Application of <i>n</i>-of-1 treatment trials in schizophrenia: systematic review

Summary The response to antipsychotic treatment in schizophrenia appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Randomised controlled trials comparing placebo and antipsychotics in acute treatment of schizophrenia listed in PubMed, EMBASE and PsycINFO from inception until November 30, 2018 were examined. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. In addition, individual patient data from two clinical trials was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. 11,006 articles were identified. 66 met inclusion criteria, reporting on 17,202 patients. Compared with placebo, antipsychotic-treated patients demonstrated greater total symptom improvement (g=0.47, p<0.001) and reduced variability in symptomatic improvement for total (CVR=0.86, p<0.001), positive (CVR=0.89, p<0.001), and negative symptoms (CVR=0.86, p=0.001). Lower variability in antipsychotic-response was associated with studies published earlier (z=3.98, p<0.001), younger patients (z=3.07, p=0.002), higher dose treatments (z=-2.62, p=0.009), and greater mean-difference in symptom-change (z=-5.70, p<0.001). In the individual patient dataset (N=522 patients), antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response. Compared to placebo, antipsychotic treatment shows greater improvement and lower variability of change in total, positive and negative symptoms. This is contrary to the hypothesis that there is a subtype of antipsychotic non-responsive schizophrenia. Instead our findings, provide evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.

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“…To fully address the question of subtypes, future work will require markedly different trial designs such as repeated N-of-1 studies. 33 , 34 …”

Section: Discussionmentioning

confidence: 99%

The efficacy and heterogeneity of antipsychotic response in schizophrenia: A meta-analysis

et al. 2019

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“…Another application of the single-subject study is to evaluate the effects and side effects of interventions in single individuals. In the field of psychiatry such experimental single-subject studies have evaluated, for example, the person-specific effects of individualized cognitive therapy for depression in women with metastatic cancer (46), pharmacological treatment for depression (47), stimulants for ADHD in children (48), and treatments for schizophrenia (49). Taken together, single-subject studies are and can be used for different reasons in the field of psychiatry.…”

Section: Introductionmentioning

confidence: 99%

Single-Subject Research in Psychiatry: Facts and Fictions

et al. 2020

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“…SCEDs currently are used in basic experimental and applied research in the field of behavior analysis. The value of SCEDs is increasingly recognized in areas outside of behavior analysis such as medicine (Gabler et al, 2011), rehabilitation (Krasny‐Pacini & Evans, 2018; Lobo et al, 2017), clinical psychology (Sexton‐Radek, 2014), health psychology (Dallery et al, 2013; Kwasnicka et al, 2019), and psychiatry (Marwick et al, 2018).…”

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confidence: 99%

Single‐case experimental designs for behavioral neuroscience

Soto

2020

J Exper Analysis Behavior

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Single-case experimental designs (SCEDs) are commonly used in behavior analytic research but rarely used in behavioral neuroscience research. The recent development of technologies that allow control of the timing of neurobiological events such as gene expression and neuronal firing enable the fruitful application of SCEDs for the study of brain-behavior relations. There are at least 3 benefits expected from applying SCEDs to study how neurobiological events affect behavior. First, SCEDs entail direct within-and across-subject assessments of reliability, likely increasing the probability of replication across studies and encouraging a search for the causes of replication failure when they occur. Second, SCEDs focus on behavior in individual organisms producing a body of knowledge that applies to individuals rather than population parameters. Finally, SCEDs require fewer animals, decreasing costs and effort and addressing the ethical obligation to reduce the number of animals used for research. Examples are provided using hypothetical data generated based on published research. Collaborations between behavior analysts and behavioral neuroscientists will bring the world within the skin under direct experimental control and broaden our understanding of the determinants of behavior.

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Application of n-of-1 treatment trials in schizophrenia: systematic review

Cited by 12 publications

References 34 publications

The efficacy and heterogeneity of antipsychotic response in schizophrenia: A meta-analysis

The efficacy and heterogeneity of antipsychotic response in schizophrenia: A meta-analysis

Single-Subject Research in Psychiatry: Facts and Fictions

Single‐case experimental designs for behavioral neuroscience

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