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Can antidepressant use be associated with emotional blunting in a subset of patients with depression? A scoping review of available literature
Abstract
Introduction:
Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research.
Method:
A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross-sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting.
Results:
A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant-induced emotional blunting included dose reduction or switching to a different antidepressant.
Conclusion:
Emotional blunting was a significant patient-reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills.
... Depresjon behandles med samtaleterapi og/eller antidepressiver, der selektive serotoninreopptakshemmere er førstevalg (5). Kjente begrensninger ved antidepressiver er virkningslatens, lav/moderat effektstyrke og bivirkninger som emosjonell avflating (6,7). Flere psykoterapiformer er effektive (8), men ingen er klart bedre enn medikamentell behandling. ...
... SSRIs function by reducing the reabsorption of serotonin into neurons and increasing intracellular serotonin levels (Etievant et al., 2020). They have downstream impacts on the dopamine system (Di Giovanni et al., 2010) and are associated with a number of side effects, including sexual dysfunction (Rothmore, 2020) and a "blunting" of positive affect (Jawad et al., 2023). SSRIs can take up to 6 weeks to become fully effective (Taylor et al., 2006) because they function by changing serotonin receptor expression (see Artigas, 2013), something which does not happen immediately. ...
... It could be hypothesized that common drugs for depression reduce symptoms like sadness or anxiety, but at the cost of emotional blunting. Recent research debates whether this blunting is a residual symptom of depression or an adverse effect of the medication (Christensen et al., 2022;Jawad et al., 2023;Peters et al., 2022). However, there is also research pointing out the importance of helpful social and physical environmental stimulation for positive drug effects also in classical drugs for depression (Rief et al., 2016). ...
Background
Recent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin’s neurobiological and psychological antidepressant mechanisms is lacking.
Aims
Systematically review potential antidepressant neurobiological and psychological mechanisms of psilocybin.
Methods
Search terms were generated based on existing evidence of psilocybin’s effects related to antidepressant mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 15 studies were systematically reviewed, exploring various therapeutic change principles such as brain dynamics, emotion regulation, cognition, self-referential processing, connectedness, and interpersonal functioning.
Results
Within a supportive setting, psilocybin promoted openness, cognitive and neural flexibility, and greater ability and acceptance of emotional experiences. A renewed sense of connectedness to the self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, characterized by reduced global and within default mode network connectivity, alongside increased between-network connectivity.
Conclusions
Together, these changes may create a fertile yet vulnerable window for change, emphasizing the importance of a supportive set, setting, and therapeutic guidance. The results suggest that psilocybin, within a supportive context, may induce antidepressant effects by leveraging the interplay between neurobiological mechanisms and common psychotherapeutic factors. This complements the view of purely pharmacological effects, supporting a multileveled approach that reflects various relevant dimensions of therapeutic change, including neurobiological, psychological, and environmental factors.
Background
Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment.
Methods
The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments.
Results
In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group.
Conclusions
This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions.
Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.
Abstract Background Emotional blunting is common in patients with depression. An online survey was undertaken to assess the experience of emotional blunting, and its impact on functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the level of concordance between patient and HCP perspectives. Methods This was a cross-sectional, observational study. Patient respondents were adults with a diagnosis of depression, who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. HCPs completed the survey for the last two eligible patients they had seen, one in each phase of depression. Assessments included the Oxford Depression Questionnaire (ODQ) ‘antidepressant as cause’ domain and the Functioning Assessment Short Test (FAST). Results Mean ODQ ‘antidepressant as cause’ domain scores were significantly higher in the patient-reported cohort (n = 752) than in the HCP-assessed cohort (n = 766) in both the acute (18.0 vs 12.5, respectively; p
Emotional blunting is frequently reported by patients with major depressive disorder (MDD) and has been identified as one of the most prominent side effects of antidepressants leading to medication discontinuation. However, antidepressant-induced emotional blunting remains largely unexplored—there lacks a clinical definition of this condition, and no agreeing conclusion has been reached regarding its etiology. Current research suggests that the onset of diminished emotional response may be related to antidepressant dose, with higher doses being more likely to induce emotional blunting. Consequently, most clinicians either reduce the dose or switch to another drug when treating this symptom. Overall, more comprehensive clinical assessments or interviews specifically designed to evaluate antidepressant-induced emotional blunting in MDD patients are in need to elucidate the neuropsychological mechanisms behind this increasingly prevalent symptom.
