Economic Implications of the Use of Antidepressantsin Adults with Learning Disabilities Su�ering fromA�ective Disorders

S. BHAUMIK1, C. DUGGIRALA1, J. BEE1 and H. WILDGUST2

1Frith Hospital (Fosse NHS Health Trust), Groby Road, Leicester LE3 9QF, UK; 2Lilly Industries, Dextra Court,Chapel Hill, Basingstoke, Hampshire, UK

The cost of treatment with TCAs and SSRIs were audited over a 9-month period in patients with major depressionand co-morbid learning disabilities, using retrospective case-note analysis. Drug costs per treatment episode werefound to be least for TCAs whilst they also incurred the highest side-e�ect costs. The average direct medical costs pertreatment episode were least for ¯uoxetine (£188.55) and highest for TCAs (£268.99) with SSRIs as a group beingintermediate (£242.66). This study has limitations of being a non-randomized retrospective audit, hence the resultsshould be viewed with caution. However, currently there are no other data available.

KEY WORDS Ð learning disability; TCAs; SSRIs; drug costs; side-e�ects costs

INTRODUCTION

Depressive illness has destructive e�ects on bothpatients and their families. The patients su�er bothphysically and mentally and may be disabled bothin their work and socially. The patient's familymay also su�er, experiencing the burden of careand accompanying economic loss. Moreover, therepercussions of depressive illness a�ect society asa whole.

Though Kind et al. (1993) estimated that the costof drug treatment for depression only represents asmall fraction of the overall treatment costs, it isstill substantial and calls for controls on theseexpenses by governments can readily be under-stood. This current debate in the UK has focusedon the relative drugs costs associated with tricyclicantidepressants (TCAs) an selective serotoninre-uptake inhibitors (SSRIs) respectively.

We carried out a retrospective study of the useof antidepressants in patients with learning dis-abilities who were also su�ering from depressiveillness (Bhaumik et al., 1995). This study estab-lished ®rstly that depressive illness in patientswith learning disabilities does respond to anti-depressants and, secondly, that the SSRIs arebetter tolerated in clinical practice and cause fewer

side-e�ects than the tricyclic/tetracyclic group ofdrugs. The e�cacy of both groups of drugs wasfound to be similar. One of the major ®ndings wasthat the overall discontinuation rates were 16 percent and 36 per cent respectively and thatdiscontinuation due to side-e�ects was 9.6 per centin SSRIs and 26 per cent in the TCA group. Such adi�erence has implications for the treatment costsof depression. Moreover, there have been noeconomic evaluations of the use of antidepressantsin this population. This paper quanti®es theeconomic impact of using TCAs and SSRIsrespectively in clinical practice for adults withlearning disabilities who were su�ering froma�ective disorders.

METHOD

The data collected from our earlier retrospectivecase-note analysis (Bhaumik et al., 1995) wereaudited, noting the costs of medication andestimating those associated with side-e�ects. Inour previous study we reviewed all adults (aged 18years and over) in contact over the last 3 years withservices provided by the Department of Psychiatryof Learning Disabilities at the Glenfrith Unit inLeicestershire. This only included patients with anICD9 diagnosis of depression and those not onany antidepressant treatment prior to the study* Author to whom correspondence should be addressed.

CCC 0885±6222/97/010047±06# 1997 by John Wiley & Sons, Ltd.

HUMAN PSYCHOPHARMACOLOGY, VOL. 12, 47±52 (1997)

period. The case-notes included details of history,symptoms, mental state examination, ICD9 diag-nosis, treatment plans, side-e�ects and outcome.

This economic evaluation determined the directdrug costs as well as the associated costs of side-e�ects. The 30-day price of a drug was calculatedfrom the drug tari� (November 1994).

