Current Psychopharmacology - Volume 8, Issue 2, 2019

Background: Neurosteroids (NS) are steroid derived molecules synthesized in the central nervous system (CNS) involved in modulating brain transmission by its activity on gamma-aminobutyric acid (GABA) receptors; this interaction has been identified as an important factor in the pathophysiology of affective disorders. Objective: The aim of the present paper is to describe the relation of neurosteroids with affective disorders in women and novel treatments in this regard in an understandable and synthesized review of the subject. Methods: A thoroughly made research has been performed in order to find the latest information in this regard using scientific databases such as PubMed and Google Scholar using the keywords Neurosteroids, affective disorders, depression, postpartum depression and dysphoric premenstrual disorder. Results: It has been seen that NS levels during physiological fluctuation such as during menstrual cycle or postpartum may modify the response to GABA by GABA-A receptors in susceptible women. Recent pharmacological assays have been developed in order to treat affective disorders in women focusing on NS fluctuations. Conclusion: Within this paper, we review recent findings in NS modulating mechanisms, its pathophysiological implications in affective disorders and recent clinical assays in this regard.

Background: Suicide rates and narcotic overdose have doubled since 2000. At least 30 percent of people with major depression are Treatment-Resistant (TR) and require novel therapeutics. ketamine at low doses has been shown in clinical trials to induce a rapid, short-lived anti-suicide and anti-depressant effect. Objective: To review the potential mechanism of action of ketamines’ alleviation of depressive symptoms from both animal and available human literature. Methods: This is a synthesis of information from papers listed in PUBMED Central. Although not exhaustive, this review highlights the most compelling work in the field related to this remarkable clinical rapid anti-depressant effect. Results: While there have been several theories and with some scientific evidence to date, the conclusion here is that currently, an exact and acceptable mechanism of action (MOA) for ketamines’ rapid anti-depressant effect is not apparent. The MOA of this compound with psychoactive abuse potential at a higher dosage and acute antidepressive effect in the most resistant patients is unknown. Discussion: Possible MOAs reviewed, include dopamine receptor modulation through epigenetic neuroadaptation via specific D1/D2 antagonism, D1 activation using optogenetic stimulation, and the role of D2/D3 availability in the ketamine therapeutic action. Conclusion: Unraveling MOA could guide the development of other unique Psychoplastogens capable of rapidly promoting structural and functional neural plasticity in cases of TR Major Depressive Episodes (MDE) and unipolar Major Depression Disorder (MDD).

Background: While negative symptoms are connected with poor functioning and quality of life, pharmacological managements have imperfect effects on deficit syndrome and may even subsidize or aggravate secondary negative symptoms. Meanwhile, management of negative symptoms by means of add-on medications has resulted in instable consequences. Objective: in the current tryout, some of the indigenous systematic issued studies have been the theme of a new meta-analysis, to assess the effectiveness of adjunctive psychotropic drugs on deficit syndrome of schizophrenia. Methods: Twelve randomized placebo-control trials (n=433), which had been implemented in Razi psychiatric hospital in the last 14 years, had been selected for the present analysis. As a shared protocol, all cases had been selected amongst the male inpatients, who were hospitalized in chronic section of the hospice and had been diagnosed schizophrenia in line with “Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision”. In this regard, the aforesaid samples had been entered into matching-group, double-blind assessments for random assignment to a psychotropic medication (like antidepressant, benzodiazepine, psycho-stimulant, Acetyl-cholinesterase inhibitors) or placebo in addition to their current drug. In these trials, “Scale for Assessment of Negative Symptoms (SANS)” had been used as the main outcome measure for evaluation of negative symptoms. Also, response was defined as a decrease in ≥20% in the severity of SANS score (over-all and/or sub-scales). Results: While the heterogeneity of the present meta-analysis was intermediate, the “Combined Effect Size” of the aforesaid assessments has revealed a significant influence respecting efficiency of psychotropic drugs on negative symptoms of schizophrenia (OR = 5.40, CI=2.69- 10.85, z= 5.32, p<0.000). Similar results, as well, could be found in connection with various negative symptoms. In this regard, ‘Anhedonia-Asociality’ showed the best “Combined Effect Size”, afterwards “Affective Blunting”, “Avolitio -Apathy”, “Attention Deficit”, and last of all “Alogia”. “Heterogeneity” of all said analysis was insignificant and therefore appropriate. Conclusion: According to the findings, psychotropic drugs, as add-on medications, have valuable influence in regard to amelioration of negative symptoms of schizophrenia.

Background: This contribution is a study on plasma antipsychotics concentrations of first episode outpatients with psychosis (FEPs), under antipsychotic treatment; it aims to attract attention to the importance of the drug-driven management of psychiatric patients for improving adherence and clinical efficacy. Methods: The plasma antipsychotic concentrations were determined retrospectively (after the completion of selection of all samples) and therefore, they were not used to monitor patients’ response to pharmacotherapy. A total of 120 plasma samples from 35 psychiatric patients were collected and tested for antipsychotics. The concentrations of eight antipsychotic drugs (amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone and paliperidone) and seven of their metabolites were determined. Results: Overall, 74% of the samples had therapeutic antipsychotic levels, 19% had subtherapeutic concentrations, while supra-therapeutic concentrations were measured for clozapine (7%). Therapeutic drug concentrations were recorded in 54% of plasma samples from patients being under olanzapine medication and in all patients under long-acting injectables. Sub-therapeutic levels were either attributed to non-adherence, or they reflected residual levels due to medication changes. Supra-therapeutic levels were recorded for clozapine and were not followed by adverse effects. Conclusion: This is the first study on antipsychotic plasma levels conducted in Greece. Our results show the importance of performing measurement of plasma antipsychotics levels, at appropriate time intervals, for improving adherence, clinical decision making and thus clinical efficacy. Especially for FEPs, such approach could contribute to early detection of treatment limitations and improve outcome.

