Project description:BackgroundDepression is the most common psychiatric comorbidity among people living with HIV/AIDS (PLWHA). Little is known about the comparative effectiveness between different types of antidepressants used to treat depression in this population. We compared the effectiveness of dual-action and single-action antidepressants in PLWHA for achieving remission from depression.MethodsWe used data from the Centers for AIDS Research Network of Integrated Clinic Systems to identify 1175 new user dual-action or single-action antidepressant treatment episodes occurring from 2005 to 2014 for PLWHA diagnosed with depression. The primary outcome was remission from depression defined as a Patient Health Questionnaire-9 (PHQ-9) score <5. Mean difference in PHQ-9 depressive symptom severity was a secondary outcome. The main approach was an intent-to-treat (ITT) evaluation complemented with a per protocol (PP) sensitivity analysis. Generalized linear models were fitted to estimate treatment effects.ResultsIn ITT analysis, 32% of the episodes ended in remission for both dual-action and single-action antidepressants. The odds ratio (OR) of remission was 1.02 (95%CI=0.63,1.67). In PP analysis, 40% of dual-action episodes ended in remission compared to 32% in single-action episodes. Dual-action episodes had 1.33 times the odds of remission (95%CI=0.55,3.21), however the result was not statistically significant. Non-significant differences were also observed for depressive symptom severity.LimitationsMissing data was common but was addressed with inverse probability weights.ConclusionsResults suggest that single-action and dual-action antidepressants are equally effective in PLWHA. Remission was uncommon highlighting the need to identify health service delivery strategies that aid HIV providers in achieving full remission of their patients' depression.
Project description:OBJECTIVE:Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. METHODS:An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. RESULTS:Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. CONCLUSION:During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.
Project description:Depression is one of the major psychiatric comorbidities associated with epilepsy. The inconclusive results of antidepressants (ADs) regarding their safety in regard to convulsions have strongly contributed towards under treatment of depression in people with epilepsy (PWE). Thus, the present study was envisaged to assess the relative safety of four different classes of ADs regarding their convulsive potential in kindled/epileptic animals.Kindling (an animal model to induce chronic epilepsy) was induced in male Swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h for 42 days. The epileptic animals were treated with saline; imipramine (20 mg/kg/day i.p.); fluoxetine (20 mg/kg/day i.p.); venlafaxine (10 mg/kg/day i.p.) and mirtazapine (10 mg/kg/day i.p.) for 15 days. Except naive, animals were challenged with pentylenetetrazole subconvulsive dose (35 mg/kg, i.p.) on every 5th day to determine convulsion severity score, latency to first myoclonic jerk, latency to first tonic-clonic convulsions and numbers of tonic-clonic convulsions. Depression was also evaluated every 5th day employing tail suspension test 2 h after pentylenetetrazole subconvulsive dose.All ADs have been reported significant antidepressant potential however regarding their safety in regard to convulsions in epileptic animals, variable results are obtained. Chronic administration of venlafaxine and mirtazapine were found to have significant anticonvulsant effect in epileptic animals. The behavioral data was further corroborated by neurochemical findings.The treatment with venlafaxine and mirtazapine can be considered safe for treatment of depression in epilepsy and may enhance anticonvulsant potential of antiepileptic drugs as an adjuvant therapy. However, pharmacokinetic studies are warranted before translating these findings in PWE.
Project description:Background: The clinical impact of the functional CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression is not well studied. Here, we evaluate the utility of pharmacogenetic (PGx) testing in psychiatry by investigating the association between the phenotype status of the cytochrome P450 (CYP) 2C19/2D6 enzymes and the one-year risks of clinical outcomes in patients with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine. Methods: This study is a population-based cohort study of 17,297 individuals who were born between 1981 and 2005 with a depression diagnosis between 1996 and 2012. Using array-based single-nucleotide-polymorphism genotype data, the individuals were categorized according to their metabolizing status of CYP2C19/CYP2D6 as normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM). The outcomes were treatment switching or discontinuation, psychiatric emergency department contacts, and suicide attempt/self-harm. By using Poisson regression analyses, we have estimated the incidence rate ratios (IRR) with 95% confidence intervals (95% CI) that were adjusted for covariates and potential confounders, by age groups (<18 (children and adolescents), 19−25 (young adults), and 26+ years (adults)), comparing the outcomes in individuals with NM status (reference) versus the mutant metabolizer status. For statistically significant outcomes, we have calculated the number needed to treat (NNT) and the number needed to genotype (NNG) in order to prevent one outcome. Results: The children and adolescents who were using (es)citalopram with CYP2C19 PM status had increased risks of switching (IRR = 1.64 [95% CI: 1.10−2.43]) and suicide attempt/self-harm (IRR = 2.67 [95% CI; 1.57−4.52]). The young adults with CYP2C19 PM status who were using sertraline had an increased risk of switching (IRR = 2.06 [95% CI; 1.03−4.11]). The young adults with CYP2D6 PM status who were using fluoxetine had an increased risk of emergency department contacts (IRR = 3.28 [95% CI; 1.11−9.63]). No significant associations were detected in the adults. The NNG for preventing one suicide attempt/suicide in the children who were using (es)citalopram was 463, and the NNT was 11. Conclusion: The CYP2C19 and CYP2D6 PM phenotype statuses were associated with outcomes in children, adolescents, and young adults with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine, therefore indicating the utility of PGx testing, particularly in younger people, for PGx-guided antidepressant treatment.
Project description:Genetic factors are believed to play a major role in the variation of treatment response and the incidence of adverse effects to medication. The aim of pharmacogenetics is to elucidate this variability according to hereditary differences. Considering current hypotheses for the mechanisms of action of antidepressants, most investigations to date have concentrated on mutations in genes coding either for the pathways in the serotonergic and noradrenergic systems or for drug-metabolizing enzymes. Recent studies shifted the emphasis on the main mechanism of drug action from changes in neurotransmitter concentration or receptor function toward long-lasting adaptive processes within the neurons. Although the results are controversial, many studies support the hypothesis that psychopharmacogenetics will help predict an individual's drug response, while minimizing the side effects. The inclusion of functional genomics, which investigates the complex gene and/or protein expression in response to a given drug, may lead to the development of novel and safer drugs.
Project description:OBJECTIVE:Depression is highly prevalent among people living with HIV/AIDS (PLWHA) and has deleterious effects on HIV clinical outcomes. We examined changes in depression symptoms, viral suppression, and CD4 T cells/?l among PLWHA diagnosed with depression who initiated antidepressant treatment during routine care, and compared the effectiveness of dual-action and single-action antidepressants for improving those outcomes. DESIGN:Comparative effectiveness study of new user dual-action or single-action antidepressant treatment episodes occurring from 2004 to 2014 obtained from the Center for AIDS Research Network of Integrated Clinical Systems. METHODS:We identified new user treatment episodes with no antidepressant use in the preceding 90 days. We completed intent-to-treat and per protocol evaluations for the main analysis. Primary outcomes, were viral suppression (HIV viral load <200 copies/ml) and CD4 T cells/?l. In a secondary analysis, we used the Patient Health Questionnaire-9 (PHQ-9) to evaluate changes in depression symptoms and remission (PHQ <5). Generalized estimating equations with inverse probability of treatment weights were fitted to estimate treatment effects. RESULTS:In weighted intent-to-treat analyses, the probability of viral suppression increased 16% after initiating antidepressants [95% confidence interval?=?(1.12, 1.20)]. We observed an increase of 39 CD4T cells/?l after initiating antidepressants (30, 48). Both the frequency of remission from depression and PHQ-9 scores improved after antidepressant initiation. Comparative effectiveness estimates were null in all models. CONCLUSION:Initiating antidepressant treatment was associated with improvements in depression, viral suppression, and CD4 T cells/?l, highlighting the health benefits of treating depression in PLWHA. Dual and single-action antidepressants had comparable effectiveness.
Project description:The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.