Efficacy of atypical antipsychotics in depressive syndromes

Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.     

Schizotypal traits and depressive symptoms in nonclinical adolescents

The main goal of this study was to examine the relationship between schizotypal personality traits and depressive symptoms in a sample of nonclinical adolescents. The Schizotypal Personality Questionnaire-Brief (J Personal Disord 1995;9:346-355) and the Reynolds Depression Adolescent Scale (Reynolds WM. Reynolds Adolescent Depression Scale. Professional Manual. Odessa: Psychological Assessment Resources, Inc; 1987) were administered. The sample was made up of 1384 adolescents (48.6% boys), with a mean (SD) age of 15.7 (1.0) years. The results of the study indicate a high degree of overlap between schizotypal experiences and depressive symptoms at a nonclinical level. Canonical correlation between the Schizotypal Personality Questionnaire-Brief scales and the Reynolds Adolescent Depression Scale scales was 0.63, which represents 39.69% of the associated variance between the 2 sets of variables. Confirmatory factor analysis showed that the 4-dimensional model made up of the Positive, Interpersonal, Disorganized, and Depressive dimensions was that which best fit the data. Moreover, the dimensional structure underlying the schizotypal traits and depressive symptoms was found to be invariant across sex and age. These findings converge with data found in previous studies of both patients with schizophrenia and nonclinical adults and suggest that affective dysregulation is also present at a subclinical level. Future research should continue to make progress in the early detection of participants at risk of developing schizophrenia-spectrum disorders based on the early identification of these types of subclinical traits.     

Normal personality traits and comorbidity among phobic, panic and major depressive disorders

High comorbidity among anxiety and depressive conditions is a consistent but not well-understood finding. The current study examines how normal personality traits relate to this comorbidity. In the Baltimore Epidemiologic Catchment Area Follow-up Study, psychiatrists administered the full Schedules for Clinical Assessment in Neuropsychiatry to 320 subjects, all of whom completed the Revised NEO Personality Inventory. The disorders of interest were simple phobia, social phobia, agoraphobia, panic disorder, and major depression. Analyses were carried out with second-order generalized estimating equations. The unadjusted summary odds ratio (SOR - or weighted mean odds ratio) for all five disorders was 1.72 (95% confidence interval=1.21-2.46). Neuroticism, introversion, younger age, and female gender were all significant predictors of prevalence of disorders. After adjustment for the relationships between these personality and demographic predictors and prevalence, the association among disorders was much weaker (SOR=1.11, 95% CI=0.79-1.56). However, subjects with high extraversion had a SOR 213% as high (95% CI=102-444%) as those with low extraversion (1.60 vs. 0.75). Therefore, neuroticism and introversion are associated with increased comorbidity due to relationships in common with the prevalence of the different disorders. In contrast, extraversion is associated with increased comorbidity per se.     

人格特质和社会支持对青少年抑郁特质和抑郁状态的影响

目的 探讨人格特质和社会支持对青少年抑郁特质和抑郁状态的独立作用，以及在压力性生活事件对抑郁特质和状态影响中的调节作用。方法 采用方便抽样法，于2022年7—8月选取四川省某所中学的303名中学生为研究对象。采用青少年生活事件量表、中国大五人格问卷简版、青少年社会支持量表、特质抑郁量表、流调用抑郁量表在线调查青少年的压力性生活事件、人格特质、社会支持、抑郁特质、抑郁状态。采用多重线性回归分析人格特质和社会支持对青少年抑郁特质和抑郁状态的影响，并分析人格特质和社会支持在青少年压力性生活事件对抑郁特质和抑郁状态影响中的交互作用。结果 多重线性回归分析结果显示，开放性人格特质与青少年抑郁特质呈负相关（β=-0.17,95%CI:-0.27～-0.08,P<0.05），社会支持与青少年抑郁特质（β=-0.16,95%CI:-0.21～-0.10,P<0.05）和抑郁状态呈负相关（β=-0.13,95%CI:-0.19～-0.07,P<0.05）。交互作用结果显示，开放性人格在生活事件对青少年抑郁特质的影响中表现出调节作用（P<0.05），社会支持在生活事件对青少年抑郁状...     

Use of atypical antipsychotics for treatment-resistant major depressive disorder

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.     

The effectiveness of atypical antipsychotic medications in depressive disorders

Clinical evidence supporting the use of atypical antipsychotic medication (broad-spectrum psychotropic agents) in the treatment of depressive disorders is increasing rapidly. Animal models suggest that when atypical antipsychotic medications are used in combination with a selective serotonin reuptake inhibitor there is additional activation of frontal dopaminergic and noradrenergic neurotransmitter systems. This stimulated the initiation of several clinical trials that showed the efficacy of atypical antipsychotic medication augmentation of selective serotonin reuptake inhibitors for patients with treatment-resistant depression. There also are few case reports of successful treatment of depression with atypical antipsychotic medication alone. When a clinician is treating a depressed patient who did not achieve relief after trials with two different antidepressant regimens, one option to consider is augmentation with an atypical antipsychotic medication to ameliorate depressive symptoms.     

Joint hypermobility, fears, and chocolate consumption

Our purpose was to evaluate joint hypermobility, an inherited disorder of the connective tissue significantly associated with anxiety disorders, in a sample of nonclinical students in relation to the frequency of severe fears and consumption of chocolate, coffee, cigarettes, and alcohol. One hundred fifty students completed the Hakim and Grahame Simple Questionnaire to detect hypermobility and the self-administered modified Wolpe Fear Scale (100 items). Severe fears and daily consumption of cigarettes, alcohol, coffee, and chocolate were compared with the hypermobility scores. We found significant differences when comparing severe fears between the groups with and without hypermobility (7.6 vs. 11; p = 0.001), reinforcing the hypothesis that the intensity of fears is greater in subjects with hypermobility. Only the frequency of chocolate intake was significantly higher among subjects with hypermobility (31.2% vs. 51.2%; p = 0.038) and may correspond to attempts of self-treatment of the collagen condition.     

伴非典型特征抑郁症的临床评估与诊治指导建议

非典型特征是抑郁症常见的临床伴随特征之一,这类患者具有起病早、病程长、共病率高、预后差、转相风险大、自杀风险高等特点。然而,目前临床实践中对伴非典型特征的抑郁症缺乏认识,针对其临床评估、诊断及治疗等方面尚未形成基于循证证据的指南或共识。鉴于此,中华医学会精神医学分会抑郁障碍研究协作组专家们立足临床实践需求,遵循循证医学证据,参考国内外指南,提出针对伴非典型特征的抑郁症的临床评估与诊治建议,以期为精神卫生工作者提供参考。     

High serum leptin levels in depressive disorders with atypical features

Leptin is thought to be related to vegetative symptoms of depression such as alterations in food intake and weight. Fifty-seven drug-free patients and 26 healthy controls were enrolled in this study. We have found that the serum leptin levels were higher in patients with atypical depressive disorder than in controls, but not in patients with non-atypical depressive disorder, however, body mass index, age, and gender were not significantly different between these groups. Probably, these findings seem to be associated with some features of the atypical depressive disorders such as weight gain, a result of hyperphagia.     

The role of questioning environment,personality traits,depressive and anxiety symptoms in tinnitus severity perception

Psychological factors have been described as important for tinnitus severity, but attempts to incorporate them in one picture are sparse. This study investigated to what extent traits (personality), states (depressive and anxiety symptoms), sociodemographic factors and questioning environment influence tinnitus severity perception and how they interplay. Data were obtained from 212 subjects in a survey that was undertaken in 2016 at Vilnius University hospital and via internet. Measures included the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Hospital Anxiety and Depression Scale (HADS), Big Five Personality Dimensions Scale and sociodemographic questions. A series of stepwise forward and multiple regression analyses were undertaken to discover how factors interconnect. Female gender, age, living in rural area, but not level of education, were found to be associated with THI and HADS. Total HADS score and of both subscales were linked to scores on THI, VAS scales and all personality traits, except agreeableness (and consciousness for anxiety). Anxiety was the most important predictor for tinnitus severity, followed by depressive symptoms. Only neuroticism from personality dimensions was a predictor of THI score, whereas THI scores did not predict scores on neuroticism. All results in scales were higher in the internet group, except agreeableness and neuroticism, while extroversion correlated negatively with THI score only in the hospital group. Tinnitus severity was highly correlated with depressive, anxiety symptoms and neuroticism. Respondents recruited through internet had higher scores on most parameters. Results emphasize the importance of psychological factors in tinnitus management.     

Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorder

Objective: Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment‐resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD. Method: Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross‐referencing the term ‘depression’ with each of the six AAPs. Results: After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia. Conclusion: The existing research provides some support for the beneficial effects of AAPs when combined with SSRI’s in TRD. These medications pose significant risks that must be considered in their use.     

Treatment of depressive mood in schizophrenia with the atypical antipsychotic quetiapine

Two patients with schizophrenia and depressive mood experienced remission in both their psychotic and depressive symptoms during treatment with the atypical antipsychotic quetiapine. These case reports illustrate the antipsychotic clinical efficacy of quetiapine and its antidepressant effects in the treatment of patients with schizophrenia and depressive mood.     

