Download PDF
Pharmacopsychiatry 2017; 50(04): 136-144
DOI: 10.1055/s-0043-106436
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder – When, Who, and How?

Rebecca Schennach
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
17   Schoen Clinic Roseneck, Prien am Chiemsee, Germany
,
Michael Obermeier
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
,
Florian Seemüller
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
,
Markus Jäger
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
,
Max Schmauss
2   Psychiatric Clinic, District Hospital Augsburg, Augsburg, Germany
,
Gerd Laux
3   Psychiatric Clinic, Inn-Salzach Hospital, Wasserburg/Inn, Germany
,
Herbert Pfeiffer
4   Psychiatric Clinic, Isar-Amper Hospital, Munich-Haar, Germany
,
Dieter Naber
5   Department of Psychiatry, University of Hamburg, Hamburg, Germany
,
Lutz G. Schmidt
6   Department of Psychiatry, Johannes Gutenberg-University of Mainz, Mainz, Germany
,
Wolfgang Gaebel
7   Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Düsseldorf, Germany
,
Joachim Klosterkötter
8   Department of Psychiatry, University of Cologne, Köln, Germany
,
Isabella Heuser
9   Department of Psychiatry, Charite Berlin, Campus Benjamin Franklin, Berlin, Germany
,
Wolfgang Maier
10   Department of Psychiatry, University of Bonn, Bonn, Germany
,
Matthias R. Lemke
11   Psychiatric Clinic, Alsterdorf Hospital, Hamburg, Germany
,
Eckart Rüther
12   Department of Psychiatry, University of Göttingen, Göttingen, Germany
,
Stefan Klingberg
13   Department of Psychiatry, University of Tübingen, Tübingen, Germany
,
Markus Gastpar
14   Department of Psychiatry, University of Essen, Essen, Germany
,
Ilja Spellmann
15   Psychiatric Clinic, District Hospital Kaufbeuren, Kaufbeuren, Germany
,
Richard Musil
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
,
Hans-Jürgen Möller
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
,
Michael Riedel
1   Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany
16   Psychiatric Clinic Nordschwarzwald, Calw, Germany
› Author Affiliations
Further Information

Publication History

received 01 September 2016
revised 15 February 2017

accepted 13 March 2017

Publication Date:
15 May 2017 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients.

Methods

Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models.

Results

Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found.

Discussion

Add-on with antidepressants is common. A final recommendation in terms of this strategy’s efficacy cannot be given.

Key words

schizophrenia spectrum disorder - antidepressants - add-on - prescribing pattern - efficacy
 

  • References

  • 1 Sacristán JA, Gómez JC, Montejo AL. et al. Doses of olanzapine, risperidone, and haloperidol used in clinical practice: Results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina. Clin Ther 2000; 22: 583-599
    CrossrefPubMedSearch in Google Scholar
  • 2 Stahl SM, Grady MM. A critical review of atypical antipsychotic utilization: Comparing monotherapy with polypharmacy and augmentation. Curr Med Chem 2004; 11: 313-327
    CrossrefPubMedSearch in Google Scholar
  • 3 Novick D, Bousono M, Suarez D. et al. Use of concomitant medication with antipsychotic treatment in outpatients with schizophrenia: Results from the European Schizophrenia Outpatients Health Outcomes (SOHO) study. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 972-982
    CrossrefPubMedSearch in Google Scholar
  • 4 Rummel C, Kissling W, Leucht S. Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: A systematic review of randomized trials. Schizophr Res 2005; 80: 85-97
    CrossrefPubMedSearch in Google Scholar
  • 5 Whitehead C, Moss S, Cardno A. et al. Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med 2003; 33: 589-599
    CrossrefPubMedSearch in Google Scholar
  • 6 Raedler TJ, Jahn H, Arlt J. et al. Adjunctive use of reboxetine in schizophrenia. Eur Psychiatry 2004; 19: 366-369
    CrossrefPubMedSearch in Google Scholar
  • 7 Addington D, Addington J, Patten S. et al. Double-blind, placebo-controlled comparison of the efficacy of sertraline as treatment for a major depressive episode in patients with remitted schizophrenia. J Clin Psychopharmacol 2002; 22: 20-25
    CrossrefPubMedSearch in Google Scholar
  • 8 Iancu I, Tschernihovsky E, Bodner E. et al. Escitalopram in the treatment of negative symptoms in patients with chronic schizophrenia: A randomized double-blind placebo-controlled trial. Psychiatry Res 2010; 179: 19-23
    CrossrefPubMedSearch in Google Scholar
  • 9 Cho SJ, Yook K, Kim B. et al. Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: A randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 208-211
    CrossrefPubMedSearch in Google Scholar
  • 10 Kishi T, Iwata N. Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia. Int J Neuropsychopharmacol 2014; 17: 343-354
    CrossrefPubMedSearch in Google Scholar
  • 11 Singh SP, Singh V, Kar N. et al. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: Meta-analysis. Br J Psychiatry 2010; 197: 174-179
    CrossrefPubMedSearch in Google Scholar
  • 12 Arango C, Kirkpatrick B, Buchanan RW. Fluoxetine as an adjunct to conventional antipsychotic treatment of schizophrenia patients with residual symptoms. J Nerv Ment Dis 2000; 188: 50-53
    CrossrefPubMedSearch in Google Scholar
  • 13 Moller HJ. Drug treatment of depressive symptoms in schizophrenia. Clin Schizophr Relat Psychoses 2008; 1: 328-340
    CrossrefPubMedSearch in Google Scholar
  • 14 Moller HJ. Non-neuroleptic approaches to treating negative symptoms in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2004; 254: 108-116
    CrossrefPubMedSearch in Google Scholar
  • 15 Suarez D, Haro JM, Novick D. et al. Marginal structural models might overcome confounding when analyzing multiple treatment effects in observational studies. J Clin Epidemiol 2008; 61: 525-530
    CrossrefPubMedSearch in Google Scholar
  • 16 Moller HJ. Effectiveness studies: Advantages and disadvantages. Dialogues Clin Neurosci 2011; 13: 199-207
    PubMedSearch in Google Scholar
  • 17 Wolwer W, Buchkremer G, Hafner H. et al. German research network on schizophrenia-bridging the gap between research and care. Eur Arch Psychiatry Clin Neurosci 2003; 253: 321-329
    CrossrefPubMedSearch in Google Scholar
  • 18 Jager M, Riedel M, Messer T. et al. Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders. Eur Arch Psychiatry Clin Neurosci 2007; 257: 47-53
    CrossrefPubMedSearch in Google Scholar
  • 19 Falkai P, Wobrock T, Lieberman J. et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: Acute treatment of schizophrenia. World J Biol Psychiatry 2005; 6: 132-191
    CrossrefPubMedSearch in Google Scholar
  • 20 World Health Organization (WHO). Collaborating centre for drug statistics methodology. Guidelines for ATC classification and DDD assignment 2010 http://www.whocc.no/atcddd
    PubMed
  • 21 American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4th ed. Washington DC: American psychiatric association; 1994
    Search in Google Scholar
  • 22 Cording C. Conceptual aspects in development and implementation of basic psychiatric documentation. Psychiatr Prax 1998; 25: 175-187
    PubMedSearch in Google Scholar
  • 23 Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res 1988; 23: 99-110
    CrossrefPubMedSearch in Google Scholar
  • 24 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiat 1960; 23: 56-62
    CrossrefPubMedSearch in Google Scholar
  • 25 Lingjaerde O, Ahlfors UG, Bech P. et al. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 1987; 334: 1-100
    PubMedSearch in Google Scholar
  • 26 American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington DC: American Psychiatric Association; 1987
    Search in Google Scholar
  • 27 Jaykaran, Mean ± SEM or Mean (SD)?. Indian J Pharmacol 2010; 42: 329
    CrossrefPubMedSearch in Google Scholar
