Download PDF
Pharmacopsychiatry 2007; 40(2): 77-81
DOI: 10.1055/s-2007-972574
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

A Randomized Controlled Clinical Trial Comparing “Guideline Exposed” and “Guideline Naive” Physicians in Respect to Dosage Selection and Treatment Outcome with Doxepin in Depressive Disorders

M. Linden 1 , K. Schotte 1
  • 1Research Group Psychosomatic Rehabilitation at the Charité, University Medical School, Berlin, Germany and the Rehabilitation Centre Seehof, Teltow/Berlin, Germany
Further Information

Publication History

received 10. 06. 06 revised 23. 12. 06

accepted 12. 01. 07

Publication Date:
19 April 2007 (online)

Also available at
    Permissions and Reprints

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
    PubMedGoogle Scholar
  • 2 Arzneimittelkommission der Deutschen Ärzteschaft . , (AKdÄ) Empfehlungen zur Therapie der Depression. , Arzneiverordnung in der Praxis, Sonderheft 5, AKdÄ 1997; 
    PubMed
  • 3 Appleton WS. Fourth psychoactive drug usage guide.  J Clin Psychiat. 1982;  43 12-27
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 5 Bridges PK. “…and a small dosage of an antidepressant might help”.  Brit J Psychiat. 1983;  142 626-628
    PubMedGoogle Scholar
  • 6 Choudhry NK, Stelfox HAT, Detsky AS. Relationship between authors of clinical practice guidelines and the pharmaceutical industry.  JAMA. 2002;  287 612-617
    CrossrefPubMedGoogle Scholar
  • 7 Dimascio A, Meyer RE, Stifler L. Effects of Imipramine on individuals varying in level of depression.  Am J Psychiat. 1968;  124 55-58
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 12 Helmchen H, Linden M. (Guest Editors) . Subthreshold disorders in psychiatry.  Comprehens Psychiat. 2000;  41 1-137
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 14 Jerling M. Dosing of antidepressants - The unknown art.  J Clin Psychopharmacol. 1995;  15 435-439
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 17 Linden M. Der Einfluss von Leitlinien, Standards und ökonomischen Vorgaben auf medizinische Entscheidungsprozesse.  Z ärztl Fortbild Qualität Gesundheitswesen. 2004;  98 200-205
    PubMedGoogle Scholar
  • 18 Linden M. Leitlinien und die Psychologie medizinischer Entscheidungsprozesse bei der Behandlung depressiver Erkrankungen.  Fortsch Neurol Psychiat. 2005;  73 249-258
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Linden M, Schuessler G. Low dosage antidepressant treatment in private practice - a replication study.  Pharmacopsychiatry. 1985;  18 44-45
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 22 Linden M, Ludewig K, Munz T. Depressive Erkrankungen und antidepressive Therapie. Ein Vergleich von Nervenarztpraxis und psychiatrischer Klinik.  Nervenarzt. 2001;  72 521-528
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 27 Nunn CMH. Efficacy of antidepressant medication.  Brit J Psychiat. 2003;  183 463-464
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 29 Paykel ES, Priest RG. Recognition and management of depression in general practice: consensus statement.  Brit Med J. 1992;  305 1198-1202
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 35 Schotte K, Linden M. Reasons for low-dosage treatment with antidepressants by psychiatrists and general practitioners.  J Pharmacoepidem Drug Safety. 2007;  , in press
    PubMedGoogle Scholar
  • 36 Stewart JW, Quitkin FM, Klein DF. The pharmacotherapy of minor depression.  Am J Psychother. 1992;  46 23-26
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 42 Weiner J, Schumacher G. Psychotropic drug therapy knowledge of health care practitioners.  Am J Hosp Pharm. 1976;  33 237-241
    PubMedGoogle Scholar
  • 43 World Health Organisation . Dosage effects of antidepressant medication in different populations A World Health organisation Collaborative Study.  J Affect Disord. 1986;  1-67
    PubMedGoogle Scholar

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

      >