Abstract
BackgroundIncomplete 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.ObjectiveThe 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.MethodsThe 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”).ResultsAmong 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.ConclusionsOur data support evidence on the effectiveness of antidepressants, MSAs, and psychotherapy for self-harm prevention in BD.Trial RegistrationClinicalTrials.gov NCT02893371; https://clinicaltrials.gov/ct2/show/NCT02893371
Highlights
Self-harming behavior is a public and mental health concern of increasing prevalence, which contributes to US hospitalization rates, morbidity, and mortality due to completed suicides
Psychotherapy alone had a lower self-harm risk than no treatment (HR 0.56, 95% CI 0.52-0.60; P=8.76×10-58)
A recent systematic review showed that bipolar disorder (BD) may be associated with the highest suicide risk among all psychiatric disorders, with over 15%-20% of deaths attributed to suicide and the standardized suicide rate being 20 to 30-fold greater than in the general population (0.2-0.4 per 100 person-years) [4]
Summary
Self-harming behavior is a public and mental health concern of increasing prevalence, which contributes to US hospitalization rates, morbidity, and mortality due to completed suicides. A previous study reported that the risk ratio of suicide in mental disorders was as high as 7.5 (95% CI 6.6-8.6) and in mood disorders was even higher at 12.3 (95% CI 8.9-17.1) [3]. A recent systematic review showed that bipolar disorder (BD) may be associated with the highest suicide risk among all psychiatric disorders, with over 15%-20% of deaths attributed to suicide and the standardized suicide rate being 20 to 30-fold greater than in the general population (0.2-0.4 per 100 person-years) [4]. The reported proportion of suicide attempts and completed suicides among individuals with BD varies from 5:1 in males over 45 years to 85:1 in females under 30 years [6]. 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
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