An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram

The selective serotonin reuptake inhibitors (SSRIs) have recently been associated with a variety of somatic and psychiatric symptoms upon abrupt drug discontinuation. These symptoms have been variously termed SSRI withdrawal, or SSRI discontinuation syndrome. Although all of the available SSRIs have been reported to cause discontinuation symptoms, some appear to have a greater propensity to cause these adverse events than others. Data from a previously completed placebo-controlled, double-blind study designed to assess citalopram in depression relapse prevention were analysed to assess patients for the emergence of discontinuation effects following randomization to placebo after 8 weeks of active drug treatment. Side-effects that occurred during the first 2 weeks following randomization to active drug (n = 150) or placebo (n = 72) were measured using the UKU unwanted side-effect list. The proportion of patients that experienced one or more events over the 2-week period following randomization was similar in the two groups, and there was no association between citalopram dose prior to randomization and the reporting of symptoms. Most of the events that did occur were mild in intensity and none resulted in discontinuation from the study. Events occurring at a higher frequency in the placebo group were most associated with the central nervous system (CNS). These events may reflect a re-emergence of depressive symptoms, since only 14.8% of patients randomized to placebo who did not relapse experienced CNS events, a low symptom incidence that was non-significant (P = 0.562) compared to patients continuing treatment (10.9%). Therefore, this assessment suggests that any symptoms associated with rapid discontinuation of citalopram are mild and transient, and emphasizes the significant role re-emerging depression and / or anxiety may play in the assessment and identification of SSRI discontinuation symptoms.     

Venlafaxine in social phobia: a study in selective serotonin reuptake inhibitor non-responders.

The study aimed to evaluate the clinical response to venlafaxine in social phobia in 12 patients who were non-responders to selective serotonin reuptake inhibitors, and to assess how the response could be influenced by the comorbidity in Axis II with avoidant personality disorder (APD). The duration of the study was of 15 weeks using open flexible doses regimen in individuals with or without concomitant APD. The venlafaxine dose ranged from 112.5 mg/day to 187.5 mg/day. Venlafaxine improves social phobia and/or APD symptomatology, as demonstrated by decreasing Liebowitz Social Anxiety Scale total scores (P < 0.05). In fact, venlafaxine significantly reduced the avoidant behaviour and specific sociophobic aspects, while notably improving the depression dimension and the basic anxiety symptoms. With regard to tolerability, the profile of venlafaxine was satisfactory with the main side-effects being nausea, headache and anxiety.     

文拉法辛缓释剂与米氮平治疗难治性抑郁症的对照研究

目的:探讨文拉法辛缓释剂与米氮平治疗难治性抑郁症(TRD)的疗效、安全性及不良反应。方法:对68例TRD病人以简单随机抽样方法分成2组,分别给予文拉法辛与米氮平治疗8 wk,用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床疗效总评量表病情严重程度(CGI-SI)评定疗效。结果:文拉法辛组治疗剂量为(196±s 48)mg·d~(-1),显效时间(8±3)d,有效率68%,米氮平组分别为(32±11)mg·d~(-1)、(12±6)d、65%。2组疗效量表评定结果均较治疗前有显著下降,特别是文拉法辛组wk 1和wk 4的HAMA减分率为(33±3)%和(50±3)%,米氮平组为(14±3)%和(31.0±2.3)%,前者下降更为明显。结论:文拉法辛缓释剂和米氮平治疗TRD疗效均较好、安全性高、不良反应少,文拉法辛缓释剂起效更快速,其抗焦虑作用更快、更佳。     

Target brain sites of the anxiolytic effect of citalopram, a selective serotonin reuptake inhibitor

The purpose of the present study was to elucidate the brain regions in which citalopram, a selective serotonin reuptake inhibitor (SSRI), exerts its anxiolytic effects in conditioned fear stress (CFS) in rats, an animal model of anxiety. The effect of citalopram on CFS-induced c-Fos expression was investigated using immunohistochemistry. Systemic administration of citalopram attenuated contextual CFS-induced c-Fos expression in the secondary motor cortex, primary somatosensory cortex, and basolateral nucleus of the amygdala. Among these regions the basolateral nucleus of the amygdala is a likely candidate region in which citalopram exerts its anxiolytic effect.     

Safety of selective serotonin reuptake inhibitor treatment in recovering stroke patients

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are widely used for psychiatric complications after stroke. Studies have indicated additional effects, and SSRIs could potentially be used as enhancers of stroke recovery. However, beneficial effects should be weighed against potential adverse effects. In particular, the possible association with cerebrovascular events has raised concern.

Areas covered: We review the literature on cerebrovascular events associated with SSRI treatment after stroke. The possible beneficial effects of SSRI treatment for stroke recovery and survival, and potential safety concerns, are discussed.

Expert opinion: Evidence suggests that SSRIs may enhance stroke recovery. Most studies on cerebrovascular risk are from non-stroke populations and little is known about recurrent events and mortality post-stroke. In non-stroke populations treatment has been associated with increased risk of intracerebral and intracranial hemorrhage; however the absolute risk is low. The association between SSRIs and ischemic stroke is less clear. Randomized stroke trials indicate that treatment is safe and well tolerated, and the most common side effects are often benign and transient. The trials are small however and not powered to detect potential differences in cerebrovascular events. We await several ongoing large randomized trials before SSRIs can be recommended as a routine pharmacotherapy in stroke recovery.     

Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression

Objective The aim of the investigation was to study the effects of withdrawing selective serotonin reuptake inhibitor (SSRI) drugs in nursing home patients, who had no documented diagnosis or symptoms of depression.Setting The setting of the study was in 11 nursing homes in the county of Stockholm, Sweden.Participants Participants were patients without dementia or history of depression who had received treatment with SSRI drugs for more than 6 months and who had no indications of anxiety disorder or major depressionDesign The included patients (n=70) were randomized to either the intervention group (withdrawal of SSRI) or the control group (no change in treatment), 35 patients to each group.Main outcome measures The patients were subjected to assessment using the following instruments: Montgomery-Åsberg depression rating scale, global assessment for functioning, health index and a symptom assessment form. Assessment was made at the start of the study and at the 3-month and 6-month follow-ups.Results We found no significant difference between the intervention and control groups in any outcome measure.Conclusion Treatment with SSRI drugs in patients without clinical major depression or anxiety disorder is often unjustified and should be discontinued.     

Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal hypersensitivity: a double-blind, placebo-controlled study

Background Tricyclic antidepressants, which have multiple pharmacological influences, have a therapeutic effect in non-cardiac chest pain, but selective serotonin reuptake inhibitors have a single pharmacological effect. Aim To evaluate the acute effect of citalopram on oesophageal hypersensitivity. Methods On two separate occasions, 10 healthy subjects (seven men, mean age 25 years) with established oesophageal hypersensitivity, underwent oesophageal manometry with evaluation of mechanical and chemical sensitivity. Subjects received placebo or citalopram 20 mg i.v. in a randomized, crossover, double-blind fashion. Results Citalopram did not alter oesophageal motility. Citalopram significantly increased the threshold inducing first perception (4.6+/-0.3 vs. 6.7+/-0.4 mL, P<0.005) and discomfort (8.6+/-0.4 vs. 9.9+/-0.6 mL, P<0.01) during balloon distention. It also significantly prolonged the acid perfusion time to induce perception of heartburn (6.0+/-0.9 vs. 10.7+/-0.6 min, P<0.005) and discomfort (12.2+/-0.8 vs. 16.7+/-0.7 mL, P<0.001). Seven subjects experienced a retrosternal sensation during edrophonium provocation with placebo, and this was reduced to two of 10 after citalopram (P=0.02). Conclusions Acute administration of citalopram significantly lowers chemical and mechanical oesophageal sensitivity in oesophageal hypersensitivity, without altering the motility.     

选择性5-羟色胺再摄取抑制剂撤药综合征42例的临床分析

目的:探讨选择性5-羟色胺再摄取抑制剂(SSRI)撤药综合征的临床特点、诱发因素及预防。方法:回顾性调查42例SSRI撤综合征的临床症状,诱发因素及处理。结果:42例撤药综合征以头晕、恶心、呕吐、头痛、感觉异常、心情低落、失眠、焦虑、激越等症状为主。撤药症状发生于停药后的1～5d,持续1～7d。42例中应用帕罗西汀27例,舍曲林6例,西酞普兰6例,氟西汀3例。诱发因素:自行突然停药30例,漏服6例,减药4例,换药2例。结论:骤停SSRI可引起撤药综合征,以帕罗西汀较易发生,应引起临床上重视。缓慢减量或使用半衰期较长的SSRI可预防撤药综合征的发生。     

N-methyl-citalopram: A quaternary selective serotonin reuptake inhibitor

We describe the synthesis and the pharmacological characterization of a new quaternary selective serotonin reuptake inhibitor (SSRI) N-methyl-citalopram (NMC) with periphery restricted action due to its inability to cross the blood brain barrier. NMC recognized and blocked the human platelet serotonin transporter (SERT) with similar affinity to that of citalopram as was evident from competition binding studies with [³H]citalopram and uptake studies with [³H]5-HT. In contrast, the affinity of NMC to rat brain SERT was 10-fold lower than its parent compound citalopram. Similarly to citalopram, NMC did not inhibit dopamine and noradrenaline uptake in rat brain synaptosomes at 10⁻⁷ M as well as [³H]ketanserin binding to rat brain membranes at 10⁻⁵ M, demonstrating its SSRI profile. A comparison of radioactivity retained in perfused mice brain following in vivo intraperitoneal injections of tritium-labeled NMC or citalopram showed that unlike citalopram, NMC did not penetrate the brain. Taken together, our observations suggest that N-methyl-citalopram is a selective serotonin reuptake inhibitor that does not penetrate the mouse brain. Epidemiological studies have suggested that chronic use of SSRI drugs may confer a protective effect against myocardial infarction (MI) apparently reflecting reduced platelet aggregation secondary to reduced platelet serotonin levels. N-methyl-citalopram may therefore have a potential as a new anti-platelet drug that does not cross the blood brain barrier and is thus devoid of the adverse CNS effects of SSRI drugs.     

