No evidence for switching the antidepressant: systematic review and meta‐analysis of RCTs of a common therapeutic strategy

Bschor T, Baethge C. No evidence for switching the antidepressant: systematic review and meta‐analysis of RCTs of a common therapeutic strategy. Objective: Switching antidepressants is a common strategy for managing treatment‐resistant depressed patients. However, no systematic reviews have been conducted to date. Method: We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double‐blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta‐analysis of response + remission rates using a fixed‐effects model. Results: A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta‐analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55–1.30) favoring continuing]. Conclusion: There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies.     

Rheumatologic Disorders Due to Immune Complexes

Circulating autologous immune complexes are considered responsible for the vasculitis of systemic lupus erythematosus and of seropositive rheumatoid arthritis and appear to contribute to the vasculitis of one form of cryoglobulinemia. Complexes of virus and immunoglobulin probably cause half of the cases of polyarteritis nodosa.     

抗抑郁治疗对2型糖尿病痛性神经病变的影响

目的观察抗抑郁治疗对2型糖尿病痛性神经病变患者情绪障碍及疼痛的影响。方法将35例2型糖尿病痛性神经病变患者随机分为治疗组(20例)和对照组(15例)。收集患者一般临床资料和糖尿病控制情况,对照组常规给予降糖药、神经营养药、止痛药、改善微循环药物治疗。治疗组在此基础上加用抗抑郁药物西酞普兰20mg,1次/d,共14d。采用汉密尔顿抑郁量表(HAMD-17)评定患者治疗前后抑郁程度的变化,采用数字疼痛分级法(NPIS)评估疼痛改善情况,同时记录镇痛药物的等级,并检测糖化血红蛋白(HbA1c)以评价糖尿病控制情况。结果治疗前两组患者的临床一般情况、HbA1c及HAMD评分差异无统计学意义;治疗组治疗后第14天HAMD评分(17.69±7.45)显著低于治疗前(26.82±9.66)及同期对照组(24.71±8.92)(P<0.05),抑郁症状明显改善;治疗组第14天NPIS评分(2.5±0.8)显著低于同期对照组(4.8±1.1)和治疗前(6.0±2.2)(分别为P<0.05,P<0.01),镇痛药物的等级亦显著低于对照组(P<0.01)。结论抗抑郁治疗不仅可缓解患者的抑郁症状,还有益于疼痛的缓解。     

Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double‐blind,randomized, placebo‐controlled study

Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short‐term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short‐term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double‐blind, randomized, placebo‐ controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short‐term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short‐term clinical advantage. © 2008 Movement Disorder Society     

Is elevated noradrenaline an aetiological factor in a number of diseases?

1 Here I put forth the hypothesis that noradrenaline (NA), which is a signalling molecule in the brain and sympathetic nervous system (SNS), is an aetiological factor in a number of diseases. 2 In a previous paper ( Fitzgerald, Int. J. Cancer, 124 , 2009 , 257), I examined evidence that elevated NA is a factor in various types of cancer. Here I extend the argument to several other diseases, including diabetes mellitus, open‐angle glaucoma, osteoarthritis and rheumatoid arthritis and asthma. 3 The principal hypothesis is that, largely as a result of genetics, elevated noradrenergic tone in the SNS predisposes a large number of individuals to a broad range of diseases. 4 For each of the above five diseases, I briefly examine the following four lines of evidence to assess the hypothesis: i) whether pharmacological studies in rodents that manipulate NA levels or receptors affect these diseases; ii) whether pharmacological manipulation of NA in humans affects these diseases; iii) whether bipolar disorder, excessive body weight, and hypertension, which may all three involve elevated NA, tend to be comorbid with these diseases and iv) whether psychological stressors tend to cause or exacerbate these conditions, since psychological stress is associated with increased release of NA. 5 The four lines of evidence tend to support the hypothesis.     

Therapeutic effects of fengabine, a new GABAergic agent, in depressed outpatients: a double-blind study versus clomipramine

The results of a double-blind clinical trial of fengabine vs clomipramine in depressed outpatients are reported. Fengabine, a new GABAergic agent, seems to be as effective as the reference drug, with a faster onset of action and a more marked effect on cognitive disturbances and retardation. The new drug is free of any significant anticholinergic or cardiovascular effect, and it is not sedative.     

Plasma MHPG and AMDP depression relations,evolution and drug effect in a follow-up study of depressed patients

Plasma MHPG levels and AMDP rating score were measured in depressed patients before treatment, and a follow-up study was performed during the next 3 months of drug therapy to detect possible relationships between the parameters. Before treatment, MHPG levels were moderately lower in depressed than in age- and sex-matched normal subjects. Bipolar depressed patients presented the lowest values. In the three diagnostic groups (DSM-III), antidepressant treatment resulted in a significant decrease of mean levels in unipolar and dysthymic depressed, but not in bipolar depressed patients. When the type of antidepressant was considered, imipramine (IMI)- or desipramine (DMI)-treated patients, but not fluvoxamine (FLU)-treated, also decreased their mean values of MHPG, with minor difference between improved and non-improved patients. However, when patients were grouped according to their pattern groups (low (LL), high (HL), or normal (NL) baseline MHPG levels), interesting information emerged: improvement of clinical state of patient (i.e. 60 per cent of AMDP baseline reduction) resulted in ‘normalization’ of erratic values (HL and NL) whatever the treatment, while in non-improved patients such evolution was not observed. In the latter group, change in MHPG levels was only drug-related (decrease in IMI–DMI-treated and no change in FLU-treated values). Results suggest that mechanisms of buffering NA activity were lost in endogenous depression and restored in patients responding to treatment.     

Venlafaxine extended release (XR) for the prophylaxis of migraine and tension-type headache: A retrospective study in a clinical setting

OBJECTIVE: To assess the efficacy of extended-release venlafaxine in the prophylaxis of migraine and chronic tension-type headache. BACKGROUND: Venlafaxine, a structurally novel antidepressant, is a selective serotonin-norepinephrine reuptake inhibitor. This study is the first to test the effects of extended-release venlafaxine on headaches. METHODS: Patients were evaluated on a retrospective basis. Fifty-six patients with chronic tension-type headache and 114 patients with migraine were prescribed extended-release venlafaxine. Nearly all the study subjects had been resistant to several previous preventive medications. Patients took venlafaxine for an average of 6 months with a median dose of 150 mg (range, 37.5 to 300 mg). RESULTS: The mean frequency of headaches in the group with chronic tension-type headache fell from 24.0 to 15.2 per month (P <.0001). The group with migraine showed a reduction from 16.1 to 11.1 headaches per month (P <.0001). The medicine was well tolerated. CONCLUSIONS: This trial indicates that extended-release venlafaxine has potential in headache prophylaxis based on its efficacy and safety profile. We recommend a double-blind, placebo-controlled study to further assess the role of extended-release venlafaxine in headache prevention.