Determining the optimal antipsychotic target dose in acute phase treatment is of high clinical relevance. The effect of antipsychotics on negative symptoms should be taken into account because patients will often continue on the treatment received in the acute phase. Therefore, we conducted a formal dose-response meta-analysis of negative symptoms and positive symptoms based on a systematic review of fixed-dose randomized controlled trials (RCTs) that examined the effectiveness of antipsychotics for the acute exacerbation of schizophrenia. Forty RCTs included a total of 15,689 patients. The 95% effective doses per day for the 13 antipsychotics included and 3 long acting were mostly different for negative and positive symptoms: amisulpride (481 mg, 690.6 mg); aripiprazole (11.9 mg, 11 mg); asenapine (7.61 mg, 5.66 mg); brexpiprazole (2.1 mg, 4 mg); cariprazine (4 mg, 6.51 mg); haloperidol (6.34 mg, 7.36 mg); lurasidone (58.2 mg, 86.3 mg); olanzapine (15.5 mg, 9.52 mg); olanzapine long-acting injection (15.7 mg, 13.5 mg); paliperidone (7.2 mg, 7 mg); paliperidone long-acting injection (7.5 mg, 5.9 mg); quetiapine instant-release (264.2 mg, 316.5 mg); quetiapine extended-release (774 mg, 707.2 mg); risperidone (7.5 mg, 7.7 mg); risperidone long-acting injection (5.13 mg, 6.7 mg); sertindole (13.5 mg, 16.3 mg); and ziprasidone (71.6 mg, 152.6 mg). The shape of the dose-response curves varied across different drugs with most drugs showing a plateau at higher doses. Most dose-response curves suggested that the near-maximum effective doses could be in the lower-to-medium range of the licensed dose. Additional RCTs are necessary to establish the optimal dose.
The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the “hippie” counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.
Introduction
Inadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) for major depressive disorder (MDD). We investigated the effectiveness of vortioxetine on emotional blunting in patients with partial response to treatment with SSRIs/SNRIs.
Methods
Patients with MDD who experienced a partial response to SSRI/SNRI monotherapy at adequate dose for ≥6 weeks were switched to 8 weeks of vortioxetine treatment 10-20 mg/day (Study NCT03835715). Key inclusion criteria were Montgomery-Åsberg Depression Rating Scale (MADRS) total score >21 and <29, current major depressive episode <12 months, Oxford Depression Questionnaire (ODQ) total score ≥50, and confirmation of emotional blunting by standardized screening question. Emotional blunting was assessed by ODQ and depressive symptoms by MADRS. Other outcomes assessed included motivation and energy (Motivation and Energy Inventory [MEI]), cognitive performance (Digit Symbol Substitution Test [DSST]), and overall functioning (Sheehan Disability Scale [SDS]).
Results
At week 8, patients (N=143) had improved by -29.8 points (p<0.0001) in ODQ total score; 50% reported no emotional blunting in response to standardized screening question. Significant improvements were observed on the DSST, MEI, and SDS at all time points assessed, and 47% of patients were in remission (MADRS total score ≤10) at week 8. The most common treatment-emergent adverse events included nausea, headache, dizziness, vomiting, and diarrhea.
Limitations
No prospective phase before medication switch.
Conclusion
Vortioxetine 10-20 mg effectively improved emotional blunting, overall functioning, motivation and energy, cognitive performance, and depressive symptoms in patients with MDD with partial response to SSRI/SNRI therapy and emotional blunting.
Purpose/Background
Emotional adverse effects due to antidepressant use may cause difficulties for the clinician in the treatment of depression. In this prospective study, the emotional adverse effects of antidepressants were evaluated in various aspects.
Methods/Procedures
Ninety eight patients diagnosed with major depressive disorder were included in the study. At 2nd, 4th, 8th, 12th, and 16th weeks, patients were assessed with Montgomery-Asberg Depression Rating Scale (MADRS), and the antidepressant dose was increased in patients with less than a 50% reduction at each visit compared with the initial MADRS score. The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQESA) was used at the 8th-week and 16th-week visits.
Findings/Results
A significant difference is found in the OQESA score at the 8th-week visit compared with the 16th-week assessment (P < 0.001, t = 5.73). There were significant correlations between MADRS scores and OQESA scores both at the 8th (r = 0.346, P = 0.05) and the 16th (r = 0.490, P < 0.001) weeks. In regression analyses, at eighth-week assessment, MADRS score (B = 1.487, P = 0.002) and selective serotonin reuptake inhibitor use (B = 14.014, P = 0.023) had a significantly predicted OQESA score.
Implications/Conclusions
In this study, it is found that, as the rate of remitted patients is increased, OQESA scores get decreased, and furthermore, the OQESA score of the remitted group is statistically low when compared with that of the nonremitted group at the 8th- and 16th-week visits. Oxford Questionnaire on the Emotional Side-effects of Antidepressants and MADRS scores are significantly correlated in all assessments. These results suggest that the score obtained from OQESA may be related not only to the emotional adverse effects of antidepressants but also to the residual symptoms of depression.
Recent guidelines regarding pharmacological interventions for major depressive disorder (MDD) recommend first using serotonin (5HT) selective reuptake inhibitors (SSRIs) or 5HT and norepinephrine (NE) reuptake inhibitors (SNRIs). Although SSRIs and SNRIs are effective and well‐tolerated, apathy occurs as an adverse effect in some SSRIs‐treated patients. Because apathy would be associated with the 5HT pathway, if a patient exhibits apathy symptoms under SSRIs treatment, a clinical strategy has been to change the SSRIs to treatment with an SNRIs. Here, I report two cases in which low‐dose venlafaxine, an SNRIs, induced apathy symptoms.