The estimated cost of side-e�ects consist of: (i)the cost of medication to control side-e�ects(e.g. use of thioridazine to control hypomania);(ii) the cost of clinical investigations and admissionto hospital if necessary (the individual costingsrelating to clinical investigations and admission tohospital were provided by the health trust ®nancialo�cer; see Appendix 1); (iii) the cost of switchingto a new antidepressant if necessary.

Detailed costing of side-e�ects is shown inAppendix 1. The average direct medical cost pertreatment episode was calculated for patients whoreceived either an SSRI or a TCA. This is made upof the average drug treatment cost per episode plusthe average side-e�ect cost per episode.

The average side-e�ect cost per treatment epi-sode, for a class of drug, is calculated by totalling

all the side-e�ect costs for each treatment episodeand dividing this by the number of treatmentepisodes.

The average drug costs per treatment episode,for a class of drug is calculated by totalling all thedrug costs for each treatment episode (cost perepisode � number of months of treatment� drugcosts per month) and dividing this sum by thenumber of treatment episodes.

RESULTS

We identi®ed 42 treatment episodes with tricyclic/tetracyclic antidepressants, 34 for ¯uoxetine,22 with paroxetine and six for other SSRIs.Detailed ®ndings were given in our previous paper(Bhaumik et al., 1995).

Tables 1 and 2 show that dothiepin andlofepramine contributed the bulk of the averagedrug cost per treatment episode for TCAs. Theaverage drug cost per treatment episode wassigni®cantly lower for TCAs (£52.17) comparedwith £172.27 for ¯uoxetine and £197.77 for theSSRIs as a whole group.

48 S. BHAUMIK ET AL.

Table 1. Total drug cost for treatment episodes

No. of episodes Daily doses 30-day price Treatment length Total drug cost(mg) (£) (months) (£)

TCAsAmitriptyline 4 150 1.58 9 56.88

3 150 1.58 1 4.74Dothiepin 9 150 9.49 9 768.69

4 150 9.49 4 37.96Doxepin 2 150 4.84 1 9.68

Imipramine 6 150 2.07 9 57.781 150 1.07 1 1.07

Lofepramine 8 210 16.51 9 1188.722 210 16.51 1 33.02

Mianserin 1 50 7.88 1 7.88Trazodone 2 150 12.45 1 24.90

Total 2191.32

SSRIsFluoxetine 31 20 20.77 9 5794.83

3 20 20.77 1 62.31Paroxetine 18 30 31.16 9 5047.92

4 30 31.16 1 124.64Sertraline 2 100 42.61 9 766.98

2 100 42.61 1 85.22Fluvoxamine 1 200 38.00 9 342.00

1 200 38.00 1 38.00

Total 12261.90

Tables 3 and 4 show that the total and averageside-e�ects cost per treatment episode are muchhigher for TCAs as compared with ¯uoxetine orthe SSRIs as a group (£216.82 versus £16.28 versus£44.89 respectively).

Table 5 shows the direct medical costs pertreatment episode for both TCAs and SSRIs,which comprised the average drug costs pertreatment episode plus the average side-e�ects pertreatment episode. Fluoxetine was associated withthe least direct medical cost per treatment episodewhilst TCAs were associated with the highest.

DISCUSSION

The results from this study (Table 5) show thatonce the side-e�ect costs of TCAs and SSRIs aretaken into account, the direct cost per treatmentepisode is lower for SSRIs as a group comparedwith those for TCAs (£242.66 versus £268.99).

The resultant cost of treating hypomania,postural hypotension and drowsiness are particu-larly expensive in connection with the use of TCAs,whilst for SSRIs the treatment of manic episodesconsumed 85 per cent of the resources used forcontrol of side-e�ects (Table 3).

A number of recent studies (Gregor, 1994;Donoghue, 1995; Navarro et al., 1995; Sclaret al., 1995) have shown that although SSRIshave the common feature of blocking the 5HTreuptake pump, in clinical practice they areprescribed di�erently, and these di�erences haveimportant health economic implications. There-fore, we split out the data for ¯uoxetine (34 epi-sodes) and compared them with the whole groupof SSRIs (62 episodes) and TCAs (42 episodes).The results of this analysis showed that theaverage direct medical costs per treatment episodefor ¯uoxetine (£188.55) were signi®cantly lowerthan for the SSRIs as a group (£242.66) or forTCAs (£268.99).

