tropisetron and Constipation

Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT3R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT3R-ANTs add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n = 311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT3R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD = -1.03, CI = -1.70 to -0.36, p = 0.003 (I (2) = 82 %, 5 studies, n = 261); on negative scores were SMD = -1.10, CI = -1.82 to -0.39, p = 0.002 (I (2) = 84 %, 5 studies, n = 261); and on PANSS general scores were SMD = -0.70, CI = -1.23 to -0.17, p = 0.01 (I (2) = 73 %, 5 studies, n = 261). However, 5-HT3R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD = -0.12, p = 0.33). Dropout due to all cause (RR = 0.80, p = 0.50), inefficacy (RR = 0.76, p = 0.65), or adverse events (RR = 0.84, p = 0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT3R-ANTs than placebo (RR = 2.05, CI = 1.07-3.91, p = 0.03, NNH = 11, p = 0.02). 5-HT3R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT3R-ANTs seem to be well-tolerated treatments.

Topics: Antipsychotic Agents; Constipation; Double-Blind Method; Drug Therapy, Combination; Granisetron; Haloperidol; Humans; Indoles; Nausea; Ondansetron; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Risperidone; Schizophrenia; Serotonin 5-HT3 Receptor Antagonists; Severity of Illness Index; Symptom Assessment; Treatment Outcome; Tropisetron; Vomiting

The objective of this study was to evaluate the efficacy and safety of ramosetron hydrochloride for the management of nausea and vomiting induced by chemotherapy in patients with hematological malignancies. A total of 30 patients with hematological malignancies were included in the ramosetron group. Ramosetron (0.3 mg i.v.) was administered 0.5 h before chemotherapy. The impact of ramosetron on anorexia, nausea and vomiting as well as other adverse effects were assessed. Meanwhile, another 39 patients received tropisetron (o.d. for 3 days). As compared to the tropisetron group, the response rate of the ramosetron group in controlling anorexia within 18-24 h after chemotherapy was higher (p < 0.05); within 18-24 h after chemotherapy, the complete response rate and effective rate in controlling nausea was higher (p < 0.05); within 12-18 h and 18-24 h after chemotherapy, the complete response rate and effective rate in controlling vomiting was higher (p < 0.05). The incidence of adverse effects was similar in both groups. We conclude that ramosetron belongs to a new generation of 5-HT3 receptor antagonists and that it is a safe, economic and effective antiemetic drug.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Appetite; Benzimidazoles; Constipation; Dizziness; Drug-Related Side Effects and Adverse Reactions; Female; Flushing; Gastrointestinal Diseases; Headache; Hematologic Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Thirst; Treatment Outcome; Tropisetron; Vomiting

Among the most distressing symptoms experienced by patients who have undergone high-dose chemotherapy and stem cell transplantation are nausea and vomiting. The chemotherapy regimens used in high-dose conditioning protocols are highly emetogenic. The 5HT3 receptor antagonists are very effective in the prevention and abolition of nausea and vomiting resulting from chemotherapeutic drugs. One of them, tropisetron, is a selective antagonist of serotonin 5HT3 receptors with proven efficacy against emesis. Dexamethasone is also known as an effective agent against nausea and vomiting. The addition of dexamethasone to a 5HT3 receptor antagonist is synergistic, as has been shown in many trials with highly emetogenic drugs. The aim of the present trial was to study the efficacy and safety profile of the combination of tropisetron and dexamethasone in controlling nausea and vomiting in patients receiving megatherapy prior to stem cell transplantation. We studied 31 patients. All of them were evaluable for response and toxicity. The majority of patients achieved complete or major protection against acute vomiting (71-83%), and 67-84% of the patients had no or mild nausea. The combination was tolerated well, and only a minority of patients reported side effects. Among them the most common were headache (in three patients) and constipation. No patient withdrew from the study because of toxicity. It has become evident from our data that the administration of 5 mg tropisetron daily in combination with 20 mg dexamethasone for 8 days can prevent the acute emesis otherwise experienced by patients receiving high-dose chemotherapy as conditioning in stem cell transplantation programmes.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Constipation; Dexamethasone; Drug Combinations; Drug Synergism; Female; Headache; Hematopoietic Stem Cell Transplantation; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Serotonin Antagonists; Transplantation Conditioning; Tropisetron; Vomiting

Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven efficacy in the control of emesis related to cancer treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential. This study was designed to determine whether a single intravenous administration of tropisetron could prevent acute nausea and vomiting in patients treated with high dose epirubicin. Forty chemotherapy naive breast cancer patients treated with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand" treatment with tropisetron 5 mg p.os was used for the rescue of patients who failed on the initial i.v. dose. Complete control of acute nausea and vomiting had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5% (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common adverse event reported in 3 patients (7.5%) and constipation in 2 patients (5%). Interestingly, patients with a negative experience of nausea and vomiting during pregnancy and those treated for metastatic disease, had a better control of chemotherapy-induced nausea and vomiting. In conclusion, a single 5 mg i.v. dose of tropisetron is safe and effective in preventing acute emesis in patients treated with high dose epirubicin.

Topics: Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Antiemetics; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Constipation; Epirubicin; Female; Granulocyte Colony-Stimulating Factor; Headache; Humans; Indoles; Injections, Intravenous; Middle Aged; Nausea; Treatment Outcome; Tropisetron; Vomiting

The abilities of selective 5-HT3-receptor antagonists to evoke constipation were examined in conscious guinea-pigs and in preparations of guinea-pig isolated colon. Compared with vehicle-treated guinea-pigs, acute doses of granisetron (0.1, 1 and 10 mg kg-1, i.p.) and tropisetron (10 mg kg-1, i.p., but not 1 and 0.1 mg kg-1, i.p.) significantly (P < 0.05) reduced the total number of faecal pellets excreted during a 12-h observation period. By contrast, BRL 46470 (0.1-10 mg kg-1, i.p.) had no significant effect on the incidence of defecation. Mid-to-distal lengths of guinea-pig isolated colon spontaneously expelled faecal pellets. Granisetron (0.1 and 1 microM) and tropisetron (1 microM) reduced or prevented the rate at which they were spontaneously expelled. Morphine (0.1 microM) and clonidine (10 nM) also showed faecal pellet transit time. Naloxone (0.1 microM) had no effects alone, but reversed the actions of granisetron, morphine and clonidine. BRL 46470 (1 microM) had no significant effect on the transit of faecal pellets in guinea-pig isolated colon. In segments of guinea-pig isolated colon which did not contain faecal pellets, granisetron, tropisetron and BRL 46470 antagonized the ability of 5-HT to evoke cholinergically-mediated contractions of the longitudinal muscle. The respective pA2 values and slopes of the Schild plots were 8.5 +/- 0.05, slope 1.06 +/- 0.03; 8.5 +/- 0.1, slope 0.91 +/- 0.04; and 7.9 +/- 0.1, slope 0.93 +/- 0.05. Our experiments suggest that not all 5-HT3-receptor antagonists are the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clonidine; Colon; Constipation; Defecation; Drug Interactions; Granisetron; Guinea Pigs; In Vitro Techniques; Indoles; Injections, Intraperitoneal; Male; Morphine; Muscle Contraction; Muscle, Smooth; Naloxone; Serotonin Antagonists; Tropisetron