The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder.

BACKGROUND: Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N-methyl-D-aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D-cycloserine - which is a partial agonist of the NMDA glutamate receptor - are potential treatment options for the core features of ASD. However, the potential effect of D-cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted. OBJECTIVES: To assess the efficacy and adverse effects of D-cycloserine compared with placebo for social and communication skills in individuals with ASD. SEARCH METHODS: In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers' websites and sources of reports of adverse events.  SELECTION CRITERIA: All randomised controlled trials (RCTs) of any duration and dose of D-cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review. MAIN RESULTS: We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA: Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D-cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D-cycloserine and placebo arms, and outcome measures were recorded at one-week post-treatment. The 'risk of bias' assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference between the two groups for all outcomes measured at one week post-treatment: social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82); social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18); restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95); serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31); non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93); and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68).  AUTHORS' CONCLUSIONS: We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa.

Treatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain.

BACKGROUND: Few effective pharmacological treatment options exist for chronic back pain, the leading cause of disability in the US, and all are associated with significant adverse effects. OBJECTIVE: To determine the efficacy and safety of D-cycloserine, a partial agonist to the N-methyl-D-aspartate receptor, in the treatment of chronic low back pain. METHODS: A total of 41 participants with chronic back pain who met all inclusion and exclusion criteria were enrolled in a double-blind, placebo-controlled randomized pilot trial of D-cycloserine. Treatment was administered orally for six weeks at escalating daily doses of 100 mg, 200 mg, and 400 mg, each for two weeks. The primary outcome measure was back pain intensity using the Numeric Rating Scale (0-10). Secondary measures were back pain-related questionnaires: McGill Pain Questionnaire short form, painDETECT, PANAS, and BDI. The pre-specified analysis was a two-way repeated measures analysis of variance. RESULTS: A treatment difference was observed between groups treated with D-cycloserine and placebo at six weeks of 1.05 ± 3.1 units on the Numeric Rating Scale, with an effect size of 0.4 and p = 0.14. This trend of better chronic back pain relief with D-cycloserine was also observed in the secondary measures. No safety issues were seen. CONCLUSION: The difference in mean pain between the D-cycloserine and placebo groups did not reach statistical significance. However, a clinically meaningful effect size in the magnitude of pain relief was observed with a consistent pattern across multiple outcome measures with good safety, supporting further research into the effectiveness of D-cycloserine for chronic back pain.

D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review.

D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits.

Gitelman-like Syndrome with Kanamycin Toxicity.

A 22 year-old lady with multi-drug-resistant pulmonary tuberculosis was on Kanamycin, Cycloserine, Ethionamide, Pyrazinamide and Moxifloxacin since more than two months. She presented with muscle cramps and carpopedal spasm. Investigation revealed hypokalemia and metabolic alkalosis. She also had hypomagnesemia, hypochloremia and hypocalciuria. Serum urea and creatinine levels were normal. Patient was treated with intravenous and oral potassium chloride. Kanamycin was stopped. Metabolic alkalosis and hypokalemia improved gradually over one month. Biochemical parameters were like Gitelman's syndrome but it reversed with stoppage of Kanamycin. Gitelman-like syndrome with Kanamycin toxicity has not been reported in literature previously.

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

BACKGROUND: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. METHODS: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. RESULTS: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. CONCLUSIONS: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. SCIENTIFIC SIGNIFICANCE: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity.

Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment.

OBJECTIVES: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. METHODS: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. RESULTS: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). CONCLUSIONS: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Augmenting transcranial direct current stimulation with (D)-cycloserine for depression: a pilot study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that causes changes in cortical excitability. Recent double-blind placebo-controlled clinical trials suggest that tDCS may be efficacious in the treatment of depression. Pharmacological agents that prolong the effects of tDCS could lead to greater cumulative changes in cortical excitability, producing greater and more prolonged efficacy. One agent shown to prolong the excitability-enhancing effects of tDCS in healthy subjects is D-Cycloserine, a partial agonist at the glycine-binding site of N-methyl-D-aspartate receptors. We investigated whether combining prefrontal tDCS with D-Cycloserine could enhance and/or prolong the antidepressant effect of tDCS. METHODS: Five depressed subjects who had relapsed or failed to achieve remission after receiving a previous course of prefrontal tDCS were recruited. In this open-label pilot study, subjects ingested 100-mg D-Cycloserine 2 hours before tDCS sessions. Subjects received 20 minutes of tDCS at 2 mA on consecutive weekdays for a total of 20 sessions. The anode was placed at pF3 and the cathode at F8 (10/20 system). Clinical response was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The change in Montgomery-Åsberg Depression Rating Scale scores was not greater with the combination of D-Cycloserine and tDCS than had previously been produced by tDCS alone. No significant additional adverse effects were reported. CONCLUSIONS: This pilot open-label study found that pretreatment with 100-mg D-Cycloserine 2 hours before tDCS was well tolerated but did not enhance the antidepressant efficacy of anodal prefrontal tDCS.

[Pharmacological activity of runihol and S-adenosyl-L-methionine in rats with experimental liver damage by reserve antituberculosis drugs].

The hepatoprotective action of runihol and S-adenosyl-L-methionine (ademethionine) has been studied in a group of 47 white outbred male rats with model liver injury induced by reserve antituberculosis drugs (PAS, prothionamide, cycloserine). The ability of test drugs to correct structural and functional liver disorders is established. Both runihol and ademethionine favored decrease in the signs of structural and functional liver disorders induced by reserve antituberculosis drugs, Showing mixed type of action, the test drugs promoted recovery of the liver parenchyma and reduced manifestations of hepatocyte dystrophy to the same extent, without manifestations of necrobiotic processes and a mononuclear infiltration.

D-Cycloserine-Induced Seizure Activity in the Emergency Department: A Case Report.

D-cycloserine (DCS) is an anti-tuberculosis medication that has been utilized for years for drug-resistant tuberculosis. DCS works via a centrally acting mechanism which can cause neurotoxic adverse effects which has limited its use. This centrally acting mechanism also allows for DCS to be utilized for various neuropsychiatric purposes. Our patient was on high-dose DCS for autism spectrum disorder and presented to the emergency department (ED) with a seizure. The seizure episode was managed with both anti-epileptics and pyridoxine. With increasing novel use of this older medication, it is imperative for ED clinicians to be aware of the different management strategies that may be required when a patient presents with a neurotoxic effect, specifically seizures, secondary to DCS.

[Psychotherapeutic and pharmacological treatment of pediatric obsessive-compulsive disorder]. / Psychotherapeutische und medikamentöse Behandlung der kindlichen Zwangsstörung.

Cognitive-behavioral therapy (CBT) and pharmacological treatments are often applied in cases of pediatric obsessive-compulsive disorder (OCD). Especially in combination both methods are particularly efficacious; nonetheless, 40 % of all patients treated remain symptomatic. Exposure with response prevention, based on the principle of habituation, is the intervention with the best evidence. More recent cognitive and metacognitive treatments focus on modifying expectations and may have the potential to improve treatment efficacy. Selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment in severe cases of OCD. With treatment resistance, the SSRI should be changed, or alternatively clomipramine can be employed. Augmentation strategies suggest the combination of two SSRIs, SSRI und clomipramin, or SSRI and (atypical) neuroleptics. Following successful treatment, medication should be reduced very slowly. Novel treatments in children and adolescent have been reported for antiglutamatergic agents as riluzole or D-cycloserine, a partial agonist of N-methyl-D-aspartic acid (NMDA).

Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis.

BACKGROUND: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited. METHODS: A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma. RESULTS: A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01). CONCLUSIONS: A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy.

Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

Importance: Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD. Objective: To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD. Design, Setting, and Participants: The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019. Interventions: All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo. Main outcomes and Measures: Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life. Results: The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported. Conclusions and Relevance: In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. Trial Registration: ClinicalTrials.gov identifier: NCT02656342.

Irreversible neuropathy in extremely-drug resistant tuberculosis: An unfortunate clinical conundrum.

Drug-resistant tuberculosis is an increasing healthcare challenge. Drug regimen building demands the use of different therapeutic groups, many of which harbor neurotoxicity as a side-effect, whether central or peripheral. Peripheral neuropathy is a major concern as it tends to be severe and usually irreversible. Anti-tubercular drugs that may contribute to peripheral neuropathy include INH, ethambutol, linezolid, cycloserine and para-amino salicylic acid. This potential adverse effect must be balanced against the intrinsically grave prognosis that drug resistant tuberculosis harbors. We present such a clinically challenging case of a 25 years-old female with extremely drug resistant tuberculosis whose treatment necessitated the use of several neurotoxic anti-tubercular drugs, leading to severe sensory peripheral neuropathy who did not improve despite the withdrawal of culprit drugs. She developed positive and negative sensory symptoms in both lower limbs. Nerve conduction studies were suggestive of sensory neuropathy affecting both lower limbs. Alternate causes of peripheral neuropathy including HIV, vasculitis, B12 deficiency and diabetes were ruled out. Despite drug withdrawal, the patient did not improve significantly. This case emphasizes the irreversibility of anti-tubercular therapy-induced peripheral neuropathy, demanding more rigorous clinical screening for the same while managing such patients.

Shedding Light on the Transcriptomic Dark Matter in Biological Psychiatry: Role of Long Noncoding RNAs in D-cycloserine-Induced Fear Extinction in Posttraumatic Stress Disorder.

Biological psychiatry scholarship on posttraumatic stress disorder (PTSD) is making strides with new omics technologies. In this context, there is growing recognition that noncoding RNAs are vital for the regulation of gene and protein expression. Long noncoding RNAs (lncRNAs) can modulate splicing, influence RNA editing, messenger RNA (mRNA) stability, translation activation, and microRNA-mRNA interactions, are highly abundant in the brain, and have been implicated in neurodevelopmental disorders. The largest subclass of lncRNAs is long intergenic noncoding RNAs (lincRNAs). We report on lincRNAs and their predicted mRNA targets associated with fear extinction induced by co-administration of D-cycloserine and behavioral fear extinction in a PTSD animal model. Forty-three differentially expressed lincRNAs and 190 differentially expressed mRNAs were found to be associated with fear extinction. Eight lincRNAs were predicted to interact with and regulate 108 of these mRNAs, while seven lincRNAs were predicted to interact with 22 of their pre-mRNA transcripts. Based on the functions of their target mRNAs, we inferred that these lincRNAs bind to nucleotides, ribonucleotides, and proteins; subsequently influence nervous system development, morphology, and immune system functioning; and could be associated with nervous system and mental health disorders. We found the quantitative trait loci that overlapped with fear extinction-related lincRNAs included traits such as serum corticosterone level, neuroinflammation, anxiety, stress, and despair-related responses. To the best of our knowledge, this is the first study to identify lincRNAs and their RNA targets with a putative role in transcriptional regulation during fear extinction in the context of an animal model of PTSD.

Neuropsychiatric reactions induced by cycloserine in the treatment of multidrug-resistant tuberculosis: what an Indian female patient tells us.

Multidrug-resistant tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people affected by drug-resistant tuberculosis. To implement tuberculosis control, in 2018, WHO recommended cycloserine as one of the Group B drugs. Following this recommendation, cycloserine should be generally included in the starting line-up in the longer regimen for the treatment of multidrug-resistant tuberculosis. However, neurological toxicity associated with this drug concerns clinicians and limits its use. In this paper, we present a case of a 48-year-old woman with a diagnosis of multidrug-resistant tuberculosis treated with cycloserine, who developed psychiatric adverse events after 3 months of administration. This case shows the need for close psychiatric follow-up to promptly detect adverse events in patients receiving regimens for multi-drug resistant tuberculosis.

[A case of multi-drug resistant tuberculosis showing psychiatric adverse effect by cycloserine].

A 45-year-old man with multi-drug resistant tuberculosis were referred to our hospital for treatment. We started chemotherapy with cycloserine (CS), ethionamide (TH), kanamycin (KM), pyrazinamide (PZA), para-aminosalicylic acid (PAS) and gatifloxacin (GFLX). Two months later, psychosis and seizure occurred and worsened day after day. We suspected that these symptoms were due to CS. After stopping CS, psychosis and seizure disappeared. After surgical operation, positive tubercle bacilli in sputum converted to negative both on smear and culture. He was successfully discharged from our hospital. We should take care on side effects with second-line drugs that are often used in treating multi-drug resistant tuberculosis.

[Rezonizat and cycloserine in complex therapy of drug resistant tuberculosis (comparative studies)].

An open comparative investigation of the Russian drugs rezonizat and cycloserine was performed. The studies made it possible to recommend the use of rezonizat in complex therapy of patients with drug resistant tuberculosis. Higher activity and better tolerability of rezonizat vs. cycloserine was shown.

Cycloserine Induced Suicidal Tendencies and Kanamycin Induced Ototoxicity in Indian MDR-TB Patient: A Case Report.

INTRODUCTION: Cycloserine and Kanamycin are approved for treatment of multidrug-resistant tuberculosis with good tolerability in Tuberculosis patients and have various labeled adverse reactions but the neuropsychiatric adverse drug reactions with cycloserine are rarely explained. CASE REPORT: We present a case report on Cycloserine induced Suicidal tendencies and Kanamycin induced decrease in hearing sensation in Indian MDR-TB patient. A 55-year-old male patient who was diagnosed with MDR-TB was prescribed with category IV anti-tubercular therapy. Within one month of initiation of therapy, he developed repeated suicidal thoughts, joint pain, restlessness, depression, constipation, insomnia, tinnitus and a decrease in hearing sensation. RESULTS AND DISCUSSION: Cycloserine and kanamycin were closely associated with suicidal tendency and tinnitus followed by a decrease in hearing sensations respectively. On causality assessment using WHO-UMC Causality assessment scale, Adverse Drug Reaction with Cycloserine was found to be certain and for kanamycin, ADR was found to be possible. CONCLUSION: Early management of such fatal ADR can improve the compliance, thus preventing the relapse of infection as well as improving therapeutic outcome in Tuberculosis patients.

Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders.

In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.