Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose-dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14 days); (3) the combination of lower doses of quetiapine (5 mg/kg) and venlafaxine (2.5 mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10 mg/kg) or venlafaxine (5 mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment-resistant depression and the negative symptoms of schizophrenia.

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Objectives:Colon cleansing for flexible sigmoidoscopy using a standard fleet enema does not provide adequate cleansing in a significant number of patients. We tested whether the addition of a low-volume oral cleansing agent could mitigate this challenge without significantly compromising patient tolerance. Hypothesis: Oral picosulfate with magnesium citrate (P/MC) would enhance the colon cleansing of patients undergoing sigmoidoscopy, as assessed by the modified Ottawa Bowel Preparation Score.Methods:A randomized single blinded trial comparing (1) a single dose (i.e., one sachet) of oral sodium picosulfate plus magnesium citrate (P/MC) administered the night before, (2) a single dose oral P/MC the night before plus sodium phosphate enema 1 h before leaving home, and (3) sodium phosphate enema alone 1 h before leaving home for flexible sigmoidoscopy was conducted on outpatients referred for sigmoidoscopy for symptom assessment.Results:A total 120 patients were randomized to the study groups. The main indication for sigmoidoscopy was investigation of rectal bleeding (n=80). There was no significant difference in bowel cleansing quality, measured by the endoscopist blinded to preparation, between P/MC, P/MC plus enema, and enema alone as measured by the modified Ottawa Bowel Preparation Scale (P=0.34) or the Aronchick Scale (P=0.13). Both oral P/MC regimens were associated with higher incidence of nausea, abdominal pain, bloating, and interrupted sleep than enema alone (P<0.05).Conclusions:A single dose of oral P/MC administered the night before did not result in better colon cleansing for sigmoidoscopy when used alone or with an enema and was associated with more side effects (NCT 01554111).

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