Use of Selective Serotonin Reuptake Inhibitors – Validity of Self-Report versus Plasma Concentrations and Pharmacy Dispensations – A Cross-Sectional Analysis of the Norwegian Women and Cancer Study

Figures & data

Figure 1 Study samples: (A) Participants with self-reported SSRI-use from specific questions in the main questionnaire (the Norwegian Women and Cancer study, NOWAC) and pharmacy dispensations from the Norwegian Prescription Database (NorPD); (B) participants with self-reported SSRI-use from open question in the small questionnaire (NOWAC), plasma concentrations and pharmacy dispensations (NorPD).

Abbreviations: SSRI, selective serotonin reuptake inhibitor; Q-data, Questionnaire data.

Table 1 Characteristics of the Total Study Population and the Two Sub-Populations

Characteristics (From Main Questionnaire)	Total Study Sample (with SSRI in Main Q)		Main Study Sample* (Main Q and NorPD)		Plasma Concentration Subsample* (Small Q, NorPD and Plasma Conc.)
	n=104,740		n=70,191		n=136
Age in years, mean (sd)	54.1 (4.4)		54.4 (4.3)		53.3 (4.3)
Education in years, mean (sd)	13.0 (3.5)		12.9 (3.5)		12.7 (3.6)
BMI in kg/m^2, mean (sd)	25.2 (4.1)		25.2 (4.2)		25.7 (5.2)
	n	%	n	%	n	%
Marital status
Single	22,933	21.9	15,521	22.1	27	19.9
Cohabiting	81,807	78.1	54,670	77.9	109	80.1
Work situation
Full time	52,341	50	35,904	51.2	59	43.4
Part time	29,292	28	19,186	27.3	38	27.9
Not working	21,487	20.5	14,457	20.6	36	26.5
Missing	1620	1.5	644	0.9	3	2.2
Health
Good	94,273	90	63,000	89.8	111	81.6
Poor	7605	7.3	5187	7.4	18	13.2
Missing	2862	2.7	2004	2.9	7	5.1
Smoking currently
Yes	17,107	16.3	8737	12.4	24	17.6
No	47,613	45.5	24,379	34.7	26	19.1
Missing	40,020	38.2	37,075	52.8	86	63.2
Co-morbidity**
Yes	14,607	13.9	13,324	19.0	45	33.1
No or missing	90,133	86.1	56,867	81.0	91	66.9
Musculo/skeletal pain
Yes	10,988	10.5	10,987	15.7	41	30.1
Cardiovascular disease
Yes	1684	1.6	1155	1.6	2	1.5
Diabetes
Yes	2748	2.6	1917	2.7	5	3.7
No	87,758	83.8	58,763	83.7	108	79.4
Missing	14,234	13.6	9511	13.6	23	16.9
SSRI previously
Yes	6698	6.4	4632	6.6	23	16.9
No	65,693	62.7	44,568	63.5	84	61.8
Missing	32,349	30.9	20,991	29.9	29	21.3
SSRI currently***
Yes	5023	4.8	3302	4.7	50	36.8
No or missing	99,717	95.2	66,889	95.3	86	63.2
Fluoxetine	317	0.3	194	0.3	0	0.0
Citalopram	1669	1.6	1053	1.5	21	15.4
Paroxetine	1130	1.1	728	1.0	14	10.3
Sertraline	985	0.9	618	0.9	9	6.6
Fluvoxamine	56	0.1	32	0.0	0	0.0
Escitalopram	1093	1.0	828	1.2	9	6.6

Notes: Text in italic denotes sub-characteristics, ie categories of comorbidity and SSRI, respectively. *Participated in NOWAC between 1 July 2004–31 Dec 2006. **Includes diabetes, cardiovascular diseases (stroke, myocardial infarction, blood clot/embolus) and various musculoskeletal disorders (myalgia, fibrositis, backache, whiplash injury, osteoporosis, or chronic fatigue syndrome). ***Information from the main questionnaire was collected 6–12 months before the blood samples.

Abbreviations: Q, questionnaire; NorPD, Norwegian Prescription Database; BMI, Body mass index; SSRI, selective serotonine reuptake inhibitor.

Table 2 Validity of Self-Reported SSRI-Use versus Plasma Concentrations and Pharmacy Dispensations

