title: Low-dose lamotrigine augmentation therapy improves residual symptoms in treatment-resistant schizophrenia: a report of five cases.
abstract: BACKGROUND
  Treatment-resistant schizophrenia (TRS) refers to the approximately 20-30% of schizophrenia patients whose symptoms are resistant to any antipsychotic treatment. For the improvement of residual symptoms in TRS, augmentation therapy using anticonvulsants such as lamotrigine (LTG) has recently attracted attention. Randomized clinical trials (RCTs) have demonstrated robust evidence; however, the results have shown both positive and negative outcomes for the use of LTG. Although RCTs have merit, they also obscure informative clinical features present in each patient, such as the types of TRS that show the most significant effects from LTG. Thus, detailed case reports examining the efficacy of LTG may help to shed light on various treatments for complex, heterogeneous diseases such as schizophrenia.
  
  
  METHODS
  We present detailed reports on the clinical course and features of TRS in five patients suffering from severe positive symptoms who were treated with LTG augmentation therapy.
  
  
  RESULTS
  After the administration of LTG augmentation therapy, two patients did not show any improvement in their residual symptoms, while the remaining three patients did experience improvement. Remarkably, patients with more severe residual positive symptoms, especially those with auditory hallucinations, seemed to respond better to low-dose LTG (50 mg daily). Additional clinical variables, such as type and dose of ongoing antipsychotics, age of onset, duration of illness, duration of untreated psychosis, number of administration cycles, and genetic heritability, were not found to be related to the effectiveness of LTG augmentation.
  
  
  CONCLUSIONS
  Low-dose LTG augmentation therapy seems to improve residual symptoms in some cases of TRS. The glutamatergic properties of LTG may be the decisive factor in these symptoms, as other glutamatergic agents have also been shown to be effective based on previous glutamate hypotheses in schizophrenia.
authors.affiliation: Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takebayashi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Higashiyama
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006212:Hallucinations / Q000188:drug therapy; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D014227:Triazines; D000077213:Lamotrigine
keywords: augmentation; glutamate; lamotrigine; schizophrenia; treatment-resistant