A six-month, placebo-controlled trial of d-cycloserine co-administered with conventional antipsychotics in schizophrenia patients

Goff, Donald C.; Herz, Lawrence; Posever, Thomas; Shih, Vivian E.; Tsai, Guochuan E.; Henderson, David C.; Freudenreich, Oliver; Evins, A. Eden; Yovel, Iftah; Zhang, Hui; Schoenfeld, David

doi:10.1007/s00213-004-2032-2

Cited by 101 publications

(55 citation statements)

References 36 publications

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“…The PANSS and/or SANS were used in almost all of the studies. Eleven trials (10,12,23,28,31,34,37,38,47,48,50) assessed specific cognitive tests.…”

Section: Resultsmentioning

confidence: 99%

“…D-cycloserine, an analog of D-serine, is an antituberculous drug rarely used nowadays due to its adverse psychiatric effects including anxiety, psychosis and seizures at doses of 500-2000 mg (12). D-cycloserine freely crosses the blood-brain barrier and has good bioavailability to the brain (13).…”

Section: Nmda-r Partial Agonistmentioning

confidence: 99%

“…Ten trials evaluated the addition of D-cycloserine to typical antipsychotics (6,12,(31)(32)(33)(34)36,37,46,47). Seven of them (6,12,31-34,47) did not find any significant change in positive symptoms and two (with higher dosages, namely 100 and 250 mg/day) reported worsening of positive symptoms (36,46).…”

Section: D-cycloserine Added To Conventional Antipsychoticsmentioning

confidence: 99%

See 2 more Smart Citations

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Chaves

Marque

Trzesniak

et al. 2009

Braz J Med Biol Res

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“…The PANSS and/or SANS were used in almost all of the studies. Eleven trials (10,12,23,28,31,34,37,38,47,48,50) assessed specific cognitive tests.…”

Section: Resultsmentioning

confidence: 99%

Section: Nmda-r Partial Agonistmentioning

confidence: 99%

Section: D-cycloserine Added To Conventional Antipsychoticsmentioning

confidence: 99%

See 1 more Smart Citation

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Chaves

Marque

Trzesniak

et al. 2009

Braz J Med Biol Res

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“…2 A potentially safer way to enhance glutamate is to exploit the fact that NMDA glutamate receptors require allosteric binding by glycine. 45 In addition to glycine itself, the glycine site of the NMDA receptor also binds the endogenous agonist D-serine, 46 the partial agonist D-cycloserine, 47,48 and D-alanine. 49 These coagonists appear to modulate, but not activate, the NMDA receptor, and therefore seem to be free of excitotoxic effects associated with glutamate.…”

Section: Glycine Agonistsmentioning

confidence: 99%

Building a Better Antipsychotic: Receptor Targets for the Treatment of Multiple Symptom Dimensions of Schizophrenia

Kim¹,

Maneen²,

Stahl

2009

Neurotherapeutics

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Summary: Attempts to develop selective ("magic bullet") drugs for the treatment of schizophrenia have been frustrated by the complex etiology of the disease. The symptomatology of schizophrenia does not appear to arise from a single neurobiological entity, but rather may be derived from pathology at one or more receptor types. This has prompted multifactorial approaches to the development of new therapeutics, as embodied by polypharmacy and an alternative (or augmentative) strategy known as "intramolecular polypharmacy," in which a single drug possesses the capacity to affect multiple receptor types.Atypical antipsychotics are a well-known example of this approach; each atypical possesses a unique portfolio of activities at receptors that may contribute to therapeutic effects (as well as side effects). In this article we present a discussion of some of the receptor targets that are currently thought to mediate symptoms of schizophrenia, as well as their possible implications for the design of future multifunctional antipsychotics.

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“…[59][60][61][62][63] The majority of prior studies involved older and more chronic patients, used a 50 mg DCS dose, and assessed working memory after 2-8 weeks of daily or weekly DCS administration. Patients in the current study were relatively young and high-functioning, had low symptom levels, and were administered a single dose of 100 mg DCS.…”

Section: Discussionmentioning

confidence: 99%

Effects of Augmenting N-Methyl-D-Aspartate Receptor Signaling on Working Memory and Experience-Dependent Plasticity in Schizophrenia: An Exploratory Study Using Acute d-cycloserine

Forsyth

Bachman

Mathalon

et al. 2017

Schizophrenia Bulletin

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Cognitive deficits in schizophrenia have been hypothesized to reflect N-methyl-D-aspartate receptor (NMDAR) dysfunction. However, the mechanisms through which the NMDAR contributes to individual cognitive functions differ. To explore how NMDAR signaling relates to specific cognitive deficits in schizophrenia, we tested the effects of enhancing NMDAR signaling on working memory and experience-dependent plasticity using d-cycloserine (DCS). Plasticity was assessed using an EEG paradigm that utilizes high-frequency visual stimulation (HFvS) to induce neural potentiation, and 2 learning tasks, the information integration (IIT) and weather prediction (WPT) tasks. Working memory was assessed using an N-back task. Forty-five schizophrenia patients were randomized to receive a single 100 mg DCS dose (SZ-DCS; n = 24) or placebo (SZ-PLC; n = 21) in a double-blind, between-groups design. Testing occurred on a single day after placebo or DCS administration; baseline values were not obtained. DCS did not affect plasticity, as indicated by similar neural potentiation, and similar IIT and WPT learning between groups. However, among patients who successfully engaged in the working memory task (ie, performed above chance), SZ-DCS (n = 17) showed superior 2-back performance compared to SZ-PLC (n = 16). Interestingly, SZ-DCS also showed larger pre-HFvS neural responses during the LTP task. Notably, this pattern of DCS effects is the opposite of those found in our prior study of healthy adults. Results are consistent with target engagement of the NMDAR by DCS, but suggest that NMDAR signaling was not translated into synaptic plasticity changes in schizophrenia. Results highlight the importance of considering how distinct NMDAR-associated processes contribute to individual cognitive deficits in schizophrenia.

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A six-month, placebo-controlled trial of d-cycloserine co-administered with conventional antipsychotics in schizophrenia patients

Cited by 101 publications

References 36 publications

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Building a Better Antipsychotic: Receptor Targets for the Treatment of Multiple Symptom Dimensions of Schizophrenia

Effects of Augmenting N-Methyl-D-Aspartate Receptor Signaling on Working Memory and Experience-Dependent Plasticity in Schizophrenia: An Exploratory Study Using Acute d-cycloserine

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