Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia.


METHODS
Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early.


RESULTS
The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p =.07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone.


CONCLUSIONS
Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.
Zucker Hillside Hospital, Glen Oaks, N.Y., USA. Stefan.Leucht@lrz.tum.de
Stefan
S
Leucht
Werner
W
Kissling
John
J
McGrath
D000342:Affective Symptoms / Q000175:diagnosis / Q000188:drug therapy; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D016651:Lithium Carbonate