Abstract
Introduction: Can prescribing of insufficient dosages and outcome of treatment with antidepressants
in routine care be improved by guidelines?
Methods: 161 general practitioners and 162 psychiatrists in private practice documented 1319
patients, receiving doxepin for individual clinical reasons. Physicians were randomly
divided into a guideline exposed and a control group. All physicians treated their
patients according to individual clinical considerations.
Results: Average maximum daily dosage was 83 mg/d in the control and 95 mg/d in the intervention
group (F=19.15; p<0). Only 3% of patients in both groups got the recommended dosage
of 150 mg/d. Guideline exposure resulted in increased dosages preferably for milder
forms of depression and in comparatively lower rates of improvement.
Conclusion: Guideline exposure did not reach its goal in respect to the recommended dosage. It
missed its goal in respect to improvement of outcome and even showed negative effects.
Guidelines should be evidence-based not only by referring to literature reviews but
by testing their clinical effects in controlled clinical trials.
Key words
treatment guidelines - prescribing patterns - treatment algorithms - quality assurance
- drug utilization observation study - tricyclic antidepressants - doxepin
References
1
Adli M, Berghofer A, Linden M, Helmchen H, Muller-Oerlinghausen B, Mackert A, Stamm T,
Bauer M.
Effectiveness and feasibility of a standardized stepwise drug treatment regimen algorithm
for inpatients with depressive disorders: results of a 2-year observational algorithm
study.
J Clin Psychiat.
2002;
63
782-790
2
Arzneimittelkommission der Deutschen Ärzteschaft .
, (AKdÄ)
Empfehlungen zur Therapie der Depression.
, Arzneiverordnung in der Praxis, Sonderheft 5, AKdÄ
1997;
3
Appleton WS.
Fourth psychoactive drug usage guide.
J Clin Psychiat.
1982;
43
12-27
4
Azocar F, Cuffel B, Goldmann W, McCarter L.
The impact of evidence-based guideline dissemination for the assessment and treatment
of major depression in a managed behavioral health care organization.
J Behav Health Service Res.
2003;
30
109-118
5
Bridges PK.
“…and a small dosage of an antidepressant might help”.
Brit J Psychiat.
1983;
142
626-628
6
Choudhry NK, Stelfox HAT, Detsky AS.
Relationship between authors of clinical practice guidelines and the pharmaceutical
industry.
JAMA.
2002;
287
612-617
7
Dimascio A, Meyer RE, Stifler L.
Effects of Imipramine on individuals varying in level of depression.
Am J Psychiat.
1968;
124
55-58
8
Donoghue JA, Tylee A.
The treatment of depression: prescribing patterns of antidepressants in primary care
in the UK.
Brit J Psychiat.
1996;
168
164-168
9
Donoghue JA, Tylee A, Wildgust H.
Cross-sectional database analysis of antidepressant prescribing in general practice
in the United Kingdom.
Brit Med J.
1996;
313
861-862
10
Furukawa TA MH, Barbui C.
Meta-analysis of effects and side effects of low dosage tricyclic antidepressants
in depression: systematic review.
Brit Med J.
2002;
325
991-999
11
Gilmer WS, Trivedi MH, Rush AJ, Wisniewski SR, Luther J, Howland RH, Yohanna D, Khan A,
Alpert J.
Factors associated with chronic depressive episodes: a preliminary report from the
STAR-D project.
Acta psychiat scan.
2005;
112
425
12
Helmchen H, Linden M. (Guest Editors) .
Subthreshold disorders in psychiatry.
Comprehens Psychiat.
2000;
41
1-137
13
Ito H, Koyama A, Higuchi T.
Polypharmacy and excessive dosing: psychiatrists' perceptions of antipsychotic drug
prescription.
Brit J Psychit Brit J Psychiat tr.
2005;
187
243-247
14
Jerling M.
Dosing of antidepressants - The unknown art.
J Clin Psychopharmacol.
1995;
15
435-439
15
Kjaergard LL, Als-Nielsen B.
Association between competing interests and authors’ conclusions: epidemiological
study of randomized clinical trials published in the BMJ.
Brit Med J.
2002;
325
249
16
Lieberman JA, Greenhouse J, Hamer RM, Krishnan KR, Nemeroff CB, Sheehan DV, Thase ME,
Keller MB.
Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative
reviews of antidepressant efficacy.
neuropsychopharmacology.
2005;
30
445-460
17
Linden M.
Der Einfluss von Leitlinien, Standards und ökonomischen Vorgaben auf medizinische
Entscheidungsprozesse.
Z ärztl Fortbild Qualität Gesundheitswesen.
2004;
98
200-205
18
Linden M.
Leitlinien und die Psychologie medizinischer Entscheidungsprozesse bei der Behandlung
depressiver Erkrankungen.
Fortsch Neurol Psychiat.
2005;
73
249-258
19
Linden M, Schuessler G.
Low dosage antidepressant treatment in private practice - a replication study.
Pharmacopsychiatry.
1985;
18
44-45
20
Linden M, Helmchen H, Mackert A, Müller-Oerlinghausen B.
Structure and feasibility of a standardized stepwise drug treatment regimen (SSTR)
for depressed patients.
Pharmacopsychiatry.
1994;
27
51-53
21
Linden M, Ahrens B, Schotte K, Golde J.
Der Einfluß von Richtlinienempfehlungen auf die Niedrigdosierung trizyklischer Antidepressiva
am Beispiel von Doxepin.
