Background

Most acute treatment studies demonstrate that antidepressants and brief evidence-based psychotherapy are equally effective in the short-term treatment of depression (Depression Guideline Panel, 1993; Reference DeRubeis, Gelfand and TangDeRubeis et al, 1999). The limited economic data available suggest that the cost of therapy exceeds that of medication plus usual care in the acute phase (Reference Scott and FreemanScott & Freeman, 1992; Reference Gabbard, Lazar and HornbergerGabbard et al, 1997). However, these cost-effectiveness findings might be transformed if a psychological treatment had a durable post-intervention effect and the studies extended the follow-up period (Reference ScottScott, 2000). There is tentative evidence from follow-up studies of randomised controlled treatment trials of acute depression that a course of cognitive therapy or interpersonal therapy may significantly reduce the later risk of relapse (Reference Elkin, Shea and WatkinsElkin et al, 1989; Reference Evans, Hollon and DeRubeisEvans et al, 1992). However, the studies followed up small numbers of subjects, were relatively low powered, did not collect data on resource utilisation and the findings were prone to the ‘differential sieve’ effect, where the subjects involved in the follow-up phase of the study were no longer representative of those included at randomisation (Reference Paykel, Scott and TeasdalePaykel et al, 1999). Our UK-based randomised controlled trial avoided these pitfalls (Reference Paykel, Scott and TeasdalePaykel et al, 1999; Reference Scott, Teasdale and PaykelScott et al, 2000). It recruited 158 individuals with persistent depressive symptoms despite adequate treatment with antidepressant medication and appropriate clinical input. As reported, the group who received cognitive therapy had significantly fewer relapses during the 1-year follow-up period than the control group, as well as experiencing significant reductions in depressive symptoms and improvements in social functioning. However, we do not know whether the additional health gain achieved offsets the additional cost of providing cognitive therapy.

This study explores whether relapse prevention with a psychological therapy is cost-effective. The direct health costs of avoiding relapse were assessed in two ways: the total cost per depressive relapse avoided and the cost per additional relapse-free day.

Subjects

Subjects were 21- to 65-year-old psychiatric out-patients with unipolar depression who gave informed consent and who had satisfied DSM—III—R (American Psychiatric Association, 1987) criteria for major depression in an episode within the past 18 months but not in the past 2 months. At randomisation, subjects were required to have current residual symptoms of at least 8 weeks' duration that reached both 8 or more on the 17-item Hamilton Rating Scale for Depression (HRSD; Reference HamiltonHamilton, 1967) and 9 or more on the Beck Depression Inventory (BDI; Reference Beck, Ward and MendelsonBeck et al, 1961). Patients were excluded if they had a past history of bipolar disorder or a current history of significant Axis I or Axis II comorbidity or other factors precluding participation in the study. Patients currently receiving formal psychotherapy and those who had previously received cognitive therapy for more than five sessions were also excluded.

Treatments

All subjects were receiving antidepressants at a minimum dose equivalent to 125 mg or more of amitryptiline. Subjects then were randomised to receive clinical management alone, or clinical management plus cognitive therapy. Clinical management comprised 30-min appointments with a psychiatrist every 4 weeks during the treatment phase (20 weeks) and every 8 weeks during the 48-week follow-up phase. Cognitive therapy comprised 16 sessions over 20 weeks, with two subsequent booster sessions. Therapists were experienced in the approach and received regular supervision. A treatment manual was used. Clinical management and cognitive therapy sessions were audiotaped and monitored to ensure protocol adherence and competency. All subjects remained on continuation and maintenance antidepressants throughout the study. An antidepressant dosage increase of 30% greater than at inclusion was allowed. Lithium also could be prescribed.

Clinical assessments

Subjects were assessed every 4 weeks up to week 20 and every 8 weeks thereafter by a study psychiatrist blind to treatment group (interrater reliability in ratings and an audit of blinding status also were undertaken). The primary outcome measure of relapse was defined as either:

1. (i) meeting the DSM—III—R criteria for major depressive disorder for a minimum duration of 1 month and also having a score of 17 or above on the HRSD at two successive face-to-face assessments at least 1 week apart; or

2. (ii) having residual depressive symptoms that persisted between two successive ratings 2 months apart, reaching a score of at least 13 on the HRSD on both occasions combined with a level of distress or dysfunction at which withholding additional active treatment was not justified.

Resource utilisation and cost assessments

The economic analysis was undertaken from the perspective of the direct costs to the National Health Service. Non-health service expenditure and indirect costs were not considered in the analysis.

