Current Psychopharmacology - Volume 4, Issue 1, 2015

Background: The side effects of psychotropic drugs are commonly encountered in clinical practice. Sexual side effects of psychotropic drugs may affect compliance to the treatment if not properly treated. Different classes of psychotropic drugs are known to cause clinically significant sexual dysfunction. Objective: In this review, authors have attempted to briefly describe the common side effects of psychotropic agents and their management in day to day clinical practice. Method: Appropriate internet search was made using keywords. Results: Antidepressants like Selective Serotonergic Reuptake Inhibitors (SSRIs) and conventional antipsychotics are associated with distressing sexual dysfunction due to their effects on neurotransmitters like dopamine, norepinephrine and serotonin. Some of the antidepressants like bupropion and antipsychotics like aripiprazole are the safest choice in terms of potential to cause sexual dysfunction. Conclusion: The management of sexual dysfunction due to psychotropics warrants a sensible approach by clinicians in their day to day practice. Management of sexual dysfunction may entail simple steps like curtailing the dose of drug, drug holidays and adding adjuvant drugs at times.

Objective: To investigate clinical response rates of Deep Brain Stimulation (DBS) as an intervention for treatment resident depression (TRD). Method: We performed a Pubmed search using the search terms deep brain stimulation, treatment resistant depression, DBS and TRD which resulted in three-hundred and seventythree records. Eighty-four articles were screened and duplicates were removed. Inclusion criteria were: 1.) Diagnosis of Major Depressive Disorder, 2.) Well documented TRD involving failure of prior established pharmacological treatments, 3.) Controlled trials, uncontrolled observational studies and case series, 4.) Intervention used was DBS and 5.) Measures of depressive symptomology pre and post treatment using a validated psychiatric scale to allow assessment of response. Exclusion criteria include: a reanalysis of pre-published data, review articles, single case reports, non-English studies and studies involving non-human animal models. Twelve articles were eligible, with 2 being excluded as they were case reports. Consequently, ten articles met criteria and were included in the systematic review. Results: Overall, 10 studies were compiled and analyzed for this systematic review, with the number of participants in the study ranging from 4 to 30. 4 of the 6 studies showed 50% or more improvement in measures of clinical response in the subcallosal cingulate white matter /brodmann area 25 neuroanatomic regions. The ventral anterior internal capsule and ventral striatum sites of stimulation showed 71% and 23% clinical response rates in 2 studies. The nucleus accumbens elicited a 45% clinical response rate. Finally, the supero-lateral branch of the medial forebrain bundle (bilaterally) resulted in 86% clinical response rate in 1 study. Conclusion: Given the morbidity and mortality associated with Major Depressive Disorder and the challenges of TRD, the studies to date strongly support further systematic investigation of the use of DBS in the treatment of refractory major depressive disorder. Clinical Implications: There is promising data to show that DBS is an effective intervention for TRD. Further investigation is needed to assess DBS as an intervention, particularly with larger sample. sizes needed in future studies Limitations: The samples sizes reviewed in the studies are small. The inclusion of open label research design. Limited comparison across studies due to differences in patient selection, electrode placement and variable duration of treatment.

Objectives: This prospective, open-label study investigated the effectiveness of Quetiapine Extended-Release (XR) in the treatment of Bipolar II Depressive Episode and its impact on quality of life in postpartum, non-lactating women. Method: Of the twenty-six women enrolled, fifteen completed the fourteen week study. Quetiapine XR was initiated at 50 mg and titrated up to 300 mg daily. Rating scales: Hamilton and Montgomery-Asberg Depression Rating Scales (HAM-D and MADRS), Quality of Life Enjoyment Satisfaction Questionnaire (QLES- Q), Pittsburgh Sleep Quality Index (PSQI), Clinical Global Impression Severity Scale (CGI-S), Mini- International Neuropsychiatric Interview (MINI). Weight, blood pressure, sexual side effects were recorded. The Wilcoxon signed rank test analyzed changes in scores. Multiple imputation accounted for missing data. Results: By week 12, depression remitted at 137.5 mg of Quetiapine XR while sleep restored at 114.3 mg. By week 14, quality of life was restored and 86.7% of women were asymptomatic. No significant changes occurred in weight or sexual functioning. Side effects were transient. Conclusion: The preliminary findings from this open-label trial of Quetiapine XR appear promising for mitigating depression and anxiety symptoms and restoring quality of life in postpartum, non-lactating women with Bipolar II Depressive Episode. This is currently the only study to prospectively investigate the medication’s efficacy in a postpartum population. Limitations of this study include its small sample size, open-label design, and lack of a control group.

