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Citation
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Nestsiarovich A, Kumar P, Lauve NR, Hurwitz NG, Mazurie AJ, Cannon DC, Zhu Y, Nelson SJ, Crisanti AS, Kerner B, Tohen M, Perkins DJ, Lambert CG. JMIR Ment. Health 2021; ePub(ePub): ePub. |
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Abstract
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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 is to compare all commonly used BD pharmacotherapies, as well as psychotherapy for 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 under-recorded within US electronic healthcare 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 5 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: Out of 529,359 patients 1.66% had imputed and/or coded self-harm following the exposure of interest (N=8,813 events). A higher self-harm risk was observed during adolescence. After multiple testing adjustment (p ≤0.012), six regimens were of higher risk of self-harm than lithium: tri/tetracyclic antidepressant+SGA, FGA+MSA, FGA, serotonin-norepinephrine reuptake inhibitors (SNRI)+SGA, lithium+MSA, and lithium+SGA [hazard ratios (HRs) ranged 1.44-2.29]. Nine were of lower risk: lamotrigine, valproate, risperidone, aripiprazole, SNRI, SSRI, "No drug", bupropion, and bupropion+SSRI (HRs ranged 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 self-harm probability threshold.
CONCLUSIONS: Our data support the evidence on the effectiveness of antidepressants, MSAs, and psychotherapy for self-harm prevention in BD. CLINICALTRIAL: ClinicalTrials.gov NCT02893371.
Language: en |