Depression is a leading cause of disability worldwide and improving its treatment is a core research priority for future programmes. A change in the view of psychological and biological processes, from seeing them as separate to complementing one another, has introduced new perspectives on pathological mechanisms of depression and treatment mode of action. This review presents a theoretical model that incorporated this novel approach, the cognitive neuropsychological hypothesis of antidepressant action. This model proposes that antidepressant treatments decrease the negative bias in the processing of emotionally salient information early in the course of antidepressant treatment, which leads to the clinically significant mood improvement later in treatment. The paper discusses the role of negative affective biases in the development of depression and response to antidepressant treatments. It also discusses whether the model can be applied to other antidepressant interventions and its potential translational value, including treatment choice, prediction of response and drug development.
Most efficacy and safety studies about medications adopt a quantitative approach, testing specific hypotheses with restricted samples. This online survey provides additional insights by directly asking people open questions. Thematic analysis was used to explore the responses of 342 antidepressant users to “Is there anything else you would like to tell us about your experience of taking medication”. 59 (17.3%) made exclusively positive comments, 146 (42.7%) purely negative comments and 137 (40.0%) offered a mixture of positive and negative. Positive themes included: daily coping, life-changing/saving and stepping stone. Negative themes included: physical adverse effects, emotional and cognitive blunting, and withdrawal effects. Many participants also commented on relationships with prescribers. Collaboration was particularly valued. Negative sub-themes included failings in relation to information (especially about adverse effects and withdrawal), support, and alternatives. Clinicians have a duty to inform potential antidepressant users about positive and adverse effects, including withdrawal effects.
There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.
Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.
Studies on the subjective effects of antidepressants suggest that they may not only improve depressed mood, but as an adverse effect also cause “emotional blunting.” This phenomenon is poorly understood and little studied. The aim of this study was to examine the association of serotonergic antidepressant use and subjective emotional awareness. Emotional awareness was assessed using the Difficulty Identifying Feelings subscale from the 20-Item Toronto Alexithymia Scale. Fifty-seven individuals on antidepressant medication and 441 controls were compared. The effects of sex, age, education, as well as current depressive symptoms were controlled for. After controlling for selected variables, the antidepressant group scored higher in subjective difficulty identifying feelings, compared to controls. (p = .043, Adjusted means by Group 14.2 vs. 15.5, 95% confidence interval for mean difference between Groups 0.04–2.5). Serotonergic antidepressant use may be associated with difficulty identifying feelings. Future studies with a longitudinal setting are warranted to clarify causality.
Antidepressant drugs are being prescribed at ever increasing rates internationally, despite marginal benefit compared to placebo and a range of adverse effects. Most studies of adverse effects focus on biological phenomena. This article presents the results of an online survey of 1,008 self-selected anti-depressant users in Britain, which asked about five adverse effects in the interpersonal domain. The most commonly reported among participants who took only antidepressants were: Sex Life – 43.7%, Work or Study – 27.0% and Social Life – 23.5%. These rates of interpersonal adverse effects were even higher for the 52% of participants who were also taking one or more other psychiatric drugs. Only about a half (48%) felt they had been given enough information about side effects by the prescriber. Those initially prescribed medication by a psychiatrist were more likely to be on several types of drugs and reported more adverse effects than those whose prescriber was a General Practitioner (GP). Researchers and prescribers are encouraged to pay greater attention to interpersonal adverse effects.
Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I ("Risk Of Bias In Non-randomised Studies-of Interventions"), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.
Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment.
Background
The pharmacological treatment of post-traumatic stress disorder (PTSD) is extremely challenging, as no specific agent has been developed exclusively to treat this disorder. Thus, there are growing concerns among the public, providers and consumers associated with its use as the efficacy of some agents is still in question.
Aims
We applied a dimensional and symptom cluster-based approach to better understand how the heterogeneous phenotypic presentation of PTSD may relate to the initiation of pharmacotherapy for PTSD initial episode.
Method
US veterans who served in the conflicts in Iraq and Afghanistan and received an initial PTSD diagnosis at the US Veterans Health Administration between 2008 and 2011 were included in this study. Veterans were followed for 365 days from initial PTSD diagnosis to identify initiation for antidepressants, anxiolytics/sedatives/hypnotics, antipsychotics and prazosin. Multivariable analyses were used to assess the relationship between the severity of unique PTSD symptom clusters and receiving prescriptions from each medication class, as well as the time from diagnosis to first prescription.
Results
Increased severity of emotional numbing symptoms was independently associated with the prescription of antidepressants, and they were prescribed after a substantially shorter period of time than other medications. Anxiolytics/sedatives/hypnotics prescription was associated with heightened re-experiencing symptoms and sleep difficulties. Antipsychotics were associated with elevated re-experiencing and numbing symptoms and prazosin with reported nightmares.
Conclusions
Prescribing practices for military-related PTSD appear to follow US VA/DoD clinical guidelines. Results of this study suggest that a novel dimensional and symptom cluster-based approach to classifying the phenotypic presentation of military-related PTSD symptoms may help inform prescribing patterns for PTSD.
Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue.
Qualitative synthesis informs important aspects of evidence-based healthcare, particularly within the practical decision-making contexts that health professionals work in. Of the qualitative methodologies available for synthesis, meta-aggregation is most transparently aligned with accepted conventions for the conduct of high-quality systematic reviews. Meta-aggregation is philosophically grounded in pragmatism and transcendental phenomenology. The essential characteristics of a meta-aggregative review are that the reviewer avoids re-interpretation of included studies, but instead accurately and reliably presents the findings of the included studies as intended by the original authors. This study reports on the methodology and methods of meta-aggregation within the structure of an a priori protocol and standardized frameworks for reporting of results by over-viewing the essential components of a systematic review report.
The recent trend for recognizing the need that patients actively participate in the assessment of the outcome of treatment is a welcome development, not only because it adds valuable data, but also because its recognition of the partnership role that the patients should have in research on outcome of mental illness.
The present study aimed at investigating the possible changes of some features of loving relationships
during long-term treatment of depression with both selective serotonin reuptake inhibitors (SSRIs) and
tricyclics(TCAs), by means of aspecifically designed test, the so-called “Sex, Attachment, Love” (SALT)
questionnaire.
The sample was composed by 192 outpatients(123 women and 69 men,mean age+/-SD: 41.2+/-10.2
years), suffering from mild or moderate depression, according to DSM-IV-TR criteria, that were selected
if they were treated with one antidepressant only for at least six months and were involved in a loving
relationship.
The results showed that SSRIs had a significant impact on the feelings of love and attachment
towards the partner especially in men, while women taking TCAs complained of more sexual side effects
than men. These data were supported also by the detection of a significant interaction between drug and
sex on the “Love” and “Sex” domains.
The present findings, while demonstrating a dimorphic effect of antidepressants on some component
of loving relationships, need to be deepened in future studies
Introducción
Se describen los casos de 7 pacientes con incapacidad para llorar tras tratamiento con un inhibidor de la recaptación de serotonina (ISRS), situación que se presenta aun en situaciones estresantes o tristes, que normalmente les habrían iniciado una respuesta de llanto. Los casos se examinan a la luz de lo que se conoce acerca del papel del sistema serotoninérgico en la expresión emocional.
Método
Serie de casos de pacientes que acuden a un servicio de atención secundaria en psiquiatría.
Resultados
Mientras el llanto excesivo sin estrés emocional ya se había descrito en la literatura asociado con una función serotoninérgica reducida, los presentes reportes apuntan casos de la disociación inversa, en los que el estrés emocional y la urgencia de llorar se encontraban presentes, pero con incapacidad para el llanto.
Discusión
Aunque la serie de casos aquí presentada es nueva, concuerdan con la neurociencia del llanto y su relación con la función serotoninérgica, y proveen evidencia preliminar para una disociación doble entre la experiencia emocional subjetiva y la expresión conductual del llanto. Esto ayuda a elucidar la neurociencia de la expresión emocional y apunta la posibilidad de que el fenómeno sea un efecto adverso poco detectado del tratamiento con ISRS.
In the present randomized, controlled, double-blind trial (12 wk treatment plus double-blind extension for 12 wk), 25-50 mg/d agomelatine (n = 164) and 10-20 mg/d escitalopram (n = 160) were compared for short- and long-term efficacy, subjective sleep and tolerability. The effects of these drugs on emotional experiences were also compared in patients having completed the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (agomelatine: n = 25; escitalopram: n = 20). Agomelatine and escitalopram similarly improved depressive symptoms, with clinically relevant score changes over 12 and 24 wk and notable percentage of remitters (week 12: 60.9 and 54.4%; week 24: 69.6 and 63.1% respectively). Over the 12 and 24-wk treatment periods, the 'global satisfaction on sleep' scores increased in both treatment groups and did not differ between groups. Satisfaction with sleep-wake quality was high in both groups; the 'wellness feeling on waking' was more improved with agomelatine than with escitalopram (p = 0.02). In patients with pronounced sleep complaints, quality of sleep and feeling on waking were significantly more improved with agomelatine than with escitalopram (p = 0.016 and p = 0.009, respectively). Emotional blunting was less frequent on agomelatine than on escitalopram. Indeed, 28% of patients on agomelatine vs. 60% on escitalopram felt that their emotions lacked intensity and 16% of patients on agomelatine vs. 53% on escitalopram felt that things that they cared about before illness did not seem important any more (p = 0.024). The tolerability profile of agomelatine was found to be superior to that of escitalopram and the incidence of patients with at least one emergent adverse event leading to treatment discontinuation was lower in the agomelatine group than in the escitalopram group (5.5 vs. 10.6%). The findings suggest that agomelatine displays additional long-term clinical benefits on sleep-wake quality and emotional experiences over escitalopram in the management of depression.
Few reports have aimed to describe the mediational effect of cognitive deficits on functional outcomes in major depressive disorder (MDD), and relatively few interventions are demonstrated to mitigate cognitive deficits in MDD.
Studies enrolling subjects between the ages of 18–65 were selected for review. Bibliographies from identified articles were reviewed to identify additional original reports aligned with our objectives.
Cognitive deficits in MDD are consistent, replicable, nonspecific, and clinically significant. The aggregated estimated effect size of cognitive deficits in MDD is small to medium. Pronounced deficits in executive function (≥1 SD below the normative mean) are evident in ∼20–30% of individuals with MDD). Other replicated abnormalities are in the domains of working memory, attention, and psychomotor processing speed. Mediational studies indicate that cognitive deficits may account for the largest percentage of variance with respect to the link between psychosocial dysfunction (notably workforce performance) and MDD. No conventional antidepressant has been sufficiently studied and/or demonstrated robust procognitive effects in MDD.
Cognitive deficits in MDD are a principal mediator of psychosocial impairment, notably workforce performance. The hazards posed by cognitive deficits in MDD underscore the need to identify a consensus-based neurocognitive battery for research and clinical purposes. Interventions (pharmacological, behavioral, neuromodulatory) that engage multiple physiological systems implicated in cognitive deficits hold promise to reduce, reverse, and prevent cognitive deficits.
Use of selective serotonin reuptake inhibitors continues to increase, as does concern about previously unrecognized, subtle side effects and questions about whether these drugs produce effects on healthy subjects. The authors report novel emotional effects identified by an experienced, psychologically healthy meditator who is a psychiatrist and researcher. On a meditation retreat, the subject identified a specific profile of emotional changes related to sertraline use. In particular, cognitive abilities and the emotions of fear and anger seemed unaffected. However, the emotions of sadness, happiness, rapture, and love were dramatically reduced in intensity and duration.
Objective:
To report 6 cases of selective serotonin reuptake inhibitor (SSRI)-associated apathy syndrome.
Case summaries:
In all 6 cases, the patient reported loss of motivation while being treated with an SSRI. Loss of motivation was of new onset and temporally associated with the use of the SSRI. A trial of discontinuation of the SSRI was performed in all 6 patients and 2 were started on bupropion while cross-tapering from the SSRI. During the treatment trials, depression and apathy were monitored in all patients. Each case was assessed using the Apathy Evaluation Scale, Clinician version (AES-C), and by evaluating how the patient responded to discontinuation of the SSRI.
Discussion:
Scores on the AES-C improved significantly in all 6 cases after the SSRI was discontinued. Improvement was also seen in the motivation, novelty, and persistence subdomain scores of the AES-C. A pretreatment AES-C score was available only in the first case. Based on the Naranjo probability scale, there was a probable cause of apathy syndrome with SSRI therapy in the first case and a possible association in the rest of the cases.
Conclusions:
In some patients SSRIs may cause an apathy syndrome that can be reversed through discontinuation of the agent. When evaluating patients being treated with an SSRI, clinicians should have a high degree of suspicion and specifically inquire for this iatrogenic form of apathy syndrome.
The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans.
A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N = 26), or placebo (N = 25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment.
Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment.
Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.
Some people who take selective serotonin reuptake inhibitor (SSRI) antidepressants report that their experience of emotions is 'blunted'. This phenomenon is poorly understood.
To understand patients' experiences of this phenomenon.
Qualitative study, gathering data through individual interviews, a group interview and validation interviews; and searching patient websites for relevant posts.
There was strong evidence that some people taking SSRIs experience significant emotional symptoms that they strongly attribute to their antidepressant. These emotional symptoms can be described within six key themes. A seventh theme represents the impact of these side-effects on everyday life, and an eighth represents participants' reasons for attributing these symptoms to their antidepressant. Most participants felt able to distinguish between emotional side-effects of antidepressants and emotional symptoms of their depression or other illness.
Emotional side-effects of SSRIs are a robust phenomenon, prominent in some people's thoughts about their medication, having a demonstrable impact on their functioning and playing a role in their decision-making about antidepressant adherence.
Objective:
Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach.
Methods:
Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States.
Results:
The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was 43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% (8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD.
Conclusions:
TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.
Introduction:
Systematic reviews provide a rigorous synthesis of the best available evidence regarding a certain question. Where high-quality evidence is lacking, systematic reviewers may choose to rely on case series studies to provide information in relation to their question. However, to date there has been limited guidance on how to incorporate case series studies within systematic reviews assessing the effectiveness of an intervention, particularly with reference to assessing the methodological quality or risk of bias of these studies.
