Randomized controlled trial comparing quetiapine with lithium and clozapine with lithium in the treatment of female patients with mania

Background:Second-generation antipsychotics are commonly used in the treatment of mania but there remains debate about the relative benefits of the different medications in these patients,particularly in female patients with mania. Objective: Compare the clinical effectiveness and safety of quetiapine and clozapine as adjunctive treatments of lithium in the treatment of female patients with mania. Methods:Sixty-four female patients who met ICD-10 criteria for a current manic episode were randomly assigned to take lithium with quetiapine (n=32) or lithium with clozapine (n=32) in a six-week,open-label trial.Clinical efficacy was evaluated at baseline and weekly thereafter by administering the Beck Rafaelson's Mania Rating Scale (BRMS).Adverse reactions were assessed by administering the Treatment Emergent Symptom Scale (TESS) at baseline and at 1,2,4,and 6 weeks after starting treatment. Results: Two patients in the clozapine group did not complete the trial due to low white blood counts.Among subjects who completed the 6 weeks of treatment there were no significant differences in the mean BRMS values between the two groups at any time during the trial.At the end of the trial 87.5% (28/32) of the patients taking quetiapine and 90.0% (27/30) of those taking clozapine meet criteria for remission (i.e.,a 50% drop in BMRS score from baseline) (χ2=0.76,P=0.385). During the course of treatment a significantly higher proportion of subjects in the clozapine group experienced dizziness,weight gain,somnolence,constipation,excessive salivation,and abnormal blood glucose and electrocardiogram results.The overall severity of adverse effects was significantly higher in the clozapine group after two weeks of treatment but there were no differences in the overall severity of adverse effects at other time periods.Despite the 23-fold higher cost for quetiapine versus clozapine,the overall cost effectiveness of the two medication regimens was similar because of the much high use of expensive auxillary drugs in the clozapine group. Conclusion: The clinical efficacy of quetiapine and clozapine as adjunctive treatment in women with mania taking lithium is similar but the two treatment regimens have different side-effect profiles.The cost benefit o using generic clozapine may be over shadowed by the costs associated with treating the adverse effects of clozapine.