Antiepileptic effect of olanzapine in epilepsy patients with atypical depressive comorbidity

Depression is relatively common among patients with epilepsy, but often with predominant atypical symptoms. Some antiepileptic drugs show positive psychotropic effects, but these are not always sufficient to stabilize mood in epilepsy patients. Antidepressants are recommended to treat atypical depression but are not always effective and present a certain risk of seizure provocation. Thus, new treatment options are welcome. Here, we describe three cases of refractory epilepsy with atypical depression in which olanzapine, contrary to its earlier reported proconvulsant effect, showed excellent antidepressant action and resulted in seizure control. Possible mechanisms of this action are discussed.     

Chronic atypical major depressive episode in private practice: unipolar and bipolar II

OBJECTIVE: The aims of the study were to determine whether chronicity was more common in atypical vs. non-atypical unipolar/bipolar II major depressive episode (MDE), whether atypical unipolar and bipolar II MDE had same chronicity, and to compare chronic with non-chronic atypical MDE. METHOD: A total of 326 unipolar/bipolar II MDE private practice outpatients were interviewed with the DSM-IV Structured Clinical Interview. RESULTS: Chronicity was not significantly different in atypical compared to non-atypical MDE. Unipolar atypical MDE showed more chronicity than bipolar II atypical MDE and unipolar non-atypical MDE. Chronicity was not significantly different in atypical compared to nonatypical bipolar II MDE. Compared to non-atypical MDE, atypical MDE had significantly lower age at onset, more recurrences and more bipolar II patients. Chronic compared to non-chronic atypical MDE had significantly longer duration, more recurrences and more unipolar patients. CONCLUSION: Unipolar atypical MDE is more chronic than unipolar nonatypical MDE. Bipolar II atypical MDE is not more chronic than bipolar II non-atypical MDE.     

The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia

Depressive symptoms and syndromal depression commonly occur in patients with schizophrenia. Schizophrenia is also associated with aggression directed at self and others. For this article, the available literature regarding the efficacy of clozapine, risperidone, olanzapine, quetiapine, and ziprasidone in the treatment of depression, hostility, and suicidality in patients with schizophrenia was reviewed. These studies suggest that atypical antipsychotics may exert therapeutic effects on depression and hostility as well as psychosis and that clozapine and olanzapine may reduce suicidality in patients with schizophrenia. These therapeutic actions appear to represent additional advantages of atypical antipsychotics compared with standard agents.     

Partial validation of the atypical features subtype of major depressive disorder.

BACKGROUND: Symptoms of the atypical features subtype of major depressive disorder include mood reactivity, hypersomnia, hyperphagia, leaden paralysis, and rejection sensitivity. This subtype was introduced into the mood disorders section of the DSM-IV following a series of antidepressant trials showing that such patients responded preferentially to monoamine oxidase inhibitors. Studies aimed at validating the atypical features subtype have yielded inconsistent results. Our study sought to reevaluate the validity of atypical depression by examining the demographic and clinical features of a large cohort of depressed patients who met DSM-IV criteria for atypical features. METHODS: We evaluated 579 psychiatric outpatients with a current diagnosis of major depressive disorder for the presence of atypical features. Detailed demographic and clinical information was obtained for each patient through semistructured interviews. Using the available literature, we made a series of a priori hypotheses regarding how depressed patients with atypical features (n = 130) would differ from those without atypical features (n = 449). In addition, we tested the strength of the associations between each of the 5 atypical symptoms. RESULTS: Although many of the predicted hypotheses were substantiated, an equal number were not. Correlation analyses revealed modest associations between several of the atypical symptoms, but mood reactivity was not associated with any of the other symptom criteria. CONCLUSION: Our results provide partial support for the validity of the atypical features subtype of major depressive disorder.     

伴非典型特征的抑郁症患者自杀未遂的危险因素分析

目的探讨伴非典型特征抑郁症患者自杀未遂的社会人口学及临床特征方面危险因素。方法来自全国13个中心的1172例抑郁症患者,纳入其中179例伴非典型特征患者,依据简明国际神经精神访谈(the Mini International Neuropsychiatric Interview,MINI)5.0中文版自杀模块的访谈结果,分为自杀未遂组和无自杀未遂组,通过多因素logistic回归分析伴非典型特征的抑郁症患者在性别、年龄等社会人口学资料及伴焦虑症状、伴精神病性症状等临床特征方面可能与自杀未遂相关的危险因素。结果伴非典型特征抑郁症患者自杀未遂的发生率为23.5%(42/179)。与无自杀未遂组患者相比,自杀未遂组患者更多伴有自杀观念、产后起病,更常使用抗抑郁剂以外的其他药物治疗(如抗精神病药、情感稳定剂及苯二氮类药)(均P0.05)。多因素logistic回归分析显示,既往住院次数(OR=1.730,95%CI:1.093~2.740)和自杀观念(OR=3.899,95%CI:1.506~10.092)与伴非典型特征的抑郁症患者发生自杀未遂相关(均P0.05)。结论既往住院次数多及伴有自杀观念是伴非典型特征抑郁症患者自杀未遂的主要危险因素。