The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

A 12-Month Open-Label Extension Study of the Safety and Tolerability of Lisdexamfetamine Dimesylate for Major Depressive Disorder in Adults.

PURPOSE/BACKGROUND: Psychostimulant augmentation is considered a potential treatment strategy for individuals with major depressive disorder who do not adequately respond to antidepressant monotherapy. The primary objective of this 12-month open-label extension study was to evaluate the safety and tolerability of lisdexamfetamine dimesylate (LDX) as augmentation therapy to an antidepressant in adults with major depressive disorder. METHODS/PROCEDURES: Eligible adults who completed 1 of 3 short-term antecedent LDX augmentation of antidepressant monotherapy studies were treated with dose-optimized LDX (20-70 mg) for up to 52 weeks while continuing on the index antidepressant (escitalopram, sertraline, venlafaxine extended-release, or duloxetine) assigned during the antecedent short-term studies. Safety and tolerability assessments included the occurrence of treatment-emergent adverse events and vital sign changes. FINDINGS/RESULTS: All 3 antecedent studies failed to meet the prespecified primary efficacy endpoint, so this open-label study was terminated early. Headache (15.5% [241/1559]), dry mouth (13.6% [212/1559]), insomnia (13.1% [204/1559]), and decreased appetite (12.1% [189/1559]) were the most frequently reported treatment-emergent adverse events. The greatest mean ± SD increases observed for systolic and diastolic blood pressure and for pulse were 2.6 ± 10.85 and 1.7 ± 7.94 mm Hg and 6.9 ± 10.27 bpm, respectively. Monitoring determined that less than 1% of participants experienced potentially clinically important changes in systolic blood pressure (10 [0.6%]), diastolic blood pressure (8 [0.5%]), or pulse (6 [0.4%]). IMPLICATIONS/CONCLUSIONS: The overall safety and tolerability of long-term LDX augmentation of antidepressant monotherapy was consistent with the profiles of the short-term antecedent studies, with no evidence of new safety signals.

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

BACKGROUND: Evidence 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. METHODS: An 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. RESULTS: Overall, 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%). CONCLUSIONS: Feelings of frustration are frequent in patients with inadequate response to ADT and this frustration may impact treatment adherence and the patient-HCP relationship.

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

BACKGROUND: Despite 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. METHODS: HCPs who frequently treat patients with MDD completed a survey and chart audit of their MDD patients currently experiencing an inadequate response to antidepressant treatment. RESULTS: 287 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%). CONCLUSIONS: This 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.

Antidepressant-induced excessive sweating: clinical features and treatment with terazosin.

BACKGROUND: Antidepressant-induced excessive sweating (ADIES) occurs in 5% to 14% of patients taking antidepressants, usually persists throughout treatment, and causes subjective distress and functional impairment. We conducted the first clinical trial of any treatment for ADIES. METHODS: Clinical features of ADIES were assessed using a semi-structured form. Twenty-three patients with moderate or greater ADIES were assessed for a 2-week baseline period , followed by 6 weeks of open-label treatment with flexible dose terazosin, 1 to 6 mg/d. Improvement in ADIES was measured by the Clinical Global Impressions (CGI) scale and other measures. RESULTS: ADIES commonly was prominent in the scalp (62%), face (95%), neck (48%), and chest (57%); usually occurred either episodically or with episodic bursts (82%); and was persistent (median 63 months). Twenty-two of the 23 patients responded to terazosin (CGI-I scores 1 or 2), with CGI-Severity improving from median of 5 to median of 2 (P < .0001). Patient-rated daytime and nighttime severity of ADIES and proportion of time in ADIES also improved significantly. The most common adverse effects of terazosin therapy were dizziness/lightheadedness (n = 9) and dry mouth (n = 4). No patient dropped out because of adverse effects. Sitting and standing systolic blood pressure decreased by median values of 3 (P = .044) and 5 (P = .063) mm Hg, respectively. CONCLUSIONS: Terazosin may be an effective treatment for ADIES. Although dizziness/lightheadedness may occur in some patients, the treatment generally was well tolerated.

