A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

Papakostas, George I.; Vitolo, Ottavio V.; IsHak, Waguih William; Rapaport, Mark Hyman; Zajecka, John; Kinrys, Gustavo; Mischoulon, David; Lipkin, Samuel; Hails, Katherine A.; Abrams, J.K.; Ward, S. A.; Meisner, Allison; Schoenfeld, David; Shelton, Richard C.; Winokur, Andrew; Okasha, Mahmoud S.; Bari, Mohammed Abdul; Fava, Maurizio

doi:10.4088/jcp.12m07670

Cited by 26 publications

(17 citation statements)

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“…38 Finally, other atypical antipsychotics show antidepressant action despite boasting of less impressive putative antidepressant mechanisms than ziprasidone. Yet, ziprasidone showed no antidepressant advantage over placebo in the MDD 34 and bipolar depression 36,37 RCTs described in the earlier sections. Important take-home messages are that preclinical research and circumstantial evidence can only guide hypothesis generation, and antidepressant action is not a class action of atypical antipsychotic drugs.…”

Section: Limitations Of Pharmacodynamics As a Predictor Of Clinical Amentioning

confidence: 94%

“…Ziprasidone was also associated with a small (about 2.5 ng/mL) but significantly greater elevation of serum prolactin relative to placebo. Adverse events and laboratory results otherwise did not differ much between the 2 groups a Data from Papakostas et al 34 Abbreviations: CGI-S = Clinical Global Impressions-Severity of Illness, HDRS = 17-item Hamilton Depression Rating Scale, QIDS-SR = Quick Inventory of Depressive Symptomatology, Self-Report.…”

Section: Ziprasidone and Bipolar Depressionmentioning

confidence: 99%

“…The ziprasidone MDD study 34 was conducted in patients who were but mildly depressed (mean HDRS score at baseline = 19.9); this may be an important reason why the trial failed, for a meta-analysis of antidepressant RCTs submitted to the US Food and Drug Administration found that antidepressant drugs separate better from placebo only when depression is more severe. 39 Thus, given that Mr J has moderately severe depression, the ziprasidone MDD study 34 provides little guidance on how patients with moderately severe depression might fare on monotherapy with the drug. Finally, the study provides no information on possible benefits with faster up-titration or higher doses of ziprasidone (which, however, could result in even higher dropout rates than those recorded in the study).…”

Section: An Evidence-based Appraisalmentioning

confidence: 99%

“…So, if the ideal evidence is unavailable, the next best evidence that is available should be applied to the clinical problem at hand. Under these circumstances, the ziprasidone MDD study 34 comes closest to providing guidance about the use of ziprasidone for Mr J. Readers are reminded here that using "next-best evidence" is widespread in clinical psychopharmacology.…”

Section: An Evidence-based Appraisalmentioning

confidence: 99%

“…The authors 34 offered several reasons why ziprasidone failed to demonstrate antidepressant efficacy; one was that the drug may have been underdosed, and another was that patients were not exposed to the highest dose for a sufficiently long period. The high dropout rate with ziprasidone and the sequential design also resulted in underpowered analyses.…”

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confidence: 99%

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Antidepressant Action of Atypical Antipsychotics

Andrade

2013

J. Clin. Psychiatry

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Section: Limitations Of Pharmacodynamics As a Predictor Of Clinical Amentioning

confidence: 94%

Section: Ziprasidone and Bipolar Depressionmentioning

confidence: 99%

Section: An Evidence-based Appraisalmentioning

confidence: 99%

Section: An Evidence-based Appraisalmentioning

confidence: 99%

mentioning

confidence: 99%

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Antidepressant Action of Atypical Antipsychotics

Andrade

2013

J. Clin. Psychiatry

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Depression and Anxiety Disorders

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Depression is widely recognised as a major public health problem around the world. The basic principles of prescribing are described in this chapter, along with a summary of NICE guidance. This chapter concentrates on the use of antidepressants and offers advice on drug choice, dosing, switching strategies and sequencing of treatments. Management of treatment‐resistant depression has been informed by the STAR*D programme. The 2019 PANDA trial results support the prescription of selective serotonin reuptake inhibitor antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder. Over the last two decades, ketamine, an uncompetitive N‐Methyl‐D‐Aspartate receptor antagonist and dissociative anaesthetic, has emerged as a novel and effective rapid‐acting antidepressant. Psychotic depression is an under‐identified disorder and may have a life‐time risk of up to 1%.

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Enrichment designs using placebo nonresponders

Benda

Haenisch

2020

Pharmaceutical Statistics

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Enrichment designs that select placebo nonresponders have gained much attention during the last years in areas with high placebo response rates, eg, in depression. Proposals were made that re-randomize patients who did not respond to placebo during a first study phase as the sequential parallel design (SPD). This design uses in a second phase an enriched patient population where the treatment effect is expected to be more pronounced. This may be problematic if an effect in the overall population is claimed. Proposals were made to combine the treatment effects in the overall population from study phase 1 and the enriched population from study phase 2, alleviating but not solving the issue of a potential selection bias. This paper shows how this bias corresponding to the effect difference between the overall population and the enriched population depends on the variability of a potential subject-by-treatment interaction. Sample sizes are given, which lead to a significant result in the combining test with a given probability if actually the average effect in the overall population is zero. If, on the other hand, no subject-by-treatment interaction is given, the enrichment is shown to be inefficient. We conclude that enrichment designs using placebo nonresponders are not able to claim a positive average effect in the overall population if a subject-by-treatment interaction cannot be excluded. It cannot be used to demonstrate positive efficacy in the overall population in a pivotal phase III trial but may be used in early phases to demonstrate varying treatment effects between patients.

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A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

Abstract: ClinicalTrials.gov identifier: NCT00555997.

Cited by 26 publications

References 0 publications

Antidepressant Action of Atypical Antipsychotics

Antidepressant Action of Atypical Antipsychotics

Depression and Anxiety Disorders

Enrichment designs using placebo nonresponders

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