Valproate or olanzapine add-on to lithium: an 8-week, randomized, open-label study in Italian patients with a manic relapse.
BACKGROUND
Breakthrough manic episodes are the rule in bipolar disorders; valproate and olanzapine are considered first-line treatments for manic episodes, nevertheless the two drugs have only been compared in monotherapy studies. In our study we compared the efficacy and safety of valproate and olanzapine added to lithium in the treatment of patients experiencing breakthrough manic episodes while on lithium monotherapy.


METHODS
Patients with bipolar I or II disorder (SCID-I), in treatment with lithium since at least one year, experiencing a manic or hypomanic relapse were randomly assigned to an open-label add-on therapy with valproate (500-1500 mg/day) or olanzapine (7.5-15.0 mg/day) for 8 weeks. The primary efficacy measure was the Young Mania Rating Scale (YMRS) total.


RESULTS
Twenty-one patients were randomized to receive the add-on therapy with valproate (n=9) or olanzapine (n=12). Both groups showed a significant baseline to endpoint reduction in YMRS total and Clinical Global Impressions-Severity (CGI-S) scores (p<0.001). At endpoint, the mean reduction of YMRS total or CGI-S scores, as well as response or remission rates, was not significantly different between the groups. However, compared with patients in the valproate add-on group, patients treated with olanzapine add-on showed significantly greater reductions in the YMRS total and CGI-S mean scores at weeks 1 through 4 (p<0.05). The rate and profile of adverse events were numerically similar in the two groups.


CONCLUSIONS
Open-label design and limited sample size.


CONCLUSIONS
Both add-on therapies were efficacious in treating patients with manic or hypomanic relapse, however the olanzapine group showed an earlier response to treatment. These findings can help clinicians in understanding the value of adding other treatments to lithium in patients experiencing a manic or hypomanic relapse.
Maina
Giuseppe
G
Department of Neuroscience, Mood and Anxiety Disorders Unit, University of Turin, Italy. giuseppemaina@hotmail.com
Albert
Umberto
U
Salvi
Virginio
V
Mancini
Michele
M
Bogetto
Filippo
F
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D012008:Recurrence; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects
D000927:Anticonvulsants; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D016651:Lithium Carbonate; D014635:Valproic Acid; D000077152:Olanzapine