Comparative efficacy between ketamine, memantine, riluzole and d-cycloserine in patients diagnosed with drug resistant depression: a meta-analysis

Background: Glutamate modulators are having immense potential and are newer entities for treating drug resistant depression. The objectives were to generate statistical evidence on basis of existing data of ketamine, memantine, riluzole and d-cycloserine in resistant depression.Methods: A total of 14 RCTs following PRISMA guidelines and matching inclusion and exclusion criteria were collected of ketamine (5), memantine (3), riluzole (2) and d-cycloserine (4) vs placebo in drug resistant depression. Only RCTs with primary diagnosis of drug resistant depression (Previously on two standard antidepressant therapy) were included. Studies with treatment response rate, 50% reduction in total score of the depression rating scale-Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale or Beck Depression Inventory was chosen as clinical outcome measure. RevMan 5.3 software was used for the analysis.Results: In ketamine group using random effect model SMD was 2.122 (95% CI 0.659-3.584). P-value was statistically significant (random effect p <0.005 and in fixed effect <0.001). In memantine group, using random effect model -0.963 was SMD and (95% CI -1.958-0.0324). P-value was <0.001, significant in fixed effect. In riluzole group, SMD was -0.564 with (95% CI -3.927-2.799) in random effect. P-value was 0.741. In d-cycloserine group SMD was 0.316 with (95% CI -1.252-1.885) in random effect. P-value was 0.690.Conclusions: Ketamine showed best efficacy followed by memantine. Riluzole and DCS as such have no efficacy although its acts by same glutamate pathway. More molecular based research is required in use of glutamate modulators in resistant depression.

Clinico-microbiological analysis of toxigenic clostridium difficile from hospitalised patients in a tertiary care hospital, Mangalore, Karnataka, India

Purpose: Prevalence of Clostridium difficile, an anaerobic, Gram-positive, spore-forming bacillus, is very much underestimated in India. The present study was intended to assess the burden of toxigenic C. difficile in hospitalised patients with clinically significant diarrhoea and analysis of their clinical picture. Materials and Methods: This cross-sectional study was conducted in a tertiary care teaching hospital, South India, from January 2012 to December 2014. Stool samples were collected consecutively from 563 inpatients from various wards. The prevalence of toxigenic C. difficile was determined by toxigenic culture and a two-step algorithm. The clinical spectrum of these patients was also analysed. Associated pathogens were identified using standard procedures. Statistical analysis was done by frequency, percentage, Chi-square test and z-test. Results: Out of the 563 stool samples analysed, the prevalence of toxigenic C. difficile was 12.79% and that of non-toxigenic C. difficile was 10.83%. The prevalence of toxigenic C. difficile among oncology patients was highly significant (HS). Antibiotic treatment, prolonged hospital stay and underlying diseases/conditions were the risk factors which were HS, and fever was the significant clinical feature among the patients. Escherichia coli was the predominant associated pathogen isolated (18.47%). Conclusion: The presence of toxigenic C. difficile in our locality is a matter of concern. Constant supervision, appropriate treatment and preventive measures are crucial in controlling C. difficile infection.

Efeito da d-cicloserina no tratamento do transtorno de estresse pós-traumático: uma revisão / The effect of d-cycloserine in the treatment of post-traumatic stress disorder: a review

Objetivo: Realizar uma revisão da literatura sobre o efeito da D-cicloserina (DCS) no tratamento do Transtorno de estresse pós-traumático (TEPT). Métodos: Foram revisados 14 ensaios clínicos, revisões sistemáticas e meta-análises selecionados na base de dados PubMed que correspondessem aos descritores D-cicloserina e Transtorno de estresse pós-traumático. Resultados: Os resultados mostram-se heterogêneos, incluindo resultados com e sem benefícios clínicos para o uso da DCS, provavelmente devido à diferença de métodos utilizados nos estudos realizados. Entretanto, a DCS apresenta efeito benéfico quando administrada em pacientes com quadros mais graves de TEPT e quando associada à terapia de exposição com realidade virtual. Conclusão: A DCS tem se mostrado uma opção terapêutica promissora quando associada à terapia de exposição; entretanto, mais estudos devem ser realizados para comprovar sua efetividade no tratamento do TEPT.

Aim: To review the literature about the effect of D-cycloserine (DCS) on the treatment of Post-traumatic stress disorder (PTSD). Methods: Were reviewed fourteen clinical trials, systematic reviews and meta-analyzes selected in the PubMed database that corresponded to the descriptors D-cycloserine and Post-traumatic stress disorder. Results: The results are heterogeneous, including results with and without clinical benefit for the use of DCS, probably due to the different methods used in the studies. However, DCS has a beneficial effect when administered to patients with severe PTSD and when associated with virtual reality exposure therapy. Conclusion: It has been shown that DCS is a promising therapeutic choice when associated with exposure therapy, however further studies should be performed to prove its effectiveness in the treatment of PTSD.

A Case of Cycloserine-Induced Lichenoid Drug Eruption Supported by the Lymphocyte Transformation Test

Lichenoid drug eruption (LDE) is a rare form of delayed-type drug eruption. Among anti-tuberculosis (Tb) agents, cycloserine (CS) has been reported as a rare cause of LDE. Positive results on the lymphocyte transformation test (LTT) have not been reported in patients with LDE. In the present case, we performed LTT and a patch test, and successfully proved CS as the offending drug in this patient, who had been treated with multiple anti-Tb drugs. These observations suggest that CS should be considered a possible cause of LDE and that LTT can be an option for the diagnosis of LDE.

Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009-2014 / 결핵및호흡기질환

BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. METHODS: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges. RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C2hr, 16.6+/-10.2 microg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2+/-1.5 microg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5+/-14.0 microg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0+/-29.1 microg/mL; all within or above); linezolid in three (mean C2hr, 11.4+/-4.1 microg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 microg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 microg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.

Psicosis inducida por fármacos antituberculosos: un caso asociado a cicloserina / Antituberculosis drug-induced psychosis: a case associated with cycloserine

Nuestro país posee una alta prevalencia e incidencia de casos de tuberculosis (para el año 2012 se registró una morbilidad de 105,2 casos por 100 000 habitantes).En el tratamiento de esta patología pueden desencadenarse numerosas reacciones adversas de índole heterogénea, siendo preponderantes las neuropsiquiátricas, por la polifarmacia antibiótica requerida y otros posibles factores de riesgo del usuario. A partir de un caso de psicosis desencadenada por cicloserina en un paciente con tuberculosis multidrogorresistente, revisamos la literatura pertinente y recomendamos la ponderación individualizada del retiro de la medicación desencadenante del efecto adverso, respecto a la necesidad de mantener la cobertura antibiótica imprescindible y adecuada.

Our country has a high prevalence of tuberculosis (morbidity in year 2012 was 105,2 cases per 100 000 people). In the treatment of this disease, a high number of diverse drug-related side-effects, with prevalent neuropsychiatric type, can be developed, because of the antibiotic polypharmacy required and other possible risk factors. From a case of cycloserine-induced psychosis, in a patient with multidrug-resistant tuberculosis, we review the relevant literature and recommend individualized consideration on the withdrawal of the side-effect trigger medication versus the need to maintain the essential and appropriate antibiotic coverage.

Neuropsychiatric adverse events associated with cycloserine therapy for multidrug resistant pulmonary tuberculosis / 中华临床感染病杂志

Objective To evaluate neuropsychiatric adverse effects of cycloserine therapy for multidrug resistant pulmonary tuberculosis (MDR-TB).Methods A total of 82 patients with MDR-TB who were enrolled in Global Fund Round Five MDR-TB Control Program were admitted in Center for Diagnosis and Treatment of Tuberculosis,Hangzhou Red Cross Hospital from May to December 2012.All patients received the standard treatment containing cycloserine for MDR-TB.The adverse reactions during the treatment were recorded,and symptom checklist-90 (SCL-90) scores at different time points were compared with t test.Results Adverse reactions were observed in 66 patients (66/82,80.5％) within 3 months after the initial treatment.Common adverse reactions included arthralgia (42.7％),gastrointestinal reactions (40.2％),central nervous system symptoms (22.0％) and electrolytes disturbance (17.1％).Nine patients had severe neuropsychiatric symptoms characterized by convulsions,depression,anxiety,schizophrenia and attempting suicide,6 of whom had used fluoroquinolones before the study.The above symptoms were relieved after stopping cycloserine or antitubercular agents,and cycloserine was replaced in the following treatment.The total SCL-90 score,depression and anxiety scores were significantly higher during onset of symptoms than those one month after the following treatment (t =2.241,2.301 and 5.659,P ＜ 0.05).Conclusion Cycloserine may induce severe neuropsychiatric adverse reactions in patients receiving standard treatment for MDR-TB.

PANSS and Cognition Change in D-Cycloserine Compination Treatment of Schizophrenia / 대한정신약물학회지

OBJECTIVE: Recently, there are many reports that glutamate receptors have close relationships with a pathophysiology of schizophrenia. The purpose of this study was to assess the effects of D-cycloserine, which is glycine site partial agonist in NMDA receptor on psychopathologic symptoms and cognitive functions. METHODS: This study was done for chronic schizophrenic inpatients taking typical antipsychotics for more than 4 months. Exclusion criteria were patients with over 8 points according to Simpson-Angus scale for EPS or those with over 17 points of Hamilton Depression Scale. Patients were randomized to classify into two groups; D-cycloserine group (n=13) and placebo group (n=13). Each group received D-cycloserine 100 mg or placebo separately for 8 weeks. Psychopathology was evaluated with PANSS at baseline, 2nd week, fourth week and eighth week. Cognitive function was evaluated with KWIS at baseline and eighth week. RESULTS: Total 26 patients completed this trial. The average period of morbidity was 10.39+/-3.87 years and the average doses of antipsychotic was 1228.35+/-720.30 mg based on chlorpromazine equivalent. In positive subscale, negative subscale, general psychopathology subscale, total PANSS scale and KWIS, there were no significant differences between D-cycloserine and placebo groups. However, negative subscale scores had decreased from 24.92+/-3.64 (Baseline) to 23.46+/-3.41 (week 8) (p=0.077). CONCLUSION: There were no clear changes in positive symptom, negative symptom, memory, language function, and performance intelligence when D-cycloserine 100 mg was given with antipsychotic medication. However, some patients showed clear improvement in negative symptom, especially blunted affect. Therefore, D-cycloserine combination therapy could be effective for negative symptom. In future, study that can show effectiveness in psychopathology and cognitive function according to drug dosage is needed.