Rajnish Mago

Cardiovascular adverse effects of newer antidepressants

Newer antidepressants that are more selective in their neurotransmitter effects include the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others (agomelatine, bupropion, mirtazapine, reboxetine, vilazodone, vortioxetine). This article systematically reviews data from a variety of sources regarding the potential adverse effects of these medications on various cardiovascular parameters. Potential biochemical mechanisms by which these antidepressants may adversely affect the cardiovascular system are also discussed. Antidepressants that are associated with higher cardiovascular risk (SNRIs, reboxetine), lower risk (SSRIs), and without current evidence of cardiovascular risk (agomelatine, mirtazapine, vilazodone, vortioxetine) are identified. The FDA’s recommendations regarding citalopram are organized and summarized, and situations with higher risk of cardiovascular adverse effects are identified.

Levomilnacipran: a newly approved drug for treatment of major depressive disorder

Levomilnacipran is a novel serotonin and norepinephrine reuptake inhibitor (SNRI) for the treatment of major depressive disorder. This paper reviews up-to-date data on the pharmacology, short- and long-term efficacy, safety and tolerability of levomilnacipran. The drug differs from previously available SNRIs in having twice the potency for norepinephrine versus serotonin reuptake inhibition. In four of the six short-term clinical trials, levomilnacipran was statistically significantly more efficacious than placebo. The only available relapse prevention study did not show reduction in time to relapse, perhaps because relapse rates were low. The commonest adverse events occurring twice as often as on placebo were nausea, hyperhidrosis, constipation, tachycardia, vomiting, erectile dysfunction, palpitations, and ejaculation disorder. In a few patients, hypertension or orthostatic hypotension may occur. Levomilnacipran has been shown to be effective in the short-term treatment of major depressive disorder and may represent an incremental advance. However, further research about its efficacy in subgroups of patients and comparing it to other antidepressants is needed.

Proposed strategies for successful clinical management with aripiprazole

Background: Aripiprazole is an effective medication for treating patients with schizophrenia and bipolar disorder , and as an adjunct in patients with major depressive disorder and an inadequate response to antidepressant treatment, that is generally safe and well tolerated. Despite its potential clinical benefits, the management of aripiprazole-treated patients can be challenging due to the lack of a simple dosing strategy and guidelines for preventing and managing potential adverse effects. Objective: Two initiation/dosing strategies with aripiprazole are presented that are based on the overall symptom profile rather than specific clinical diagnosis: a rapid titration/high-dose strategy and a slow titration/low-dose strategy. Methods: The dosing strategy recommendations are based on clinical experience and a PubMed database search conducted with no date restrictions for English-language literature. Keywords included aripiprazole, dose switching or strategy, schizophrenia or bipolar disorder and adverse effects. Conclusions: Two strategies have been designed to help clinicians tailor aripiprazole therapy to the specific needs of individual patients and manage common adverse effects that may be encountered during therapy.

Role of adverse effects in medication nonadherence in bipolar disorder.

AbstractNonadherence to medications is common and associated with poor or limited clinical outcomes in the treatment of bipolar disorder. A review of the literature discloses that adverse effects are one of the commonly reported reasons for nonadherence to mood stabilizers by patients with bipolar disorder. Nevertheless, other than such broad summaries, relatively little attention has been given to the role of adverse effects in relation to nonadherence. This review article is the first to consolidate the available data on this topic. Weight gain, perceived cognitive impairment, tremors, and sedation are the adverse effects most likely to lead to nonadherence. Further research is needed to anticipate, identify, manage, and potentially minimize the impact of adverse effects.

Glycopyrrolate for antidepressant-associated excessive sweating.

To the EditorsAntidepressant-associated excessive sweating occurs in 5% to 14% of patients on an antidepressant (www.pdr.net) and with almost all available antidepressants. It can cause significant distress, functional impairment, and nonadherence to the antidepressant.1 This adverse effect may cont

Understanding the emotions of patients with inadequate response to antidepressant treatments: results of an international online survey in patients with major depressive disorder

BackgroundEvidence suggests that nearly half of patients with major depressive disorder (MDD) do not achieve an adequate response to antidepressant treatments (ADTs), which impacts patients’ functioning, quality of life (QoL), and well-being. This patient survey aimed to better understand patient perspectives on the emotional impact of experiencing an inadequate response to ADTs.MethodsAn online survey was conducted in 6 countries with respondents diagnosed with MDD and experiencing an inadequate response to ADTs. The survey was designed to explore how patients felt about their medications and health care provider (HCP). Those indicating they were ‘frustrated’ with their medications and/or HCP were asked to provide reasons for their frustration and its impact on their relationship with their HCP and decisions about their treatment.ResultsOverall, 2096 respondents with MDD and inadequate response to ADT completed the survey. The most frequent emotion reported by patients regarding their medication was frustration (29.8% of respondents) followed by hopeless (27.4%) and apprehensive/anxious/scared (27.4%). Regarding their HCP, patients reported feeling understood (31.6%) and trusting/confident (28.8%) most often; however, 19.2% reported feelings of frustration. Main reasons for frustration with medication were poor symptom control/lack of efficacy (59.3%) and tolerability issues (19.7%), and the main reasons for frustration with their HCP were not feeling heard (22.4%), ineffective treatment (13.5%) and feeling rushed/lack of quality visit (12.5%). The longer the current episode duration and the greater the disruption to daily living, the more likely the respondents experienced feelings of frustration with medication. Feelings of frustration lead to adherence issues, with 33.3 and 27.3% of respondents indicating their frustration with their medication and HCP, respectively, made them want to quit their medication. Approximately one in six patients frustrated with either their medication and/or HCP indicated their frustration had resulted in them not taking their medication regularly. Frustration with their HCP also impacted patient’s confidence in HCPs abilities (34.7%), sharing less information with their HCP (28.9%) as well as missing appointments (17.4%) and medications (14.5%).ConclusionsFeelings of frustration are frequent in patients with inadequate response to ADT and this frustration may impact treatment adherence and the patient-HCP relationship.

