Add-on Memantine Research Articles

The Effect of Add-on Memantine in New Onset Combat-Related Posttraumatic Stress Disorder Core Symptoms: A Pilot Study.

Objective: Studies using standard neuropsychological instrumentation have shown memory deficits in posttraumatic stress disorder (PTSD) patients. We examined the efficacy and safety of memantine in new cases of combat-related PTSD in the military by conducting a 16-week prospective double-blind randomized controlled trial. Method : Twenty-six new combat-related PTSD cases were recruited from among the military personnel based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Patients were assigned to memantine and Placebo groups. They were monitored at baseline, week eight, and week 16. Memantine was added to each patient's current medication with an initial dosage of 5 mg/day, raised by 5 mg/day every week until it reached the maintenance level of 20 mg/day. The concurrent drugs were essentially kept unchanged during the trial. The primary outcome was PTSD severity as assessed by the Clinician-administered PTSD Scale (CAPS). The CAPS is a valid and reliable tool for the diagnosis of PTSD and measurement of its severity according to the DSM-4. Results: CAPS mean score in baseline (P = 0.811) and weeks eight (P = 0.389) and 16 (P = 0.066) did not show any significant differences between the two groups. The mean CAPS score in the memantine group significantly (P = 0.006) decreased (Mean differences = -8.79) compared to the placebo group, showing that intervention with memantine was effective. The mean total CAPS in weeks eight (Mean differences = -14.21) and 16 (Mean differences = -27) were less than the baseline, which was significantly meaningful (P < 0.001). Conclusion: Findings of this study suggest that add-on memantine can be effective in veteran patients with PTSD. So our data provide useful insight into the management of new cases of combat-related PTSD.

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.

BackgroundAntipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis.AimsThis investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine.Materials and EquipmentAntipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment.Outcome MeasuresThe primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes.Anticipated ResultsWe hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning.PerspectivesBy combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04789915].

Improvement in Memory Deficits With Memantine in Mania Secondary to Traumatic Brain Injury and Preexisting Perinatal Birth Injury

Cognitive deficits are known to occur after brain injury, be it perinatal injury, traumatic brain injury (TBI), or any other type of insult to the brain. The problem may be compounded if psychiatric illness is present in addition to the brain injury because the illness itself or the psychotropic medications used in its management may lead to worsening of cognitive functioning. We present the case of a patient who presented to the hospital with symptoms suggestive of mania with psychotic features that had started after a recent TBI, with the brain scan also revealing the presence of a preexisting perinatal birth injury. When the patient recovered from the psychiatric symptoms, he still appeared to have memory problems that improved with the use of add-on memantine, an N-methyl-D-aspartate receptor antagonist. To date, there is some literature supporting the off-label use of memantine as a cognitive enhancer in patients with TBIs and other psychiatric illnesses, such as bipolar disorder.

Add-on memantine may improve cognitive functions and attenuate inflammation in middle- to old-aged bipolar II disorder patients

ObjectivesChronic inflammation and neuroprogression underlie bipolar disorder (BP) and associated cognitive deficits. Memantine (MM) exerts neuroprotective effects by reducing neuroinflammation. Therefore, we investigated whether add-on low-dose MM (5 mg/day) in BP-II patients may improve cognition and inflammation. MethodsWe combined two 12-week randomized, double-blind, placebo-controlled studies (NCT 01188148 and NCT 03039842) for analysis. Each participant was allocated to the MM or placebo group. Symptom severity, neuropsychological tests, and the cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were evaluated at baseline and endpoint. A subgroup analysis of middle- to old-aged BP-II patients was also performed. ResultsWe recruited 155 BP-II patients (23 of which were middle- to old-aged) for the MM group and 170 patients (20 of which were middle- to old-aged) for the placebo group. Add-on MM did not result in significant improvements in cognitive functions in all BP-II patients, but a group difference in TNF-α levels was found in the MM group (P=0.04). Specifically, in middle- to old-aged BP-II patients, there was a significant time and group interaction effect on omission T-scores, hit reaction time T-scores, and hit reaction time standard error T-scores on continuous performance tests (CPTs) in the MM group (P=0.007, 0.02, and 0.01, respectively), and a decrease in plasma TNF-α levels (P=0.04). LimitationsThe sample size of middle- to old-aged BP-II patients were limited. ConclusionAdd-on MM may attenuate inflammation in BP-II and improve cognition in middle- to old-aged BP-II patients.

Add-On Memantine May Improve Cognition and Attenuate Inflammatory Status in Middle-To-Old Aged Bipolar II Disorder Patients

Chronic inflammation and neuroprogression underlie bipolar disorder (BP) and associate with cognitive deficits in BP. Memantine (MM) has neuroprotective effects through reducing neuroinflammation. Therefore, we investigated whether add-on low dose MM (5 mg/day) in BP-II patients treated with valproic acid (VPA) may improve the cognition and inflammatory status.

Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.

Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

MEMANTINE, AS A P-GLYCOPROTEIN EXPRESSION MODULATOR, ENHANCES LEVETIRACETAM THERAPEUTIC RESPONSE IN EPILEPTIC PATIENTS

Objective: The principal aim of the present study was to assess the importance of multidrug transporter; P-glycoprotein (P-gp) as a potential therapeutic target in patients with epilepsy. Can P-gp transporter expression modulation by memantine add to the standard antiepileptic drugs (AEDs) response?&#x0D; Methods: A cohort of 56 epilepsy patients was included in a 4 monthly visits prospective study. Patients were on levetiracetam (LEV) 1000 mg/ day alone or combined with other AEDs. They were randomly assigned into two groups; LEV only group including LEV-treated patients and LEV + memantine group including patients on LEV with add-on oral memantine 10 mg/day until the end of the study. During monthly follow-up visits, therapeutic responses were evaluated for each patient by recording the monthly seizures frequency. Blood samples were drawn from every patient twice (on the first and last visits) for assessment of P-gp mRNA expression level.&#x0D; Results: Fifty patients completed the study. At the end of 4th month, LEV only group showed a non-significant decrease in P-gp expression and seizure frequency compared to the 1st month, whereas, in LEV + memantine group, P-gp expression was significantly reduced and associated with significant seizure control.&#x0D; Conclusion: Memantine by hindering P-gp overexpression was apt to enhance LEV efficacy and exhibit a better seizure control.

Acute and Long-term Memantine Add-on Treatment to Risperidone Improves Cognitive Dysfunction in Patients with Acute and Chronic Schizophrenia

Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.

Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis.

We examined whether memantine add-on to antipsychotic treatment is beneficial in schizophrenia treatment. This systematic review and meta-analysis aimed to achieve stronger evidence on the efficacy and safety of memantine add-on for treating schizophrenia. We analyzed double-blind, randomized, placebo-controlled trials of memantine add-on treatment in schizophrenia patients receiving antipsychotics. The primary outcomes were amelioration of negative symptoms and all-cause discontinuation. Dichotomous outcomes are presented as risk ratios (RRs), and continuous outcomes are presented as mean differences (MDs) or standardized mean differences (SMDs). Eight studies (n=448) were included. Although memantine add-on treatment was superior to placebo for ameliorating negative symptoms (SMD=-0.96, p=0.006, I 2=88%; N=7, n=367) in the Positive and Negative Syndrome Scale general subscale (MD=-1.62, p=0.002, I 2=0%; N=4, n=151) and Mini-Mental Status Examination score (MD=-3.07, p<0.0001, I 2=21%; N=3, n=83), there were no statistically significant differences in the amelioration of overall (SMD=-0.75, p=0.06, I 2 =86%; N=5, n=271), positive (SMD=-0.46, p=0.07, I 2=80%; N=7, n=367), and depressive symptoms (SMD=-0.127, p=0.326, I 2=0%; N=4, n=201); all-cause discontinuation (RR=1.34, p=0.31, I 2=0%; N=8, n=448); and individual adverse events (fatigue, dizziness, headache, nausea, constipation) between the groups. For negative symptoms, the significant heterogeneity disappeared when risperidone studies alone were considered (I 2=0%). However, memantine add-on treatment remained superior to placebo (SMD=-1.29, p=0.00001). Meta-regression analysis showed that patient age was associated with memantine-associated amelioration of negative symptoms (slope=0.171, p=0.0206). Memantine add-on treatment may be beneficial for treating psychopathological symptoms (especially negative symptoms) in schizophrenia patients. The negative-symptom effect size may be associated with younger adult schizophrenia patients.

