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Treatment of depression in schizophrenia: Systematic review and meta-analysis

  • Angharad Gregory (a1), Pavan Mallikarjun (a2) and Rachel Upthegrove (a2)
Abstract
Background

Depression in schizophrenia predicts poor outcomes, including suicide, yet the effectiveness of antidepressants for its treatment remains uncertain.

Aims

To synthesise the evidence of the effectiveness of antidepressants for the treatment of depression in schizophrenia.

Method

Multiple databases Were searched and inclusion Criteria included participants aged over 18 years with schizophrenia or related psychosis with a depressive episode. Papers were quality assessed used the Cochrane risk bias tool. Meta-analyses were performed for risk difference and standardised mean difference of all antidepressants, antidepressant class and individual antidepressant where sufficient studies allowed.

Results

A total of 26 moderate- to low-quality trials met inclusion criteria. In meta-analysis a significant risk difference was found in favour of antidepressant treatment, with a number needed to treat of 5 (95% CI 4–9). Studies using tools specifically designed to assess depression in schizophrenia showed a larger effect size. However, after sensitivity analysis standardised mean difference of all antidepressants did not show a statistically significant improvement in depression score at end-point, neither did any individual antidepressant class.

Conclusions

Antidepressants may be effective for the treatment of depression in schizophrenia, however, the evidence is mixed and conclusions must be qualified by the small number of low- or moderate-quality studies. Further sufficiently powered, high-quality studies are needed.

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Copyright
Corresponding author
Rachel Upthegrove, The Barberry, University of Birmingham, 25 Vincent Drive Edgbaston Birmingham B152FG, UK. Email: r.upthegrove@bham.ac.uk
Footnotes
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Declaration of interest

None.

Footnotes
References
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1 Conley, RR, Ascher-Svanum, H, Zhu, B, Faries, DE, Kinon, BJ. The burden of depressive symptoms in the long-term treatment of patients with schizophrenia. Schizophr Res 2007; 90: 186–97.
2 Hafner, H, Maurer, K, Trendler, G, van der Heiden, W, Schmidt, M, Konnecke, R. Schizophrenia and depression: challenging the paradigm of two separate diseases – a controlled study of schizophrenia, depression and healthy controls. Schizophr Res 2005; 77: 1124.
3 Buckley, PF, Miller, BJ, Lehrer, DS, Castle, DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35: 383402.
4 Whitehead, C, Moss, S, Cardno, A, Lewis, G. Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev 2002; 2: CD002305.
5 Addington, J, Duchak, V. Reasons for substance use in schizophrenia. Acta Psychiatr Scand 1997; 96: 329–33.
6 Reine, G, Lancon, C, Di Tucci, S, Sapin, C, Auquier, P. Depression and subjective quality of life in chronic phase schizophrenic patients. Acta Psychiatr Scand 2003; 108: 297303.
7 Saha, S, Chant, D, McGrath, J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007; 64: 1123–31.
8 Barnes, TR, Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25: 567620.
9 National Insitute for Health and Care Excellence. Psychosis and Schizophrenia in Adults: Treatment and Management. Clinical Guideline 178. NICE, 2014.
10 Siris, SG, Addington, D, Azorin, JM, Falloon, IR, Gerlach, J, Hirsch, S, et al. Depression in schizophrenia: recognition and management in the USA. Schizophr Res 2001; 47: 185–97.
11 Ballon, J, Stroup, TS. Polypharmacy for schizophrenia. Curr Opin Psychiatry 2013; 26: 208–13.
12 Upthegrove, R, Marwaha, S, Birchwood, M. Depression and schizophrenia: cause, consequence or trans-diagnostic issue? Schizophr Bull 2017; 43; 240–4.
13 Heifer, B, Samara, MT, Huhn, M, Klupp, E, Leucht, C, Zhu, Y, et al. Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. Am J Psychiatry 2017; 173: 876–86.
14 Upthegrove, R, Gregory, A. Antidepressant treatment of depression in schizophrenia: a systematic review and meta-analysis. PROSPERO, 2016 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016030089).
15 Higgins, JP, Green, S. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, 2011.
16 Collins, AA, Remington, G, Coulter, K, Birkett, K. Depression in schizophrenia: a comparison of three measures. Schizophr Res 1996; 20: 205–9.
17 World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO, 1992.
18 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder (4th edn) (DSM-IV). APA, 1994.
19 Spitzer, RL, Endicott, J, Robins, E. Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 1978; 35: 773–82.
20 Kurland, AA, Nagaraju, A. Viloxazine and the depressed schizophrenic – methodological issues. J Clin Pharmacol 1981; 21: 3741.
21 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.
22 Johnson, DA. Studies of depressive symptoms in schizophrenia. Br J Psychiatry 1981; 139: 89101.
23 Singh, AN, Saxena, B, Nelson, HL. A controlled clinical study of trazodone in chronic schizophrenic patients with pronounced depressive symptomatology. Curr Ther Res 1978; 23: 485501.
24 Omranifard, V, Hosseini, GM, Sharbafchi, MR, Maracy, M, Ghasemi, F, Aminoroaia, M. Sertraline as an add-on treatment for depressive symptoms in stable schizophrenia: a double-blind randomized controlled trial. J Res Med Sci 2012; 17: S17.
25 Addington, D, Addington, J, Patten, S, Remington, G, Moamai, J, Labelle, A, 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: 20–5.
26 Zisook, S, Kasckow, JW, Golshan, S, Fellows, I, Solorzano, E, Lehman, D, et al. Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: a randomized controlled trial. J Clin Psychiatry 2009; 70: 562–71.
27 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.
28 Prusoff, BA, Williams, DH, Weissman, MM, Astrachan, BM. Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine. Arch Gen Psychiatry 1979; 36: 569–75.
29 Hogarty, GE, McEvoy, JP, Ulrich, RF, DiBarry, AL, Bartone, P, Cooley, S, et al. Pharmacotherapy of impaired affect in recovering schizophrenic patients. Arch Gen Psychiatry 1995; 52: 29.
30 Siris, S, Pollack, S, Bermanzohn, P, Stronger, R. Adjunctive imipramine for a broader group of post-psychotic depressions in schizophrenia. Schizophr Res 2000; 44: 187–92.
31 Izakova, L, Andre, I, Halaris, A. Combination therapy or monotherapy for the depressed type of schizoaffective disorder. Neuropsychiatr Dis Treat 2009; 91101.
32 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.
33 Kasckow, JW, Mohamed, S, Thallasinos, A, Carroll, B, Zisook, S, Jeste, DV. Citalopram augmentation of antipsychotic treatment in older schizophrenia patients. Int J Geriatr Psychiatry 2001; 16: 1163–7.
34 Hinkelmann, K, Yassouridis, A, Kellner, M, Jahn, H, Wiedemann, K, Raedler, TJ. No effects of antidepressants on negative symptoms in schizophrenia. J Clin Psychopharmacol 2013; 33: 686–90.
35 Niitsu, T, Fujisaki, M, Shiina, A, Yoshida, T, Hasegawa, T, Kanahara, N, et al. A randomized, double-blind, placebo-controlled trial of fluvoxamine in patients with schizophrenia: a preliminary study. J Clin Psychopharmacol 2012; 32: 593601.
36 Mico, U, Bruno, A, Pandolfo, G, Romeo, VM, Mallamace, D, D'Arrigo, C, et al. Duloxetine as adjunctive treatment to clozapine in patients with schizophrenia: a randomized, placebo-controlled trial. Int Clin Psychopharmacol 2011; 26: 303–10.
37 Terevnikov, V, Stenberg, J-H, Tiihonen, J, Joffe, M, Burkin, M, Tchoukhine, E, et al. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase. Hum Psychopharmacol 2011; 26: 188–93.
38 Taiminen, TJ, Syvälahti, E, Saarijärvi, S, Niemi, H, Lehto, H, Ahola, V, et al. Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic dimension in schizophrenia. Int Clin Psychopharmacol 1997; 12: 31–5.
39 Upthegrove, R, Ross, K, Brunet, K, McCollum, R, Jones, L. Depression in first episode psychosis: the role of subordination and shame. Psychiatry Res 2014; 217: 177–84.
40 Chavda, N, Kantharia, N. Effects of fluoxetine and escitalopram on C-reactive protein in patients of depression. J Pharmacol Pharmacother 2011; 2: 11–6.
41 Arroll, B, Elley, CR, Fishman, T, Goodyear-Smith, FA, Kenealy, T, Blashki, G, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev 2009; 3: cd007954.
42 Gardsjord, ES, Romm, KL, Friis, S, Barder, HE, Evensen, J, Haahr, U, et al. Subjective quality of life in first-episode psychosis. A ten year follow-up study. Schizophr Res 2016; 172: 23–8.
43 NHS England. Guidance to Support the Introduction of Access and waiting Time Standards for Mental Health Services in 2015/16. NHS England, 2015.
44 Jauhar, S, McKenna, PJ, Radua, J, Fung, E, Salvador, R, Laws, KR. Cognitive–behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias. Br J Psychiatry 2014; 204: 20–9.
45 Hazell, CM, Hayward, M, Cavanagh, K, Strauss, C. A systematic review and meta-analysis of low intensity CBT for psychosis. Clinical Psychol Rev 2016; 45: 183–92.
46 Medicines and Healthcare Products Regulatory Agency. Citalopram and escitalopram: QT interval prolongation. MHPRA, 2011 (https://www.gov.uk/drug-safety-update/citalopram-and-escitalopram-qt-interval-prolongation).
47 Tiihonen, J, Suokas, JT, Suvisaari, JM, Haukka, J, Korhonen, P. Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry 2012; 69: 476–83.
48 Nutt, DJ, Sharpe, M. Uncritical positive regard? Issues in the efficacy and safety of psychotherapy. J Psychopharmacol 2008; 22: 36.
49 Klingberg, S, Herrlich, J, Wiedemann, G, Wolwer, W, Meisner, C, Engel, C, et al. Adverse effects of cognitive behavioral therapy and cognitive remediation in schizophrenia: results of the treatment of negative symptoms study. J Nerv Ment Dis 2012; 200: 569–76.
50 Taylor, M, Perera, U. NICE CG178 Psychosis and Schizophrenia in Adults: Treatment and Management – an evidence-based guideline? Br J Psychiatry 2015; 206: 357–9.
51 Upthegrove, R, Birchwood, M, Ross, K, Brunett, K, McCollum, R, Jones, L. The evolution of depression and suicidality in first episode psychosis. Acta Psychiatr Scand 2010; 122: 211–8.
52 Sandhu, A, Ives, J, Birchwood, M, Upthegrove, R. The subjective experience and phenomenology of depression following first episode psychosis: a qualitative study using photo-elicitation. J Affect Disord 2013; 149: 166–74.
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Treatment of depression in schizophrenia: Systematic review and meta-analysis

  • Angharad Gregory (a1), Pavan Mallikarjun (a2) and Rachel Upthegrove (a2)
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