Augmentation of atypical antipsychotics with valproic acid. An open-label study for most difficult patients with schizophrenia.
OBJECTIVE
Most difficult inpatients with schizophrenia are in serious needs but obviously underrepresented in clinical trials.


METHODS
Very challenging patients received open-label treatment with atypical antipsychotics concurrently augmented with valproic acid. The primary outcome was the newly developed Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Patients improving more than 20 points were classified as responders.


RESULTS
Mean age and illness duration of 28 participants (22 male) were 42 y.o. and 20 years, respectively. They had spent a half of their life admitted after the onset. The average Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) were very severe at 79 and 6.1, respectively, with the baseline Global Assessment of Functioning (GAF) of as low as 21. As a result of augmentation, there were nine responders, 12 partial responders, and seven non-responders including only two patients who got worse. The main antipsychotics were mostly either risperidone or olanzapine. Mean maximum oral dose and blood level of valproic acid were 1907 mg and 91.7 microg/ml, respectively. Overall significant improvements whilst to an inadequate degree were noted in clinical parameters. Valproate augmentation was generally well tolerated but serious adverse effects included thrombocytopenia, anaemia and sedation/falls.


CONCLUSIONS
While these preliminary results need to be tested against tenacious monotherapy or polypharmacy involving clozapine, augmenting atypical antipsychotics with valproic acid can be useful for very severe schizophrenia.
Suzuki
Takefumi
T
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. takefumi@oak.dti.ne.jp
Uchida
Hiroyuki
H
Takeuchi
Hiroyoshi
H
Nakajima
Shinichiro
S
Nomura
Kensuke
K
Tanabe
Akira
A
Yagi
Gohei
G
Watanabe
Koichiro
K
Kashima
Haruo
H
D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011567:Psychiatric Department, Hospital; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid