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. 2021 Apr 21;8(4):e24522. doi: 10.2196/24522

Table 1.

Cox regression model comparing 64 pharmacotherapies and “no drug” to lithium for the risk of subsequent coded and/or imputed self-harm in patients with bipolar disorder of all ages.

Covariatesa HRb,c Lower 95% Upper 95% P value Patients
(N=529,359)		 Intervals (N=1,749,468) Events (N=8813)
Tri/tetracyclic antidepressants + SGAd,e 2.33 1.28 4.26 5.73×10-3 180 1044 11
SSRIf + FGAg,e 2.26 1.16 4.38 1.61×10-2 195 1014 9
FGA + MSAh,e 1.82 1.15 2.89 1.12×10-2 481 2448 19
SSRI + lithium + MSA + SGAe 1.72 1.00 2.97 4.96×10-2 192 1424 14
FGA monoclass therapye 1.69 1.19 2.39 3.20×10-3 1069 5853 35
SNRIi + SGAe 1.59 1.18 2.14 2.27×10-3 1466 6803 50
SNRI + MSA + SGAe 1.56 1.06 2.29 2.25×10-2 805 4200 29
Asenapine 1.50 0.77 2.90 2.31×10-1 160 1494 9
Lithium + MSA + SGAe 1.42 1.07 1.90 1.52×10-2 1143 7748 57
Lurasidone 1.42 0.97 2.07 7.25×10-2 459 3919 29
NDRIj + SSRI + MSA + SGA 1.40 0.66 2.96 3.84×10-1 170 1251 7
SSRI + lithium + SGA 1.39 0.94 2.05 9.85×10-2 725 3898 28
NDRI + lithium + MSA 1.38 0.65 2.93 3.95×10-1 193 1438 7
Aripiprazole + MSA + SGA 1.38 0.86 2.22 1.87×10-1 411 2641 18
Lithium + MSAe 1.35 1.09 1.67 5.32×10-3 2763 18,728 116
Lithium + SGAe 1.34 1.11 1.62 2.86×10-3 3757 18,980 155
Polypharmacy 4k 1.33 0.97 1.82 7.60×10-2 1274 8867 47
SSRI + MSA + SGAe 1.31 1.05 1.62 1.52×10-2 3153 16,322 118
NDRI + MSA + SGA 1.25 0.86 1.81 2.47×10-1 836 5558 30
Aripiprazole + SGA 1.22 0.79 1.88 3.72×10-1 715 3987 22
NASSAl + SGA 1.20 0.62 2.33 5.86×10-1 321 1457 9
NDRI + lithium 1.16 0.74 1.80 5.18×10-1 728 4559 21
Tri/tetracyclic antidepressants 1.15 0.71 1.88 5.66×10-1 693 4130 17
SSRI + lithium + MSA 1.10 0.66 1.82 7.10×10-1 499 3,514 16
Uncommon monotherapy 1.09 0.49 2.45 8.29×10-1 169 1205 6
NDRI + SSRI + MSA 1.08 0.68 1.72 7.44×10-1 720 4754 19
SSRI + lithium 1.06 0.81 1.39 6.61×10-1 2457 13,235 64
MSA + SGA 1.05 0.91 1.21 5.15×10-1 13,348 67,185 421
Lithium (reference) 1.00  N/Am  N/A N/A  13,759 66,760 351
Polypharmacy 3n 1.00 0.79 1.25 9.66×10-1 3794 23,234 95
NDRI + aripiprazole + MSA 0.99 0.51 1.91 9.67×10-1 254 2316 9
Lithium + aripiprazole + MSA 0.97 0.50 1.89 9.30×10-1 227 1797 9
SNRI + lithium 0.97 0.54 1.72 9.06×10-1 529 2814 12
SSRI + SGA 0.96 0.80 1.15 6.36×10-1 7896 33,503 188
SSRI + MSA 0.95 0.81 1.11 5.32×10-1 12,315 58,789 286
Quetiapine 0.95 0.82 1.10 5.03×10-1 13,795 60,422 342
Aripiprazole + MSA 0.94 0.76 1.17 5.90×10-1 3401 21,368 108
Ziprasidone 0.94 0.71 1.24 6.63×10-1 2381 11,773 58
Multi-SGA 0.93 0.56 1.57 7.94×10-1 677 3479 15
Lithium + aripiprazole 0.92 0.60 1.42 7.19×10-1 665 4268 22
SNRI + MSA 0.90 0.68 1.20 4.80×10-1 2939 13,995 58
FGA + lithium 0.89 0.40 1.99 7.73×10-1 315 1472 6
NDRI + SGA 0.89 0.62 1.27 5.07×10-1 1408 8336 33
Multi-MSA 0.87 0.61 1.24 4.49×10-1 1451 8792 34
SSRI + aripiprazole 0.85 0.64 1.14 2.83×10-1 2285 11,695 52
Olanzapine 0.84 0.66 1.07 1.57×10-1 4040 16,759 83
NASSA + MSA 0.82 0.42 1.60 5.65×10-1 438 2313 9
NDRI + MSA 0.82 0.64 1.05 1.20×10-1 3460 21,294 74
Oxcarbazepine 0.81 0.65 1.02 6.91×10-2 4436 20,633 97
Carbamazepine 0.74 0.54 1.02 6.45×10-2 2284 10,662 42
Lamotriginee 0.74 0.65 0.85 1.13×10-5 28,624 131,786 549
NDRI + aripiprazole 0.73 0.41 1.30 2.91×10-1 564 4038 12
Valproatee 0.71 0.61 0.84 4.57×10-5 14,718 61,544 253
SSRI + aripiprazole + MSA 0.70 0.43 1.15 1.56×10-1 784 5148 17
Aripiprazolee 0.70 0.59 0.84 9.40×10-5 8872 47,373 186
Polypharmacy 2o 0.68 0.46 1.01 5.32×10-2 2017 11,269 28
Risperidonee 0.68 0.56 0.83 1.82×10-4 7084 28,302 138
SNRIe 0.65 0.51 0.83 5.51×10-4 6120 27,921 78
