Metabolic and body mass parameters after treatment with JNJ-37822681, a novel fast-dissociating D2 receptor antagonist, vs olanzapine in patients with schizophrenia.
BACKGROUND
The highly selective and fast dissociating D2 receptor antagonist JNJ-37822681 may be associated with lower risk for weight gain and undesirable metabolic effects compared with available antipsychotics.


METHODS
In this double-blind, randomized study, patients were randomly assigned (1:1:1:1:1) to 12 weeks of JNJ-37822681 (10 mg, 20 mg, or 30 mg, twice daily) or olanzapine (10 mg/d during week 1; 15 mg/d after week 1), or 6 weeks of placebo (followed by 6 weeks of olanzapine, 15 mg/d). Metabolic and body mass parameters were assessed at weeks 6 and 12.


RESULTS
For metabolic parameters, at week 6 none of the JNJ-37822681 groups demonstrated significant change vs placebo; however, significant changes (P < .05) were observed in the olanzapine vs placebo group in triglycerides, low-density lipoprotein (LDL) and very-LDL cholesterol, and free fatty acids. For all JNJ-37822681 groups, mean weight changes at week 12 (-0.3 [10 mg], + 0.3 [20 mg], + 0.8 kg [30 mg]) were significantly less (P < .001) than for the olanzapine group (+ 2.7 kg). A higher percentage of overweight or obese patients (baseline body mass index: ≥25 kg/m2) receiving olanzapine had ≥7% increase in weight than those receiving JNJ-37822681 (9.8% vs 2.3%, respectively).


CONCLUSIONS
JNJ-37822681 treatment was associated with a more favorable outcome on weight and metabolic adverse effects vs olanzapine for treating schizophrenia; the 10 mg twice-daily dose demonstrated minimal to no weight gain.
Janssen Research and Development, LLC, Raritan, NJ, USA. edaly2@its.jnj.com
Ella J
EJ
Daly
Justine M
JM
Kent
Luc
L
Janssens
John W
JW
Newcomer
Gitta
G
Hüsken
Peter
P
De Boer
Luc
L
Tritsmans
Mark E
ME
Schmidt
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000187:drug effects
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006442:Glycated Hemoglobin; D007328:Insulin; D000077152:Olanzapine; D010880:Piperidines; D011724:Pyridazines; D014280:Triglycerides; C576398:N-(1-(3,4-difluorobenzyl)piperidin-4-yl)-6-(trifluoromethyl)pyridazin-3-amine; C517652:hemoglobin A1c protein, human