A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia
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Yechiel Levkovitz1, Shlomo Mendlovich, Sharon Riwkes
1The Emotion-Cognition Research Center, The Shalvata Mental Health Care Center, P.O.B. 94. Hod-Hasharon, Israel. ylevk@clalit.org.il
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.
Insights
Minocycline add-on therapy improved negative symptoms and executive functions in early schizophrenia patients. This suggests minocycline is a promising treatment for schizophrenia, particularly for cognitive deficits and negative symptoms.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Schizophrenia's core symptoms, negative and cognitive deficits, are poorly addressed by current antipsychotics.
- Minocycline, a tetracycline antibiotic, shows promise for neurological disorders and schizophrenia treatment.
- Potential mechanisms include modulation of glutamatergic and dopaminergic systems, and inhibition of microglial activation.
Purpose of the Study:
- To evaluate minocycline's efficacy as an adjunctive treatment for negative and cognitive symptoms in early-phase schizophrenia.
- To assess the impact of minocycline on overall clinical and functional outcomes in schizophrenia patients.
Main Methods:
- A 6-month, double-blind, randomized, placebo-controlled trial involving 54 early-phase schizophrenia patients.
- Patients received atypical antipsychotics plus either minocycline (200 mg/d) or placebo.
- The Scale for the Assessment of Negative Symptoms (SANS) was the primary outcome measure, with cognitive and functional assessments also performed.
Main Results:
- Minocycline was well-tolerated with minimal adverse events.
- Significant improvements were observed in negative symptoms (SANS) and general outcome.
- Cognitive functioning, particularly executive functions like working memory and planning, showed notable enhancement.
Conclusions:
- Minocycline add-on therapy demonstrated efficacy in improving negative symptoms and executive functions in early schizophrenia.
- Findings support minocycline's role in addressing frontal-lobe related deficits in schizophrenia.
- Minocycline represents a potentially valuable therapeutic option for early-phase schizophrenia management.
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