Methods:
An international working group was formed to review the methodological literature regarding case series as a form of evidence for inclusion in systematic reviews. The group then developed a critical appraisal tool based on the epidemiological literature relating to bias within these studies. This was then piloted, reviewed and approved by the international Scientific Committee of JBI.
Results:
The JBI critical appraisal tool for case series studies includes 10 questions addressing the internal validity and risk of bias of case series designs, particularly confounding, selection and information bias, in addition to the importance of clear reporting.
Conclusion:
In certain situations, case series designs may represent the best available evidence to inform clinical practice. The JBI critical appraisal tool for case series offers systematic reviewers an approved method to assess the methodological quality of these studies.
Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
Background:
Studies of the adverse effects of antidepressants tend to focus on biological symptoms. The prevalence of suicidality and withdrawal effects are currently a source of controversy.
Objective:
To directly ascertain the experiences of an international sample of antidepressant users.
Method:
An online survey asked adult antidepressant users whether they had experienced 20 adverse effects 'as a result of taking the antidepressant', and if so, to what degree of severity. 1,431 people from 38 countries responded.
Results:
61% of the respondents reported at least ten of the 20 effects, most commonly: 'Feeling emotionally numb' (reported by 71%), 'Feeling foggy or detached' (70%); 'Feeling not like myself' (66%), 'Sexual difficulties' (66%), 'Drowsiness' (63%), and 'Reduction in positive feelings' (60%). 'Suicidality' as a result of the drugs was reported by 50%. Withdrawal effects were reported by 59%, and 'Addiction' by 40%. Rates of adverse effects were higher for those prescribed multiple antidepressants and those who also took antipsychotics. Younger age and longer use of ADs were positively related to total adverse effects. One third did not recall being told about any side effects by the prescriber. Less than 5% were told about suicidality, emotional numbing, withdrawal effects or addiction.
Conclusions:
Asking people directly reveals far higher rates of adverse responses to antidepressants than previously understood, especially in the emotional, psychological and interpersonal domains. Given recent findings that antidepressants are only marginally more effective than placebo, the findings of the current study imply a cost-benefit analysis that cannot justify the extremely high prescription rates for these drugs.
Adverse effects (AEs) are an important factor in antidepressant treatment decision-making, though common AE profiles from clinical trial research highlight physical AEs to the neglect of emotional and behavioral AEs. First-hand accounts of antidepressant users on the Internet can supplement AE profiles with information gained from real-world treatment experiences. We examined online user reviews of two older (escitalopram; duloxetine) and two newer (vilazodone; vortioxetine) antidepressants for differences in their AE profiles and determined which categories of AEs were associated with users' satisfaction. A codebook of 60 physical, emotional, and behavioral AEs was used for line-by-line coding of effects reported among 3,243 user reviews from three popular health websites. Psychiatric effects were commonly reported (41%), followed by sleep (31.9%) and gastrointestinal (25.0%) effects. Specific AEs statistically significantly varied across drugs, creating potentially meaningful differences in AE profiles. Users of newer drugs more often reported emotional instability, while users of older drugs reported more emotional blunting. Psychiatric AEs demonstrated moderate to substantial relationships with users' satisfaction, whereas gastrointestinal, metabolic, or sexual AEs were minimally related. More specific and systematic assessment of a broader range of AEs is needed in both research and practice.
Highlights • Psychiatric adverse effects (AEs) are widely reported among antidepressant users online • Psychiatric AEs demonstrate a substantial relationship with user drug satisfaction • Young users and initial months of antidepressant use show higher psychiatric AEs • AE profiles of new and old antidepressants show potentially meaningful differences Adverse effects and satisfaction 1
Background:
Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms.
Methods:
A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint.
Results:
The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not.
Limitations:
Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered.
Conclusions:
The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments.
Purpose:
Among antidepressants, selective serotonin reup-take inhibitors (SSRIs) have enjoyed great popularity among clinicians as well as generally wide acceptance and tolerance among patients. A potentially overlooked side effect of SSRIs is the occasional occurrence of extrapyramidal symptoms (EPS), which could be a concern when SSRIs are used with antipsychotics. This study was designed to explore the possible association between SSRI antidepressant use and the incidence of EPS side effects in patients who take concomitant antipsychotic medications.
Methods:
The University of Michigan conducted a study at the four Michigan state mental health hospitals between May 2010 and October 2010. The Michigan Public Health Institute collected data using the InterRAI Mental Health Assessment (InterRAI MH). The present study is a retrospective cohort analysis of the cross-sectional data that were collected. Within these institutions, 693 residents were using antipsychotics. We measured the observed frequency of seven EPS recorded in the InterRAI MH within three groups of patients: 1) those on antipsychotic drugs who were taking an SSRI antidepressant; 2) those on antipsychotic drugs who were not taking an antidepressant; and 3) those on antipsychotic drugs who were taking a non-SSRI antidepressant. Differences in the prevalence of EPS were tested using one-way analysis of variance.