  • 28 Leucht S, Davis JM, Engel RR. et al. Defining ‘response’ in antipsychotic drug trials: Recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology 2007; 32: 1903-1910
    CrossrefPubMedSearch in Google Scholar
  • 29 Andreasen NC, Carpenter Jr WT, Kane JM. et al. Remission in schizophrenia: Proposed criteria and rationale for consensus. Am J Psychiatry 2005; 162: 441-449
    CrossrefPubMedSearch in Google Scholar
  • 30 Jager M, Riedel M, Schmauss M. et al. Depression during an acute episode of schizophrenia or schizophreniform disorder and its impact on treatment response. Psychiatry Res 2008; 158: 297-305
    CrossrefPubMedSearch in Google Scholar
  • 31 Robins JM, Hernan MA, Brumback B. Marginal structure models and causal inference in epidemiology. Epidemiology 2000; 11: 550-560
    CrossrefPubMedSearch in Google Scholar
  • 32 Hernán MA, Brumback B, Robins JM. Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000; 11: 561-570
    CrossrefPubMedSearch in Google Scholar
  • 33 Van der Wal WM, Geskus RB. An R package for inverse probability weighting. J Stat Softw 2011; 43: 1-23
    PubMedSearch in Google Scholar
  • 34 R Development Core Team. A language and environment for statistical computing.http//:www.r-project.org Accessed 2008
    PubMed
  • 35 Rittmannsberger H, Meise U, Schauflinger K. et al. Polypharmacy in psychiatric treatment. Patterns of psychotropic drug use in Austrian psychiatric clinics. Eur Psychiatry 1999; 14: 33-40
    CrossrefPubMedSearch in Google Scholar
  • 36 Chakos M, Patel JK, Rosenheck R. et al. Concomitant psychotropic medication use during treatment of schizophrenia patients: longitudinal results from the CATIE study. Clin Schizophr Relat Psychoses 2011; 5: 124-134
    CrossrefPubMedSearch in Google Scholar
  • 37 Xiang YT, Ungvari GS, Wang CY. et al. Adjunctive antidepressant prescriptions for hospitalized patients with schizophrenia in Asia (2001–2009). Asia Pac Psychiatry 2013; 5: E81-E87
    CrossrefPubMedSearch in Google Scholar
  • 38 Taylor M. Balancing act: psychiatrist preference versus patient choice. Progress in Neurology and Psychiatry 2007; 8:
    PubMed
  • 39 Hausmann A, Fleischhacker WW. Depression in patients with schizophrenia. CNS Drugs 2000; 14: 289-299
    CrossrefPubMedSearch in Google Scholar
  • 40 Dremencov E, El MM, Blier P. Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area. J Psychiatry Neurosci 2009; 34: 223-229
    PubMedSearch in Google Scholar
  • 41 El Mansari M, Crnic A, Oosterhof C. et al. Long-term administration of the antidepressant vilazodone modulates rat brain monoaminergic systems. Neuropharmacology 2015; 99: 696-704
    CrossrefPubMedSearch in Google Scholar
  • 42 Lako IM, Taxis K, Bruggeman R. et al. The course of depressive symptoms and prescribing patterns of antidepressants in schizophrenia in a one-year follow-up study. Eur Psychiatry 2012; 27: 240-244
    CrossrefPubMedSearch in Google Scholar
  • 43 Fusar-Poli P, Frascarelli M, Valmaggia L. et al. Antidepressant, antipsychotic and psychological interventions in subjects at high clinical risk for psychosis: OASIS 6-year naturalistic study. Psychol Med 2015; 45: 1327-1339
    CrossrefPubMedSearch in Google Scholar
  • 44 Himelhoch S, Slade E, Kreyenbuhl J. et al. Antidepressant prescribing patterns among VA patients with schizophrenia. Schizophr Res 2012; 136: 32-35
    CrossrefPubMedSearch in Google Scholar
  • 45 Lam RW, Peters R, Sladen-Dew N. et al. A community-based clinic survey of antidepressant use in persons with schizophrenia. Can J Psychiatry 1998; 43: 513-516
    CrossrefPubMedSearch in Google Scholar
  • 46 Kishi T, Iwata N. Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia. Int J Neuropsychopharmacol 2014; 17: 343-354
    CrossrefPubMedSearch in Google Scholar
  • 47 Leung A, Chue P. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl 2000; 401: 3-38
    PubMedSearch in Google Scholar
  • 48 Rosenberg PB, Rosse RB, Schwartz BL. et al. Nefazodone in the adjunctive therapy of schizophrenia: an open-label exploratory study. Clin Neuropharmacol 2000; 23: 222-225
    CrossrefPubMedSearch in Google Scholar
  • 49 Polcwiartek C, Nielsen J. The clinical potentials of adjunctive fluvoxamine to clozapine treatment: A systematic review. Psychopharmacology (Berl) 2016; 233: 741-750
    CrossrefPubMedSearch in Google Scholar
  • 50 Barnes TR, Paton C. Do antidepressants improve negative symptoms in schizophrenia?. BMJ 2011; 342: d3371
    CrossrefPubMedSearch in Google Scholar
  • 51 Glick ID, Pham D, Davis JM. Concomitant medications may not improve outcome of antipsychotic monotherapy for stabilized patients with nonacute schizophrenia. J Clin Psychiatry 2006; 67: 1261-1265
    CrossrefPubMedSearch in Google Scholar
  • 52 Langle G, Steinert T, Weiser P. et al. Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Acta Psychiatr Scand 2012; 125: 372-381
    CrossrefPubMedSearch in Google Scholar
  • 53 Terevnikov V, Joffre G, Stenberg JH. Randomized controlled trials of add-on antidepressants in schizophrenia. Int J Neuropsychopharmacol 2015; 19: 18
    PubMedSearch in Google Scholar
  • 54 Kirkman BL, Chen G. Maximizing your data or data slicing? Recommendations for managing multiple submissions from the same dataset. Management and Organization Review 2011; 7: 433-446
    CrossrefPubMedSearch in Google Scholar