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Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients

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Abstract

Introduction: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron®, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.

Objective: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (≥25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).

Methods: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15–60 mg/day (n = 147) or fluoxetine 20–40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.

Results: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (∼15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a ≥50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (−10.9 vs −8.5, p = 0.006) and the proportion of patients with ≥50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of ‘much/very much improved’ patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on ‘sleeping assessment 1’ (14.9 ± 5.2 vs 13.7 ± 5.4, p = 0.028) and ‘sleeping assessment 2’ (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7kg compared with a mean decrease in weight of 0.4 ± 2.1kg for fluoxetine-treated patients (p < 0.001).

Conclusions: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement

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Acknowledgements

This study was supported by Organon NV, The Netherlands.

Dr Versiani has received research grants and Dr Moreno has received consulting and research fees from Organon. CJA Ramakers and AJ Schutte are both current employees of Organon.

We would like to acknowledge the efforts of Dimensione Ricerca in performing all the data management and statistics for the study. An electronic data capture system owned by Dimensione Ricerca was successfully employed for data management.

We would also like to thank all the investigators who participated in the trial:

Portugal: Dr P Pahla, Casa de Suade do Bom Jesus, Nogueiro, Braga.

Brazil: Dr R Moreno, GRUDA, Universidade de São Paulo, Rua Tabapua 500 - ci41, Sao Paulo; Dr Schestaky, Hospital de Clinicas de Porto Alegre, Av. Taguara 594, Porto Alegre; Dr M Versiani, Rua Vinconde de Pirajá, 407 - sala 805, Rio de Janeiro.

Spain: Dr M González de Chávez, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, Madrid; Dr G Ferrer, Hospital Clinico y Provincial de Barcelona, Villarroel 170, Barcelona; Dr J Saiz Ruíz, Servicio de Psiquiatria, Hospital Ramón y Cajal, Carretera de Colmenar Viejo, Km. 9, 100, Madrid; Dr C Laraña, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani 3, Sevilla; Dr R Moreno, Servicio de Psiquiatria, Hospital Clinico Universitario de Valencia, Avda. Blasco Ibañez 17, Valencia.

Greece: Dr C Ierodiakonou, AHEPA University Hospital, Ciriakioi str. 546-36, Thessaloniki; Dr V Alevizos, Eginitio Hospital, Vas. Sofias Av. 74, Athens; Dr G Kaprinis, State Psychiatry Hospital, Konstantinoupoleos 36, Thessaloniki; Dr G Tzanakaki, State Psychiatry Hospital of Chania, Soudas 27, Chania.

Italy: Dr M Pavan, Universita’ di Padova, Via Guistiani 2, Padova; Dr Maestri, Ospedale di Piacenza, Via Taverna 49, Piacenza; Dr Garonna, Reparto Psichiatria, Via Panica 17, Marostica; Dr Desana, DSM ASL 6, Corso Francia 347, Ciriè; Dr E Pirfo, DSM ASL 3, Via Cardinal Masaia 11, Torino; Dr Lomonaco, Unita Modulare 1 Biella, DSMASL 12, Via Gramsci 21/A, Biella; DrL Scarzella, Ospedale Evangelico Valdese, Via Silvio Pellico 19, Torino; Dr Mencacci, Ospedale S. Maria delle Stelle - Clinica Psichiatrica, Viale Trieste, Melzo Milano; Dr Antignani, Ospedale Umberto I - Serv. Psichiatrico di Diagnosi e Cura, Viale Mazzini, Frosinone; Dr M Casacchia, Ospedale Civile S. Salvatore, Clinica Psichiatrica, Via Marra, L’Aquila; Dr Munizza, Psichiatria Ospedale Don Bosco, Piazza Donatori di Sangue, Torino; Dr Caserta, Ospedale Guadagna, Via di Villa Grazia 46, Palermo; Dr Commodari, CIM, Corso Italia, Catania; Dr Robotti, Ospedale Borgo Trento, Borgo Trento - Verona; Dr Cappellari, Ospedale Civile CIM, Via Pietro Cosma 1, Camposampiero - Padova.

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Authors and Affiliations

  1. Institute of Psychiatry, Federal University of Rio de Janeiro, 71 (back), Avenue Venceslau Bras, Botafogo, 22490-140, Rio de Janeiro, Brazil

    Marcio Versiani

  2. Affective Disorders Study Group (GRUDA), University of São Paulo, São Paulo, Brazil

    Ricardo Moreno

  3. Clinical Trial Operations, Organon NV, Oss, The Netherlands

    Catharina J. A. Ramakers-van Moorsel

  4. Medical Services CNS, Organon International Inc., Roseland, New Jersey, USA

    Albert J. Schutte

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  1. Marcio Versiani
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  2. Ricardo Moreno
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  3. Catharina J. A. Ramakers-van Moorsel
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  4. Albert J. Schutte
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Correspondence to Marcio Versiani.

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Versiani, M., Moreno, R., Ramakers-van Moorsel, C.J.A. et al. Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients. CNS Drugs 19, 137–146 (2005). https://doi.org/10.2165/00023210-200519020-00004

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