Conventional antidepressants have several important limitations, including a lack of direct effects on negative self-schema, which is at the core of Beck's cognitive theory of depression. Based on previous studies showing a positive effect of ketamine on negative cognition, we compared reductions in negative self-schema between responders and non-responders to a single infusion of ketamine. In an open-label study, 26 participants with treatment-resistant depression received 0.5 mg/kg ketamine via infusion. Depression symptoms were assessed at baseline, 24 h, and 7 days after treatment with Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI-II). Nine of the 26 participants fulfilled response criteria after 24 h. Of these, eight still fulfilled response criteria after 7 days. Response was defined as a reduction in MADRS total score of 50% or more. Responders improved significantly more than non-responders both 24 h and 7 days after ketamine treatment on the following BDI-II items: item 1 ("Sadness"), item 7 ("Self-Dislike"), and item 8 ("Self-Criticalness"). These results suggest an important therapeutic effect of ketamine on negative self-schema, which is a fundamental cognitive aspect of depression. This effect is unique and might be associated with ketamine's profound effects on neuroplasticity. Small sample size and lack of a placebo control group are the major limitations of this study.

suggestion, the effect of lithium on the rate of suiciderelated events increased in both bipolar I and bipolar II disorder when patients diagnosed with mixed episodes were excluded (1). However, the association remained nonsignificant for patients with bipolar I disorder. Two points should be noted, however. First, even though the patient register uses ICD-10 codes, many clinicians in Sweden used DSM-IV and translated diagnoses to ICD-10. In addition, DSM-IV requires that the criteria for both depression and mania be met (except the time criterion) in order to diagnose a mixed episode. This means that it is still possible that the bipolar I disorder group contains individuals with mixed features according to DSM-5. Thus, we cannot refute Dr. Terao and colleagues' suggestion. Future studies using DSM-5 criteria are needed to answer their question. Second, because ICD-10 does not distinguish between bipolar I and bipolar II disorder, we used data from a quality register for the subgroup analyses. This quality register contains only one-third of all Swedish patients with bipolar disorder, which decreases the size of the study sample. Thus, the fact that the results in bipolar I disorder do not reach statistical significance might be a power issue. Therefore, we agree with Terao et al. that more efforts are needed to explore the effect of lithium in preventing suicidal behavior in specific subgroups, where not only the subtype of bipolar disorder is taken into account, but also mixed features.

ist eine der häufigsten psychiatri schen Erkrankungen. Die WHO schätzt, dass weltweit 350 Mio. Menschen an einer Depression leiden. Die Erkrankung führt zu schwerem persönlichem Leid, welches -mehr als jeder andere Zustand -das Suizid risiko erhöht. Durch Selbstmord sterben weltweit je des Jahr 800 000 Menschen. Suizid ist die zweithäu figste Todes ursache in der Gruppe der 15 bis 29jährigen. Die Depression verursacht zudem grosse individuelle, gesellschaftliche und soziökonomische Schäden [1]. Sie ist der häufigste medizinische Grund für Arbeits unfähigkeit und eine der wichtigsten Ursachen für bleibende Behinderungen weltweit [2]. Verschiedene wirksame psychotherapeutische und pharmakologi sche Therapieoptionen stehen für die Behandlung der Summary Despite effective pharmacological and psychotherapeutic treatment options for depression, about one third of patients affected by depression prove resistant to therapy. The injection of botulinum toxin A (BTA) into the glabellar muscles of the forehead constitutes a new approach to treating depression. Such treatment exhibits relatively significant effectiveness and demonstrates considerably different properties than conventional antidepressants. BTA injections into the glabella are associated with an antidepressant effect lasting several months, which sets them apart from other pharmacological antidepressant interventions thus far. The local injection of BTA entails no expected pharmacological interactions with other medications. Such properties may make BTA injections a potentially cost-effective alternative to standard antidepressant treatments, exhibiting only very few undesirable events. Three randomized, placebo-controlled clinical studies have demonstrated the effectiveness of BTA treatment for patients affected by unipolar depressive disorder. Studies conducted to date display a few methodological weaknesses. The sample size in the individual studies tended to be small, with blinding methods for BTA treatment being not ideal. Currently, several hypotheses are under discussion concerning the mechanism of action of BTA treatment, namely the information-processing hypothesis, the aesthetic hypothesis, as well as the social hypothesis.