Background: comorbidity with cardiovascular disorders and metabolic syndrome influences QTc elongation in psychiatric sufferers, rather than antipsychotic treatment. Female gender and advanced age predict QTc elongation in psychiatric patients, while some studies questioned the impact of antipsychotic treatment. Objective: we hypothesized that female gender, advanced age, metabolic syndrome, smoking, somatic and cardiovascular comorbidities would predict QTc elongation in a sample of 84 persons with severe mental disorders consecutively admitted in the psychiatric ward of Portogruaro Hospital from January to June 2012. Method: all participants to this naturalistic, cross-sectional study were treated with antipsychotics only, antipsychotics plus antidepressants/mood stabilizers or antidepressants/mood stabilizers. The cut-off for prolonged QTc interval was set at 420 ms. Results: statistically significant differences in weight, HDL cholesterol and BMI were found between patients taking antipsychotics only, antipsychotics plus mood stabilizers/antidepressants and mood stabilizers/antidepressants only. Pearson’s positive correlations were found among QTc, history of cardiovascular diseases and mean drug dosage, while inverted correlations appeared among drug dose, total cholesterol, and HDL cholesterol. HDL cholesterol was negatively associated with weight. Correlations among total cholesterol, weight and BMI were negative as well. Linear regression evidenced three predictors of QTc elongation: age, mean antipsychotics dosage and non-cardiovascular somatic comorbidities. In participants older than 50, only drug dosage and weight predicted QTc increment. Conclusion: differently than previous researches, female gender, smoking and cardiovascular comorbidities did not predict QTc elongation, despite a higher proportion of female participants. Further studies will clarify the influence of metabolic syndrome in causing severe electrocardiographic alterations in psychiatric sufferers.

Background: Negative symptoms are categorized by some of the scholars into ‘primary vs secondary ‘, ‘enduring vs transitory ‘and ‘treatment-resistant vs treatmentresponsive’ groups. But it seems that such kind of grouping may not be practically supportable. Objective: Exploring the genuineness of the abovementioned grouping and reports regarding resistance of negative symptoms against current treatments. Method: After a primary survey regarding the frequency of negative symptoms amongst two hundreds and seventy schizophrenic patients, by means of Scale for Assessment of Negative Symptoms (SANS), in three random, double-blind, clinical trials (RCTs), and based on definite inclusion and exclusion criteria, the effectiveness of different adjunctive drugs respecting improvement of negative symptoms had been assessed. Results: the frequency of affecting blunting, alogia, avolition-apathy, anhedonia-asociality and attention deficit was %96.28, %94.80, %99.62, %98.88 and %99.25, respectively. Citalopram, alprazolam, and clomipramine in the first tryout, nortriptyline in the second study, and maprotiline in the third trial were significantly more efficacious then placebo. In 31.2%, 28%, 26.4%, 24%and 22.4% of the patients there was about 20% reduction in the severity of attention deficit, alogia, affective blunting, anhedonia- asociality and avolition-apathy, respectively. Conclusion: Conventional classification of negative symptoms into above-mentioned groups may not be practically supportable. Also maybe it is better to consider them solely in the Criterion B of diagnostic criteria, which considers the level of functioning.

Introduction: Some studies have shown that more than 40% of patients with first episode psychosis (FEP) are non - adherent and treatment with long - acting antipsychotics (LAIs) may increase their compliance. However, studies on efficacy of LAIs versus oral antipsychotics for preventing relapse among schizophrenia patients have produced conflicting results. Objectives: The aim of the present study is to assess in naturalistic settings if patients with FEP treated with LAIs have a decreased incidence of readmission compared with patients in treatment with oral antipsychotics over 6 months follow - up. Methods: 188 FEP patients had been consecutively admitted to Hospital del Mar since January 2008 to September 2014. Psychometric assessment included: sociodemographic data, duration of untreated psychosis (DUP), diagnosis, substance use and clinical data at baseline. At 6 - months follow - up, antipsychotic treatment and number of admissions and emergencies over 6 months were also recorded. We investigated whether group treatments differ in readmission rates, attendance rates at emergencies services emergencies. Results: We found a significant decreased incidence of readmission (p=0,000) and a lower number of emergencies (p=0,017) in the group of FEP patients treated with LAIs versus the group treated with oral antipsychotics. Conclusion: In this naturalistic study, treatment with LAIs is associated with a reduced readmission rate and a lower number of emergencies in patients with FEP. These findings are in agreement with the results of other studies showing a significant reduced relapse rate and lowest risk of re - hospitalization in FEP patients treated with LAIs.

Background: A number of studies in rodents suggest that antipsychotic drug treatment can either alter the levels or functionality of the N-methyl-D-aspartate receptor (NMDAR). This raises the possibility that some of the therapeutic actions or side-effects of antipsychotic drugs could be mediated through the NMDAR. Objective: To determine if treatments with combinations of psychotropic drugs change the levels of the NMDAR in rat Central Nervous System (CNS). Methods: In situ radioligand binding and autoradiography were used to quantify [3H]MK-801 binding to NMDAR in frozen CNS sections from rats treated with vehicle, haloperidol (0.1 mg/kg/day), olanzapine (1.0 mg/kg/ day), lithium (25.5 mg/kg/day) or, at the same doses, haloperidol and lithium or olanzapine and lithium for 28 days. Results: There was a significant variation of [3H]MK-801 binding with treatment in the rat striatum due to higher levels of radioligand in rats treated with haloperidol compared to those treated with olanzapine and lithium (p < 0.01; Cohen’s d = 1.47). Levels of radioligand binding did not vary with drug treatment in the cortex. Conclusion: These data argue for some effect of polypharmacy on NMDAR levels, possibly localized to the striatum. Further studies of mood stabilisers with known effects on NMDAR functionality, such as valproate and lamotrigine, with and without antipsychotic drugs could be worthwhile as they may show a greater effect on NMDAR density in the CNS.