The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
A Double-Blind, Randomized Study of Minocycline for the Treatment of Negative and Cognitive Symptoms in Early-Phase Schizophrenia
Abstract
BACKGROUND: Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia: negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders. Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia. These findings may be linked to the effect of minocycline on the glutamatergic system, through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity. Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation. OBJECTIVE: To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia. METHOD: A longitudinal double-blind, randomized, placebo-controlled design was used, and patients were followed for 6 months from August 2003 to March 2007. Seventy early-phase schizophrenia patients (according to DSM-IV) were recruited and 54 were randomly allocated in a 2:1 ratio to minocycline 200 mg/d. All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry (risperidone, olanzapine, quetiapine, or clozapine; 200-600 mg/d chlorpromazine-equivalent doses). Clinical, cognitive, and functional assessments were conducted, with the Scale for the Assessment of Negative Symptoms (SANS) as the primary outcome measure. RESULTS: Minocycline was well tolerated, with few adverse events. It showed a beneficial effect on negative symptoms and general outcome (evident in SANS, Clinical Global Impressions scale). A similar pattern was found for cognitive functioning, mainly in executive functions (working memory, cognitive shifting, and cognitive planning). CONCLUSIONS: Minocycline treatment was associated with improvement in negative symptoms and executive functioning, both related to frontal-lobe activity. Overall, the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00733057.
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In the citing paper
“Various clinical trials have been conducted using minocycline alone or as an adjunct to risperidone in patients with schizophrenia and have demonstrated overall improvement in negative symptoms and executive functioning (Miyaoka et al., 2008; Levkovitz et al., 2010; Khodaie-Ardakani et al., 2014).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Levkovitz et al., 2010
In the citing paper
“The sole exception was a trial29 that assessed the effects of a 6-month add-on treatment with either minocycline or placebo on cognitive impairment in young subjects in early phase schizophrenia, aged 18–35 years.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“In this study, minocycline, a tetracycline antibiotic with a distinct neuroprotective profile, was found to be significantly superior to placebo at endpoint in improving cognitive functioning as well as negative symptoms and general outcome.29”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“• Minocycline showed a beneficial effect on negative symptoms and general outcome (evident in SANS, Clinical Global Impressions scale).”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“• Overall, the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“• A similar pattern was found for cognitive functioning, mainly in executive functions (working memory, cognitive shifting, and cognitive planning).”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“A trial performed in younger subjects with recent illness onset29 may yield more positive results than those conducted in patients with an average illness duration of >20 years (See table 1).”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“In this study, minocycline, a tetracycline antibiotic with a distinct neuroprotective profile, was found to be significantly superior to placebo at endpoint in improving cognitive functioning as well as negative symptoms and general outcome.29”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“In this study, minocycline, a tetracycline antibiotic with a distinct neuroprotective profile, was found to be significantly superior to placebo at endpoint in improving cognitive functioning as well as negative symptoms and general outcome.29”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [29]
In the citing paper
“add-on administration of minocycline for 22 weeks was associated with improvements in executive functions in individuals with early-phase schizophrenia [107].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [107]
Citations
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Cited by
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Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment
Khandaker, G. M., Cousins, L., Deakin, J., Lennox, B. R., Yolken, R., & Jones, P. B. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(14)00122-9 · Cited by 926
Neuroinflammation and psychiatric illness
Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733
Calcia, M., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4218-9 · Cited by 748
Glutamate and dopamine in schizophrenia: An update for the 21 st century
Howes, O., McCutcheon, R., & Stone, J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114563634 · Cited by 702
Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations.
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Metadata
- Authors
- Levkovitz, Y., Mendlovich, S., Riwkes, S., Braw, Y., Levkovitch-Verbin, H., Gal, G., Fennig, S., Treves, I., & Kron, S.
- Affiliations
- Shalvata Mental Health Center (IL)
- Corresponding author
- Levkovitz, Yechiel
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2009-11-03
- Volume
- 71
- Issue
- 02
- Pages
- 138-149
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2084588595
- Cited by
- 387
- References
- 112
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 10 · 2023: 17 · 2022: 16 · 2021: 23 · 2020: 26 · 2019: 22 · 2018: 26 · 2017: 15 · 2016: 33 · 2015: 42 · 2014: 34 · 2013: 44 · 2012: 27
- FWCI
- 13.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- minocycline, early-phase schizophrenia, negative symptoms, cognitive impairment, executive function, adjunctive therapy, glutamatergic system, nitric oxide synthase inhibition, microglial activation, atypical antipsychotics, Scale for the Assessment of Negative Symptoms
- MeSH terms
- Adolescent, Adult, Cognition, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Minocycline, Placebos, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Outcome
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