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Figure S1 - The raw numbers of prescribed items by class, from 1998 to 2018. MAOI = monoamine oxidase inhibitor, SNRI = selective - inhibitor, SSRI = selective serotonin .

Figure S2 - The raw numbers of prescribed antidepressant items for the ten most commonly prescribed (in 2018), from 1998 to 2018.

Figure S3 - Practice level percentile charts for the proportions of the ten most commonly prescribed antidepressants (in 2018), prescribed between August 2010 and November 2019. Deciles are in blue, with median shown as a heavy blue line, and extreme percentiles are in red.

Figure S4 - Practice level percentile charts for the proportions of specific MAOIs prescribed between August 2010 and November 2019. Deciles are in blue, with median shown as a heavy blue line, and extreme percentiles are in red.

Figure S5 - CCG level heat map for the percentage proportions of MAOIs prescribed between December 2018 and November 2019. MAOI = monoamine oxidase inhibitor.

Figure S6 - CCG level heat maps for the percentage proportions of , , and prescribed between December 2018 and November 2019. Table S1 - Antidepressant , by category. MAOI = monoamine oxidase inhibitor, SNRI = selective serotonin-norepinephrine reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor.

Class

MAOI , , ,

SNRI ,

SSRI , , , , paroxetine,

Tricyclic , , , dosulepin, , , , , , trimipramine

Other , , , , , , , oxitriptan, , , ,

Table S2 - Basic descriptive statistics for practice level class-specific proportions of antidepressants prescribed between December 2018 and November 2019. IDR = interdecile range, IQR = interquartile range, MAOI = monoamine oxidase inhibitor, SNRI = selective serotonin- norepinephrine reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor.

Standard Lowest Lower Upper Highest Mean Median IQR IDR deviation Decile quartile quartile Decile

SSRI % 54.5 6.6 46.4 50.5 54.7 58.5 62.2 8.0 15.8

Tricyclic % 21.5 5.4 15.3 18.2 21.2 24.5 27.9 6.3 12.6

Other % 14.7 5.3 8.7 11.1 14.2 17.6 21.0 6.5 12.2

SNRI % 9.2 3.3 5.5 7.1 9.0 11.1 13.3 3.9 7.7

MAOI % 0.1 0.2 0 0 0 0 0.2 0 0.2

Table S3 - Practice level basic descriptive statistics for the proportions of the ten most prescribed antidepressants (in 2018) prescribed between December 2018 and November 2019. IDR = interdecile range, IQR = interquartile range.

Standard Lowest Lower Upper Highest Mean Median IQR IDR deviation decile quartile quartile decile

Sertraline% 21.6 5.8 14.6 18.0 21.4 25.1 28.6 7.1 14.0

Citalopram % 20.0 6.1 12.6 15.8 19.7 23.8 27.8 8.0 15.2

Amitriptyline % 18.9 5.2 13.0 15.6 18.6 21.8 25.1 6.1 12.1

Mirtazapine % 12.9 4.9 7.5 9.6 12.4 15.5 18.6 5.8 11.1

Fluoxetine % 9.1 3.3 5.4 6.9 8.7 10.9 13.2 3.9 7.9

Venlafaxine % 6.0 2.6 3.1 4.3 5.8 7.5 9.3 3.2 6.2

Duloxetine % 3.2 2.0 1.1 1.8 2.8 4.1 5.7 2.3 4.6

Paroxetine % 1.9 1.3 0.7 1.2 1.7 2.4 3.3 1.3 2.6

Trazodone % 1.4 1.6 0 0.4 0.9 1.9 3.3 1.5 3.3 Escitalopram % 1.8 2.1 0.2 0.6 1.1 2.1 3.9 1.6 3.7

Table S4 - Practice level basic descriptive statistics for the proportions of specific MAOIs prescribed between December 2018 and November 2019. IDR = interdecile range, IQR = interquartile range.