Results:
There were no significant differences in the observed EPS frequencies among the three groups (F 2,18 = 0.01; P < 0.9901).
Conclusion:
In this study, SSRIs did not appear to potentiate the occurrence of EPS in patients using antipsychotics.
Vortioxetine (Brintellix): a new serotonergic antidepressant.
The present study aims to evaluate cognitive tolerability profile of SSRIs in long-term treatment. The secondary aim is to explore differences of side effects profile between patients with major depression (MD) and anxiety disorders (AD).
Sixty-seven consecutive patients, successfully treated with SSRIs in monotherapy for at least six months for MD or AD, were assessed for side effects, with a special focus on cognition.
Over 20% of MD and AD patients in long term treatment with SSRIs reported cognitive symptoms including fatigue, inattentiveness, lack of concentration, memory impairment and apathy. Recall memory impairment, attention deficit and somnolence were most frequently rated as moderate or severe. There were no significant differences in SSRI cognitive side effects profile between MD and AD patients.
Subjective measure of cognitive functioning, limited sample size, lack of a control group.
A large proportion of depressed and anxious patients treated successfully with SSRIs for over six months reported cognitive, affective, motivational symptoms. These symptoms are likely to represent SSRI side effects rather than residual depressive symptomatology.
Copyright © 2014 Elsevier B.V. All rights reserved.
Background
In the context of rapidly increasing antidepressant use internationally, and recent reviews raising concerns about efficacy and adverse effects, this study aimed to survey the lived experience of the largest sample of AD recipients to date.
Methods
An online questionnaire about experiences with, and beliefs about, antidepressants was completed by 1829 adults who had been prescribed antidepressants in the last five years (53% were first prescribed them between 2000 and 2009, and 52% reported taking them for more than three years).
Results
Eight of the 20 adverse effects studied were reported by over half the participants; most frequently Sexual Difficulties (62%) and Feeling Emotionally Numb (60%). Percentages for other effects included: Feeling Not Like Myself - 52%, Reduction In Positive Feelings - 42%, Caring Less About Others - 39%, Suicidality - 39% and Withdrawal Effects - 55%. Total Adverse Effect scores were related to younger age, lower education and income, and type of antidepressant, but not to level of depression prior to taking antidepressants.
Conclusions
The adverse effects of antidepressants may be more frequent than previously reported, and include emotional and interpersonal effects.
Background:
Depression is one of the most commonly encountered mental health problems leading to significant morbidity and mortality and high medical and societal costs. Antidepressant prescribing in the UK has more than doubled in the last decade. There are a variety of factors that have been shown to affect a patient's experience of taking antidepressants The aim of this research was to explore patient narratives interviews about depression and its treatment in order to improve patient and health professional understanding of what it is like to use antidepressants.
Methods:
This study involved a supplementary secondary qualitative analysis of 80 in-depth narrative interviews from Healthtalkonline. Patients' experiences of using medicines for depression were explored in the context of their social, occupational and emotional impact, to identify any additional issues and to clarify what type of information people want to find after being prescribed a medicine. The interviews were conducted by the University of Oxford and had received ethical approval and been consented and copyrighted for this purpose. Data were analyzed thematically.
Results:
The most prominent theme was the coexistence of several conflicting issues around the use of medicines and participants were mostly influenced by the reality of their experiences, beliefs, attitudes and interaction with health care. Antidepressants appear to occupy a central place in many people' lives. Many people described how their medicines had helped them and how this served as a reinforcement to continue taking them in order to maintain a "normal life." Those who had stopped taking their antidepressants were likely to have experienced adverse reactions and had unsatisfactory interactions with health care professionals. A lack of information about antidepressants was a major cause of dissatisfaction often shaping attitudes to antidepressants'.
Conclusions:
People's experiences with antidepressant use have a major impact on treatment continuation and hence treatment outcomes. Further studies are needed on depressed patients' beliefs about their depression and treatment and how they relate to different stages of illness, their interactions with health care and their adherence to antidepressants.
Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder.
The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli.
Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects.
The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidalthalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal.
Some patients with major depression report a restricted range of emotions that may appear to arise as a side-effect of treatment with antidepressants. It is uncertain whether this phenomenon, sometimes called emotional blunting, represents residual symptoms of depression or side-effects of antidepressant treatment. There is currently no adequate instrument to measure this phenomenon.
A draft questionnaire was developed from patient-derived qualitative data, refined using cognitive interviewing, and administered on three occasions to patients taking antidepressants. Statistical methods including factor analysis were used to reduce the size of the draft questionnaire, and to assess the performance of the resulting Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA).
207 patients completed the OQuESA on at least one occasion. Their BDI-II scores and self-reported emotional blunting were spread across the possible range. The factor analysis resulted in four dimensions: 'not caring', 'emotional detachment', 'reduction in positive emotions', and 'general reduction in emotions'. The OQuESA appears to be acceptable, valid, and reliable, with sensitivity to change.
The OQuESA offers promise as an effective self-report measure of the symptoms of emotional blunting in patients with depression. It can be used as a clinical tool, to facilitate the identification of patients with the syndrome of emotional blunting. It should also be used in research studies, to advance our understanding of the nature, causes and treatment of this phenomenon.
All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.
Apathy has a significant negative impact on the quality of life. It can be a part of other axis I and axis III disorders such as depression. It has also been reported as a treatment emergent side effect of SSRI drugs. A 48 year old male with diagnosis of personality change due to medical condition and depressive symptoms was started on Sertraline. Although his depressive symptoms, impulse control and his irritability improved significantly he became quite apathetic. This responded positively to a reduction in the dose of sertraline. Since apathy can be a residual symptom of depression it may be a valid consideration to increase the dose of the SSRI. However if apathy was not a significant part of depressive syndrome prior to SSRI treatment then antidepressant treatment emergent apathy needs to be considered and one option is to reduce the dose of the SSRI. Other options appear to be addition of other pharmacological agents such as stimulants, dopamine agonists, acetylcholinesterase inhibitors and NMDA antagonists.
In the existing literature, selective serotonin reuptake inhibitor exposure has been occasionally associated with both behavioral apathy and emotional blunting. While frequently described as separate entities, these two syndromes are mutually characterized by indifference and may be united under the single moniker, "selective serotonin reuptake inhibitor-induced indifference." Little is known about the epidemiology or etiology of selective serotonin reuptake inhibitor-induced indifference and few empirical studies have been undertaken. However, this syndrome may be under-recognized by both clinicians and patients (i.e., low insight, particularly among children and adolescents), and is characterized by an insidious onset, dose-dependent effects (i.e., higher selective serotonin reuptake inhibitor doses are more likely to result in symptoms), and complete resolution of symptoms with the discontinuation of the offending drug. Treatment strategies may include a dose reduction of the offending selective serotonin reuptake inhibitor, augmentation with a second drug, and/or discontinuation of the selective serotonin reuptake inhibitor and subsequent treatment with a nonselective serotonin reuptake inhibitor antidepressant.
The psychological mechanisms by which antidepressant drugs act to improve mood remain underspecified. In this paper we consider the evidence to suggest that early changes in emotional processing underlie subsequent mood improvement following antidepressant treatment. Negative biases in information processing are consistently found in depression, and we argue that primary mode of action of antidepressant drugs may be to remediate these biases providing a more positive social environment in which the patient can relearn emotional associations fostering later improvement in mood. Evidence from behavioural and functional magnetic resonance imaging studies supports this hypothesis. Experimental medicine models developed under this premise have the potential to screen for new treatments, to predict individual treatment response and to consider the effects of pharmacological vs psychological treatments.
Human adolescence has been characterized by increases in risk-taking, emotional lability, and deficient patterns of behavioral regulation. These behaviors have often been attributed to changes in brain structure that occur during this developmental period, notably alterations in gray and white matter that impact synaptic architecture in frontal, limbic, and striatal regions. In this review, we provide a rationale for considering that these behaviors may be due to changes in dopamine system activity, particularly overactivity, during adolescence relative to either childhood or adulthood. This rationale relies on animal data due to limitations in assessing neurochemical activity more directly in juveniles. Accordingly, we also present a strategy that incorporates molecular genetic techniques to infer the status of the underlying tone of the dopamine system across developmental groups. Implications for the understanding of adolescent behavioral development are discussed.
The neuropharmacological actions of antidepressants are well characterised but our understanding of how these changes translate into improved mood are still emerging.
To investigate whether actions of antidepressant drugs on emotional processing are a mediating factor in the effects of these drugs in depression.
We examined key published findings that explored the effects of antidepressants on behavioural and functional magnetic resonance imaging (fMRI) measures of emotional processing.
Negative emotional bias has been reliably associated with depression. Converging results suggest that antidepressants modulate emotional processing and increase positive emotional processing much earlier than effects on mood. These changes in emotional processing are associated with neural modulation in limbic and prefrontal circuitry.
Antidepressants may work in a manner consistent with cognitive theories of depression. Antidepressants do not act as direct mood enhancers but rather change the relative balance of positive to negative emotional processing, providing a platform for subsequent cognitive and psychological reconsolidation.
Apathy, indifference, loss of initiative, or disinhibition (without concurrent sedation or hypomania) were observed among five patients receiving the serotonin reuptake blocking antidepressants fluvoxamine or fluoxetine. These effects appeared to be dose related. They disappeared rapidly when the dose of fluvoxamine, which has a short half-life, was reduced. Fluoxetine, which has a long half-life, was more difficult to titrate. A possible relationship between mild drug-induced indifference and the therapeutic effects of serotonin reuptake blocking medication in anxiety disorders is discussed.