Objective-Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of α 7 -nicotinic receptors. Patients' heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial α 7 -nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia.Method-Thirty-one subjects with schizophrenia received DMXB-A at two different doses and placebo for periods of 4 weeks in a three-arm, two-site, double-blind, crossover phase 2 trial. The MATRICS Consensus Cognitive Battery assessed cognitive effects, and the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS) assessed clinical effects. Subjects continued their current antipsychotic drug during the trial and were nonsmokers.Results-There were no significant differences in the MATRICS cognitive measures between DMXB-A and placebo over the three treatment arms, but the patients experienced significant improvement at the higher DMXB-A dose on the SANS total score and nearly significant improvement on the BPRS total score. Improvement was most notable on the SANS anhedonia and alogia subscales. Examination of the first treatment arm showed effects of DMXB-A on the attention/vigilance and working memory MATRICS domains, compared to baseline. Five subjects developed mild tremor, and nearly half had mild nausea while taking DMXB-A.Address correspondence and reprint requests to Dr. Freedman, Department of Psychiatry C249-32, University of Colorado Health Sciences Center, Denver, CO 80262; Robert.Freedman@UCHSC.edu. Dr. Freedman has a patent through the Department of Veterans Affairs (VA) on the CHRNA7 gene sequence. The VA has also filed a patent disclosure for the use of nicotinic agonists for schizophrenia. Drs. Kem and Soti have patents through the University of Florida on the manufacture and use of DMXB-A (also known as GTS-21) and have a research grant from CoMentis; Dr. Kem is also a consultant for CoMentis. Dr. Buchanan is on the data safety monitoring boards of Pfizer and Wyeth; is a consultant for Memory Pharmaceuticals, Roche, and Organon; is on advisory boards for AstraZeneca, GlaxoSmithKline, Pfizer, and Solvay; and has received drug samples for research from Ortho-McNeil Neurologics and Janssen. Ms. Ball receives grant support and study medication from Eli Lilly. Dr. Gold has been a consultant for Pfizer and receives royalty payments for the Brief Assessment of Cognition in Schizophrenia. Dr. Stevens receives research support from GlaxoSmithKline and Johnson & Johnson and owns equity in Sierra Puente. Drs. Olincy, Martin, and Johnson receive re-search support from Lundbeck. All other authors report no competing interests. One therapeutic target identified by the MATRICS is the α 7 -nicotinic acetylcholine receptor. A possible role for the receptor in schizophrenia was first identi...

This study evaluated the effectiveness of a Weight Watchers program for patients with schizophrenia who had olanzapine-related weight gain and ascertained whether the severity of patients' psychiatric symptoms was correlated with the patients' success in losing weight. Seven men and four women who had been treated with olanzapine and who had gained at least 7 percent of their pretreatment body weight attended Weight Watchers meetings and were offered supervised exercise sessions. The patients' weight, body mass index, and psychiatric symptoms were assessed and were compared with those of a matched comparison group who did not attend the Weight Watchers program. Only the men experienced significant weight loss. No correlation was found between weight loss and exercise or change in psychiatric symptoms.

Background In a previous pilot study, MK-0777, a GABAA α2/α3 partial agonist, was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia. Methods Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to either: MK-0777 3mg BID (n=18); MK-0777 8mg BID (n=21); or placebo (n=21). Participants were clinically stable. The MATRICS Consensus Cognitive Battery (MCCB), AX-CPT and N-Back were used to assess cognition. The UCSD Performance Based Skills Assessment-2 (UPSA-2) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity and served as functional outcome co-primary measures. Results There were no significant group differences on the primary outcome measure, the MCCB composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-CPT or N-Back d prime scores or UPSA-2 and SCoRS total scores. In general, MK-0777 was well tolerated with minimal side effects. Conclusions The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABAA receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABAA α2 site may be needed for cognitive enhancement in schizophrenia.

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Use of sustained-release bupropion in combination with supportive group therapy may help patients with schizophrenia decrease their cigarette consumption.