The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis.
BACKGROUND
Clozapine is the drug of choice for patients with unsatisfactory response to routine antipsychotic treatment. Polypharmacy is widely used among patients having clozapine-resistant schizophrenia, although no solid evidence exists for any effective augmentation therapy for this patient population. We aimed to study the efficacy of lamotrigine in the treatment of clozapine-resistant schizophrenia.


METHODS
We conducted electronic searches of the Cochrane PsiTri database, the Website of metaRegister of Controlled Trials, including NIH ClinicalTrials.gov, and a clinical trial register by the manufacturer of lamotrigine (GlaxoSmithKline). All randomized placebo-controlled studies on patients receiving clozapine were included in the analysis. The primary outcome measure was a total score for symptoms of psychosis, and the secondary outcome measures were scores for positive and negative symptoms of psychosis. For continuous and binary data, standardized mean differences (SMD), and odds ratios (OR) and the number needed to treat (NNT) were calculated, respectively.


RESULTS
Five trials with 10 to 24 weeks duration and total of 161 randomized clozapine patients were included in the meta-analysis. Lamotrigine was superior to placebo augmentation in both the primary outcome measure (SMD 0.57, 95%CI 0.25-0.89, p<0.001; OR 0.19, 95%CI 0.09-0.43, p<0.001; NNT 4, 95%CI 3-6) and secondary outcome measures (SMD 0.34, 95%CI 0.02-0.65 for positive symptoms, SMD 0.43, 95%CI 0.11-0.75 for negative symptoms).


CONCLUSIONS
This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia. A substantial proportion of these most severely ill patients appeared to obtain clinically meaningful benefit from this combination treatment.
Tiihonen
Jari
J
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, FI-70240 Kuopio, Finland. jari.tiihonen@niuva.fi
Wahlbeck
Kristian
K
Kiviniemi
Vesa
V
D000367:Age Factors; D000927:Anticonvulsants / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D000077213:Lamotrigine; D017063:Outcome Assessment, Health Care; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D014227:Triazines; D003024:Clozapine; D000077213:Lamotrigine