Quetiapine with lithium or divalproex for the treatment of bipolar mania: A randomized, double-blind, placebo-controlled study

Harvard Bipolar Research Program, Massachusetts General Hospital, Boston, 02114, USA.
Bipolar Disorders (Impact Factor: 4.97). 07/2004; 6(3):213-23. DOI: 10.1111/j.1399-5618.2004.00115.x
Source: PubMed


Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania.
Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL.
Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension.
Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.

15 Reads
  • Source
    • "Quetiapine is a dibenzothiazepine derivative that is a serotonin type 2 (5-HT2 A) and dopamine type 2 (D2) receptor antagonist and it also interacts with other neurotransmitter receptors e.g., 5HT7, 5HT2c, alpha1 and 2 antagonist, Histaminic (H1) receptor antagonist, 5HT1A partial antagonist etc... [1] [2]. It is an orally administered atypical antipsychotic [3] that is indicated for the treatment of schizophrenia, manic episode in bipolar disorder [4] and bipolar depression [5] [6] or as an adjunct to lithium or valporate semisodium; [7] and as maintenance treatment for bipolar disorder [8]. The antidepressant mechanism of action of quetiapine is uncertain, but may be related to its effects on 5-HT1 A and 5-HT2 A receptors in the prefrontal cortex, modulation of dopamine transmission and/ or inhibition of synaptic noradrenaline reuptake as a result of the blocking of norepinephrine transporter (NET) by norquetiapine [9]. "

  • Source
    • "RSP + SH > PBO + SH Sachs et al., 2004 [41] QTP + SH (91) PBO + SH (100) QTP + SH > PBO + SH Akhondzadeh et al., 2006 [47] ALP + HAL + Li (38) PBO + HAL + Li (37) ALP + HAL + Li > PBO + HAL + Li McIntyre et al., 2007 [42] QTP + SH (197) PBO + SH (205) QTP + SH > PBO + SH Yatham et al., 2007 [43] QTP + SH (104) PBO + SH (96) QTP + SH > PBO + SH Sussmam et al., 2007 [48] QTP + SH (197) PBO + SH (205) QTP + SH > PBO + SH Vieta et al., 2008 [44] ARI + SH (253) PBO + SH (131) ARI + SH > PBO + SH Tohen et al., 2008 [49] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bipolar disorder (BD) is the seventh leading cause of disability per year of life among all diseases in the population aged 15 to 44. It is a group of heterogeneous diseases, with frequent comorbid psychiatric or somatic disorders, variable treatment response and frequent residual symptoms between episodes. The major impairment associated with this disorder is related to the high relapse and recurrence rates, the functional impact of comorbidities and cognitive impairment between episodes. The prognosis of the disease relies on the efficacy of relapse and recurrence prevention interventions. Given the heterogeneity of the disorder, relapse and recurrence prevention needs to develop a personalized care plan from the start of the acute phase. In such a complex situation, guideline-driven algorithms of decision are known to improve overall care of patients with bipolar disorder, compared to standard treatment decisions. Although guidelines do not account for all the situations encountered with patients, this systematic approach contributes to the development of personalized medicine. We present a critical review of recent international recommendations for the management of manic phases. We summarize treatment options that reach consensus (monotherapy and combination therapy) and comment on options that differ across guidelines. The synthesis of recent international guidelines shows a consensus for the initial treatment for manic phases. For acute and long-term management, the anti-manic drugs proposed are traditional mood stabilizers (lithium or valproate) and atypical antipsychotics (APA - olanzapine, risperidone, aripiprazole and quetiapine). All guidelines indicate stopping antidepressant drugs during manic phases. International guidelines also present with some differences. First, as monotherapy is often non sufficient in clinical practice, combination therapy with a traditional mood stabilizer and an APA are disputed either in first line treatment for severe cases or in second line. Second, mixed episodes treatment is not consensual either and some guidelines propose in first line valproate, carbamazepine and some APA, and advice not to use lithium. On the other hand, some guidelines do not propose specific treatment for mixed episodes and group them with manic episodes management. Duration of treatment is unclear. Guidelines utilization has shown that the systemic use by clinicians of decision algorithms in comparison to "treatment as usual" modality improves the overall care of patients with BD. Future data from cohorts of patients seem necessary to complement the existing data from clinical trials. These cohort studies will help to take into account the different individual profiles of BD and thus may help to propose a more personalized medicine.
    L Encéphale 02/2014; · 0.70 Impact Factor
  • Source
    • "tion recognition perfor - mance was correlated with better performance on the WCST and that patients with schizophrenia performed worse than control subjects on emotion . Bryson et al . ( 1997 ) investigated 63 patients diagnosed with schizophrenia or schizoaffective disorder and found a moderate relationship between emotion recognition and WCST . Sachs et al . ( 2004 ) , in a study involving 40 patients with schizophrenia and 43 healthy volunteers , also reported that patients with schizophrenia performed worse than control subjects on all emotions and found that happy facial emotion recognition corre - lated with WCST score . Some studies in BD have shown a correlation of EF with some aspects of em"
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability to recognize facial emotions is altered in patients with Bipolar Disorder (BD) during mood episodes and even in euthymia, while cognitive functioning is similarly impaired. This recognition is considered a fundamental skill for successful social interaction. However, it is unclear whether the ability to recognize facial emotions is correlated with the cognitive deficits observed in BD. The objective of this study was to evaluate Facial Emotion Recognition (FER) and its correlation with executive function (EF) in BD I patients during mania, depression and euthymia compared to healthy controls. A total of 110 patients with BD I, 18-40 years old were included (41 in manic episode; 31 in depressive episode and 38 euthymic). Patients were assessed for FER and EF (Wisconsin card sorting test - WCST), along with 96 healthy volunteers (18-40 years old) recruited from the University of São Paulo. The results showed that BD I patients had lower FER performance compared to controls on fear subtests, happiness, the surprise test, and FER total scores. Moreover, BD I manic patients showed poorer performance for EF compared to controls. Six out of the seven variables of the WCST correlated with FER in both healthy controls and BD euthymic subjects but not in BD patients during mood episodes. Cognitive deficits and difficulties recognizing facial emotions are present in all mood episodes in BD I patients, even during remission. Although FER is not considered a cognitive domain, these results suggest that, along with EF, it has a complementary function. Hence, further studies should investigate this issue in larger samples and verify whether these similarities also occur at a neurobiological level.
    Journal of Affective Disorders 10/2013; 152(1). DOI:10.1016/j.jad.2013.09.027 · 3.38 Impact Factor
Show more

Preview (2 Sources)

15 Reads
Available from