Standard Lowest Lower Upper Highest Mean Median IQR IDR deviation decile quartile quartile decile

Moclobemide % 0 0.1 0 0 0 0 0.1 0 0.1

Phenelzine % 0 0.1 0 0 0 0 0.1 0 0.1

Tranylcypromine % 0 0.1 0 0 0 0 0 0 0

Isocarboxazid % 0 0 0 0 0 0 0 0 0

Table S5 - Unadjusted and adjusted estimates for any practice-level prescribing of dosulepin and trimipramine from logistic regression analysis. CI = confidence interval, GP = general practitioner, IMD = Index of Multiple Deprivation, OR = odds ratio, QOF = Quality Outcomes Framework.

Mean % of Unadjusted OR Adjusted OR dosulepin and (95% CI) (95% CI) trimipramine

Proportion of 0 to 11.1 0.74 Reference Reference patients over 65 11.2 to 15.7 0.90 1.16 (1.13 to 1.18) 1.23 (1.20 to 1.26)

15.7 to 19.25 0.94 1.24 (1.21 to 1.26) 1.36 (1.33 to 1.40)

19.26 to 23.2 1.01 1.35 (1.33 to 1.38) 1.53 (1.49 to 1.57)

23.2 to 90.3 1.08 1.46 (1.43 to 1.48) 1.59 (1.55 to 1.64)

Proportion of 15.7 to 44.4 0.85 Reference Reference patients with a long term health 44.4 to 49.7 0.97 1.15 (1.13 to 1.18) 1.06 (1.04 to 1.09) condition 49.7 to 53.9 0.93 1.11 (1.09 to 1.13) 0.99 (0.97 to 1.01)

53.9 to 58.6 0.99 1.15 (1.13 to 1.17) 1.02 (1.00 to 1.04)

58.6 to 100 0.94 1.09 (1.07 to 1.11) 0.98 (0.96 to 1.00)

List size <4.3 0.95 Reference Reference (thousands) 4.3 to 6.4 0.91 0.98 (0.96 to 1.00) 0.98 (0.96 to 1.00)

6.4 to 8.8 0.96 1.01 (0.99 to 1.04) 1.01 (0.99 to 1.04)

8.8 to 12.0 0.94 1.01 (0.99 to 1.03) 1.04 (1.02 to 1.07)

>12.0 0.91 0.98 (0.96 to 1.00) 1.04 (1.02 to 1.06)

GPs per 1000 <3.6 0.91 Reference Reference patients 3.7 to 4.8 0.99 1.06 (1.05 to 1.08) 1.04 (1.03 to 1.06)

4.8 to 5.9 0.93 1.01 (0.99 to 1.03) 0.99 (0.97 to 1.01)

5.9 to 7.4 0.93 0.99 (0.97 to 1.00) 0.98 (0.96 to 1.00)

>7.4 0.92 0.98 (0.96 to 0.99) 0.94 (0.92 to 0.95) Rurality Rural village and 0.93 Reference Reference dispersed

Rural town and 0.85 0.94 (0.91 to 0.96) 0.95 (0.89 to 1.01) fringe

Urban city and town 0.87 0.95 (0.94 to 0.96) 0.87 (0.84 to 0.90)

Urban minor 1.05 1.11 (1.09 to 1.12) 0.92 (0.89 to 0.95) conurbation

Urban major 1.28 1.35 (1.32 to 1.39) 1.11 (1.06 to 1.16) conurbation

IMD Least deprived 1.05 Reference Reference

| 1.04 1.00 (0.99 to 1.02) 1.01 (0.99 to 1.02)

| 0.88 0.86 (0.85 to 0.87) 0.94 (0.92 to 0.96)

| 0.84 0.81 (0.79 to 0.82) 0.91 (0.89 to 0.93)

Most deprived 0.86 0.82 (0.81 to 0.84) 0.94 (0.91 to 0.96)

QOF score 160-532 0.95 Reference Reference

532-546 0.96 1.01 (0.99 to 1.02) 1.04 (1.02 to 1.06)

546-554 0.92 0.98 (0.96 to 0.99) 1.00 (0.98 to 1.01)

554-558 0.95 0.97 (0.96 to 0.99) 0.97 (0.95 to 0.98)

558-559 0.90 0.96 (0.94 to 0.97) 0.93 (0.92 to 0.95)