematic” in nature, the present review provides inputs and hints about the clinical use of lurasidone which would pave the ground for further development and address of some of the unmet needs faced by the clinical prescribers and the suffering onesPublication biasI = 1
II = 2
III = 2
IV = 1
V = 2
VI = 3
VII = 2
VIII = 1
IX = 3
X = 3
XI = 3
Total score = 23
Percentile in the present set = 33.3
Quartile-derived grade letter = B

BD = bipolar disorder; randomized clinical trial = RCT. R-AMSTAR = revised “assessment of multiple systematic reviews.” TRBD = treatment-resistant bipolar depression; PP = predominant polarity (of mood episodes over the lifetime course of BD) [53]. FDA = Food and Drug Administration; BD = bipolar disorder; SGA = second generation antipsychotics. NNT = number needed to treat; NNH = number needed to harm. PICO/PICO research questions: population, intervention, comparison, prediction, and outcome.

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