Cost effectiveness of escitalopram versus SNRIs in second-step treatment of major depressive disorder in Sweden

Figures & data

Figure 1.  Model framework for second-line treatment. (1) Remission by 24 weeks: Patients who achieved remission by 8 weeks following initiation of second-step therapy and remained in remission by 24 weeks. Patients were to continue taking the same medication for another 4 months. (2) Relapse at 24 weeks: Patients who achieved remission by 8 weeks following initiation of second- step therapy but experienced relapse during the following 4-month period. (3) No remission at 8 weeks: Patients who did not achieve remission during the first 8 weeks of second-step therapy.

Table 1.  Clinical probabilities – remission, relapse, adverse events, titration rates.

Parameter	Escitalopram	Venlafaxine	Duloxetine	Reference
Remission rate at 8 weeks*, %	62.1	40.9	40.9	13
Relapse rate after 6 months, %	19.3	18.1	18.1	20
Adverse events rate at 8 weeks*				18
Nausea, %	16.8	32.1	24.0	17
Headache, %	15.4	12.8	16.2	15
Sweating, %	5.0	10.3	7.8	16
Insomnia, %	6.3	7.4	19.7
Dry mouth, %	8.2	11.9	12.7
Somnolence, %	6.9	8.2	4.2
Diarrhoea, %	7.4	7.4	9.5
Fatigue, %	5.3	9.0	7.4
Dizziness, %	4.8	8.2	9.5
Constipation, %	4.0	15.0	5.3
Ejaculation disorder, %	1.7	8.6	2.8
Titration rates*, %	15.5	29.2	0†	19

*Beta distribution was used in Monte Carlo simulation for all clinical parameters above.

†Assumption.

Table 2.  Unit costs (€2009), including additional medications for adverse events.

Resource use item		Unit cost (€)
Inpatient*†	Psychiatrist (bed day)	456.38
Outpatient*†	General practitioner	85.82
	Follow-up call (GP)	35.04
	Psychiatrist	288.99
	Other doctors (e.g., neurologist, cardiologist)	184.99
	Acute & Emergency	229.44
	Other healthcare professionals (e.g., psycho-therapist)	150.43
	Counsellor	150.43
	Psychologist	150.43
	Nurse	35.04
Sick leave†‡	Daily wage	180
Antidepressants§	Escitalopram 10 mg	0.93
	Escitalopram 20 mg	1.62
	Venlafaxine 75 mg	0.7
	Venlafaxine 150 mg	0.97
	Duloxetine 60 mg	1.29
	Other AD (4 most prescribed)	0.3
Medication for AEs¶	Nausea (promethazine 25 mg + buclizine 25 mg or metoclopramide 10 mg)	8.5
	Headache (paracetamol 500 mg or Panodil 500 mg)	5.57
	Insomnia (zopiclone 7.5 mg)	3.94
	Dry mouth (Salivin 50 g or Xerodent 0.25 mg)	5.06
	Diarrhoea (loperamide 2 mg)	5.66
	Constipation (lactulose 670 mg or Vi-Siblin granulat)	5.9

*The Regional Joint Committee of the Southern Sweden Healthcare Region, price list for 2007.

†Unit costs in source were from 2007 and they were inflated to 2008 for the model. Costs were inflation-corrected to year 2008 using Ekonomifakta website; www.ekonomifakta.se/en [Accessed June 26, 2009].

‡Confederation of Swedish Enterprise, 2007. www.svensktnaringsliv.se.

§Pharmaceutical use – assumed that medication continued for 180 days. Titration, if applicable, after day 30. Switch to alternative AD therapy after day 60 if no remission.

¶Adverse event treatment costs – the treatment cost for each AE was assumed to be the price of the lowest package, and was taken from the Dental and Pharmaceuticals Benefit Agency (TLV). If different medications were reported by the two experts, then the average cost for the two different drugs was used in the model calculations.

Table 3.  Resource utilization per patient for inpatient care, outpatient care, production loss (24-week data), according to remission status and titration.

	Remission	No remission
Utility mean (SE)*
Baseline	0.47 (0.013)	0.47 (0.013)
Endpoint	0.81 (0.015)	0.57 (0.020)
Inpatient care (bed days)* mean (SD)
Psychiatric inpatient stay	0.36 (3.10)	0.28 (2.39)
Outpatient care (number of contacts)* mean (SD)
GP	4.24 (2.23)	5.89 (4.29)
GP phone (follow-up)	1.19 (1.70)	1.71 (2.92)
Psychiatrist	0.03 (0.18)	0.15 (0.52)
Acute & Emergency	0.05 (0.39)	0.33 (1.54)
Other doctors (e.g., neurologist, cardiologist)	0 (0.06)	0.06 (0.37)
Nurse	0.01 (0.11)	0.06 (0.52)
Psychologist	0.06 (0.30)	0.31 (1.20)
Counsellor	0.1 (0.55)	0.22 (0.83)
Other health professionals (e.g., psychotherapist)	0.04 (0.29)	0.08 (0.36)
Production loss* mean (SD)
Sick-leave days	34.14 (55.58)	56.06 (69.98)
Additional GP contact for titration† mean (SD)
GP visit	2.87 (5.41)	2.87 (5.41)
GP telephone call	0.9 (2.55)	0.9 (2.55)

SE, standard error, SD, standard deviation.