An economic evaluation of antidepressants in aHealth Care Maintenance Organization in theUSA (Sclar et al., 1994) showed similar cost trendsto those in our present study: the direct medical

49ECONOMIC IMPLICATIONS OF ANTIDEPRESSANT USE

Table 2. Average drug cost per treatment episode(ADCTE)

Class of Total drugs Number of Averagedrugs cost for all episodes drugs costs

episodes per episode(£) (£)

TCA 2191.32 42 52.17Fluoxetine 5857.14 34 172.27All SSRIs 12261.90 62 197.77

Table 3. Total side-e�ects costs for treatment episodes

Side-e�ects Number of Total costepisodes (£)

TCAsAgitation 3 107.87Drowsiness 4 3370.50Dry mouth 2 186.93Epileptic seizure 2 473.86Hypomania 1 2871.15Insomnia 1 0.05Leucopenia 1 135Obesity 1 186.93Postural hypotension 3 1773.86

Total 9106.15

SSRIs Ð FluoxetineAgitation 2 170.82Diarrhoea 1 158.59Manic episodes 1 224

Total 553.41

SSRIs Ð excluding ¯uoxetineAgitation 2 93.51Mania 3 2136.72

Total 2230.23

Table 4. Average side-e�ect cost per treatment episode

Class of drug Total Number of Averageside-e�ect episodes side-e�ect

costs cost per(£) treatment

episode (£)

TCA 9106.5 42 216.82Fluoxetine 553.41 34 16.28SSRIs 2783.64 62 44.89

Table 5. Average medical cost per treatment episode ofdepression

Class of drug Average costs per treatment episodeDrug Side-e�ect Averagecost costs direct costs(£) (£) (£)

TCAs 52.17 216.82 268.99Fluoxetine 172.27 16.28 188.55SSRIs 197.77 44.89 242.66

costs associated with ¯uoxetine were $313 less pertreatment episode of depression than treatmentwith a TCA. In an economic evaluation of SSRIs(Sclar et al. 1995), it was found that ¯uoxetine wasassociated with signi®cantly lower direct medicalcosts than either paroxetine or sertraline, corres-ponding to the ®ndings in the present study. A UKstudy (Donoghue, 1995) showed similar ®ndingswith ¯uoxetine being associated with lowerprojected costs than with either paroxetine orsertraline. One common factor seen in our studyand others (Gregor, 1994; Donoghue, 1995;Navarro et al., 1995; Sclar et al., 1995) is that¯uoxetine was associated with the least dosagetitration amongst the SSRIs.

The debate on whether SSRIs or TCAs are morecost-e�ective is complex. On the one hand there arestudies (Song et al., 1993; Freemantel et al., 1995)which used randomized control data in theoreticalmodels, and these suggest that the SSRIs areconsiderably more expensive than TCAs. Otherstudies also using randomized controlled trial data(Gross, 1991; Le Pen et al., 1994; Jonnson et al.,1994; Bentkover et al., 1995) support the oppositethesis with SSRIs being associated with lowerhealth care costs than TCAs. A further study(Stewart, 1994) showed a small advantage forTCAs over SSRIs in terms of lower cost. In anattempt to resolve this debate, it has beensuggested (Anderson, 1995) that one shouldmeasure the direct medical costs which occur inclinical practice. There have now been a number ofstudies looking at real costs in clinical practice(Sclar et al., 1994) and, together with the presentstudy, they strongly support the thesis that TCAsare associated with higher direct medical coststhan SSRIs. Moreover, a study in primary care(Donoghue et al., 1996) found that the doses forSSRIs were adequate in over 99 per cent of cases,whereas for TCAs they were only adequate in 13per cent of cases. It has also been shown (Beuzenet al., 1993) that patients spend more time o� workwhen prescribed a TCA rather than an SSRI.

