Research report
Lithium versus carbamazepine in the maintenance treatment of bipolar disorders – a randomised study

https://doi.org/10.1016/S0165-0327(96)01427-9Get rights and content

Abstract

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63±0.12 mmol/l, carbamazepine dose: 621±186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P=0.041) and/or adverse effects (P=0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P=0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P=0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

Section snippets

General study design

The MAP study group consisted of nine psychiatric university hospitals in the Federal Republic of Germany (Aachen, Berlin, Düsseldorf, Heidelberg, Lübeck, Munich, Münster, Tübingen, Würzburg). Approval of local ethical committees was obtained according to legal requirements.

At the beginning of the study, all patients with affective syndromes admitted to one of the hospitals were screened (recruitment phase). Patients fulfilling the inclusion criteria were followed in the out-patient department

Study patients and non-completers

Table 1 shows sociodemographic and clinical characteristics of the 144 patients. 74 (51%) patients were randomised to lithium, 70 (49%) to carbamazepine. No significant differences regarding age, sex, number of previous episodes, attempted suicides, severity of symptomatology and other characteristics were observed between the treatment groups. Using the Structured Clinical Interview for DSM-III-R (SCID; Wittchen et al., 1987), 91% of the ICD-9 diagnosed patients fulfilled the DSM-III-R

Discussion

In the present study on maintenance treatment of bipolar disorder, the efficacy of lithium was comparable to that of carbamazepine as far as hospitalisations and recurrences are concerned. However, for the latter a trend in favour of lithium was observed. If treatment failure was defined as “recurrence and/or the necessity of antidepressant or neuroleptic comedication for a period of at least 6 months”, lithium was significantly superior to carbamazepine. Following Montgomery and Dunbar (1993),

Conclusion

The results indicate that in maintenance treatment of bipolar disorder lithium and carbamazepine might be equipotent when using hospitalisation or recurrence as outcome criteria. Considering, however, need of concomitant psychotropic medication and occurrence of severe side effects as additional failure criteria, lithium demonstrates a clear superiority. On the other hand, concerning long-term tolerability, carbamazepine seems to cause fewer slight and moderate side effects as reported by the

Acknowledgements

The authors gratefully thank all participating patients and the psychiatrists who were involved in recruitment and data collection in the individual centres. For supporting manuscript preparation we thank B. Henkel and U. Hegerl.

References (39)

  • Aitken, R.C.B. (1969) Measurement of feelings using visual analogue scales. Proc. Roy. Soc. Med. 62,...
  • Angst, J. (1981) Ungelöste Probleme bei der Indikationsstellung zur Lithiumprophylaxe affektiver und schizoaffektiver...
  • Bellaire, W., Demisch, K. and Stoll, K.D. (1990) Carbamazepin versus Lithium. Münch. Med. Wschr. 132 (Suppl),...
  • Breslow, N. (1970) A generalized Kruskal–Wallis test for comparing k samples subject to unequal patterns of censorship....
  • Coppen, A., Montgomery, S.A., Gupta, R.K. and Bailey, J.E. (1976) A double-blind comparison of lithium carbonate and...
  • Coxhead, N., Silverstone, T. and Cookson, J. (1992) Carbamazepine versus lithium in the prophylaxis of bipolar...
  • Dardennes, R., Even, C., Bange, F. and Heim, A. (1995) Comparison of carbamazepine and lithium in the prophylaxis of...
  • Efron, B. (1971) Forcing a sequential experiment to be balanced. Biometrica 58,...
  • Endicott, J., Spitzer, R.L., Fleiss, J.L. and Cohen, J. (1976) The global assessment scale. A procedure for measuring...
  • Gelenberg, A.J., Kane, J.M., Keller, M.B., Lavori, P., Rosenbaum, J.F., Cole, K. and Lavelle, J. (1989) Comparison of...
  • Greil, W., Haag, M., Huber, D. and Schmidt, St. (1986) Maintenance treatment in affective disorders: overview and...
  • Greil, W., Ludwig-Mayerhofer, W., Steller, B., Czernik, A., Giedke, H., Müller-Oerlinghausen, B., Osterheider, M.,...
  • Greil, W., Ludwig-Mayerhofer, W., Erazo, N., Engel, R.R., Czernik, A., Giedke, H., Müller-Oerlinghausen, B.,...
  • Greil, W., Ludwig-Mayerhofer, W., Erazo, N., Engel, R.R., Czernik, A., Giedke, H., Müller-Oerlinghausen, B., Sauer, H.,...
  • Grof, P., Schou, M., Angst, J., Baastrup, P.C. and Weis, P. (1970) Methodological problems of prophylactic trials in...
  • Kaplan, E.L. and Meier, P. (1958) Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53,...
  • Kupfer D.J. (1991) Long-term treatment of depression. J. Clin. Psychiatry 52 (Suppl 5),...
  • Lawless, J.F. (1992) Statistical Models and Methods for Lifetime Data. John Wiley, New...
  • Luznat, R.M., Murphy, D.P. and Nunn, C.M.H. (1988) Carbamatepine vs Lithium in the treatment and prophylaxis of mania....
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