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy:

Background: This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy. Methods: Eligible adults (18–65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling. Results: For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were −1.4 (−3.9, 1.2), 0.1 (−2.5, 2.7), −0.7 (−3.4, 2.0), and −0.9 (−3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were −0.7±9.90 and −0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies. Conclusions: Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures.

Identifying potential adverse effects by patients' ratings: a proof-of-concept study of a novel approach.

OBJECTIVE Methods to evaluate adverse effects of medications are significantly underdeveloped compared to those for efficacy. In this pilot proof-of-concept study, we preliminarily compared a novel approach-the Symptom Assessment Tool (SAT)-to a systematic and detailed assessment by a physician for identifying symptoms that were potentially adverse effects (sensitivity) and excluding symptoms that were unlikely to be adverse effects (specificity). METHODS A symptom inventory and rating of symptom severity were completed before starting a psychotropic medication (or increasing its dose), and again 2 weeks later. Each symptom was systematically assessed by the patient-rated SAT and by a physician and was classified as either a potential or unlikely adverse effect. The primary analysis compared the classification of symptoms by the SAT to that by the physician. Potential adverse effects were also subcategorized as possible or probable adverse effects. RESULTS A sample of 193 symptoms from 15 adults was evaluated, only 37.3% of which were considered potential adverse effects by the physician. Sensitivity of the SAT compared to physicians assessment was 90.3% for potential adverse effects and 97.5% for the subgroup of probable adverse effects. The SAT correctly identified 63.6% of the symptoms as unlikely adverse effects (specificity), and its negative predictive value was 91.7%. CONCLUSIONS The SAT, appropriate for its intended use as a screening tool, had high sensitivity and moderate specificity and could present physicians with a limited number of potential adverse effects for further assessment and intervention. Further evaluation and refinement of this approach is warranted.

Healthcare professionals’ perceptions on the emotional impact of having an inadequate response to antidepressant medications: survey and prospective patient audit

BackgroundDespite the availability of effective antidepressants, about half of patients with major depressive disorder (MDD) display an inadequate response to their initial treatment. A large patient survey recently reported that 29.8% of MDD patients experiencing an inadequate treatment response felt frustrated about their medication and 19.2% were frustrated with their healthcare provider. This survey and chart audit evaluated healthcare professionals’ (HCP) views on the emotional impact of having an inadequate response to antidepressant medication.MethodsHCPs who frequently treat patients with MDD completed a survey and chart audit of their MDD patients currently experiencing an inadequate response to antidepressant treatment.Results287 HCPs completed 1336 chart audits. HCPs reported that 38% of their patients were trusting/accepting of their MDD medications and 41% of their patients trusted/felt confident with their healthcare provision. Conversely, HCPs reported that 11% of their patients were frustrated with their medication and 5% with their healthcare benefits. HCPs cited impact on daily life (53%) and treatment issues (lack of efficacy and side effects; 50%) as the main drivers for their patients’ feelings of frustration. When HCPs recognized patients’ feelings of frustration, the top concerns of the HCPs were worsening of symptoms (43%) and non-compliance (41%).ConclusionsThis survey and chart audit highlights the emotional burden associated with inadequate responses to MDD treatment in addition to persistent symptoms. Differences between the views of the HCPs and patients are highlighted and suggest that HCPs may underestimate the full impact that having to try numerous medications has on their patients.

The Neglected Side of Suffering

Adverse effects of psychotropic medications have substantial impact on patient suffering, on nonadherence to treatment, and ultimately, on the success of treatment. Yet, somewhat surprisingly, adverse effects have been considerably neglected in research and in publications. Thus, this issue of the Psychiatric Clinics of North America should be a welcome addition to the literature. The first article in this issue is a “call to action” that aims to draw attention to the importance of adverse effects. It highlights some of the many problems related to how adverse effects are identified and assessed, how patients are educated about adverse effects, and the relative paucity of research about their prevention and management. A series of recommendations aimed at beginning to remedy these problems is also made. This is followed by an article by Goldberg and Ernst that provides an insightful discussion of the complexity of how clinical and pharmacogenetic factors contribute to the incidence and severity of adverse effects of psychotropic medications. It also provides valuable clinical guidance on several issues, like how to counsel patients about adverse effects, how to differentiate adverse effects from symptoms of the illness, and so on. The articles that follow are up-to-date reviews of the literature, all by leading experts, on some of the most important topics related to adverse effects of mental health treatments. Though second-generation antipsychotics have reduced the incidence of extrapyramidal and related adverse effects, these continue to be significant problems for some patients. Clinicians, therefore, need to be well-versed in their identification and management. Caroff and Campbell provide us with a pithy, up-to-date review of dystonia, parkinsonism, akathisia, catatonia, neuroleptic malignant syndrome, and tardive dyskinesia that will be helpful to clinicians. Andrade and Sharma succinctly review the state-of-the-art on abnormal bleeding that can be caused by antidepressant medications. They also summarize current