Quetiapine or haloperidol as monotherapy for bipolar mania - A 12-week, double-blind, randomised, parallel-group, placebo-controlled trial

Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Canada.
European Neuropsychopharmacology (Impact Factor: 4.37). 11/2005; 15(5):573-85. DOI: 10.1016/j.euroneuro.2005.02.006
Source: PubMed


Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score.
YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day.
Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.

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    • "Several previous studies have shown that quetiapine can be used as monotherapy1–3 or in combination therapy with a classical mood stabilizer to treat bipolar mania4 and bipolar depression.5 Further, quetiapine has been shown to be effective in the prevention of relapses in bipolar disorder.6–8 The practice guideline for the treatment of patients with bipolar disorder published by the American Psychiatric Association in 2002 indicates that “… following remission of an acute episode, patients may remain at particularly high risk of relapse for a period of up to 6 months; this phase of treatment, sometimes referred to as continuation treatment, is considered in this guideline to be part of the maintenance phase. "
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    ABSTRACT: Although quetiapine has often been used as monotherapy or adjunctive therapy in bipolar disorder, there is very limited clinical evidence regarding prescribing practices for quetiapine as maintenance treatment for bipolar disorder. We reviewed the inpatient and outpatient records of 175 Chinese patients who received treatment with quetiapine for bipolar disorder both during and following hospitalization. We compared patients treated with high-dose (>300 mg/day) and low-dose (≤300 mg/day) quetiapine during the acute treatment phase and in the subsequent 6 months of maintenance treatment, with assessments at months 1, 3, and 6. Multifactor logistic regression analysis was performed to identify factors associated with quetiapine dosage. The proportion of patients receiving combination therapy of quetiapine and a mood stabilizer as acute and maintenance treatment was 99.4% and 84.6%, respectively. The mean dose of quetiapine when used for acute treatment in the 175 patients was 395.7 mg/day. The following factors were found to be independently associated with use of high-dose quetiapine: male gender (odds ratio [OR] 2.712, 95% confidence interval [CI] 1.372-5.362, P < 0.01), a manic or mixed episode (OR 2.786, 95% CI 1.362-5.699, P < 0.01), and psychotic features (OR 2.658, 95% CI 1.318-5.361, P < 0.01). In the subsequent 6 months, the mean dose of quetiapine prescribed steadily decreased to 375.0 mg/day, 330.6 mg/day, and 293.7 mg/day at months 1, 3, and 6. The main factors associated with high-dose quetiapine in maintenance treatment were male gender (month 1, OR 2.761; month 3, OR 2.583; month 6, OR 2.686; P < 0.01) and a manic or mixed episode (month 1, OR 2.626; month 3, OR 2.334; P < 0.01). Higher doses of quetiapine (>300 mg/day) are more likely to be prescribed to patients who are male, those who are experiencing a manic or mixed episode, and those who have psychotic features during acute treatment of bipolar disorder. For patients who remain clinically stable during the subsequent months, the quetiapine dose should be adjusted according to patient gender and the most recent type of episode experienced.
    Neuropsychiatric Disease and Treatment 04/2013; 9:575-80. DOI:10.2147/NDT.S42473 · 1.74 Impact Factor
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    • "At week 3, the decrease in YMRS scores was significantly greater for both drugs compared with placebo (P < 0,001); the extent of the improvement was virtually identical for the two drugs. The other study McIntyre et al. (2005) was of the same size using the same design, except for the active comparator which was haloperidol; the results obtained were similar, except for the effect of haloperidol at week 3 which was slightly more robust than that of quetiapine. In both studies, quetiapine has shown significantly greater efficacy than placebo. "
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    ABSTRACT: Bipolar affective disorder is a serious mental disease associated with significant morbidity and mortality. Good-quality research available to guide treatment strategies remains insufficient, particularly with regard to manic or hypomanic episodes. A critical review of the various stages of mania might be helpful for pharmamaceutical companies and investigators as a prerequisite for the clinical evaluation of potential antimanic properties of medications. The main difficulty remains the comparison between antipsychotics and mood stabilizers such as lithium (with equal efficacy in the acute phase and the prevention of recurrent manic episodes) No consensus has been reached with regard to the treatment of bouts of acute mania in various parts of the world. Controlled clinical trials have, at last, provided irrefutable evidence of the activity of lithium, which has long been used alone, as well asthat of divalproate or its derivatives and, to a lesser extent, carbamazepine. The new antipsychotic agents have more recently established their efficacy, especially aripiprazole, asenapine, quetiapine; olanzapine, risperidone and ziprazidone. It is paradoxical to note that, in Europe, haloperidol is still the reference substance used in clinical trials despite the fact that it is not officially indicated in the treatment of mania. In the USA, lithium, divalproate or antipsychotics can be prescribed as first-line treatment. In Europe, lithium remains the first-line medication, whereas divalproate and atypical antipsychotic agents are used only as second-line therapy. Although both types of medication (antipsychotics, normothymic agents and/or anticonvulsants) have proved to be clinically effective in the management of mania by reducing the mania scores overall, the same does not apply, however, to all symptoms of mania. Factorial approaches to mania have all shown that since there are several clinical forms of mania, several lines of manic symptoms can be identified. Antipsy
    Frontiers in Pharmacology 01/2013; 4:4. DOI:10.3389/fphar.2013.00004 · 3.80 Impact Factor
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    • "RCTs with haloperidol were included (McElroy et al. 1996 ; McIntyre et al. 2005 ; Smulevich et al. 2005 ; Tohen et al. 2003a ; Vieta et al. 2005, 2008 ; Young et al. 2009 "

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