Adjunctive memantine in clozapine-treated refractory schizophrenia: An open-label one-year extension study

IntroductionIn a recent placebo-controlled, double blind crossover trial (n = 52), we found significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) after 12 weeks memantine augmentation in patients with clozapine-refractory schizophrenia.AimsIn this open-label 1 year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.MethodsCompleters of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for one year. Primary endpoints were memory and executive function using the Cambridge neuropsychological test automated battery (CANTAB), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S).ResultsOf 31 RCT completers who experienced beneficial effects from memantine, 24 received memantine for one year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50), and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects.ConclusionsIn the one-year extension phase, the favorable effect of adjunctive memantine on memory was sustained and we observed further improvement of positive, negative and overall symptoms of schizophrenia.Disclosure of interestP.F.J.S. reports personal fees from H. Lundbeck A/S, outside the submitted work and he is a board member of the Dutch Clozapine Collaboration Group. L.d.H., has received investigator-led research grants or recompense for presenting his research from Eli Lilly, Bristol-Myers Squibb, Janssen-Cilag and AstraZeneca.

Efficacy of memantine in schizophrenic patients: A systematic review

IntroductionSeveral evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few year great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Memantine is a noncompetitive NMDARs antagonist, binds the same site of NMDARs of Mg2+, endogenous blocker of NMDARs, with moderate affinity, rapid unblocking kinetics and strong functional voltage-dependency. Memantine does not affect the physiological activation of NMDARs whereas it blocks the sustained activation under pathological conditions. Preclinical studies have demonstrated that memantine at high concentrations targets many receptors, including serotonin, nicotinic acetylcholine, sigma-1 and serotonin and dopamine receptors.ObjectivesIncreasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia.AimsThe aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients.MethodsWe searched on PubMed to identify original studies about the use of memantine in treatment of schizophrenic patients. The search conducted on June 16th, 2016 yielded 135 records. Neuf papers met our inclusion criteria.ResultsNegative symptoms improved in the large majority of patients treated, however there is not a clear evidence on cognitive and positive symptoms (Table 1)ConclusionsMemantine therapy in schizophrenic patients has given unclear results. It seems that memantine improves mainly negative symptoms, while cognitive and positive symptoms did not improve significantly. Further trials with a more numerous sample are required obtain an objective result.Table 1Observation during Memantime administration.↓: reduction in severity of symptoms; -: no relevant modifications; +: onset of new symptomsDisclosure of interestThe authors have not supplied their declaration of competing interest.

Efficacy of Memantine in Schizophrenic Patients: A Systematic Review.

Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly.

Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.

In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine. Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S). Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects. In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

Adjunctive memantine in clozapine-treated refractory schizophrenia: A one-year extension study

IntroductionIn a recent 26-week placebo-controlled, crossover trial (n = 52) we found significant positive effects on verbal and visual memory, and negative symptoms in clozapine-treated patients with refractory schizophrenia.ObjectivesIn this 1-year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.AimsTo evaluate the persistence of improvements in cognitive functioning and symptoms of memantine add-on therapy to clozapine in schizophrenia.MethodsCompleters of the first trial who experienced a beneficial effect of memantine after 12 weeks continued memantine for one year. Primary endpoints were change from baseline to 26 weeks treatment and 26 weeks to 52 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Secondary endpoints were change on the Health of the Nation Outcome Scales (HoNOS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).ResultsOf 32 completers who experienced a beneficial effect of memantine 23 patients continued memantine for one year. Memory improvement was sustained, verbal recognition memory improved even further between t = 26 weeks and t = 52 weeks. Continued treatment with memantine add-on to clozapine was associated with significantly improved PANSS positive, negative and overall score, CGI-S and HoNOS scores.ConclusionsIn the extension phase the positive effect of memantine add-on therapy on verbal memory sustained and positive, negative and overall symptoms of schizophrenia, clinical global status and psychosocial functioning significantly improved. Memantine was well tolerated without serious adverse effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Memantine ER/Donepezil: A Review in Alzheimer's Disease.

A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10mg (Namzaric™) is available in the USA for patients with moderate to severe Alzheimer's disease (AD) on stable memantine and donepezil therapy. The fixed-dose formulation is bioequivalent to coadministration of the individual drugs. In a 24-week, phase III trial in patients with moderate to severe AD, addition of memantine ER 28mg once daily to stable cholinesterase inhibitor (ChEI) therapy was more effective than add-on placebo on measures of cognition, global clinical status, dementia behaviour and semantic processing ability, although between-group differences on a measure of daily function did not significantly differ. In subgroup analyses in donepezil-treated patients, add-on memantine ER was more effective than add-on placebo on measures of cognition, dementia behaviour and semantic processing, although there were no significant between-group differences on measures of global clinical status and daily function. Memantine ER plus ChEI combination therapy was generally well tolerated in the phase III trial, with diarrhoea, dizziness and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients. Thus, memantine ER plus donepezil combination therapy is an effective and well tolerated treatment option for patients with moderate to severe AD. The fixed-dose combination is potentially more convenient than coadministration of the individual agents.

Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial.

Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (P = 0.039). They also had significantly lower plasma TNF-α and significantly higher TGF-β1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT.

Low-dose add-on memantine treatment may improve cognitive performance and self-reported health conditions in opioid-dependent patients undergoing methadone-maintenance-therapy.

An important interaction between opioid and dopamine systems has been indicated, and using opioids may negatively affect cognitive functioning. Memantine, a medication for Alzheimer's disease, increasingly is being used for several disorders and maybe important for cognitive improvement. Opioid-dependent patients undergoing methadone-maintenance-therapy (MMT) and healthy controls (HCs) were recruited. Patients randomly assigned to the experimental (5 mg/day memantine (MMT+M) or placebo (MMT+P) group: 57 in MMT+M, 77 in MMT+P. Those completed the cognitive tasks at the baseline and after the 12-week treatment were analyzed. Thirty-seven age- and gender-matched HCs, and 42 MMT+P and 39 MMT+M patients were compared. The dropout rates were 49.4% in the MMT+P and 26.3% in the MMT+M. Both patient groups' cognitive performances were significantly worse than that of the HCs. After the treatment, both patient groups showed improved cognitive performance. We also found an interaction between the patient groups and time which indicated that the MMT+M group's post-treatment improvement was better than that of the MMT+P group. Memantine, previously reported as neuroprotective may attenuate chronic opioid-dependence-induced cognitive decline. Using such low dose of memantine as adjuvant treatment for improving cognitive performance in opioid dependents; the dose of memantine might be a worthy topic in future studies.

Add-on Memantine Treatment for a Complicated Case of Juvenile Bipolar Mood Disorder with Co-morbid Obsessive-compulsive Disorder

Comorbid Bipolar Mood Disorder (BMD) and Obsessive-Compulsive Disorder (OCD) is not a rare clinical scenario as was once thought. Treatment of such cases poses a pharmacologic conundrum as the serotonin reuptake inhibitors (SRIs), constituting the mainstay of treatment in OCD, can destabilize BMD. No guidelines are currently available to dictate the most appropriate course of action in these cases. Memantine, a drug that is approved for Alzheimer's Disease (AD) with putative antiglutamate activity has been reported in successful management of some refractory cases of OCD as well as BMD. Here, we report a pharmacologicallychallenging case of an adolescent with comorbid BMD and OCD masquerading as school refusal behaviour (SRB) , that ultimately improved with add-on memantine to her treatment combo with great tolerability. This could open new treatment venues for such complicated cases.

The effect of add-on memantine on global function and quality of life in schizophrenia: A randomized, double-blind, controlled, clinical trial.

Background:Schizophrenia severely influences function and quality of life. The benefit of newer antipsychotics in improving the quality of life in schizophrenia still remains controversial. The aim of the present study is to evaluate the effect of memantine on global function and quality of life in patients with schizophrenia.Materials and Methods:This was a randomized controlled trial on inpatient cases of schizophrenia in Noor University Hospital, Isfahan, Iran. A number of 64 patients were selected through sequential sampling; patients were randomly allocated in intervention and placebo groups. The intervention group was treated with memantine plus previously administered, stabled-dose, atypical antipsychotic, while the control group received placebo plus previously administered, stabled-dose, atypical antipsychotic. Memantine administration was initiated at 5 mg daily; the dosage was increased at weekly intervals by 5 mg and finally up-titrated to 20 mg daily within 4 weeks. All patients were assessed by means of Global Assessment of Functioning (GAF) and quality of life scale (QLS) initially and every four weeks to the end of the 12th week.Results:Analysis of baseline GAF and QLS scores showed no significant differences between the two groups (P = 0.081 and P = 0.225, respectively). GAF and QLS scores increased in both groups; but it was higher in the intervention group. The difference between the two groups was statistically significant. (P < 0.001 and P < 0.001, respectively) memantine was well tolerated, with no significant side effects.Conclusion:Add-on memantine was significantly effective in improving the global function of patients as well as their quality of life.