Skip to main content
×
×
Home

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

  • Surendra P. Singh (a1), Vidhi Singh (a2), Nilamadhab Kar (a3) and Kelvin Chan (a4)
Extract
Background

Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.

Aims

To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.

Method

Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.

Results

There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (–0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.

Conclusions

Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis
      Available formats
      ×
Copyright
Corresponding author
Surendra P. Singh, Step to Health, Mental Health Directorate, Wolverhampton City Primary Care Trust, Wolverhampton, WV10 9TH, UK. Email: Dr.S.Singh@wlv.ac.uk
Footnotes
Hide All

Declaration of interest

None.

Footnotes
References
Hide All
1 Mäkinen, J, Miettunen, J, Isohanni, M, Koponen, H. Negative symptoms in schizophrenia: a review. Nord J Psychiatry 2008; 62: 334–41.
2 Kar, N, Jagdisha, Murali N. Efficacy of somatic treatment in treatment resistant schizophrenia. Psychiatry Online 2000 (http://priory.com/psych/TRS.htm).
3 González-Maeso, J, Sealfon, SC. Psychedelics and schizophrenia. Trends Neurosci 2009; 32: 225–32.
4 Mulholland, C, Lynch, G, King, DJ, Cooper, SJ. A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia. J Psychopharmacol 2003; 17: 107–12.
5 Salokangas, RK, Saarijärvi, S, Taiminen, T, Kallioniemi, H, Lehto, H, Niemi, H, et al. Citalopram as an adjuvant in chronic schizophrenia: a double-blind placebo-controlled study. Acta Psychiatr Scand 1996; 94: 175–80.
6 Lee, MS, Kim, YK, Lee, SK, Suh, KY. A double-blind study of adjunctive sertraline in haloperidol-stabilized patients with chronic schizophrenia. J Clin Psychopharmacol 1998; 18: 399403.
7 Poyurovsky, M, Pashinian, A, Gil-Ad, I, Maayan, R, Schneidman, M, Fuchs, C, et al. Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition. Am J Psychiatry 2002; 159: 1058–60.
8 Bustillo, JR, Lauriello, J, Parker, K, Hammond, R, Rowland, L, Bogenschutz, M, et al. Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients. Neuropsychopharmacology 2003; 28: 527–9.
9 Friedman, JI, Ocampo, R, Elbaz, Z, Parrella, M, White, L, Bowler, S, et al. The effect of citalopram adjunctive treatment added to atypical antipsychotic medications for cognitive performance in patients with schizophrenia. J Clin Psychopharmacol 2005; 25: 237–42.
10 Lehmann, HE, Ban, TA. A placebo-controlled clinical study with trazodone in schizophrenic patients. Psychopharmacol Bull 1977; 13: 11–2.
11 Berk, M, Ichim, C, Brook, S. Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol 2001; 16: 8792.
12 Berk, M, Gama, CS, Sundram, S, Hustig, H, Koopowitz, L, D'Souza, R, et al. Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: a double-blind, randomised, placebo-controlled clinical trial. Hum Psychopharmacol 2009; 24: 233–8.
13 Waehrens, J, Gerlach, J. Antidepressant drugs in anergic schizophrenia. A double-blind cross-over study with maprotiline and placebo. Acta Psychiatr Scand 1980; 61: 438–44.
14 Vartiainen, H, Tiihonen, J, Putkonen, A, Koponen, H, Virkkunen, M, Hakola, P, et al. Citalopram, a selective serotonin reuptake inhibitor, in the treatment of aggression in schizophrenia. Acta Psychiatr Scand 1995; 91: 348–51.
15 Wynchank, D, Berk, M. Efficacy of nefazodone in the treatment of neuroleptic induced extrapyramidal side effects: a double-blind randomised parallel group placebo-controlled trial. Hum Psychopharmacol 2003; 18: 271–5.
16 Silver, H, Nassar, A. Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study. Biol Psychiatry 1992; 31: 698704.
17 Duinkerke, SJ, Botter, PA, Jansen, AAI, van Dongen, PAM, van Haaften, AJ, Boom, AJ, et al. Ritanserin, a selective 5-HT2/1C antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry 1993; 163: 451–5.
18 Decina, P, Mukherjee, S, Bocola, V, Saraceni, F, Hadjichristos, C, Scapicchio, P. Adjunctive trazodone in the treatment of negative symptoms of schizophrenia. Hosp Community Psychiatry 1994; 45: 1220–3.
19 Spina, E, De Domenico, P, Ruello, C, Longobardo, N, Gitto, C, Ancione, M, et al. Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients. Int Clin Psychopharmacol 1994; 9: 281–5.
20 Goff, DC, Midha, KK, Sarid-Segal, O, Hubbard, JW, Amico, E. A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia. Psychopharmacology (Berl) 1995; 117: 417–23.
21 Buchanan, RW, Kirkpatrick, B, Bryant, N, Ball, P, Breier, A. Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. Am J Psychiatry 1996; 153: 1625–7.
22 Hayashi, T, Yokota, N, Takahashi, T, Tawara, Y, Nishikawa, T, Yano, T, et al. Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study. Int Clin Psychopharmacol 1997; 12: 199205.
23 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: 50–3.
24 Silver, H, Barash, I, Aharon, N, Kaplan, A, Poyurovsky, M. Fluvoxamine augmentation of antipsychotics improves negative symptoms in psychotic chronic schizophrenic patients: a placebo-controlled study. Int Clin Psychopharmacol 2000; 15: 257–61.
25 Schutz, G, Berk, M. Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study. Int Clin Psychopharmacol 2001; 16: 275–8.
26 Shiloh, R, Zemishlany, Z, Aizenberg, D, Valevski, A, Bodinger, L, Munitz, H, et al. Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia. Int Clin Psychopharmacol 2002; 17: 5964.
27 Poyurovsky, M, Isaacs, I, Fuchs, C, Schneidman, M, Faragian, S, Weizman, R, et al. Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study. Am J Psychiatry 2003; 160: 297302.
28 Poyurovsky, M, Koren, D, Gonopolsky, I, Schneidman, M, Fuchs, C, Weizman, A, et al. Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study. Eur Neuropsychopharmacol 2003; 13: 123–8.
29 Zoccali, R, Muscatello, MR, Cedro, C, Neri, P, La Torre, D, Spina, E, et al. The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study. Int Clin Psychopharmacol 2004; 19: 71–6.
30 Jockers-Scherübl, MC, Bauer, A, Godemann, F, Reischies, FM, Selig, F, Schlattmann, P. Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study. Int Clin Psychopharmacol 2005; 20: 2731.
31 Poyurovsky, M, Fuchs, C, Pashinian, A, Levi, A, Faragian, S, Maayan, R, et al. Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study. Psychopharmacology (Berl) 2007; 192: 441–8.
32 Akhondzadeh, S, Malek-Hosseini, M, Ghoreishi, A, Raznahan, M, Rezazadeh, S. Effect of ritanserin, a 5HT2A/2C antagonist, on negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Neuropsychopharmacol Biol Psychiatry 2008; 32: 1879–83.
33 Joffe, G, Terevnikov, V, Joffe, M, Stenberg, J, Burkin, M, Tiihonen, J. Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: a double-blind, randomized, placebo-controlled trial. Schizophr Res 2009; 108: 245–51.
34 World Health Organization. ATC/DDD Index. WHO Collaborating Centre of Drug Statistics Methodology. WHO, 2009.
35 Winkley, K, Ismail, K, Landau, S, Eisler, I. Psychological interventions to improve glycaemic control in patients with type 1 diabetes: systematic review and meta-analysis of randomised controlled trials. BMJ 2006; 333: e65.
36 Schünemann, HJ, Oxman, AD, Vist, GE, Higgins, JP, Deeks, JJ, Glasziou, P, et al. Interpreting results and drawing conclusions. In Cochrane Handbook for Systematic Reviews of Interventions (Wiley Cochrane Series): 359–84. John Wiley and Sons, 2008.
37 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: 8597.
38 Cohen, J. Statistical Power Analysis for the Behavioral Sciences (2nd edn). Lawrence Erlbaum Associates, 1988.
39 Kirsch, I, Deacon, BJ, Huedo-Medina, TB, Scoboria, A, Moore, TJ, Johnson, BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45.
40 Salaffi, F, Stancati, A, Alberto Silvestri, C, Ciapetti, A, Grassi, W. Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Euro J Pain 2004; 8: 283–91.
41 Rummel, C, Kissling, W, Leucht, S. Antidepressants for the negative symptoms of schizophrenia. Cochrane Database Syst Rev 2006; 3: CD005581.
42 Sepehry, AA, Potvin, S, Elie, R, Stip, E. Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis. J Clin Psychiatry 2007; 68: 604–10.
43 Ruiu, S, Marchese, G, Saba, PL, Gessa, GL, Pani, L. The 5-HT2 antagonist ritanserin blocks dopamine re-uptake in the rat frontal cortex. Mol Psychiatry 2000; 5: 673–7.
44 Arroll, B, Macgillivray, S, Ogston, S, Reid, I, Sullivan, F, Williams, B, et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med 2005; 3: 449–56.
45 Guaiana, G, Barbui, C, Hotopf, M. Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev 2003; CD004186.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
PDF
Supplementary materials

Singh et al. supplementary material
Supplementary Material

 PDF (228 KB)
228 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

  • Surendra P. Singh (a1), Vidhi Singh (a2), Nilamadhab Kar (a3) and Kelvin Chan (a4)
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *