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Augmentation strategies for clozapine resistance: a systematic review and meta-analysis

Published online by Cambridge University Press:  16 November 2022

Sandeep Grover Open the ORCID record for Sandeep Grover [Opens in a new window] ,
Siddharth Sarkar  and
Swapnajeet Sahoo Open the ORCID record for Swapnajeet Sahoo [Opens in a new window]
Sandeep Grover*
Affiliation:
Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Siddharth Sarkar
Affiliation:
Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
Swapnajeet Sahoo
Affiliation:
Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
*
Author for correspondence: Sandeep Grover, Email: drsandeepg2002@yahoo.com
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Abstract

Background:

Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.

Methods:

Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.

Results:

Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288–0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was −0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094–1.392). Risk of bias was low (mean Jadad score – 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.

Conclusions:

To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.

Keywords

augmentationclozapinemeta-analysisresistance
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 35 , Issue 2 , April 2023 , pp. 65 - 75
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Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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References

Afshar, H, Roohafza, H, Mousavi, G, Golchin, S, Toghianifar, N, Sadeghi, M and Talaei, M (2009) Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial. Journal of Psychopharmacology (Oxford, England) 23(2), 157–162.CrossRefGoogle ScholarPubMed
Barber, S, Olotu, U, Corsi, M and Cipriani, A (2017) Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia. The Cochrane Database of Systematic Reviews 3(3), CD006324.Google ScholarPubMed
Barbui, C, Signoretti, A, Mulè, S, Boso, M and Cipriani, A (2009) Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophrenia Bulletin 35(2), 458–468.CrossRefGoogle ScholarPubMed
Barnes, TR, Leeson, VC, Paton, C, Marston, L, Davies, L, Whittaker, W, Osborn, D, Kumar, R, Keown, P, Zafar, R, Iqbal, K, Singh, V, Fridrich, P, Fitzgerald, Z, Bagalkote, H, Haddad, PM, Husni, M and Amos, T (2017) Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness. Health Technology Assessment (Winchester, England) 21(49), 1–56.CrossRefGoogle ScholarPubMed
Barretto, EMP, Kayo, M, Avrichir, BS, Sa, AR, Camargo, MGM, Napolitano, IC, Nery, FG, Pinto, JA, Bannwart, S, Scemes, S, Di Sarno, E and Elkis, H (2009) A preliminary controlled trial of cognitive behavioral therapy in clozapine-resistant schizophrenia. The Journal of Nervous and Mental Disease 197(11), 865–868.CrossRefGoogle ScholarPubMed
Bartoli, F, Crocamo, C, Di Brita, C, Esposito, G, Tabacchi, TI, Verrengia, E, Clerici, M and Carrà, G (2019) Adjunctive second-generation antipsychotics for specific symptom domains of schizophrenia resistant to clozapine: a meta-analysis. Journal of Psychiatric Research 108, 24–33.CrossRefGoogle ScholarPubMed
Behdani, F, Hebrani, P, Rezaei Ardani, A and Rafee, E (2011) Effect of topiramate augmentation in chronic schizophrenia: a placebo-controlled trial. Archives of Iranian Medicine 14(4), 270–275.Google ScholarPubMed
Berk, M (2014) Navigating therapeutic waters with a faulty diagnostic compass. Australian and New Zealand Journal of Psychiatry 48(12), 1075–1076.CrossRefGoogle ScholarPubMed
Buchain, PC, Vizzotto, ADB, Henna Neto, J and Elkis, H (2003) Randomized controlled trial of occupational therapy in patients with treatment-resistant schizophrenia. Revista Brasileira De Psiquiatria (Sao Paulo, Brazil: 1999) 25(1), 26–30.CrossRefGoogle ScholarPubMed
Buchanan, RW, Kirkpatrick, B, Bryant, N, Ball, P and Breier, A (1996) Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. The American Journal of Psychiatry 153(12), 1625–1627.Google ScholarPubMed
Buchanan, RW, Kreyenbuhl, J, Kelly, DL, Noel, JM, Boggs, DL, Fischer, BA, Himelhoch, S, Fang, B, Peterson, E, Aquino, PR, Keller, W and Schizophrenia Patient Outcomes Research Team (PORT) (2010) The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophrenia Bulletin 36(1), 71–93.CrossRefGoogle ScholarPubMed
Chang, JS, Ahn, YM, Park, HJ, Lee, KY, Kim, SH, Kang, UG and Kim, YS (2008) Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. The Journal of Clinical Psychiatry 69(5), 720–731.CrossRefGoogle ScholarPubMed
Clark, HD, Wells, GA, Huët, C, McAlister, FA, Salmi, LR, Fergusson, D and Laupacis, A (1999) Assessing the quality of randomized trials: reliability of the Jadad scale. Controlled Clinical Trials 20(5), 448–452.CrossRefGoogle ScholarPubMed
De Berardis, D, Fornaro, M, Anastasia, A, Vellante, F, Valchera, A, Cavuto, M, Perna, G, Di Nicola, M, Serafini, G, Carano, A, Pompili, M, Orsolini, L, Tomasetti, C, Di Emidio, G, Martinotti, G and Di Giannantonio, M (2019) When clozapine fails: augmentation strategies in the management of clozapine-resistant schizophrenia. In Kim, Y-K (ed), Treatment Resistance in Psychiatry: Risk Factors, Biology, and Management. Singapore: Springer, pp. 349–367. doi: 10.1007/978-981-10-4358-1_23.CrossRefGoogle Scholar
de Jesus, DR, Gil, A, Barbosa, L, Lobato, MI, Magalhães, PVS, Favalli, GPS, Marcolin, MA, Daskalakis, ZJ and Belmonte-de-Abreu, PS (2011) A pilot double-blind sham-controlled trial of repetitive transcranial magnetic stimulation for patients with refractory schizophrenia treated with clozapine. Psychiatry Research 188(2), 203–207.CrossRefGoogle ScholarPubMed
de Lucena, D, Fernandes, BS, Berk, M, Dodd, S, Medeiros, DW, Pedrini, M, Kunz, M, Gomes, FA, Giglio, LF, Lobato, MI, Belmonte-de-Abreu, PS and Gama, CS (2009) Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine. The Journal of Clinical Psychiatry 70(10), 1416–1423.CrossRefGoogle ScholarPubMed
Dean, OM, Mancuso, SG, Bush, AI, Copolov, D, Do, KQ, Cuénod, M, Conus, P, Rossell, SL, Castle, DJ and Berk, M (2015) Benefits of adjunctive N-acetylcysteine in a sub-group of clozapine-treated individuals diagnosed with schizophrenia. Psychiatry Research 230(3), 982–983.CrossRefGoogle Scholar
Diaz, P, Bhaskara, S, Dursun, SM and Deakin, B (2005) Double-blind, placebo-controlled, crossover trial of clozapine plus glycine in refractory schizophrenia negative results. Journal of Clinical Psychopharmacology 25(3), 277–278.CrossRefGoogle ScholarPubMed
Doruk, A, Uzun, O and Ozşahin, A (2008) A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia. International Clinical Psychopharmacology 23(4), 223–227.CrossRefGoogle ScholarPubMed
Elkis, H and Meltzer, HY (2007) Refractory schizophrenia. Brazilian Journal of Psychiatry 29(suppl 2), S41–S47.CrossRefGoogle ScholarPubMed
Evins, AE, Fitzgerald, SM, Wine, L, Rosselli, R and Goff, DC (2000) Placebo-controlled trial of glycine added to clozapine in schizophrenia. The American Journal of Psychiatry 157(5), 826–828.CrossRefGoogle ScholarPubMed
Fleischhacker, WW, Heikkinen, ME, Olié, J-P, Landsberg, W, Dewaele, P, McQuade, RD, Loze, J-Y, Hennicken, D and Kerselaers, W (2010) Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. The International Journal of Neuropsychopharmacology 13(8), 1115–1125.CrossRefGoogle ScholarPubMed
Freudenreich, O, Henderson, DC, Macklin, EA, Evins, AE, Fan, X, Cather, C, Walsh, JP and Goff, DC (2009) Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. The Journal of Clinical Psychiatry 70(12), 1674–1680.CrossRefGoogle ScholarPubMed
Freudenreich, O, Henderson, DC, Walsh, JP, Culhane, MA and Goff, DC (2007) Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial. Schizophrenia Research 92(1), 90–94.CrossRefGoogle ScholarPubMed
Friedman, JI, Lindenmayer, J-P, Alcantara, F, Bowler, S, Parak, M, White, L, Iskander, A, Parrella, M, Adler, DN, Tsopelas, ND, Tsai, W-Y, Novakovick, V, Harvey, PD and Davis, KL (2011) Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacology 36(6), 1289–1295.CrossRefGoogle ScholarPubMed
Goff, DC, Henderson, DC, Evins, AE and Amico, E (1999) A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia. Biological Psychiatry 45(4), 512–514.CrossRefGoogle ScholarPubMed
Goff, DC, Keefe, R, Citrome, L, Davy, K, Krystal, JH, Large, C, Thompson, TR, Volavka, J and Webster, EL (2007) Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials. Journal of Clinical Psychopharmacology 27(6), 582–589.CrossRefGoogle ScholarPubMed
Goff, DC, Leahy, L, Berman, I, Posever, T, Herz, L, Leon, AC, Johnson, SA and Lynch, G (2001) A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. Journal of Clinical Psychopharmacology 21(5), 484–487.CrossRefGoogle ScholarPubMed
Grover, S and Sahoo, S (2019) Treatment of clozapine nonresponders. Current Treatment Options in Psychiatry 6(1), 32–63. doi: 10.1007/s40501-019-0166-4.CrossRefGoogle Scholar
Harbour, R and Miller, J (2001) A new system for grading recommendations in evidence based guidelines. BMJ: British Medical Journal 323(7308), 334–336.CrossRefGoogle ScholarPubMed
Honer, WG, Thornton, AE, Chen, EYH, Chan, RCK, Wong, JOY, Bergmann, A, Falkai, P, Pomarol-Clotet, E, McKenna, PJ, Stip, E, Williams, R, MacEwan, GW, Wasan, K, Procyshyn, R and Clozapine and Risperidone Enhancement (CARE) Study Group (2006) Clozapine alone versus clozapine and risperidone with refractory schizophrenia. The New England Journal of Medicine 354(5), 472–482.CrossRefGoogle ScholarPubMed
Jadad, AR, Moore, RA, Carroll, D, Jenkinson, C, Reynolds, DJ, Gavaghan, DJ and McQuay, HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials 17(1), 1–12.CrossRefGoogle ScholarPubMed
Josiassen, RC, Joseph, A, Kohegyi, E, Stokes, S, Dadvand, M, Paing, WW and Shaughnessy, RA (2005) Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial. The American Journal of Psychiatry 162(1), 130–136.CrossRefGoogle ScholarPubMed
Kelly, DL, Sullivan, KM, McEvoy, JP, McMahon, RP, Wehring, HJ, Gold, JM, Liu, F, Warfel, D, Vyas, G, Richardson, CM, Fischer, BA, Keller, WR, Koola, MM, Feldman, SM, Russ, JC, Keefe, RSE, Osing, J, Hubzin, L, August, S, Walker, TM and Buchanan, RW (2015) Adjunctive minocycline in clozapine treated schizophrenia patients with persistent symptoms. Journal of Clinical Psychopharmacology 35(4), 374–381.CrossRefGoogle ScholarPubMed
Kremer, I, Vass, A, Gorelik, I, Bar, G, Blanaru, M, Javitt, DC and Heresco-Levy, U (2004) Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biological Psychiatry 56(6), 441–446.CrossRefGoogle ScholarPubMed
Kudva, GK and Gupta, DK (2016) Strategies in clozapine-resistant schizophrenia: a literature review. Journal of Mental Health and Human Behaviour 21(1), 6.CrossRefGoogle Scholar
Lane, H-Y, Huang, C-L, Wu, P-L, Liu, Y-C, Chang, Y-C, Lin, P-Y, Chen, P-W and Tsai, G (2006) Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia. Biological Psychiatry 60(6), 645–649.CrossRefGoogle ScholarPubMed
Leung, CC-Y, Gadelrab, R, Ntephe, CU, McGuire, PK and Demjaha, A (2019) Clinical course, neurobiology and therapeutic approaches to treatment resistant schizophrenia. Toward an integrated view. Frontiers in Psychiatry 10, 601.CrossRefGoogle ScholarPubMed
Morrison, AP, Pyle, M, Gumley, A, Schwannauer, M, Turkington, D, MacLennan, G, Norrie, J, Hudson, J, Bowe, SE, French, P, Byrne, R, Syrett, S, Dudley, R, McLeod, HJ, Griffiths, H, Barnes, TR E, Davies, L, Kingdon, D, Aydinlar, S, Courtley, J, Douglas-Bailey, M, Graves, E, Holden, N, Hutton, J, Hutton, P, Irving, S, Jackson, C, Lebert, T, Mander, H, McCartney, L, Munro-Clark, T, Murphy, EK, Spanswick, M, Steele, A, Tip, L and Tully, S (2018) Cognitive behavioural therapy in clozapine-resistant schizophrenia (FOCUS): an assessor-blinded, randomised controlled trial. The Lancet Psychiatry 5(8), 633–643.CrossRefGoogle ScholarPubMed
Mossaheb, N, Sacher, J, Wiesegger, G, Klein, N, Spindelegger, CJ, Asenbaum, S, Dudczak, R and Kasper, S (2006) Haloperidol in combination with clozapine in treatment-refractory patients with schizophrenia. European Neuropsychopharmacology 16, S416.CrossRefGoogle Scholar
Muscatello, MRA, Bruno, A, Pandolfo, G, Micò, U, Bellinghieri, P, Scimeca, G, Cacciola, M, Campolo, D, Settineri, S and Zoccali, R (2011a) Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study. Journal of Psychopharmacology 25(5), 667–674. doi: 10.1177/0269881110372548.CrossRefGoogle ScholarPubMed
Muscatello, MRA, Bruno, A, Pandolfo, G, Micò, U, Scimeca, G, Di Nardo, F, Santoro, V, Spina, E and Zoccali, RA (2011b) Effect of aripiprazole augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study. Schizophrenia Research 127(1-3), 93–99.CrossRefGoogle ScholarPubMed
Muscatello, MRA, Pandolfo, G, Micò, U, Lamberti Castronuovo, E, Abenavoli, E, Scimeca, G, Spina, E, Zoccali, R and Bruno, A (2014) Augmentation of clozapine with ziprasidone in refractory schizophrenia: a double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology 34(1), 129–133.CrossRefGoogle ScholarPubMed
Nielsen, J, Emborg, C, Gydesen, S, Dybbro, J, Aagaard, J, Haderup, K, Glyngdal, P, Fabricius, S, Thode, D, Lublin, H, Andersen, T, Damkier, P and Taylor, D (2012) Augmenting clozapine with sertindole: a double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology 32(2), 173–178.CrossRefGoogle ScholarPubMed
Petrides, G, Malur, C, Braga, RJ, Bailine, SH, Schooler, NR, Malhotra, AK, Kane, JM, Sanghani, S, Goldberg, TE, John, M and Mendelowitz, A (2015) Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study. The American Journal of Psychiatry 172(1), 52–58.CrossRefGoogle ScholarPubMed
Porcelli, S, Balzarro, B and Serretti, A (2012) Clozapine resistance: augmentation strategies. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology 22(3), 165–182.CrossRefGoogle ScholarPubMed
Potkin, SG, Jin, Y, Bunney, BG, Costa, J and Gulasekaram, B (1999) Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. The American Journal of Psychiatry 156(1), 145–147.CrossRefGoogle ScholarPubMed
Roerig, JL (2019) Clozapine augmentation strategies. The Mental Health Clinician 9(6), 336–348.CrossRefGoogle ScholarPubMed
Rosa, MO, Gattaz, WF, Rosa, MA, Rumi, DO, Tavares, H, Myczkowski, M, Sartorelli, MC, Rigonatti, SP, Elkis, H, Cabral, SB, Teixeira, MJ and Marcolin, MA (2007) Effects of repetitive transcranial magnetic stimulation on auditory hallucinations refractory to clozapine. The Journal of Clinical Psychiatry 68(10), 1528–1532.CrossRefGoogle ScholarPubMed
Šagud, M (2015) Treatment-resistant schizophrenia: challenges and implications for clinical practice. Psychiatria Danubina 27(3), 319–326.Google ScholarPubMed
Shiloh, R, Zemishlany, Z, Aizenberg, D, Radwan, M, Schwartz, B, Dorfman-Etrog, P, Modai, I, Khaikin, M and Weizman, A (1997) Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. a double-blind, placebo-controlled study. The British Journal of Psychiatry: The Journal of Mental Science 171(6), 569–573.CrossRefGoogle ScholarPubMed
Siskind, DJ, Lee, M, Ravindran, A, Zhang, Q, Ma, E, Motamarri, B and Kisely, S (2018) Augmentation strategies for clozapine refractory schizophrenia: a systematic review and meta-analysis. The Australian and New Zealand Journal of Psychiatry 52(8), 751–767.CrossRefGoogle ScholarPubMed
Souza, JS, Kayo, M, Neto, JH, Elkis, H and Buckley, PF (2010) New therapeutic strategies for resistance to clozapine and treatment-resistant schizophrenia. Therapy-Resistant Schizophrenia 26, 152–164.CrossRefGoogle Scholar
Taylor, D, Shapland, L, Laverick, G, Bond, J and Munro, J (2000) Clozapine – a survey of patient perceptions. Psychiatric Bulletin 24(12), 450–452.CrossRefGoogle Scholar
Tiihonen, J, Hallikainen, T, Ryynänen, O-P, Repo-Tiihonen, E, Kotilainen, I, Eronen, M, Toivonen, P, Wahlbeck, K and Putkonen, A (2003) Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Biological Psychiatry 54(11), 1241–1248.CrossRefGoogle ScholarPubMed
Tiihonen, J, Halonen, P, Wahlbeck, K, Repo-Tiihonen, E, Hyvärinen, S, Eronen, M, Putkonen, H, Takala, P, Mehtonen, O-P, Puck, M, Oksanen, J, Koskelainen, P, Joffe, G, Aer, J, Hallikainen, T, Ryynänen, O-P and Tupala, E (2005) Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. The Journal of Clinical Psychiatry 66(8), 1012–1015.CrossRefGoogle ScholarPubMed
Tiihonen, J, Wahlbeck, K and Kiviniemi, V (2009) The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Research 109(1-3), 10–14.CrossRefGoogle ScholarPubMed
Tsai, GE, Yang, P, Chung, LC, Tsai, IC, Tsai, CW and Coyle, JT (1999) D-serine added to clozapine for the treatment of schizophrenia. The American Journal of Psychiatry 156(11), 1822–1825.CrossRefGoogle ScholarPubMed
Vayısoğlu, S, Anıl Yağcıoğlu, AE, Yağcıoğlu, S, Karahan, S, Karcı, O, Gürel, SC and Yazıcı, MK (2013) Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment. Schizophrenia Research 143(1), 207–214.CrossRefGoogle ScholarPubMed
Veerman, SRT, Schulte, PFJ, Smith, JD and de Haan, L (2016) Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study. Psychological Medicine 46(9), 1909–1921.CrossRefGoogle ScholarPubMed
Wagner, E, Löhrs, L, Siskind, D, Honer, WG, Falkai, P and Hasan, A (2019) Clozapine augmentation strategies - a systematic meta-review of available evidence. Treatment options for clozapine resistance. Journal of Psychopharmacology (Oxford, England) 33(4), 423–435.CrossRefGoogle ScholarPubMed
Wang, G, Zheng, W, Li, X-B, Wang, S-B, Cai, D-B, Yang, X-H, Ungvari, GS, Xiang, Y-T and Correll, CU (2018) ECT augmentation of clozapine for clozapine-resistant schizophrenia: a meta-analysis of randomized controlled trials. Journal of Psychiatric Research 105, 23–32.CrossRefGoogle ScholarPubMed
Weiner, E, Conley, RR, Ball, MP, Feldman, S, Gold, JM, Kelly, DL, Wonodi, I, McMahon, RP and Buchanan, RW (2010) Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology 35(11), 2274–2283.CrossRefGoogle ScholarPubMed
Yağcioğlu, AEA, Kivircik Akdede, BB, Turgut, TI, Tümüklü, M, Yazici, MK, Alptekin, K, Ertuğrul, A, Jayathilake, K, Göğüş, A, Tunca, Z and Meltzer, HY (2005) A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety. The Journal of Clinical Psychiatry 66(1), 63–72.CrossRefGoogle Scholar
Zheng, W, Xiang, Y-T, Yang, X-H, Xiang, Y-Q and de Leon, J (2017) Clozapine augmentation with antiepileptic drugs for treatment-resistant schizophrenia: a meta-analysis of randomized controlled trials. The Journal of Clinical Psychiatry 78(5), e498–e505.CrossRefGoogle ScholarPubMed
Zoccali, R, Muscatello, MR, Bruno, A, Cambria, R, Micò, U, Spina, E and Meduri, M (2007) The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophrenia Research 93(1-3), 109–116.CrossRefGoogle Scholar
Zoccali, R, Muscatello, MR, Cedro, C, Neri, P, La Torre, D, Spina, E, Di Rosa, AE and Meduri, M (2004) The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study. International Clinical Psychopharmacology 19(2), 71–76.CrossRefGoogle ScholarPubMed
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