Double-blind, Placebo-Controlled, Crossover Trial of Clozapine Plus Glycine in Refractory Schizophrenia Negative Results

Diaz, Pablo; Bhaskara, Sreenivasa; Dursun, Serdar; Deakin, Bill

doi:10.1097/01.jcp.0000165740.22377.6d

Cited by 42 publications

(25 citation statements)

References 12 publications

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“…With the notable exception of clozapine, the addition of GLY-site agonists to typical or newer atypical antipsychotics has lead to improvement (range, 9-39%) of cognitive and negative symptoms. In studies with clozapine, GLY-site agonist adjuvant therapy either resulted in no improvement (GLY, Evins et al 2000;Diaz et al 2005; D-serine, Tsai et al 1999) or worsening (D-cycloserine, Goff et al 1999a) of symptoms. As D-cycloserine functions as a GLY-site agonist in the presence of low GLY concentrations and as an antagonist in the presence of high GLY concentrations (Hood et al 1989), these negative results suggest that clozapine may already increase synaptic GLY levels through modulation of GLY transport .…”

Section: Introductionmentioning

confidence: 96%

Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

Linn¹,

O'Keeffe²,

Lifshitz³

et al. 2007

Psychopharmacology

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Section: Introductionmentioning

confidence: 96%

Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

Linn¹,

O'Keeffe²,

Lifshitz³

et al. 2007

Psychopharmacology

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“…Five of them (26,(28)(29)(30)45) did not find a large change of positive symptoms with the adjuvant use of glycine in combination with clozapine. One study (2) found worsening of positive symptoms.…”

Section: Glycine Added To Clozapinementioning

confidence: 99%

“…Twelve articles were selected regarding the addition of glycine to the antipsychotic treatment as usual (Table 1), including 9 placebo-controlled double-blind trials (divided into 4 parallel and 5 crossover studies) (2,7,(25)(26)(27)(28)(29)(30)(31), and 3 open-label trials (43)(44)(45). The duration of the studies ranged from 6 to 28 weeks.…”

Section: Glycinementioning

confidence: 99%

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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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“…[17][18][19][20][21][22][23] Two previous metaanalyses have reported the effects of glutamate modulators on cognitive deficits in schizophrenia. Tsai et al noted beneficial effects of NMDA enhancing agents (that is, Dalanine, D-cycloserine (DCS), D-serine, glycine, and sarcosine) on cognitive deficits of schizophrenia (Cohen's d = 0.28, 13 studies, n = 485).…”

Section: Introductionmentioning

confidence: 99%

Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials

et al. 2015

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Hypofunction of N-methyl-D-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N = 1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD = 0.08, 95% confidence interval = − 0.06 to 0.23) (11 studies, n = 858) nor each of eight cognitive domains (SMDs = − 0.03 to 0.11) (n = 367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.

show abstract

Double-blind, Placebo-Controlled, Crossover Trial of Clozapine Plus Glycine in Refractory Schizophrenia Negative Results

Cited by 42 publications

References 12 publications

Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

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

Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials

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