Jun 1, 2017 - Zuclopenthixol. Yes. 298 (0·24). 355. 636·32. 1·29 (0·98â1·70). 1·36 (1·03â1·78). 0·029. No. 123 414 (99·76). 946 493. 162·24. 1·00. 1·00.
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Tiihonen J, Tanskanen A, Hoti F, et al. Pharmacological treatments and risk of readmission to hospital for unipolar depression in Finland: a nationwide cohort study. Lancet Psychiatry 2017; published online June 1. http://dx.doi.org/10.1016/ S2215-0366(17)30134-7.
1
SUPPLEMENTARY MATERIAL Pharmacological treatments and risk of re-hospitalization due to unipolar depression in a nationwide cohort of 123,712 patients Jari Tiihonen, Antti Tanskanen, Fabian Hoti, Pia Vattulainen, Juha Mehtälä, Heidi Taipale, Markku Lähteenvuo ICD-10 codes: F-code indicates any mental disorder, F20-29 schizophrenia and other non-affective psychoses, F30-39 affective disorders, and F30-31 mania and bipolar disorders. Supplementary Table 1a. Definition of adjusting variables in the within-individual and traditional Cox PH by treatment effect studied. Supplementary Table 1b. Definition of additional adjusting variables in the traditional Cox PH models by study outcome. Supplementary Table 2. The association between use vs. no use of medications and risk of re-hospitalization due to mental disorder (except schizophrenia and bipolar disorder) in within-individual analysis in the total cohort (N = 123,712). Results are based on the within-individual Cox PH model, and are adjusted for time since diagnoses, temporal order of treatment, current use of other treatments, and polypharmacy. Number of individuals with at least one rehospitalization was 49,146. Supplementary Table 3. The association between use vs. no use of medications and risk of re-hospitalization due to mental disorder (except schizophrenia and bipolar disorder) in within-individual analysis in the incident cohort (N = 30,004). Results are based on the within-individual Cox PH model, and are adjusted for time since diagnoses, temporal order of treatment, current use of other treatments, and polypharmacy. Number of individuals with at least one rehospitalization was 9,521. Supplementary Table 4. The association between use vs. no use of medications and risk of re-hospitalization due to all cause in within-individual analysis in the total cohort (N = 123,712). Results are based on the within-individual Cox PH model, and are adjusted for time since diagnoses, temporal order of treatment, current use of other treatments, and polypharmacy. Number of individuals with at least one re-hospitalization was 98,662. Supplementary Table 5. Comparison between results obtained with time-reset at initiation of treatment and with timereset at outcome. Supplementary Table 6. The association between use vs. no use of medications and risk of re-hospitalization due to mental disorder in traditional analysis in the total cohort (N = 123,712). Supplementary Table 7. The association between use vs. no use of medications and risk of re-hospitalization due to mental disorder in traditional analysis in the incident cohort (N = 30,004). Supplementary Table 8. The association between use vs. no use of medications and risk of all-cause re-hospitalization in traditional analysis in the total cohort (N = 123,712). Supplementary Table 9. Risk of re-hospitalization due to any mood disorder except bipolar disorder (ICD-10 F32– F39) during psychotropic medications. Number of individuals with re-hospitalization was 32,288. Results are based on the within-individual Cox PH model. Supplementary Table 10. Risk of risk of re-hospitalization due to mental disorder during psychotropic medications. First month of antipsychotics, antidepressants and lithium excluded. Number of individuals with re-hospitalization was 45,402. Supplementary Table 11. Risk of suicide during psychotropic medications. There was no time resetting in the analysis. Number of individuals with suicide was 2,908. Supplementary Table 12. Risk of re-hospitalization due to mental disorder during psychotropic medications among sub-population of individuals using both antidepressants, antipsychotics, and lithium during follow-up (n=1956).
2 Results are based on the within-individual Cox PH model. Number of patients with at least one re-hospitalization was 1,380. Supplementary Figure 1. Exposure to psychotropics during follow-up and time resetting in within-individual Cox PH model.
References
Appendix
3 Supplementary Table 1a. Definition of adjusting variables in the within-individual and traditional Cox PH by treatment effect studied. Drug classes: Benzodiazepines, Hypnotics, Antidepressants, Antipsychotics, Mood stabilizers Time since diagnosis (05, 5-10,>10; years)
Specific Antipsychotics
Lithium
Lithium with antidepressants, Lithium without antidepressants
Time since diagnosis (0-5, 5-10,>10; years)
Time since diagnosis (05, 5-10,>10; years)
Order of treatment
Order of drug classes (01,2,>2; cumulative number of different drug classes)
Order of antipsychotics (01,2,>2; cumulative number of different antipsychotic drugs)
Current use of other treatments
Current use of other drug classes (yes/no; for each drug class separately)
Polypharmacy
Polypharmacy (yes/no; concomitant use of more than one drug class)
Current use of other antipsychotics (yes/no; for each individual antipsychotic separately) Polypharmacy (yes/no; concomitant use of more than one antipyschotic)
Time since diagnosis (0-5, 510,>10; years) Order of mood stabilizers (0-1,2,>2; cumulative number of different mood stabilizers) Current use of other mood stabilizers (yes/no; for each individual mood stabilizer separately) Polypharmacy (yes/no; concomitant use of more than one mood stabilizer)
Polypharmacy (yes/no; concomitant use of more than one mood stabilizer)
Treatment studied
Time since diagnosis
Adjusting covariates
Order of mood stabilizers (0-1,2,>2; cumulative number of different mood stabilizers) Current use of other mood stabilizers (Yes/no; for each individual mood stabilizer separately)
Supplementary Table 1b. Definition of additional adjusting variables in the traditional Cox PH models by study outcome. Hospitalization due to mental disorders
Hospitalizations due to all causes
Gender
Number of re-hospitalizations due to mental disorders within 2 years prior to index date (0,1-2,>2) Age at index date (70; years) Gender (Female/male)
Number of re-hospitalizations due to all causes within 2 years prior to index date (0,1-2,>2) Age at index date (70; years) Gender (Female/male)
Calendar year of index date
Calendar year of index date (1996-1999,20002003,2004-2007,2008-2012)
Calendar year of index date (19961999,2000-2003,2004-2007,2008-2012)
Study outcome Number of rehospitalizations within 2 years prior to index date Age at index date Adjusting variables
4 Supplementary Table 2. The association between use vs. no use of medications and risk of re-hospitalization due to mental disorder (except F20-29 and F30-31) in within-individual analysis in the total cohort (N = 123,712). Results are based on the within-individual Cox PH model, and are adjusted for time since diagnoses, temporal order of treatment, current use of other treatments, and polypharmacy. Number of individuals with at least one re-hospitalization was 49,146.
