Using Machine Learning Imputed Outcomes to Assess Drug-Dependent Risk of Self-Harm in Patients with Bipolar Disorder: A Comparative Effectiveness Study.

Abstract

BACKGROUND:

Incomplete suicidality coding in administrative claims data is a known obstacle for observational studies. With most of the negative outcomes missing from the data, it is challenging to assess the evidence on treatment strategies for the prevention of self-harm in bipolar disorder (BD), including pharmacotherapy and psychotherapy. There are conflicting data from studies on the drug-dependent risk of self-harm, and there is major uncertainty regarding the preventive effect of monotherapy and drug combinations.

OBJECTIVE:

The aim of this study was to compare all commonly used BD pharmacotherapies, as well as psychotherapy for the risk of self-harm, in a large population of commercially insured individuals, using self-harm imputation to overcome the known limitations of this outcome being underrecorded within US electronic health care records.

METHODS:

The IBM MarketScan administrative claims database was used to compare self-harm risk in patients with BD following 65 drug regimens and drug-free periods. Probable but uncoded self-harm events were imputed via machine learning, with different probability thresholds examined in a sensitivity analysis. Comparators included lithium, mood-stabilizing anticonvulsants (MSAs), second-generation antipsychotics (SGAs), first-generation antipsychotics (FGAs), and five classes of antidepressants. Cox regression models with time-varying covariates were built for individual treatment regimens and for any pharmacotherapy with or without psychosocial interventions ("psychotherapy").

RESULTS:

Among 529,359 patients, 1.66% (n=8813 events) had imputed and/or coded self-harm following the exposure of interest. A higher self-harm risk was observed during adolescence. After multiple testing adjustment (P≤.012), the following six regimens had higher risk of self-harm than lithium: tri/tetracyclic antidepressants + SGA, FGA + MSA, FGA, serotonin-norepinephrine reuptake inhibitor (SNRI) + SGA, lithium + MSA, and lithium + SGA (hazard ratios [HRs] 1.44-2.29), and the following nine had lower risk: lamotrigine, valproate, risperidone, aripiprazole, SNRI, selective serotonin reuptake inhibitor (SSRI), "no drug," bupropion, and bupropion + SSRI (HRs 0.28-0.74). Psychotherapy alone (without medication) had a lower self-harm risk than no treatment (HR 0.56, 95% CI 0.52-0.60; P=8.76×10-58). The sensitivity analysis showed that the direction of drug-outcome associations did not change as a function of the self-harm probability threshold.

CONCLUSIONS:

Our data support evidence on the effectiveness of antidepressants, MSAs, and psychotherapy for self-harm prevention in BD.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02893371; https://clinicaltrials.gov/ct2/show/NCT02893371.

• Authors: Anastasiya Nestsiarovich, Praveen Kumar, Nicolas Raymond Lauve, Nathaniel G Hurwitz, Aurélien J Mazurie, Daniel C Cannon, Yiliang Zhu, Stuart James Nelson, Annette S Crisanti, Berit Kerner, Mauricio Tohen, Douglas J Perkins, Christophe Gerard Lambert
• Journal: JMIR mental health (JMIR Ment Health) Vol. 8 Issue 4 Pg. e24522 (Apr 21 2021) ISSN: 2368-7959 [Print] Canada
• PMID: 33688834 (Publication Type: Journal Article)
• Copyright: ©Anastasiya Nestsiarovich, Praveen Kumar, Nicolas Raymond Lauve, Nathaniel G Hurwitz, Aurélien J Mazurie, Daniel C Cannon, Yiliang Zhu, Stuart James Nelson, Annette S Crisanti, Berit Kerner, Mauricio Tohen, Douglas J Perkins, Christophe Gerard Lambert. Originally published in JMIR Mental Health (https://mental.jmir.org), 21.04.2021.