Current Psychopharmacology - Volume 4, Issue 2, 2015

Background: The term Treatment- Resistant Depression is frequently used to describe patients that show poor response to conventional antidepressant therapy. Therefore a search for better and more efficacious treatment options is needed. The dopaminergic hypothesis for depression has been an attractive topic according to the growing evidence from basic research and clinical trials that have suggested the important role of this neurotransmitter in the pathophysiology of depression. Currently, the dopaminergic drugs used in clinical practice are employed mainly for neuropsychiatric conditions and some of them specifically pramipexole and ropirinole have exhibited an antidepressant action that had led to the postulate that these may be considered as potential agents with antidepressive effects. Objective: Our aim was to explore current data from preclinical and clinical trials that place pramipexole and ropirinole as options for augmentation strategies. Method: We performed a literature review about the use of dopaminergic agents to provide an overview about its efficacy and safety in the treatment of treatment-resistant depression. Conclusion: Reviewing briefly the hypothetical role of dopamine mechanisms in depression, the findings from basic research, nonclinical studies and clinical trials, we certainly can say that dopaminergic drugs had brought a broad opportunity with novel benefits and risks to the mood disorders treatment, although further research and more randomized controlled trials in larger samples are needed to prove their efficacy and safety.

Background: Bipolar Disorder is a psychiatric condition highly disabling, with elevated rates of psychiatric and medical comorbidities that contribute substantially to morbidity and mortality. Pathophysiology of the illness is not well known but recent biologic and pharmacological studies suggest that altered receptor-mediated signal transduction mechanisms contribute to the pathophysiology of the disease. Accordingly, medications with effect in these signal transduction mechanisms are supposed to be useful in the treatment of Bipolar Disorder, such is the case of tamoxifen. Animal model studies and clinical trials have been conducted to address the efficacy and side-effect profile of tamoxifen. Objective: In this review we take a closer look to some of the findings regarding the potential role of tamoxifen in the treatment of patients with Bipolar Disorder. Method: We conducted a systematic literature search on PubMed looking for studies that used tamoxifen for the treatment of Bipolar Disorder. Results: A limited number of clinical studies concerning the effect of tamoxifen as a treatment in Bipolar patients were identified. Conclusion: Mechanism of action of tamoxifen suggests that it could be useful in patients with manic episodes; however more evidence is desirable to evaluate the efficacy of tamoxifen in different clinical profiles of patients with bipolar disorder.

Background: Bipolar Disorder is a severe psychiatric condition, characterized by depressive and manic mood states. Depressive mood remains a problem for most patients, as this is the predominant mood state, and because the options we have for treating depression remain scarce. Therefore, the quest for new treatment options is ongoing. Objective: We focus here on one approach in particular, regarding the known influence of factors that disrupt the circadian rhythm in the precipitation of new episodes, as well as the methods available to restore this rhythm, and a new treatment which could theoretically be particularly good for this purpose: Agomelatine. How does it work? What relation does it have to circadian timing? What do we know of its efficacy in treating bipolar depression? And finally, is it an acceptable treatment? Method: We performed a literature review about the relation of melatonin to circadian cycles, the disruption of circadian rhythms in Bipolar Disorder, chronotherapeutics and finally on agomeltine’s pharmacodynamic profile and use to treat bipolar depression. Conclusion: Agomelatine shows two very interesting mechanisms of action, a potent overactivation of dopaminergic and noradrenergic neurons in the prefrontal cortex and the amelioration of sleep and more importantly, the amelioration of sleep structure and regulation of circadian rhythms. These may represent an effective option for the depressive phase in bipolar disorder, both as an acute treatment and as a prevention for future relapse.

Background: Lithium has been considered the "gold standard" in the management of bipolar disorder, being the agent compared with "new mood stabilizer". It has also shown effect in the reduction of suicidal thoughts. Among the known mechanisms of action of lithium it has been described the inhibition in inositol monophosphatase (IMP) as resulting in non-competitive inhibition of IMP, resulting in a decrease of inositol in the central nervous system leading to a decrease in the synthesis of inositol triphosphate, affecting the transmission and translation of signals. Added to this, lithium inhibits kinase glycogen synthase enzyme (GSK) 3-β; it’s regulated by different signaling pathways and its dysfunction has been related to the pathophysiology of mood disorders, schizophrenia, diabetes and Alzheimer's disease. The neuroprotective effects have been shown of lithium in preclinical studies. The chronic administration of lithium enhances the proliferation of progenitor cells and inhibits cell loss induced by glutamate and glucocorticoids. In addition to a neurotrophic and neuroprotective role, lithium can also exert beneficial effect through its ability to improve mitochondrial function. Objective: Our aim was to explore the current information on the findings relating to lithium as a substance with possible neuroprotector effect in patients with diagnosis of bipolar disorder, as well as other conditions. Method: We performed a literature review regarding the use of Lithium and its potential neuroprotective effect in patients Conclusion: There is enough evidence that lithium may slow the progression of neurocognitive impairment in long term treatment patients, suggesting a potential use for the treatment of neurodegenerative diseases.