Background: Monosodium glutamate (MSG) is a flavour enhancer which induces behavioural changes in animals. However the influence of sex on the behavioural response to MSG has not been investigated. Objective: The sex-differential effects of MSG on open-field behaviours, anxiety-related behaviour, behavioural despair, place-preference, and plasma/brain glutamate levels in adult mice were assessed. Methods: Mice were assigned to three groups (1-3), based on the models used to assess behaviours. Animals in group 1 were for the elevated-plus maze and tail-suspension paradigms, group 2 for the open-field and forced-swim paradigms, while mice in group 3 were for observation in the conditioned place preference paradigm. Mice in all groups were further assigned into five subgroups (10 males and 10 females), and administered vehicle (distilled water at 10 ml/kg) or one of four doses of MSG (20, 40, 80 and 160 mg/kg) daily for 6 weeks, following which they were exposed to the behavioural paradigms. At the end of the behavioural tests, the animals were sacrificed, and blood was taken for estimation of glutamate levels. The brains were also homogenised for estimation of glutamate levels. Results: MSG was associated with a reduction in locomotion in males and females (except at 160 mg/kg, male), an anxiolytic response in females, an anxiogenic response in males, and decreased behavioural despair in both sexes (females more responsive). Postconditioning MSG-associated place-preference was significantly higher in females. Plasma/ brain glutamate was not significantly different between sexes. Conclusion: Repeated MSG administration alters a range of behaviours in a sex-dependent manner in mice.

Introduction: Since around half of the patients with obsessive-compulsive disorder do not respond efficiently to current serotonin- reuptake inhibitors, the objective of the present study was to compare the effectiveness and safety of quetiapine against aripiprazole in patients with obsessive-compulsive disorder, who had not responded successfully to fluvoxamine. Methods: Forty-four patients with obsessive-compulsive disorder, who had not responded efficaciously to fluvoxamine, at maximum dose (300 milligrams per day) and duration (twelve weeks), were allocated randomly in a double-blind assessment to take quetiapine (n=22) or aripiprazole (n=22), plus their serotonin-reuptake inhibitor for twelve weeks. While treatment response was evaluated by the Yale- Brown Obsessive-Compulsive Scale (YBOCS), as the main outcome scale, Clinical Global Impressions-Severity Scale (CGI-S) was also used as an ancillary measure. Results: 54.54% of patients in the quetiapine group and 27.27% of them in the aripiprazole group responded partially to the abovementioned on treatment adds. According to the findings, the YBOCS score dropped from 31.18+/-4.93 to 27.97+/-3.71 (p< 0.01), and 33.27 +/- 3.90 to 30.72+/-4.67 (p < 0.06), for quetiapine and aripiprazole, respectively. In this regard, no substantial alteration regarding CGI-S was evident in each of the aforementioned groups. Conclusion: This assessment indicated that patients with treatment-resistant obsessivecompulsive disorder could benefit more from adding quetiapine, in comparison with aripiprazole, to their current serotonergic medication.

Background: Treatment-resistant psychosis makes schizophrenia a disabling and costly illness. Clozapine is an effective treatment for treatment-resistant psychosis, though it is underutilized mainly due to prescribing providers’ fear of a serious yet uncommon complication, clozapine-induced neutropenia. Clozapine-induced neutropenia predisposes patients to potentially life-threatening infections leading prescribers to stop use when blood counts start to drop even well above the recommended cut-off point. Colonystimulating factors are effective options for reducing risk and duration of neutropeniarelated events though they add a significant cost burden to the patient and healthcare system. There is a great need for feasible and cost-effective pharmacotherapies in the mental health care setting for the management of clozapine-induced neutropenia. Objective: We evaluated adjunctive use of lithium when prescribed at a low-dose to stabilize dropping blood count in patients receiving clozapine for treatment-resistant psychosis. Methods & Results: A case series analysis of three patients who were followed in a mental health outpatient clinic for the management of schizophrenia. Blood counts of all the patients were stabilized by low-dose lithium treatment and continued to receive long term treatment of clozapine. Conclusion: Results suggest low-dose lithium as a feasible and cost-effective pharmacotherapeutic option enabling the continuation of clozapine, an effective treatment for treatment-resistant psychosis.

Background: REM sleep behavior disorder (RBD) is manifested by abnormal motor behavior with an endurance of tone during REM sleep. Studies suggest that patients taking Selective serotonin reuptake inhibitors (SSRIs) are at greater risk of developing REM sleep behavior disorder. Case Presentation: We present a case of 39-year-old female with a past medical history of spinal cord injury from a gunshot wound 19 years ago resulting in paraplegia, posttraumatic stress disorder(PTSD), chronic pain, and chronic sleep problem. After sertraline started and up-titrated to 200 mg for her anxiety, she noticed worsening of her nighttime sleep behavior. Her mother also witnessed sleepwalking episode and doing things which the patient had no recollection in the morning, including trying to take a bath and eat from the refrigerator. On her follow-up appointment, her sertraline was discontinued altogether and she was started on Escitalopram 5 mg. She tolerated the medication well, it helped moderately with her anxiety and by the time of this case report (approximately 1 month) patient did not report any sleep-related behavior. Conclusion: Since antidepressant medication is very commonly prescribed, it is important to be cautious of physiologic changes they may induce, even if the clinical significance of these changes is not fully elucidated. In addition, RBD may predict neurodegenerative disorders a couple of years earlier, so it may be used as an effective early marker of neurodegenerative diseases.