In Spain, an open, prospective, 6-week study was carried out with 20 patients with an acute manic episode (Y.M..RS score of 20 or more) YMRS, the Hamilton Rating Scale for Depression (HAM-D),the Clinical Global Impressions Scale for Bipolar Disorder, Modified (CGI-BP-M) and the systematic report of adverse events were used to evaluate results. No other antipsychotics were used. Seventy

percent completed the study. Amisulpride significantly improved the YMRS (P=0.0001), the HAM-D (P<0.0141) and the overall (P=0.0003), mania (P=0.0001) and depression (P=0.0268) subscales of the CGI-BP-M. Researchers conclude that despite design limitations (open, observational, small size) Inhibitors,research,lifescience,medical their prospective study suggests that amisulpride could be an effective and reasonably safe treatment for acute mania.80 Amisulpride may carry some risk of extrapyramidal side effects and hyperprolactinemia. JNK signaling inhibitor zotepine A group from Germany has recently reported an open study with zotepine.81 Inhibitors,research,lifescience,medical Zotepine blocks

D1D7, 5-HT1, and 5-HT2receptors. It behaves as a noradrenaline reuptake inhibitor and antagonizes muscarine acetylcholine (mAch) and H, receptors, being sedative. Thus, its profile is that of an atypical antipsychotic. Twelve patients with severe manic episodes (mean YMRS 45+-7) and previous diagnosis Inhibitors,research,lifescience,medical of bipolar or schizoaffective disorder were included and received zotepine as monotherapy Ten patients finished the study Nine of them responded (50% reduction in YMRS), 5 of them within 4 days. One was an inadequate responder. Response is described by the authors as rapid. Inhibitors,research,lifescience,medical Four patients had extrapyramidal symptoms as a side effect.

Unfortunately, there arc no controlled studies of zotepine as yet. Asenapine Asenapine is not yet available for clinical use, but it has been tried in two placebo-controlled trials with overall positive results.82 A further advantage Inhibitors,research,lifescience,medical is that it does not seem to cause as much weight gain as other antipsychotics, such as olanzapine.83 Paliperidone Placebo-controlled trials with paliperidone are currently underway. As the active metabolite of risperidone, there is no reason to expect anything but antimanic Cell press efficacy, and a similar side-effect profile, but until the trials are finalized, little else can be said. Summary A summary of the current evidence available for the treatment of mania can be found in Table II (monotherapy) and Table III (combination). Obviously, there are still many gaps between the evidence from clinical trials and the use of drugs in clinical practice. Table II Evidence base for the efficacy of drugs used to treat mania. Strength of evidence base (regardless of antimanic potency): +++, strong evidence (positive large placebo-controlled trials); ++, some evidence (from secondary outcomes of placebo-controlled … Table III Evidence base for combinations of antipsychotics with lithium or anticonvulsants.