Quetiapine in the treatment of acute bipolar mania: efficacy across a broad range of symptoms.
OBJECTIVE
An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine's antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms.


METHODS
Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed.


RESULTS
Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy. The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP.


CONCLUSIONS
Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.
McIntyre
Roger S
RS
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. roger.mcintyre@uhn.on.ca
Konarski
Jakub Z
JZ
Jones
Martin
M
Paulsson
Björn
B
D000208:Acute Disease; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018020:Lithium Compounds; D000069348:Quetiapine Fumarate; D014635:Valproic Acid