Selective activation of D1 dopamine receptors exerts antidepressant-like activity in rats.

BACKGROUND: Major depressive disorder is a common illness that severely decreases psychosocial functioning. Due to the major limitations of current treatments including response failure, it is crucial to develop better therapy strategies. Evidence suggests that dopamine dysregulation might play a major role in major depressive disorder physiopathology. AIMS: This study investigates whether the dopamine D1 receptor agonist A77636 modulates antidepressant-like activity in rats. METHODS: Rats were injected with an acute single dose of A77636 (0.75, 1.5 or 3 mg/kg), a potent and selective dopamine D1-like receptor agonist. Their locomotor activity, social interactions and behavioural response to the forced swim test were analysed 30 min after the injection. RESULTS: During the forced swim test, the D1 agonist dose dependently reduced the immobility while the time of bursting was increased. Social interactions were significantly increased in the animals exposed to 3 mg/kg of A77636 whereas no significant changes were measured in general motor activity. CONCLUSIONS: The present results provide evidence that pharmacological modulation of D1 receptor by the selective agonist A77636 induces antidepressant-like effects in rats, which encourages further studies regarding D1-specific modulation in major depressive disorder treatment.

Antidepressants Promote and Prevent Cancers.

The review states that antidepressants (ADs) increase brain-derived neurotrophic factor (BDNF) transmission concomitantly in the brain and the blood: ADs increasing BDNF synthesis in specific areas of the central nervous system (CNS) could presumably affect megakaryocyte's production of platelets. ADs increase BDNF levels in the CNS and improve mood. In the blood, ADs increase BDNF release from platelets. The hypothesis presented here is that the release of BDNF from platelets contributes to the ADs effects on neurogenesis and on tumor growth in the cancer disease. Oncological studies indicate that chemicals ADs exert an aggravating effect on the cancer disease, possibly by promoting proplatelets formation and enhancing BDNF release from platelets in the tumor.

A new strategy for antidepressant prescription.

From our research and literature search we propose an understanding of the mechanism of action of antidepressants treatments (ADTs) that should lead to increase efficacy and tolerance. We understand that ADTs promote synaptic plasticity and neurogenesis. This promotion is linked with stimulation of dopaminergic receptors. Previous evidence shows that all ADTs (chemical, electroconvulsive therapy, repetitive transcranial magnetic stimulation, sleep deprivation) increase at least one monoamine neurotransmitter serotonin (5-HT), noradrenaline (NA) or dopamine (DA); this article focuses on DA release or turn-over in the frontal cortex. DA increased dopaminergic activation promotes synaptic plasticity with an inverted U shape dose-response curve. Specific interaction between DA and glutamate is mediated by D1 receptor subtypes and Glutamate (NMDA) receptors with neurotrophic factors likely to play a modulatory role. With the understanding that all ADTs have a common, final, DA-ergic stimulation that promotes synaptic plasticity we can predict that (1) AD efficiency is related to the compound strength for inducing DA-ergic stimulation. (2) ADT efficiency presents a therapeutic window that coincides with the inverted U shape DA response curve. (3) ADT delay of action is related to a "synaptogenesis and neurogenesis delay of action." (4) The minimum efficient dose can be found by starting at a low dosage and increasing up to the patient response. (5) An increased tolerance requires a concomitant prescription of a few ADTs, with different or opposite adverse effects, at a very low dose. (6) ADTs could improve all diseases with cognitive impairments and synaptic depression by increasing synaptic plasticity and neurogenesis.

Onset of improvement and response to mirtazapine in depression: a multicenter naturalistic study of 4771 patients.

The purpose of this open multicenter study of 4771 patients with a DSM-IV diagnosis of Major Depressive Episode was to analyse the response to mirtazapine in general practice and primary care. Patients with a baseline score of at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were treated with mirtazapine for 6 weeks (30 mg/day) and clinically assessed by their psychiatrists at weekly intervals through the MADRS and Clinical Global Improvement (CGI) rating scales. The data analysis was carried out on an "intent-to-treat" basis to collect outcome information on all patients. Our results suggested that the efficacy of the antidepressant effect relates to a nonspecific process. Nearly all patients (95%) showed at least slight improvement at the end of the observation period, while the response to treatment was independent of the clinical forms of depression. In particular, all measures of efficacy displayed the maximum change within the first 2 weeks of treatment, with further improvement occurring at much slower rates. Significant improvement within the first 2 weeks of treatment was highly predictive of the final response, and can serve as a guideline for clinicians when deciding about increased dosage, augmentation, or change of medication in unresponsive patients. Detailed analyses of individual MADRS items showed that mirtazapine's pharmacological profile, unlike selective serotonin reuptake inhibitors, led relatively quickly to a significant reduction of suicidal thoughts, a fact of particular clinical relevance.

Relationship between body-mass index and depressive symptoms in patients with major depression.

BACKGROUND: Appetite and weight changes are commonly occurring symptoms of depressive illness. The occurrence of these symptoms may not only be related to depressive mood but may also be related to body weight. AIM: To examine the relationship between symptoms of depression and body weight. METHODS: Symptoms of depression were assessed by the Montgomery-Asberg depression rating scale (MADRS) in 1694 patients seeking medical help and fulfilling DSM-IV criteria for a major depressive episode. The level of anxiety was evaluated by Covi's anxiety scale. Body weight was expressed as body-mass index (BMI, kg/m(2)) and treated both categorically and continuously. RESULTS: The total MADRS score was not statistically different across the four BMI categories (underweight: 32.3 +/- 0.6, normal weight: 30.9 +/- 0.2, grade 1: 30.6 +/- 0.3, and 2 overweight: 30.6 +/- 0.6, P = 0.053 (NS)). In women with BMI

Effects of mirtazapine on sleep polygraphic variables in major depression.

Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively.