JMIR Publications

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 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 66 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 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 1.6% had imputed and/or coded self-harm following the exposure of interest (N=8,509 events). A higher self-harm risk was observed during adolescence. Three regimens were of higher risk of self-harm than lithium (tri/tetracyclic antidepressant+SGA, serotonin-norepinephrine reuptake inhibitors (SNRI)+SGA, selective serotonin reuptake inhibitors (SSRI)+MSA+SGA) [hazard ratios (HRs) ranged 1.44-2.29, p<0.01], and ten were of lower risk (lamotrigine, valproate, risperidone, aripiprazole, oxcarbazepine, SNRI, SSRI, “No drug”, bupropion, and bupropion+SSRI) (HRs ranged 0.45-0.74, p<0.01). Psychotherapy alone (non-adjunctive) had a lower self-harm risk than no treatment (HR=0.64, 95%CI=0.60-0.69, p=7.05×10-33). 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. Clinical Trial: ClinicalTrials.gov NCT02893371