Background: Both Bipolar Disorder (BD) and Obsessive Compulsive Disorder (OCD) are chronic psychiatric conditions, the first characterized by depressive and manic mood episodes and the latter characterized by obsessions and compulsions. The comorbidity between BD and OCD is not rare, and the presence of both conditions conveys important complications. The treatment supposes a challenge since antidepressants, first choice of treatment for OCD, carry an important risk for bipolar patients. Objective: In the present review our aim was to find evidence on Quetiapine's efficacy in the treatment of bipolar disorder with comorbid OCD. Method: We performed a literature review on the treatment options for comorbid BD and OCD, Quetiapine’s use in OCD and anxiety disorders and finally a MEDLINE search about the use of Quetiapine for this specific indication. Conclusion: The use of Quetiapine could be justified in patients with cycling OCD and in those who have shown benefit from this antipsychotic for BD and can tolerate adjunctive antidepressants. Still, clinical trials including this specific comorbid population should be performed to consider Quetiapine as part of BD-OCD patient’s treatment.

Background: Pharmacological management of geriatric patients in acute settings is complex due to the presence of medical comorbidities, risk of drug-drug interactions, and potential patient sensitivity to side effects. Objectives: This article will review the basic pharmacologic principles of management of older adults in acute settings. Method: The aforementioned principles will be described and illustrated with two clinical examples. These principles include prioritizing the safety of patients and staff; obtaining a history that is as complete as possible, in order to support the working diagnosis; using the lowest medication dose that controls the symptoms; closely monitoring for side effects and drug-drug interactions; minimizing polypharmacy and discontinuing medications that are no longer necessary; double-checking all orders, so as to avoid medication errors; and involving the patients family and caregivers in treatment planning. Additionally, agents with anticholinergic properties, antipsychotics, benzodiazepines, nonbenzodiazepine hypnotics, and opioids should be used cautiously in older individuals, particularly those with dementia. Practical tips, formulations, dosages, and selected adverse effects of antipsychotics and mood stabilizers used with geriatric patients in acute settings are included. Results: This clinical review will be useful for psychiatrists and other clinicians who treat older adults in acute medical settings.

For clinical management of psychosis, both classical and novel antipsychotic drugs are available, but teratogenic potential of second generation antipsychotic drugs in general and third generation in particular has not been established so far in clinical and preclinical studies. Reports on third generation antipsychotic drugs are not available. Therefore, present study has been undertaken to compare the teratogenic potential, and fetal toxicity of quetiapine and aripiprazole in in utero rat fetuses since equivalent therapeutic doses were administered during critical period of somatic and neural development. Pregnant nulliparous Wistar rats (≈ 10 weeks age and 180 ± 5 g weight) were exposed to selected doses of quetiapine (55, 80 and 100 mg/kg) and aripiprazole (2, 3 and 5 mg/kg) from gestation day 6 to 21 through oral route. Similarly control subjects were also treated to vehicle of the drugs with similar protocol. On gestation day 22, after mild anesthesia, pregnant subjects were sacrificed and their fetuses were collected, weighed and examined for birth defects, if any. Results indicate that prenatal exposure to quetiapine induced gross external anomalies and fetal toxicity (limb deformities, body and brain weight) than ARI. These data indicate the 3rd generation antipsychotic drug, aripiprazole is safer than quetiapine for teratogenic potential point of view. Hence, aripiprazole could be an alternate and safe option to treat pregnant women after extrapolation of animal data to human beings.

Background: High fats in diet are often considered as a root cause for metabolic alterations which turns to lead obesity, a serious health problem in developed countries.. Obesity is characterized as abnormal storage of fats in adipose tissue, which appear as a bodyweight beyond to the limit. It negatively affects diverse aspects of health and strongly correlated with other complications like diabetes type 2 and heart diseases. Objective: The study aimed to evaluate the manifestations of high fat diet on physiological changes undergoing in the body and their association in developing obesity. Method: Study conducted on male wistar rats, treated with high fats for 5 weeks to produce the animal model of obesity. Food intake, Body weight, activity in familiar (home cage) and novel (open field) environment were monitored once per week which was shown disturbed in animal model of obesity. Results: The consumption of fats causes disturbance in food intake and appeared as positively associated with body weight gain and obesity. Locomotor activity was found significantly decreased in animals consuming fat rich diet as it was expected. Fat diet also produced anxiogenic behavior in animals as the time spent in light box was decreased with the long term treatment. Conclusion: This pre clinical trial suggests that the diet with strong fat profile can be a big promoter of adiposity with different health hazards.