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 physician's 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.

Antidepressants and the risk of abnormal bleeding during spinal surgery: a case­control study.

INTRODUCTION: Antidepressant medications are widely used by patients requiring spinal surgery. In spite of a generally favorable safety profile of newer antidepressants, several prior studies have suggested an association between use of serotonergic antidepressants and excessive bleeding. This study was designed to determine if there was any association between antidepressant use and the risk of excessive intraoperative blood loss during spinal surgery, and whether particular types of antidepressants were specifically associated with this increased blood loss. MATERIALS AND METHODS: A retrospective case control study was conducted utilizing a population of 1,539 patients who underwent elective spinal fusion by a single surgeon at one medical center. Of the included patients, 213 used antidepressant medication and 1,326 patients did not use any type of antidepressant medication. Of patients taking antidepressants, 37 patients were excluded based on exclusion criteria, leaving 176 patients suitable for inclusion. The study group (176 patients) consisted of all patients who used an antidepressant medication for at least a 2-week period prior to spinal surgery. A control group of 352 patients were assembled from a random sample of 1,326 patients operated on by the same surgeon during the same time period in a two-to-one ratio with study group. Intraoperative blood loss was the primary outcome variable and was compared between the study and control group and between individuals in the study group taking serotonergic (SSRIs or SNRIs) or non-serotonergic antidepressants. Other variables, including length of hospital stay and surgical category, were also collected and analyzed separately. RESULTS: Overall, the mean blood loss (BL) for the antidepressant group was 298 cc, 23% more than the 241 cc lost by the procedure- and level-matched control group (p = 0.01). Patients taking serotonergic antidepressants also had statistically significant higher blood loss than the matched control group as a whole (334 vs. 241 cc, p = 0.015). This difference was also found in subgroups of patients who underwent anterior cervical discectomy and fusion, lumbar instrumented fusion, or anterior/posterior lumbar fusion. Blood loss was also higher in the subgroup of patients taking bupropion (708 cc, p = 0.023) compared with the control group. The mean length of hospital stay was 33.3% greater in patients on antidepressant medications compared to patients not taking an antidepressant (mean of 4 vs. 3 days, respectively, p = 0.0001). Antidepressant medications may be associated with increased intraoperative blood loss during spinal surgery, although the magnitude of the increased blood loss may not be clinically significant in all cases. The increase was greatest in patients undergoing anterior/posterior lumbar fusions, in whom the intraoperative blood loss was 2.5 times greater than that in the matched control group. CONCLUSION: Clinicians treating patients who are planning to undergo elective spinal surgery and are on an antidepressant medication should be aware of this potential effect and should consider tapering off the serotonergic antidepressant prior to surgery.

Medically serious adverse effects of newer antidepressants.

Although safer than tricyclic antidepressants and monoamine oxidase inhibitors, the newer antidepressants may be associated with certain medically serious adverse effects, of which cardiovascular adverse effects, seizures, abnormal bleeding, hyponatremia, and agranulocytosis are discussed in this review. Data regarding the incidence and risk factors are summarized, and strategies for reducing the risk of these adverse effects and managing them are suggested. Identification of risk factors, appropriate antidepressant choice, and, when possible, careful monitoring may substantially reduce the incidence of these adverse effects and the morbidity associated with them.

[Side effects of psychotropic medication: Suggestions for clinical practice]. / Nebenwirkungen von Psychopharmaka: Tipps für die Praxis.

Psychotropics are highly effective medications that, however, have adverse drug reactions attached to them. They are indispensable for many patients. How to cope with side effects - watchful waiting, dose reduction, change of medication, addition of an "antidote" and behavioural modifications - depends on their nature, severity and finally the patients wish. This review is meant to aid clinician's and patient's decisions in case of the occurrence of compromising, frequent adverse drug reactions.