This study has limited itself to include only thecosts of drug therapy and those associate with side-e�ects. It has not attempted to include costsassociated with accidents, suicide attempts, orquality of life. Currently, there appears to be noagreed methodology for carrying out such eco-nomic evaluations, and this represents a majorlimitation for research although `real life' trialmethodology which include randomization arebeing developed (Simon et al., 1995). Although

no randomization of patients occurred inthis study, the groups had very similar patientcharacteristics. We cannot rule out the possibilityof selection bias of patients, however, all patientstreated with antidepressants were included inthe evaluation. Moreover, it is unlikely thatany of our patients, for ethnical reasons,could have been recruited into a randomizedclinical trial.

CONCLUSIONS

This is possibly the ®rst economic evaluation of theuse of antidepressants in patients with learningdisabilities su�ering from major depression wheredirect treatment costs, including that of side-e�ects, were audited. The study has its limitationsof being non-randomized and being retrospectiveand, accordingly, its ®ndings should be interpretedwith caution. However, its ®ndings support theview that, in clinical practice, the average directcost of treating a depressive episode in patientswith learning disabilities is likely to be least for¯uoxetine and highest for TCAs with the SSRIs asa group being intermediate.

It is to be hoped that future studies willprospectively measure direct costs in clinicalpractice, which will avoid the potential pitfallsof retrospective analysis and will also shedfurther light on the real overall costs of treatingdepression, thereby avoiding the tendency to focusonly on one aspect, such as the unit cost ofantidepressants.

REFERENCES

Anderson, I., et al. (1995). Treatment discontinuationwith the selective serotonin reuptake inhibitorscompared with tricyclic antidepressants: a metaanalysis. British Medical Journal, 310, 1433±1438.

Bentkover, J. D., et al. (1995). Cost analysis ofparoxetine versus imipramine in major depression.Pharmco Economics 8 3, 223±232.

Beuzen, J. N., et al. (1993). Impact of ¯uoxetine on workloss in depression. International Clinical Psycho-pharmacology, 8, 319±321.

Bhaumik, S., et al. (1995). A naturalistic study in the useof antidepressants in adults with learning disabilitiesand a�ective disorders. Human Psychopharmacology,10, 283±288.

Donoghue, J. (1995). A comparison of prescribingpatterns of selective reuptake inhibitors in the treat-ment of depression in primary care in the UnitedKingdom. Journal of Serotonin Research, 1, 47±51.

50 S. BHAUMIK ET AL.

Donoghue, J., et al. (1996). The treatment of depression:prescribing patterns of antidepressant in primarycare in the UK. British Journal of Psychiatry, 168,164±168.

Freemantel, N., et al. (1995). Prescribing selectiveserotonin reuptake inhibitors as a strategy for pre-vention of suicide. British Medical Journal, 309,215±218.

Gross, P. F. (1991). The economic cost of depression inAustralia and New Zealand, and the potentialeconomic impact of ¯uoxetine. Journal of the Amer-ican Medical Association, December (Suppl. RecentAdvances in the Treatment of Depression), 12±18.

Gregor, K. J. (1994). Selective serotonin reuptakeinhibitor dose titration in the naturalistic setting.Clinical Therapeutics, 16, 2, 306±315.

Kind, P., et al. (1993). The costs of depression. Inter-national Clinical Psychopharmacology, 7, 3,4, 191±195.

Jonnson, B., et al. (1994). What price depression? BritishMedical Journal, 164, 665±673.

Le Pen, C., et al. (1994). The cost of treatment dropout.A cost±bene®t analysis of ¯uoxetine vs. tricyclics.Journal of A�ective Disorders, 31, 1±18.

Navarro, R., et al. (1995). Antidepressant utilizationin managed care. An evaluation of SSRI use intwo HMO settings. Medical Interface, August, 114±123.

Sclar, D., et al. (1994). Antidepressant pharmaco-therapy: Economic outcomes in a health mainten-ance organisation. Clinical Therapeutics, 16, 4, 715±730.

Sclar, D., et al. (1995). Antidepressant pharmacother-apy: Economic evaluation of ¯uoxetine, paroxetineand sertraline in a health maintenance organization.Journal of International Medical Research, 23, 6, 395±412.

Simon, G., et al. (1995). Cost-e�ectiveness comparisonsusing `real world' randomized trials: The case of newantidepressant drugs. Journal of Clinical Epidemiol-ogy, 48, 3, 363±373.

Song, F., et al. (1993). Selective serotonin reuptake e�-cacy, acceptability and e�ectiveness, a meta analysis.British Medical Journal, 306, 683±687.

Stewart, A., (1994). Antidepressant pharmacotherapy:cost comparison of SSRIs and TCAs. British Journalof Medical Economics, 7, 67±79.

51ECONOMIC IMPLICATIONS OF ANTIDEPRESSANT USE

52 S. BHAUMIK ET AL.

APPENDIX 1. DETAIL SIDE-EFFECT COST TABLE

Class of drug How cost is incurred Length of treatment Total

TCAsAgitation

Incident 1 Switch to thioridazine 3 months (£6.12) £18.36Incident 2 Add lithium 9 months (£7.905) £71.15Incident 3 Switch to thioridazine 3 months (£6.12) £18.36

DrowsinessIncident 1 Switch to ¯uoxetine 9 months (£20.77) £186.93Incident 2 Switch to ¯uoxetine 9 months (£20.77) £186.93

Plus 28 days in treatment unit 28 days (£100.00) £2,800.00Incident 3 Day centre for 3 days 3 days (£16.00) £48.00Incident 4 Switch to lofepramine 9 months (£16.51) £148.59

Dry mouthIncident 1 Continued treatment £0 £0Incident 2 Switched to ¯uoxetine 9 months (£20.77) £186.93

Epileptic seizureIncident 1 Switch to ¯uoxetine 9 months (£20.77) £186.93Incident 2 Switch to ¯uoxetine 8 months (£20.77) £186.93

Plus 1 day in treatment unit 1 day (£100.00) £100.00

HypomaniaIncident 1 Switch to lithium 9 months (£7.905) £71.15

Plus admission to treatment unit 28 days (£100.00) £2800.00

InsomniaIncident 1 Add temazepam 1 month (£0.49) £0.05

LeucopeniaIncident 1 Blood counts 4 times (£2.27) £11.00

Visits to haematologist 4 visits (£31.00) £124.00

ObesityIncident 1 Switch to ¯uoxetine 9 months (£20.77) £186.93

Postural hypotensionIncident 1 Admission to treatment unit 14 ?? (£100) £1400.00Incident 2 Switch to ¯uoxetine 9 months (£20.77) £186.93Incident 3 Switch to ¯uoxetine 9 months (£20.77) £186.93

SSRIsFluoxetine

AgitationIncident 1 Switch to dothiepin 9 months (£9.49) £85.41Incident 2 Switch to dothiepin 9 months (£9.49) £85.41

DiarrhoeaIncident 1 Switch to lofepramine 9 months (£16.51) £148.59

Plus 1 GP visit 1 (£10.00) £10.00

Manic episodeDay centre 14 days (£16.00) £224.00

Paroxetine/sertraline/¯uvoxamineAgitation

Incident 1 Switch to ¯uoxetine 9 months (£10.39) £93.51Alternate day dosage

Incident 2 Agitation disappeared Nil Nil

Hypomania/maniaIncident 1 Admission to treatment unit 21 days (£100.00) £2100.00Incident 2 Switch to thioridazine 3 months (£6.12) £18.36Incident 3 Switch to thioridazine 3 months (£6.12) £18.36