Trajectories Across Symptoms and Functioning in High-Risk Psychosis Highlight Need for Individualized Treatment

Psychiatry Advisor Contributing Writer
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Lumateperone, a 5-HT2A receptor antagonist for schizophrenia, is set to undergo FDA review. Data from 20 trials involving more than 1900 patients were submitted in the New Drug Application. The drug and its follow-up compounds are also being evaluated for MDD, bipolar disorder, autism, and behavioral disturbances associated with dementia.
Lumateperone, a 5-HT2A receptor antagonist for schizophrenia, is set to undergo FDA review. Data from 20 trials involving more than 1900 patients were submitted in the New Drug Application. The drug and its follow-up compounds are also being evaluated for MDD, bipolar disorder, autism, and behavioral disturbances associated with dementia.
Within each of the 3 trajectory groups at high risk for psychosis, similar patterns of change were observed across the 4 symptom domains and functioning, suggestive of different degrees of need for clinical interventions.

When 3 replicable subgroups (rapid, moderate, and no improvement) of help-seeking individuals at high risk of psychosis were identified, the trajectory of change across the 4 symptom domains and functioning remained consistent over time, according to a study published in the American Journal of Psychiatry.

This study was designed to characterize differences in outcomes between 3 different subgroups of help-seeking individuals at clinical high risk for psychosis by identifying covariant longitudinal patterns of symptoms and functioning. Group-based multi-trajectory modeling was applied to the longitudinal ratings of general functioning and 4 symptom domains (positive, negative, disorganized, general) among an initial discovery sample of clinical high-risk individuals (n=422), and replicability was tested using an independent sample (n=133).

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Group 1 included patients who rapidly improved across all symptom domains and general functioning and exhibited minimal impairment at end of study (29.6%). Group 2 included patients exhibiting moderate baseline levels of symptoms and impairment in all areas and showed some improvement by end of study (48.9%). Group 3 included those with high levels of symptom severity and functional impairment with no improvement (ie, nonsignificant quadratic and linear parameters) by end of study across all domains, with the exception of positive symptom severity (21.5%).

The groups did not significantly differ by sex, age, race, or mean number of visits, but they did significantly differ on parental level of education, with group 2 showing the lowest percentage of parents completing high school or less (11.3%), followed by group 3 (20.9%) and group 1 (25.2%; x²=11.27; df=2; P =.007). These trajectory patterns were tested and replicated in another sample of 133 patients (group 1, 26.7%; group 2, 54.9%; group 3, 18.4%). Dropout analyses suggest that the size estimates of group 1 may be inflated in the final model by 3% to 5%, and group 2 size estimates may be deflated by a similar proportion.

There are several limitations to this study, mainly associated with the data-driven approaches of trajectory modeling. A majority of study participants missed at least 1 out of 4 follow-up visits, which influences model parameters. Only participants with at least 3 visits were included in the patient sample, which narrows the overall study group. Additionally, as a result of the study design, the groups did not capture the prior functional and symptomatic patterns of individuals who converted to psychosis within the first year of study follow-up.

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Study investigators concluded that the subgroups suggest different degrees of clinical intervention need, from minimal to supportive for approximately one-third of cases, to increasingly intensive across the remainder. Additionally, “these differences in outcomes highlight the need for individualized treatment for this population and the potential for prediction of subgroup outcomes to improve opportunities for early intervention and treatment.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Allswede DM, Addington J, Bearden CE, et al. Characterizing covariant trajectories of individuals at clinical high risk for psychosis across symptomatic and functional domains [published online September 6, 2019]. Am J Psychiatry. doi:10.1176/appi.ajp.2019.18111290