Information on health and social care utilisation was collected using an adapted version of the Client Service Receipt Inventory (Reference Knapp and BeechamKnapp & Beecham, 1990). The questionnaire was administered alongside the clinical assessments. Direct health care costs were derived by using activity data and applying an appropriate unit cost to each recorded consultation, contact or episode of care (see Table 1). All unit costs were adjusted to 1998/1999 prices using the relevant price indices. The unit cost estimates were obtained from a variety of sources, including the relevant local providers, the Personal Social Services Research Unit (Reference Netten, Dennet and KnightNetten et al, 1999) and the British National Formulary (British Medical Association & Royal Pharmaceutical Society of Great Britain, 1999). The treatment costs for cognitive therapy were calculated by using a cost per minute taken from the mid-point of the relevant 1998/1999 salary scales and included employers' national insurance and superannuation contributions, and overhead costs. The additional costs of non-face-to-face activities (e.g. writing up notes, supervision) were estimated by using a ratio provided by each therapist. The unit costs of other therapies were derived using a similar bottom-up approach.

Table 1

Unit costs for services

Service	Unit cost	Source
Cognitive therapy	£ 26 per hour	Mid-point salary scale (bottom-up estimates)
Clinical management	£ 24 per hour	Mid-point salary scale (bottom-up estimates)
In-patient	£ 119—£128 per day	Local provider accounts
Day hospital	£ 59 per day	Unit costs of health and social care
General practitioner	£ 14 per visit	Unit costs of health and social care
Social worker	£ 18 per hour, £86 per hour of face-to-face contact	Unit costs of health and social care
Community psychiatric nurse	£ 19 per hour, £21 per home visit	Unit costs of health and social care
Therapist/counsellor	£ 43—£59 per hour face-to-face contact	Mid-point salary scale (bottom-up estimates)
Group therapy	£ 4—£9 per hour of face-to-face contact	Mid-point salary scale (bottom-up estimates)
Marital therapy	£ 54 per hour of face-to-face contact	Mid-point salary scale (bottom-up estimates)
Medication	Cost per drug per mg	British National Formulary

The unit cost estimates were combined with the resource utilisation data to obtain a net cost per patient over the entire trial. Costs are reported in net present value terms by discounting costs at the annual rate of 6%, as recommended by the UK Treasury.

Data analysis

Clinical outcome

Initial characteristics of the two treatment groups showed that they were closely comparable on all key variables (see Table 2). Subjects' mean age was about 43 years, and 50% were male. Severity ratings were now in the middle of the residual depression range, with a mean HRSD score of about 12 and a mean BDI score of 22, although over 50% of index episodes were originally classified as severe. The median duration of the current episode was about 14 months. Only 30% of subjects were in their first episode of depression. Doses of antidepressants were equivalent to 186 mg of amitriptyline daily for those on TCAs and 33 mg of fluoxetine for those on SSRIs. About 60% of subjects were on SSRIs and about 15% were receiving lithium augmentation.

Table 2

Baseline characteristics of subjects

	Control group (n=77)	Cognitive therapy group (n=77)
Mean age, years (s.d.)	43.2 (11.2)	43.5 (9.8)
Female, n (%)	41 (53%)	37 (46%)
Severe index episode, n (%)	43 (55%)	41 (51%)
Median duration of index episode, months	13.0	14.5
History of major depressive disorder, n (%)	50 (65%)	51 (64%)
Mean dose of medication at inclusion, mg (s.d.)
TCA, amitriptyline equivalent	188 (45)	186 (45)
SSRI, fluoxetine equivalent	36 (15)	31 (11)
Symptom ratings at inclusion, mean (s.d.)
Hamilton Rating Scale for Depression	12.2 (2.9)	12.1 (2.7)
Beck Depression Inventory	22.3 (8.0)	21.9 (7.7)

As reported by Paykel et al (Reference Paykel, Scott and Teasdale1999), actuarial cumulative relapse rates for the cognitive therapy and the control group, respectively, in the intention-to-treat analyses were 10% and 18% at 20 weeks and 29% and 47% at 68 weeks (adjusted hazard ratio=0.51; 95% CI 0.32-0.93). The number needed to treat with cognitive therapy per additional depressive relapse avoided was six (95% CI 3-11).

Total costs

The mean direct health care costs (excluding the cost of cognitive therapy) were significantly lower in the cognitive therapy group in comparison with the control group (see Table 3). Cognitive therapy resulted in a mean cost saving of £385 (95% CI £ 1-£769). These cost savings accrued primarily from savings on inpatient admissions and day-patient services. When the additional costs of cognitive therapy were considered, patients in the intervention group were significantly more expensive than those who received conventional treatment. On average, patients receiving cognitive therapy were £779 (95% CI £ 387-£1170) more costly. However, because cognitive therapy resulted in significant cost offsets in other areas of health care expenditure, the incremental cost incurred by patients receiving cognitive therapy (£779) was lower than the overall mean therapy cost of cognitive therapy (£1164).

