Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

Quetiapine: novel uses in the treatment of depressive and anxiety disorders

Importance of the field: Quetiapine, an atypical antipsychotic, has been approved for the treatment of schizophrenia, acute mania, bipolar depression and unipolar major depression. However, it is often used (off-label) to treat other depressive disorders and anxiety disorders in children and adults.

Areas covered in this review: This article reviews the evidence for the safety and efficacy of quetiapine in these populations, as both monotherapy and augmentation to other psychotropics.

What the reader will gain: This article provides an in-depth review of the published literature on the topic and also provides recommendations for use.

Take home message: There is strong evidence to support the use of quetiapine in major depressive and generalized anxiety disorders, and preliminary support for treatment-resistant and psychotic depression. There is reasonable evidence of its benefits as an augmenting agent in obsessive-compulsive disorder, while data in other anxiety disorders are limited but promising. While long-term tolerability data are limited, quetiapine appears well tolerated in the short-term. Further randomized controlled trials are needed to confirm the efficacy and tolerability of quetiapine, both short- and long-term, in many of these conditions.     

丁螺环酮治疗焦虑性障碍伴发的抑郁症状的疗效

目的 :探讨丁螺环酮对焦虑性障碍伴发的抑郁症状的疗效。方法 :136 9例焦虑性障碍的患者口服丁螺环酮治疗 4周 ,剂量 5～ 6 0mg ,在治疗前后进行HAMD评定。结果 :治疗后HAMD减分率为 (5 6 .31± 33.76 ) % ,显效率为 6 1.4 % ,有效率为 85 .5 %。结论 :丁螺环酮对焦虑性障碍伴发的抑郁症状具有一定疗效。     

Current status of beta-blocking drugs in the treatment of anxiety disorders

beta-Adrenoceptor blocking drugs have been used for the treatment of acute stress reactions, adjustment disorders, generalised anxiety, panic disorder and agoraphobia. In general they are effective in these disorders if somatic or autonomic symptoms are prominent but not extreme in degree. Thus, they are of more value for the relatively mild tremor of the anxious violinist in public performance than in the severe shaking noticed during a panic attack. It is most likely that beta-blockers act primarily by blocking peripheral adrenergic beta-receptors; symptoms that are mediated through beta-stimulation, such as tremor and palpitations, are helped most. Improvement is noted within 1 to 2 hours and with relatively low doses (e.g. propranolol 40 mg/day). Some recent studies, however, have suggested that when longer treatment using higher doses (e.g. propranolol 160 mg/day) is given, improvement in other forms of anxiety is noted after several weeks of treatment. beta-blocking drugs are useful adjuncts to existing treatments for anxiety and are likely to enjoy wider use now that benzodiazepines are being avoided due to their dependence risks.     

Antiepileptic drugs in the treatment of anxiety disorders: role in therapy

Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.     

Managing depressive and anxiety disorders with escitalopram

This article reviews escitalopram, the S-stereoisomer of the racemic compound citalopram, and a highly selective and potent member of the selective serotonin re-uptake inhibitor class of antidepressants. Escitalopram has a straightforward pharmacokinetic profile, little effect on hepatic metabolism, and is relatively safe in overdose. Similar to other members of the selective serotonin re-uptake inhibitor class, escitalopram (10-20 mg/day) is a well-tolerated and effective treatment of major depressive disorder. Although relatively few head-to-head comparative studies with other antidepressants have been published, pooled analyses of studies using citalopram as the active comparator suggest a modest advantage for the stereoisomer. This advantage, which is more apparent among patients with greater symptom levels, may be attributable to a greater than predicted potency compared with citalopram, presumably as a result of the greater effect of escitalopram at the allosteric binding site of the serotonin transporter. Results of two published studies versus venlafaxine also suggest better tolerability in the context of comparable efficacy. Escitalopram is also approved for the treatment of generalised anxiety disorder (in the US) and social anxiety disorder and panic disorder (in the EU). Pharmacoeconomic models suggest that the greater drug acquisition cost of this patent-protected compound may be offset by greater efficacy (relative to generic citalopram) and tolerability (compared with extended release venlafaxine).     

Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence

Despite the availability of different classes of drugs for the treatment of depressive and anxiety disorders, there are a number of clinically significant unmet needs, such as a high prevalence of treatment resistance, partial response, subsyndromal symptomatology, recurrence and relapse. With the approval of atypical antipsychotics, which are associated with a lower adverse effect burden than typical antipsychotics, consideration of their off-label use for the treatment of affective disorders and various other psychiatric disorders has become a viable option. However, consideration should be given to the US FDA black box warning indicating that atypical antipsychotics may increase mortality risk, particularly in the elderly population with dementia-related psychosis. There has been much conjecture about the utility of these atypical drugs to facilitate traditional antidepressant therapy, either in combination (from the initiation of therapy) or as adjunctive therapy (in the case of partial/incomplete response). Nevertheless, at present, available evidence from randomized, placebo-controlled trials is sparse, and a formal risk/benefit assessment of the use of these agents in a nonpsychotic patient population is not yet possible. As a representative agent from the atypical antipsychotic class with a novel mechanism of action and a relatively low adverse effect burden, aripiprazole represents an interesting potential treatment for depressive and anxiety disorders. In this review, we focus on the rationale for the use of aripiprazole in these disorders. Preclinical data suggests that aripiprazole has a number of possible mechanisms of action that may be important in the treatment of depressive and anxiety disorders. Such mechanisms include aripiprazole action at serotonin (5-HT) receptors as a 5-HT1A partial receptor agonist, a 5-HT2C partial receptor agonist and a 5-HT2A receptor antagonist. Aripiprazole also acts as a dopamine D2 partial receptor agonist, and has a possible action at adrenergic receptors. Furthermore, aripiprazole may have possible neuroprotective effects. Clinical studies demonstrate that aripiprazole may be useful in the treatment of bipolar depression, major depressive disorder, treatment-resistant depression and possibly anxiety disorders. Clinical data also suggest that aripiprazole may have a lower adverse effect burden than the other atypical drugs. Future research may confirm the potential utility of aripiprazole in the treatment of depressive and anxiety disorders.     

Moclobemide and specific serotonin re-uptake inhibitor combination treatment of resistant anxiety and depressive disorders

This retrospective study was undertaken with the objective of determining how effective and safe moclobemide, a specific and reversible inhibitor of monoamine oxidase-A (RIMA), is when used in combination with specific serotonin re-uptake inhibitors (SSRIs), in a clinical setting. A thorough chart review was done of all patients with affective and anxiety disorders seen at our centre who received combination treatment with moclobemide and an SSRI. Combination moclobemide-SSRI treatment demonstrated good efficacy in treating treatment-resistant patients. The combination treatment was well tolerated with very few drug interactions. Dosages should be started low, titrated slowly and carefully, and patients should be monitored closely.     

Antidepressant use and salivary cortisol in depressive and anxiety disorders

Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic–pituitary–adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy. The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety who were grouped into ‘serotonin reuptake inhibitor (SSRI) users’ (n = 309), ‘tricyclic antidepressant (TCA) users’ (n = 49), ‘other antidepressant users’ (n = 100), and ‘non-users’ (n = 1068). All subjects had a current or past diagnosis of anxiety and/or depression. Subjects provided 7 saliva samples from which 3 cortisol indicators were calculated: cortisol awakening response (CAR), evening cortisol, and cortisol suppression after ingestion of 0.5 mg dexamethasone. As compared to non-users, TCA users had a flattened CAR (effect size: Cohen's d = 0.34); SSRI users had higher evening cortisol levels (d = 0.04); and SSRI users showed decreased cortisol suppression after dexamethasone ingestion (d = 0.03). These findings suggest that antidepressant subtypes are associated with distinct alterations of the HPA axis. TCA users, who showed a flattened CAR, displayed the strongest alterations of salivary cortisol.     

Stimulation of the beta3-Adrenoceptor as a novel treatment strategy for anxiety and depressive disorders.

The characterization of the first selective orally active and brain-penetrant beta3-adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stress-induced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the beta3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide. Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the beta3 adrenoceptor suggested that these effects of SR58611A are mediated by beta3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of beta3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.     

曲唑酮治疗焦虑症

目的 :观察曲唑酮对焦虑症的疗效。方法 :选择符合CCMD 2 R诊断标准的焦虑症病例 90例(实际完成 87例 :男性 2 7例 ,女性 6 0例 ) ,随机分 3组 ,每组 30例 ,分别用曲唑酮 50～ 10 0mg·d- 1,po ,阿普唑仑 1.6mg·d- 1,po ,劳拉西泮 2mg·d- 1,po ,共观察 4wk。结果 :曲唑酮组的总有效率基本与其他 2组相仿 (P >0 .0 5) ,仅wk 4优于阿普唑仑组 (P <0 .0 5)。HAMA减分率与wk 1阿普唑仑组及各周劳拉西泮组差别无显著意义 (P >0 .0 5) ,但与wk 2 ,wk 4阿普唑仑组比较差别有显著和非常显著意义 (P <0 .0 5或P <0 .0 1)。药物副作用少而轻 ,以胃肠道不适和困倦感为主 ,仅 3例分别出现头痛伴焦虑、头晕伴烦躁不安、焦虑症状加重。结论 :曲唑酮是有效的抗焦虑药物 ,且副作用小。     

