fluvoxamine and Cognition-Disorders

Cognitive impairment is a primary feature of patients with major depressive disorder (MDD) and is characterised by stress-induced neural atrophy. Via alpha-adrenergic, anti-cholinergic and anti-histaminic activities, several antidepressants can cause significant counter-therapeutic cognitive impairment. Evidence is emerging of the involvement of sigma-1 receptor agonism in the mechanism of action of some antidepressants, notably fluvoxamine. Sigma-1 receptors are abundant in areas affected by depression/stress-induced cerebral atrophy and their ligands have a unique pharmacological profile; they may promote neurogenesis and initiate adaptive neural plasticity as a protection/reaction to stress. Fluvoxamine, as a potent sigma-1 receptor agonist, has shown ameliorating effects in animal models of psychosis, depression, stress, anxiety, obsessive-compulsive disorder (OCD) and aggression and has been shown to improve cognitive impairments. In humans, fluvoxamine may repair central nervous system (CNS) atrophy and restore cognitive function. The current review explores the mechanisms through which sigma-1 receptors can modulate cognitive function and examines how antidepressant therapy with fluvoxamine may help improve cognitive outcomes in patients with depression.

Topics: Animals; Cognition; Cognition Disorders; Depressive Disorder; Fluvoxamine; Humans; Receptors, sigma; Sigma-1 Receptor; Treatment Outcome

Depression is a highly prevalent concomitant of dementia. Concurrent depression (DD) can meet full criteria for a disorder or take the form of a depressive syndrome. Although phenomenologic overlap can confound diagnosis, careful assessment demonstrates that a true depressive component is present in a substantial percentage of dementia cases. DD has been associated with excess disability, increased caregiver burden, and greater mortality. Efficacy studies have demonstrated high placebo response rates, indicating transience of many depressive symptoms, and adverse cognitive effects of older antidepressants. Studies demonstrating that new antidepressants can be efficacious and improve cognitive functioning are reviewed.

Topics: Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Benzamides; Citalopram; Clomipramine; Cognition Disorders; Comorbidity; Dementia; Depression; Female; Fluoxetine; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Moclobemide; Monoamine Oxidase Inhibitors; Neuropsychological Tests; Nortriptyline; Selective Serotonin Reuptake Inhibitors; Sertraline

Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-Åsberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-Åsberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.

Topics: Adult; Chronic Disease; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Receptors, sigma; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor; Time Factors; Treatment Outcome

Topics: Anti-Anxiety Agents; Cognition Disorders; Epilepsy; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Female; Fluvoxamine; Humans; Long QT Syndrome; Middle Aged; Multiple Sclerosis; Obsessive-Compulsive Disorder; Potassium Channel Blockers; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Cognition Disorders; Female; Fluvoxamine; Humans; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Young Adult

Topics: Adult; Cognition Disorders; Female; Fluvoxamine; Humans; Receptors, sigma; Schizophrenic Psychology; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor

This study was undertaken to examine the effects of the selective serotonin reuptake inhibitors fluvoxamine and paroxetine on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). In the novel object recognition test, repeated administration of PCP (10 mg/kg/day, 10 days) significantly decreased the exploratory preference in the retention test session, but not in the training test session. PCP-induced cognitive deficits were significantly improved by subsequent subchronic (2-week) administration of fluvoxamine (20 mg/kg/day), but not paroxetine (10 mg/kg/day). Furthermore, the effect of fluvoxamine on PCP-induced cognitive deficits was antagonized by co-administration of the selective sigma-1 receptor antagonist NE-100 (1 mg/kg/day). Moreover, PCP-induced cognitive deficits were also significantly improved by subsequent subchronic (2-week) administration of the selective sigma-1 receptor agonist SA4503 (1 mg/kg/day) or neurosteroid dehydroepiandrosterone 3-sulfate (DHEA-S; 25 mg/kg/day). The effects of SA4503 or DHEA-S were also antagonized by co-administration of NE-100 (1 mg/kg/day), suggesting the role of sigma-1 receptors in the active mechanisms of these drugs. In contrast, acute single administration of these drugs (fluvoxamine, paroxetine, SA4503) alone or combination with NE-100 did not alter PCP-induced cognitive deficits. The present study suggests that agonistic activity of fluvoxamine at sigma-1 receptors plays a role in the active mechanisms of fluvoxamine on PCP-induced cognitive deficits in mice. Therefore, sigma-1 receptor agonists such as fluvoxamine would be potential therapeutic drugs for the treatment of the cognitive deficits of schizophrenia.

Topics: Analysis of Variance; Animals; Anisoles; Antipsychotic Agents; Behavior, Animal; Choice Behavior; Cognition Disorders; Dehydroepiandrosterone Sulfate; Drug Administration Schedule; Drug Interactions; Exploratory Behavior; Fluvoxamine; Mice; Mice, Inbred ICR; Motor Activity; Nootropic Agents; Phencyclidine; Piperazines; Propylamines; Receptors, sigma; Retention, Psychology; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor

The pathological eating behaviour of patients with anorexia nervosa reflects a deficit in planning real-life strategies that can be observed in an experimental setting through the Gambling Task, a tool designed to detect and measure decision-making abilities. We examined the role of Gambling Task performance as a predictor of treatment outcome in anorectic patients, and we evaluated changes in decision-making after clinical improvement. Performance on the Gambling Task was evaluated, and a clinical-nutritional assessment of 38 anorectic patients was carried out before and after a cognitive-behavioural and drug treatment program. Task performance of anorectic patients was compared with that of 30 healthy control participants. Patients who had a better decision-making profile at baseline showed significantly greater improvement in nutritional status. The decision-making deficiency of some anorectic patients is probably linked to those individual features that contribute to the phenomenological expression of the disorder and to its different treatment outcomes.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Cognition Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Decision Making; Demography; Female; Fluoxetine; Fluvoxamine; Gambling; Humans; Interview, Psychological; Neuropsychological Tests; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Topics: Cognition Disorders; Corpus Striatum; Fluoxetine; Fluvoxamine; Frontal Lobe; Humans; Nerve Net; Neuropsychological Tests; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The serotonin reuptake inhibitors (SSRIs) are generally better tolerated than the traditional tricyclic antidepressants (TCAs) in the treatment of major depression. In particular the SSRIs are relatively free from cognitive and psychomotor effects likely to cause behavioural toxicity. Behavioural toxicity is studied using a battery of psychometric assessments. This paper discusses the effects of the TCAs and SSRIs on two such assessments, choice reaction time (CRT) and critical flicker fusion threshold (CFFT). CRT measures psychomotor speed, and CFFT assesses the information processing capacity of the CNS. The behavioural toxicity associated with the traditional TCAs can lead to an increased accident risk, whereas the SSRIs are not associated with such effects. Clinically relevant differences in the behavioural toxicity of the SSRIs are highlighted.

Topics: Accidents, Traffic; Antidepressive Agents, Tricyclic; Automobile Driving; Cognition Disorders; Depressive Disorder; Dothiepin; Flicker Fusion; Fluvoxamine; Humans; Psychomotor Performance; Reaction Time; Selective Serotonin Reuptake Inhibitors; Time Factors