N (%) Benzodiazepines Hypnotics Antidepressants Amitriptyline Doxepin Sertraline Escitalopram Duloxetine Venlafaxine Mianserin Citalopram Mirtazapine Paroxetine Fluoxetine Moclobemide Other Antipsychotics Clozapine Prochlorperazine Sulpiride Aripiprazole
Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No
58 447 (47·24) 65 265 (52·76) 63 016 (50·94) 60 696 (49·06) 106 991 (86·48) 16 721 (13·52) 11 752 (9·50%) 111 960 (90·50%) 8 721 (7·05%) 114 991 (92·95%) 16 999 (13·74%) 106 713 (86·26%) 24 759 (20·01%) 98 953 (79·99%) 10 148 (8·20%) 113 564 (91·80%) 26 583 (21·49%) 97 129 (78·51%) 12 176 (9·84%) 111 536 (90·16%) 43 745 (35·36%) 79 967 (64·64%) 49 394 (39·93%) 74 318 (60·07%) 9 488 (7·67%) 114 224 (92·33%) 20 459 (16·54%) 103 253 (83·46%) 5 877 (4·75%) 117 835 (95·25%) 18 114 (14·64%) 105 598 (85·36%) 58 544 (47·32) 65 168 (52·68) 286 (0·23) 123 426 (99·77) 1 306 (1·06) 122 406 (98·94) 2 805 (2·27) 120 907 (97·73) 1 965 (1·59) 121 747 (98·41)
Person Years 164 950 781 898 178 106 768 742 394 847 552 001 23 257 923 591 19 271 927 576 28 868 917 980 34 839 912 009 12 028 934 820 53 431 893 417 21 804 925 044 94 378 852 469 86 634 860 214 18 192 928 656 37 197 909 651 8 495 938 353 30 207 916 640 146 267 800 581 1 008 945 840 627 946 220 4 732 942 116 2 248 944 600
Incidence/1000 person years 311·88 130·89 256·40 140·64 249·10 100·41 182·96 161·90 222·87 161·16 232·96 160·20 236·29 159·59 266·46 161·08 273·96 155·75 320·04 158·70 239·29 153·91 291·71 149·40 267·48 160·36 286·50 157·34 307·47 161·10 305·49 157·70 357·43 126·79 406·83 162·16 310·85 162·32 279·39 161·83 458·71 161·71
Drug Adjusted Model
Fully Adjusted Model
p value
1·15 (1·12–1·18) 1·00 0·93 (0·90–0·95) 1·00 1·08 (1·05–1·10) 1·00 0·71 (0·67–0·77) 1·00 0·85 (0·78–0·93) 1·00 0·84 (0·80–0·89) 1·00 0·77 (0·73–0·81) 1·00 0·72 (0·65–0·78) 1·00 0·81 (0·78–0·85) 1·00 0·99 (0·93–1·05) 1·00 0·98 (0·95–1·02) 1·00 0·93 (0·89–0·96) 1·00 1·05 (0·97–1·13) 1·00 1·19 (1·14–1·25) 1·00 1·25 (1·15–1·36) 1·00 0·94 (0·89–0·98) 1·00 1·02 (0·99–1·05) 1·00 0·50 (0·36–0·70) 1·00 0·82 (0·63–1·05) 1·00 0·80 (0·69–0·92) 1·00 0·65 (0·54–0·79) 1·00
1·22 (1·18–1·26) 1·00 1·02 (0·99–1·06) 1·00 1·10 (1·06–1·13) 1·00 0·75 (0·70–0·81) 1·00 0·85 (0·78–0·93) 1·00 0·93 (0·88–0·98) 1·00 0·95 (0·90–1·00) 1·00 0·95 (0·87–1·05) 1·00 0·96 (0·91–1·00) 1·00 0·98 (0·92–1·04) 1·00 1·04 (1·00–1·08) 1·00 1·06 (1·02–1·11) 1·00 1·09 (1·02–1·17) 1·00 1·12 (1·06–1·17) 1·00 1·20 (1·10–1·31) 1·00 0·98 (0·93–1·04) 1·00 1·16 (1·12–1·20) 1·00 0·65 (0·46–0·90) 1·00 0·77 (0·60–0·98) 1·00 0·79 (0·68–0·91) 1·00 0·82 (0·67–1·00) 1·00
< 0·0001* 0·13 < 0·0001*
