Brand-Name Antidepressants Outperform Their Generic Counterparts in Preventing Hospitalization for Depression: The Real-World Evidence from Taiwan

BackgroundGeneric antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders.MethodsIn a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes.ResultsA total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20–2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs.ConclusionsCompared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder.     

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.     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Combination of low-dose mirtazapine and ibuprofen for prophylaxis of chronic tension-type headache

Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P  = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache.     

帕罗西汀替换三环类抗抑郁剂治疗抑郁症对照研究

目的：了解帕罗西汀替换三环类抗抑郁剂(TCAs)治疗抑郁症的有效性和安全性。方法：将经TCAs足量治疗6周疗效达好转及以下的、符合反复发作抑郁症诊断标准的患者随机分为帕罗西汀组和三环类组。帕罗西汀组渐停TCAs，渐增帕罗西汀治疗，剂量20～40mg／d；三环类组继续使用TCAs150～250mg／d治疗。用Hamilton抑郁量表(HAMD)、大体评定量表(GAS)、临床疗效总评量表病情严重程度(GGI-SI)，分别于人组时，治疗1周末、2周末、4周末、8周末评定其病情变化；副反应量表(TESS)评定不良反应。结果：与入组时比较，帕罗西汀组治疗2周末各种量表评分差异即有显著性；三环类组治疗4周末HAMD、GAS评分差异有显著性，CGI—SI评分治疗8周末差异有显著性。帕罗西汀组治疗后HAMD、GAS、CGI—SI减分明显多于三环类组，帕罗西汀组不良反应发生率显著少于三环类组。结论：帕罗西汀替换TCAs治疗效差的抑郁症安全有效，可在临床上试用。     

老年人脑卒中后抑郁症的发病机制及预防

[目的]探讨脑卒中后老年患者抑郁症的发病机制及预防措施。[方法]归纳相关资料,对命题进行分析。[结论]医护人员应采取针对性的用药及护理措施,预防患者卒中后抑郁症的发生。     

Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.     

Decreased R-R variation: A criterium for overdosage of tricyclic psychotropic drugs

Objective Since intoxication with tricyclic antidepressants is common, a supplementary screening method for differentiation between therapeutic and supratherapeutic ranges would be a valuable diagnositc tool, particularly in delirious and unconscious patientsSetting 109 patients treated with amitriptyline, 8 patients treated with doxepin, 10 patients treated with clozapine, and 72 normal control subjects matched for age and sex were tested for heart rate variability while resting.Results Considering time and frequency derived measures, which are rather independent of heart rate, the patients showed significantly decreased heart rate variability parameters (p<0.0001), as compared with the normal subjects. Of the patients presenting delirious symptoms 6 showed coefficients of variation more than 4 standard deviations below the mean control value.Conclusions As heart rate variability can be easily calculated, this measurement is suggested as a useful tool to quickly exclude or support the diagnosis of chronic intoxication with tricyclic antidepressants or clozapine.