	n	Non-Users	Users			Sensitivity (95% CI)	Spesificity (95% CI)	PPV (95% CI)	NPV (95% CI)	Cohen’s κ (95% CI)	Prevalence of SSRI-use (%)
Data source to be compared with SSRI plasma concentrations		Both sources	Both sources	NorPD or SmallQ only	SSRI-concentration only	%	%	%	%
SmallQ, open question	136	68	67	1	0	100.0 (93.2–100.0)	98.6 (91.1–99.9)	98.5 (91.0–99.9)	100.0 (93.3–100.0)	0.985 (0.957–1.000)
NorPD
SSRI-use defined by
LTD	136	68	62	1	5	92.5 (82.7–97.2)	98.6 (91.1–99.9)	98.4 (90.3–99.9)	93.2 (84.1–97.5)	0.912 (0.843–0.981)
FTF 180 days		68	63	1	4	94.0 (84.7–98.1)	98.6 (91.1–99.9)	98.4 (90.5–99.9)	94.4 (85.7–98.2)	0.926 (0.863–0.990)
FTF 90 days		68	56	1	11	83.6 (72.1–91.1)	98.6 (91.1–99.9)	98.2 (89.4–99.9)	86.1 (76.0–92.5)	0.823 (0.728–0.919)
Data source to be compared with pharmacy dispensations (NorPD)		Both sources	Both sources	NOWAC main Q only	NorPD only						NorPD	NOWAC
MainQ, specific questions
NorPD SSRI-use defined by
LTD	70191	66,601	2447	855	288	89.5 (88.2–90.6)	98.7 (98.6–98.8)	74.1 (72.6–75.6)	99.6 (99.5–99.6)	0.802 (0.791–0.814)	3.9	4.7
FTF 180 days		66,383	2761	541	506	84.5 (83.2–85.7)	99.2 (99.1–99.3)	83.6 (82.2–84.9)	99.2 (99.2–99.3)	0.833 (0.823–0.843)	4.7
FTF 90 days		66,607	2166	1136	282	88.5 (87.1–89.7)	98.3 (92.2–98.4)	65.6 (63.9–67.2)	99.6 (99.5–99.6)	0.743 (0.730–0.756)	3.5

Abbreviations: SSRI, selective serotonin reuptake inhibitor; SmallQ, questionnaire following blood samples; MainQ, Main questionnaire; NOWAC, the Norwegian Women and Cancer study; NorPD, the Norwegian Prescription Database; PPV, positive predictive value; NPV, negative predictive value; LTD, Legend Time Duration; FTF, Fixed Time Frame (sensitivity analyses); CI, Confidence Interval.

Figure 2 Distribution of SSRI-users according to three data sources: self-report from open questions in the small questionnaire (the Norwegian Women and Cancer study, NOWAC), plasma concentrations from NOWAC and pharmacy dispensations from the Norwegian Prescription Database (NorPD).

Abbreviation: Q, Questionnaire.

Table 3 Factors Associated with Discordance Between Self-Reported SSRI-Use (Specific Questions in the NOWAC Main Questionnaire, n = 70,191) and Pharmacy Dispensation (NorPD)

Variables	Concordant Population						Discordant Population						Concordant versus Discordant
	User Both		Non-User Both		Concordant Total		NOWAC Main Q Only		NorPD Only		Discordant Total		Univariate Analyses			Multivariable Analysis*
	N=2447		N=66601		N=69048		N=855		N=288		N=1143
													OR	95% CI		OR	95% CI
	Mean(sd)		Mean(sd)		Mean(sd)		Mean(sd)		Mean(sd)		Mean(sd)
Age, years	54.4(4.3)		54.3(4.3)		54.3(4.3)		54.7(4.2)		54.8(4.4)		54.7(4.2)		1.01	1.00	1.02	0.99	0.98	1.01
Education, years	12.3(3.5)		12.9(3.5)		12.9(3.5)		11.8(3.3)		12.2(3.5)		11.9(3.4)		0.95	0.93	0.96	0.96	0.95	0.98
BMI, kg/m^2	26.6(5.0)		25.2(4.1)		25.3(4.2)		26.1(4.7)		25.8(5.3)		26.0(4.8)		1.05	1.04	1.06	1.01	1.00	1.03
	n	%	n	%	n	%	n	%	n	%	n	%
Marital status
Cohabiting	1711	69.9	52,168	78.3	53,879	78.0	599	70.1	192	66.7	791	69.2	1.00			1.00
Single	736	30.1	14,433	21.7	15,169	22.0	256	29.9	96	33.3	352	30.8	1.60	1.47	1.75	1.64	1.43	1.89
Work situation
Full time	648	26.5	34,954	52.5	35,602	51.6	224	26.2	78	27.7	302	26.4	1.00			1.00
Part time	685	28.0	18,184	27.3	18,869	27.3	254	29.7	63	21.9	317	27.7	1.90	1.70	2.11	1.84	1.55	2.19
Not working	1085	44.3	12,867	19.3	13,952	20.2	364	42.6	141	50.0	505	44.2	4.13	3.75	4.55	2.79	2.34	3.32
Missing	29	1.2	596	0.9	625	0.9	13	1.5	6	2.1	19	1.7
Health
Good	1823	74.5	60,352	90.6	62,175	90.0	653	76.4	172	59.7	825	72.2	1.00			1.00
Poor	561	22.9	4377	6.6	4938	7.2	175	20.5	74	25.7	249	21.8	3.72	3.37	4.10	2.22	1.88	2.63
Missing	63	2.6	1872	2.8	1935	2.8	27	3.2	42	14.6	69	6.0
Co-morbidity
No or missing	826	33.8	12,162	18.3	56,060	81.2	264	30.9	72	25.0	807	70.6	1.00			1.00
Yes	1621	66.2	54,439	81.7	12,988	18.8	591	69.1	216	75.0	336	29.4	1.29	1.16	1.43	1.34	1.16	1.54

Notes: *Multiple binary logistic regression: Hosmer & Lemeshow p = 0.219; Nagelkerke r² = 0.054; 9.3% missing cases, statistically significant associations are in bold print.

Abbreviations: SSRI, selective serotonin reuptake inhibitors; NOWAC, the Norwegian Women and Cancer study; NorPD, the Norwegian Prescription Database; OR, Odds Ratio; CI, Confidence Interval; BMI, Body Mass Index.