NASSA 0.65 0.38 1.08 9.77×10-2 950 4964 15
Paliperidone 0.61 0.29 1.30 2.03×10-1 292 1858 7
SSRIe 0.61 0.53 0.71 6.05×10-11 30,138 131,895 381
NDRI + SSRI + SGA 0.60 0.25 1.45 2.57×10-1 345 2079 5
“No drug”e 0.56 0.50 0.63 2.79×10-22 299,295 621,467 3694
NDRI (bupropion)e 0.50 0.39 0.65 1.18×10-7 6005 35,433 72
SNRI + aripiprazole 0.45 0.19 1.09 7.85×10-2 457 2765 5
NDRI (bupropion) +SSRIe 0.28 0.13 0.60 1.00×10-3 1263 7496 7
Prior self-harme 3.32 2.68 4.11 3.17×10-28 704 1652 70
Alcohol/substance abuse or dependencee 1.92 1.81 2.03 7.17×10-106 57,392 149,679 1065
Deliriume 1.69 1.36 2.10 1.92×10-6 1694 4086 60
Prior hospitalizatione 1.63 1.54 1.72 1.78×10-64 131,613 342,122 1905
Mental procedure before index exposuree 1.50 1.42 1.58 3.43×10-50 81,943 247,474 841
Liver diseasee 1.49 1.29 1.71 4.27×10-8 9063 23,559 121
Unknown polarity of index mood episodee 1.33 1.24 1.43 1.67×10-15 307,243 1,000,348 2447
Conduct disordere 1.26 1.14 1.39 3.65×10-6 13,728 39,657 255
Seizure disordere 1.18 1.11 1.25 2.07×10-7 90,276 307,887 667
External injurye 1.12 1.06 1.19 2.31×10-5 117,722 338,635 1350
Pulmonary disorder 1.12 0.99 1.26 7.60×10-2 18,960 48,974 160
Depression during the index meta-visite 1.10 1.02 1.18 1.52×10-2 72,386 245,707 487
Male sexe 1.07 1.03 1.12 1.46×10-3 227,507 733,963 1966
Exposure to sedative or antianxiety druge 1.06 1.00 1.12 4.24×10-2 130,186 431,040 929
Number of prior unique BDp drugs tried (linear component of spline fit)e 1.02 1.01 1.04 4.17×10-3  N/A  N/A  N/A
Psychotic features present during the index meta-visit 1.01 0.92 1.11 7.73×10-1 23,846 78,579 345
Age (linear component of spline fit)e 0.98 0.97 0.98 6.99×10-201  N/A  N/A  N/A
Exposure to central nervous system stimulant 0.95 0.88 1.01 9.62×10-2 55,140 195,116 396
BD type II during the index meta-visite 0.93 0.87 0.99 2.49×10-2 90,741 331,720 497
Manic episode during the index meta-visite 0.92 0.85 0.99 3.40×10-2 82,955 250,285 512
Exposure to glucocorticoidse 0.83 0.77 0.89 1.04×10-7 80,626 246,182 472
Exposure to antibacterial agentse 0.80 0.76 0.84 3.77×10-17 144,933 453,129 951
Exposure to sex hormonese 0.79 0.74 0.85 3.08×10-10 67,550 217,335 372
Neoplasme 0.77 0.70 0.85 1.70×10-7 42,628 130,488 220
Psychotic features unknown during the index meta-visite 0.67 0.63 0.72 2.85×10-30 401,789 1,295,408 2709
Psychotherapy (psychosocial interventions)e 0.59 0.57 0.62 1.12×10-114 249,328 704,937 1369
Outpatient visit present during the index meta-visite 0.56 0.50 0.63 4.69×10-23 522,232 1,732,715 3475
Age (nonlinear components of the spline model)e N/A N/A N/A 4.58×10-32 N/A N/A N/A
Number of prior unique BD drugs tried (nonlinear components of spline fit)e N/A N/A N/A 1.21×10-9 N/A N/A N/A

aCovariates labeled “prior” are related to the 1-year period before the index exposure.

bCovariates are sorted by their hazard ratio value.

cHR: hazard ratio.

dSGA: second-generation antipsychotic.

eCovariates with significant P values (<.05; no multiple testing correction).

fSSRI: selective serotonin reuptake inhibitor.

gFGA: first-generation antipsychotic.

hMSA: mood stabilizing anticonvulsant.

iSNRI: serotonin-norepinephrine reuptake inhibitor.

jNDRI: norepinephrine-dopamine reuptake inhibitor (represented by bupropion only).

kPolypharmacy 4: uncommon combination of four or more bipolar disorder drug classes.

lNASSA: noradrenergic and specific serotonergic antidepressant (represented by mirtazapine only).

mN/A: not applicable.

nPolypharmacy 3: uncommon combination of three bipolar disorder drug classes.

oPolypharmacy 2: uncommon combination of two bipolar disorder drug classes.

pBD: bipolar disorder.