Psychopharmakotherapie.
2000;
7
75-79
22
Linden M, Ludewig K, Munz T.
Depressive Erkrankungen und antidepressive Therapie. Ein Vergleich von Nervenarztpraxis
und psychiatrischer Klinik.
Nervenarzt.
2001;
72
521-528
23
Linden MLK, Munz T, Dierkes W.
Dosage finding and outcome of venlafaxine treatment in psychiatric outpatients and
inpatients. Results of a drug utilization observation study.
Pharmacopsychiatry.
2003;
36
197-205
24
McCombs JS, Nichol MB, Stimmel GL, Sclar DA, Beasley CM, Gross LS. et al .
The cost of antidepressant drug therapy failure: A study of antidepressant use patterns
in a medicaid population.
J Clin Psychiat.
1990;
51
60-69
25
MacDonald TM, McMahon AD, Reid IC, Fenton GW, McDevitt DG.
Antidepressant drug use in primary care: A record linkage study in Tayside, Scotland.
Brit Med J.
1996;
313
860-861
26
Munizza C, Tibaldi G, Bollini P, Pirfo E, Punzo F, Gramaglia F.
Prescription pattern of antidepressants in outpatient psychiatric practice.
Psychol Med.
1995;
25
771-778
27
Nunn CMH.
Efficacy of antidepressant medication.
Brit J Psychiat.
2003;
183
463-464
28
Paykel ES HJ, Freeling P. et al .
Predictors of therapeutic benefit from amitriptyline in mild depression: A general
practice placebo-controlled trial.
J Affect Disord.
1988;
14
83-95
29
Paykel ES, Priest RG.
Recognition and management of depression in general practice: consensus statement.
Brit Med J.
1992;
305
1198-1202
30
Perlis RH, Alpert J, Nierenberg AA, Mischoulon D, Yeung A, Rosenbaum JF, Fava M.
Clinical and sociodemographic predictors of response to augmentation or dose increase
among depressed outpatients resistant to fluoxetine 20 mg/day.
Acta psychiat scand.
2003;
108
432-438
31
Pincus HA, Marcus SC, Olfson M, Zarin DA, Thompson J.
Prescribing trends in psychotropic medications: primary care, psychiatry, and other
medical specialties.
JAMA.
1998;
279
32
Rao ML, Deister A, Laux G. et al .
Low serum levels of tricyclic antidepressants in Amitriptyline- and doxepin-treated
inpatients with depressive syndromes are associated with non-response.
Pharmacopsychiatry.
1996;
29
97-102
33
Schaaf B, Linden M, Weber HJ.
An investigation of the representativity of neuropsychiatrists and their patients
in a drug utilization observation study.
Pharmacopsychiatry.
1997;
30
44-51
34
Schneider F, Harter M, Brand S, Sitta P, Menke R, Hammer-Filipiak U, Kudling R, Heindl A,
Herold K, Frommberger U, Elmer O, Hetzel G, Witt G, Wolfersdorf M, Berger M, Gaebel W.
Adherence to guidelines for treatment of depression in in-patients.
Brit J Psychiat.
2005;
187
462-469
35
Schotte K, Linden M.
Reasons for low-dosage treatment with antidepressants by psychiatrists and general
practitioners.
J Pharmacoepidem Drug Safety.
2007;
, in press
36
Stewart JW, Quitkin FM, Klein DF.
The pharmacotherapy of minor depression.
Am J Psychother.
1992;
46
23-26
37
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stuart JW, Warden D, Niederehe G,
Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackheim HA, Kupfer DJ,
Luther J, Fava M.
Acute and longer-term outcomes in depressed outpatients requiring one or several treatment
steps. A STAR* D report.
Am J Psychiat.
2006;
163
1905-1917
38
Thiels C, Linden M, Grieger F, Leonhard J.
Gender differences in routine treatment of depressed outpatients with the selective
serotonin reuptake inhibitor sertraline.
Int Clin Psychopharmacol.
2005;
20
1-7
39
Toprac MG, Dennehy EB, Carmody TJ, Crismon ML, Miller AL, Trivedi MH, Suppes T, Rush AJ.
Implementation of the Texas Medication Algorithm Project patient and family education
program.
J Clin Psychiat.
2006;
67
1362-1372
40
Verdoux H, Begaud B.
Pharmaco-epidemioloy: What do (and don’t) we know about utilization and impact of
psychotropic medications in real life conditions.
Brit J Psychiat.
2004;
185
93-94
41
Wang PS, Schneeweiss S, Brookhart MA, Glynn RJ, Mogun H, Patrick AR, Avorn J.
Suboptimal antidepressant use in the elderly.
J Clin Psychopharmacol.
2005;
25
118-126
42
Weiner J, Schumacher G.
Psychotropic drug therapy knowledge of health care practitioners.
Am J Hosp Pharm.
1976;
33
237-241
43
World Health Organisation .
Dosage effects of antidepressant medication in different populations A World Health
organisation Collaborative Study.
J Affect Disord.
1986;
1-67
Correspondence
Prof. Dr. M. Linden
Research Group Psychosomatic Rehabilitation
Rehabilitation Centre Seehof
Lichterfelder Allee 55
14513 Teltow
Germany
Phone: +49/3328/34 56 78
Fax: +49/3328/34 55 55
Email: michael.linden@charite.de