Table 3

Mean cost of treatment using the last value carried forward (LVCF)¹

	Control group (n=77)			Cognitive therapy (CT) group (n=77)			Mean cost difference:
	Mean	Median	s.d.	Mean	Median	s.d.	CT — control (95% CI)
Cognitive therapy	0	0	0	1164	1222	346	1164 (1084 to 1244)
Planned clinical management	172	170	29	164	158	34	-8 (-19 to 2)
Additional clinical management	27	15	43	18	0	38	-10 (-23 to 3)
In-patient services	177	0	856	16	0	101	-161 (-356 to 35)
Day patient services	206	0	1144	0	0	0	-206 (-466 to 54)
General practitioner	110	98	71	107	95	81	-4 (-28 to 21)
Community psychiatric nurse	17	0	56	23	0	124	5 (-25 to 36)
Social worker	13	0	71	0	0	0	-13 (-29 to 4)
Counsellor/therapist	32	0	135	40	0	195	8 (-46 to 61)
Group therapy	8	0	47	7	0	46	-1 (-16 to 14)
Marital/family therapy	4	0	37	3	0	19	-1 (-11 to 8)
Other mental health contacts	8	0	38	28	0	104	20 (-6 to 45)
Neuroleptics	3	0	11	2	0	5	-1 (-4 to 2)
Hypnotics	3	0	11	4	0	11	1 (-2 to 5)
Lithium	6	0	11	7	0	15	1 (-3 to 5)
Antidepressants	331	323	237	315	308	227	-16 (-91 to 58)
All medication	343	323	242	329	308	230	-15 (-90 to 61)
Direct health care costs
Excluding cognitive therapy costs	1119	700	1633	734	602	447	-385 (-769 to -1)*
Including cognitive therapy costs	1119	700	1632	1898	1870	564	779 (387 to 1170)**

Cost-effectiveness

On the basis of a deterministic comparison of mean costs and effects, cognitive therapy is more effective but more costly than standard clinical management and antidepressants alone. The resulting ICER is £4328 per relapse prevented (£779/0.18). This translates to a cost of about £ 12.50 per additional relapse-free day.

Figure 1 presents the resulting cost-effectiveness—acceptability curve for cognitive therapy. The curve indicates the probability of adjunctive cognitive therapy being more cost-effective than clinical management and antidepressants alone for a range of potential maximum amounts (ceiling ratio) that a decision-maker is willing to pay to prevent an additional relapse. For example, if the decision-maker is prepared to pay £6000, the probability of cognitive therapy being cost-effective is over 60%, and at £8500 the probability of cognitive therapy being cost-effective is over 80%.

Fig. 1

Cost-effectiveness—acceptability curve: probability that preventing an additional relapse is cost-effective as a function of a decision-maker's ceiling cost-effectiveness ratio.

Sensitivity analysis

The sensitivity of the cost-effectiveness analysis to the method of handling the missing data was examined by recalculating the ICER and the cost-effectiveness—acceptability curves using the alternative imputation approaches. The results indicate that the findings are relatively robust to the choice of method used to impute the missing assessments. The ICER increases to £4667 (£840/0.18) using mean imputation and to £ 5028 (£905/0.18) using non-parametric multiple imputation. In contrast to the imputation approaches, the ICER increases to £7056 (£1270/0.18) per relapse prevented using only the 65% of subjects in the complete case analysis. As shown in Fig. 2, the distance of the cost-effectiveness—acceptability curve using the complete case analysis from the three imputation curves (which are clustered together) clearly illustrates that the results are highly sensitive to the decision to impute the missing data.

Fig. 2

Sensitivity analysis for cost—acceptability curves: imputation techniques v. complete case analysis. Curves: — last value carried forward; - - - mean imputation; — — — multiple imputation; — complete case data analysis only.

CLINICAL IMPLICATIONS

1. ▪ In individuals with medication-refractory depression, the addition of cognitive therapy to intensive clinical treatment is more costly but more effective than intensive treatment alone.

2. ▪ The cost of providing this therapy is about £12.50 per additional relapse-free day.

3. ▪ The balance between the costs and benefits of psychological v. pharmacological treatments may change significantly if judged against the longitudinal course of depressive disorders.

LIMITATIONS

1. ▪ Indirect costs, such as loss of earning by subjects or their carers, were not measured.

2. ▪ The study assumes that all the benefits from cognitive therapy come to an abrupt end at 17 months, which may have led to an overestimate of the incremental cost-effectiveness ratio.

3. ▪ Quality-adjusted life-years were not measured, so the findings for depression cannot be compared directly with cost-effectiveness studies of physical disorders with similar levels of morbidity.