In the probabilistic analyses, gamma distributions (based on mean and SD) were used for unit costs and normal distributions (based on mean and SE) were used for utility values.

*Reference 21.

†Reference 19.

Table 4.  Utilities for QALY calculation.

Patient group	First 8 weeks	Subsequent 4 months
Remission and continued therapy	Average of baseline and remission utilities	Remission utility
Remission followed by relapse	Average of baseline and remission utilities	Average of remission and no remission utility
No remission	Average of baseline and no remission utilities	No remission utility

Table 5.  Model effectiveness results: escitalopram versus venlafaxine and duloxetine.

	Mean			Incremental (95% CI) versus escitalopram
	Escitalopram	Venlafaxine	Duloxetine	Venlafaxine	Duloxetine
Effectiveness
QALY	0.322	0.298	0.297	0.025	0.025
				(0.009, 0.042)	(0.009, 0.042)
Sustained remission, %	50.1	33.6	33.6	16.4	16.4
				(2.7, 30.2)	(2.7, 30.2)
Costs (in €)
Total direct costs	973.25	1,014.43	990.43	−41.18	−17.18
				(−477.12, 224.74)	(−403.01, 365.95)
Indirect costs	5,741.09	6,206.59	6,206.59	−465.50	−465.50
				(−5,144.83, 3,404.16)	(−5,144.83, 3,404.16)
Total costs	6,714.37	7,221.02	7,197.02	−506.59	−482.69
				(−5,249.47, 3,427.10)	(−5,230.27, 3,443.81)

CI, credibility interval.

Figure 2.  (a) The cost effectiveness of escitalopram compared with venlafaxine (base-case scenario): incremental effectiveness (on QALYs) versus incremental total costs. 1 SEK = €0.0960. (b)The cost effectiveness of escitalopram compared with duloxetine: incremental effectiveness (on QALYs) versus incremental total costs. 1 SEK = €0.0960.

Figure 3.  Cost-effectiveness acceptability curve – escitalopram compared with venlafaxine and duloxetine. 1 SEK = €0.0960.

Table 6.  Cost effectiveness of escitalopram.

Escitalopram	Versus venlafaxine	Versus duloxetine
Base case ICER (€/QALY)	Dominant	Dominant
Dominant, %	65.4	64.6
Cost effective, %
– with willingness to pay £20,000 (€22,080)	81.5	80.9
– with willingness to pay £30,000 (€33,600)	85.8	85.5

Table 7.  Sensitivity analyses – effect of variation in key effectiveness parameters on costs (mean, €2009) and QALYs for escitalopram versus venlafaxine and duloxetine.

Values		Incremental vs. venlafaxine	Incremental vs. duloxetine
Remission rates (base case 62.1%) at 8 weeks
Low 50.2%	Direct	−25.82	−1.82
	Indirect	−197.86	−197.86
	Total	−223.49	−199.58
	QALYs	0.014	0.014
High 73.2%	Direct	−59.9	−35.9
	Indirect	−721.25	−721.25
	Total	−781.06	−757.15
	QALYs	0.036	0.036
Relapse rates (base case 19.3%) after 6 months
Low 16.0%	Direct	−49.44	−25.44
	Indirect	−526.08	−526.08
	Total	−575.42	−551.52
	QALYs	0.026	0.026
High 22.7%	Direct	−37.25	−13.25
	Indirect	−408.77	−408.77
	Total	−445.92	−422.02
	QALYs	0.025	0.025
No. of sick leave days in 6 months* Base case: rem 34.14, no rem 56.06
Low 26.75 (rem) 47.26 (no rem)	Direct	−19.49	−25.44
	Indirect	−438.91	−526.08
	Total	−458.40	−551.52
High 42.19 (rem) 66.51 (no rem)	Direct	−19.49	0.00
	Indirect	−520.42	−13.25
	Total	−540	−408.77
No. of GP visits in 6 months* Base case: rem 4.24, no rem 5.89
Low 3.96 (rem) 4.54 (no rem)	Direct	−39.74	−15.74
	Indirect	−469.15	−469.15
	Total	−508.8	−484.9
High 5.35 (rem) 6.57 (no rem)	Direct	−48.96	−24.96
	Indirect	−469.15	−469.15
	Total	−517.92	−494.02
Nausea rates, base case 16.8%
Low 0.137	Direct	−43.78	−19.78
	Indirect	−469.15	−469.15
	Total	−512.74	−488.83
High 0.201	Direct	−43.2	−19.2
	Indirect	−469.15	−469.15
	Total	−512.26	−488.35

*The values in this case were changed simultaneously, to investigate the potential impact of over/under-reporting of this resource in HEADIS. rem, remission.