Iris E. Sommer

OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHOD: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. RESULTS: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. CONCLUSIONS: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment method with few side effects. However, efficacy for various psychiatric disorders is currently not clear. DATA SOURCES: A literature search was performed from 1966 through October 2008 using PubMed, Ovid Medline, Embase Psychiatry, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and PsycINFO. The following search terms were used: transcranial magnetic stimulation, TMS, repetitive TMS, psychiatry, mental disorder, psychiatric disorder, anxiety disorder, attention-deficit hyperactivity disorder, bipolar disorder, catatonia, mania, depression, obsessive-compulsive disorder, psychosis, posttraumatic stress disorder, schizophrenia, Tourette's syndrome, bulimia nervosa, and addiction. STUDY SELECTION: Data were obtained from randomized, sham-controlled studies of rTMS treatment for depression (34 studies), auditory verbal hallucinations (AVH, 7 studies), negative symptoms in schizophrenia (7 studies), and obsessive-compulsive disorder (OCD, 3 studies). Studies of rTMS versus electroconvulsive treatment (ECT, 6 studies) for depression were meta-analyzed. DATA EXTRACTION: Standardized mean effect sizes of rTMS versus sham were computed based on pretreatment-posttreatment comparisons. DATA SYNTHESIS: The mean weighted effect size of rTMS versus sham for depression was 0.55 (P < .001). Monotherapy with rTMS was more effective than rTMS as adjunctive to antidepressant medication. ECT was superior to rTMS in the treatment of depression (mean weighted effect size -0.47, P = .004). In the treatment of AVH, rTMS was superior to sham treatment, with a mean weighted effect size of 0.54 (P < .001). The mean weighted effect size for rTMS versus sham in the treatment of negative symptoms in schizophrenia was 0.39 (P = .11) and for OCD, 0.15 (P = .52). Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations. CONCLUSIONS: It is time to provide rTMS as a clinical treatment method for depression, for auditory verbal hallucinations, and possibly for negative symptoms. We do not recommend rTMS for the treatment of OCD.

BACKGROUND: Cerebral lateralisation appears to be decreased in schizophrenia. Results of studies investigating this, however, are equivocal. AIMS: To review quantitatively the literature on decreased lateralisation in schizophrenia. METHOD: Meta-analyses were conducted on 19 studies on handedness, 10 dichotic listening studies and 39 studies investigating anatomical asymmetry in schizophrenia. RESULTS: The prevalence of mixed- and left-handedness ('non-right-handedness') was significantly higher in patients with schizophrenia as compared to healthy controls, and also as compared to psychiatric controls. The analysis of dichotic listening studies revealed no significant difference in lateralisation in schizophrenia. However, when analysis was restricted to studies using consonant-vowel or fused word tasks, significantly decreased lateralisation in schizophrenia emerged. Asymmetry of the planum temporale and the Sylvian fissure was significantly decreased in schizophrenia, while asymmetry of the temporal horn of the lateral ventricle was not. CONCLUSION: Strong evidence is provided for decreased cerebral lateralisation in schizophrenia.