Riluzole in the treatment of mood and anxiety disorders

Recent advances implicate amino acid neurotransmission in the pathophysiology and treatment of mood and anxiety disorders. Riluzole, which is approved and marketed for the treatment of amyotrophic lateral sclerosis, is thought to be neuroprotective through its modulation of glutamatergic neurotransmission. Riluzole has multiple molecular actions in vitro; the two that have been documented to occur at physiologically realistic drug concentrations and are therefore most likely to be clinically relevant are inhibition of certain voltage-gated sodium channels, which can lead to reduced neurotransmitter release, and enhanced astrocytic uptake of extracellular glutamate.Although double-blind, placebo-controlled trials are lacking, several open-label trials have suggested that riluzole, either as monotherapy or as augmentation of standard therapy, reduces symptoms of obsessive-compulsive disorder, unipolar and bipolar depression, and generalized anxiety disorder. In studies of psychiatrically ill patients conducted to date, the drug has been quite well tolerated; common adverse effects include nausea and sedation. Elevation of liver function tests is common and necessitates periodic monitoring, but has been without clinical consequence in studies conducted to date in psychiatric populations. Case reports suggest utility in other conditions, including trichotillomania and self-injurious behaviour associated with borderline personality disorder. Riluzole may hold promise for the treatment of several psychiatric conditions, possibly through its ability to modulate pathologically dysregulated glutamate levels, and merits further investigation.     

米安色林治疗脑卒中后抑郁症

目的：观察米安色林治疗由脑卒中所致抑郁症的疗效。方法：用米安色林６０ｍｇ／ｄ晚上１次顿服，疗程４ｗｋ，治疗３２例脑卒中后抑郁症。用全国统一的４级标准及ＨＡＭＤ，ＨＡＭＡ，ＣＧＩ，ＡＳＢＳ量表进行疗效和副作用评定。结果：在治疗ｗｋ２时已有明显疗效，ＨＡＭＤ，ＨＡＭＡ评分明显下降，疗效指数（ＥＩ）上升；ｗｋ４时已取得稳定疗效，总显效率为８４％；副作用有轻微头昏、嗜睡、口干、便秘、排尿困难及视物模糊；３例病人有一过性ＡＬＴ升高。结论：米安色林治疗脑卒中所致的抑郁症有良好效果，值得推广。     

综合医院住院患者焦虑抑郁障碍调查分析

目的调查分析综合医院住院患者焦虑抑郁障碍的患病情况,提高临床医生对焦虑抑郁障碍的识别诊断能力。方法采用自编的一般情况及医院焦虑抑郁量表(HAD)对2013年4月至2014年3月该院住院患者(600例)进行调查,所有数据应用SSPS19.0统计软件进行分析。结果综合住院患者焦虑抑郁障碍阳性率为28.0%(168/600),除年龄、婚姻对焦虑抑郁障碍患病率的影响较大外,其他因素对焦虑抑郁障碍患病率的影响不明显,各项目间患病率比较,差异无统计学意义(P>0.05)。结论综合医院住院患者焦虑抑郁障碍患病率相当高,提高综合医院临床医生对心理障碍的识别及治疗将有助于改善患者的临床疗效,在综合性医院成立专门的心理科显得尤为重要。     

Unmet needs in the treatment of anxiety disorders

There are a number of unmet needs in the treatment of anxiety disorders including the need for more effective, rapidly acting, and better tolerated medications; early identification of nonresponse; effective treatments for refractory disorders; prevention of relapse; and promotion of resilience and long-lasting response. Rates of response to contemporary antidepressants and other anxiolytics are often less robust than might be hoped, and remission rates, which have until recently been infrequently measured, are even lower. A small number of mostly uncontrolled studies suggest a role for augmentation of initial therapy with a second modality in patients who do not fully remit to treatment. There also is a small but growing literature which suggests the use of novel anticonvulsants and atypical antipsychotics in the treatment of anxiety disorders should be further studied. However, a definitive place for these newer therapeutic strategies in the anxiety disorder treatment armamentarium awaits evidence from large, controlled studies. Psychopharmacology Bulletin. 2004;38(Suppl 1): 31-37.     

New directions in the treatment of anxiety disorders

Anxiety disorders play a prominent role in general medical and psychiatric practice, and their lack of recognition leads to significant morbidity. A major thrust of recent patent activity builds on clinical successes provided by serotonergic and GABA-ergic agents. A new understanding of the molecular basis for GABA_A receptor subtype selectivity presents new possibilities for designing drugs that are highly specific for subpopulations of this receptor family. Despite a lack of clinical experience with less well-known neuropeptide agents, corticotrophin-releasing hormone (CRH) antagonists appear promising. This paper reviews the most prevalent anxiety disorders, their pharmacological treatments and describes trends in therapeutic patent activity since 1997.