A single dose of the selective serotonin reuptake inhibitor citalopram exacerbates anxiety in humans: a fear-potentiated startle study.

Serotonin reuptake inhibitors may increase symptoms of anxiety immediately following treatment initiation. The present study examined whether acute citalopram increased fear-potentiated startle to predictable and/or unpredictable shocks in healthy subjects. Eighteen healthy subjects each received two treatments, placebo and 20 mg citalopram in a crossover design. Participants were exposed to three conditions including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Changes in aversive states were investigated using acoustic startle stimuli. Citalopram did not affect baseline startle. However, the phasic startle potentiation to the threat cue in the predictable condition was robustly increased by acute citalopram. The sustained startle potentiation in the unpredictable conditions was also increased by citalopram, but only when the drug was given during the first session. These results indicate that a single dose of citalopram is not anxiogenic in itself, but can exacerbate the expression of fear and anxiety.     

Clinical significance of selective serotonin reuptake inhibitor (SSRI) in the treatment of depression

SSRIs have had a great impact on the diagnosis and treatment of depression, as well as the search for its pathophysiology. Since SSRIs have relatively few adverse effects, it is also effective for treating in a mild forms of depression, which were formerly thought to be treated adequately with only psychotherapy or anti-anxietics. Recent studies on the natural history of depression have revealed the chronicity of this disease. SSRI is now the first-line drug for the continuation and maintenance therapy of depression. Since SSRI primary acts on the serotonergic system, wide use of this drug has questioned the postulated dichotomy of the biological hypothesis of depression, the so-called serotonin depression or norepinephrine depression. A new insight into the monoamine hypothesis of depression has been yielded by SSRI. SSRIs are also effective in the treatment of anxiety disorders such as obsessive-compulsive disorder, panic disorder and social phobia. Thus, SSRIs have also brought new insight into the role of serotonin in the pathophysiology of anxiety.     

哺乳期使用选择性5羟色胺再摄取抑制剂类抗抑郁药的安全性

抑郁症是哺乳期常见的疾病之一,目前关于哺乳期使用选择性5羟色胺再摄取抑制剂(SSRI)类抗抑郁药的安全性尚缺乏足够的证据。本文就哺乳期常用的SSRI类抗抑郁药安全性研究作一综述,并给出建议。     

Treatment of depression in acute coronary syndromes with selective serotonin reuptake inhibitors

Depression in patients with acute coronary syndromes (ACS) is common and associated with impaired cardiovascular prognosis in terms of cardiac mortality and new cardiovascular events. It remains unclear whether antidepressant treatment may reverse these effects. In this review, the literature is evaluated on (i) the antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) for depression in patients with ACS; (ii) the pleiomorphic effects of SSRIs that may be associated with cardiovascular prognosis; and (iii) the effects of SSRIs on cardiovascular prognosis.SSRIs provide modest relief of depressive symptoms in selected subgroups of depressed patients with ACS. With respect to the pleiomorphic effects of SSRIs, three mechanisms of how SSRIs may improve cardiovascular prognosis are discussed: via platelet function, via the autonomic nervous system (ANS) and via vasomotor tone. Some studies show that SSRIs may reduce platelet activity and sympathetic nervous system activation, but results are inconclusive. SSRIs are associated with vasodilation but this needs to be confirmed with in vivo experiments. Some non-experimental studies describe favourable effects of SSRIs on cardiovascular prognosis. Despite recent developments, much of the effect of SSRIs on cardiovascular prognosis remains unclear. Although some studies suggest effects of SSRIs on platelet function, ANS and vasomotor tone, which may lead to improved cardiovascular prognosis, results are largely inconclusive. More well designed studies addressing these questions are needed. Moreover, since the effects of SSRIs on depression itself are limited, efforts should be dedicated to study the diagnostic validity and homogeneity of depression in the context of ACS and the presence of clinically relevant subtypes.     

阿立哌唑增效与换用文拉法辛治疗对选择性5-羟色胺再摄取抑制剂治疗抵抗抑郁症的对照研究

目的探讨加用阿立哌唑与换用文拉法辛对选择性5-羟色胺再摄取抑制剂(SSRI)类药物治疗抵抗抑郁症的疗效及安全性。方法 84例SSRI类药物系统治疗后未见显著疗效的抑郁症患者按随机数字表法分为增效组42例和换药组42例。增效组在原治疗方案的基础上加用阿立哌唑(9±5)mg/d治疗,换药组在停用原治疗药物后改用文拉法辛(154±47)mg/d治疗,疗程均为8周。采用汉密尔顿抑郁量表(HAMD-24)和大体评定量表(GAS)评定疗效,以治疗前后HAMD-24减分率≥50%作为判定显效率的依据;采用副反应量表(TESS)评价治疗的安全性。结果治疗8周后,2组患者HAMD-24评分均较治疗前显著减少(P<0.01),GAS评分均较治疗前显著增加(P<0.01)。2组患者治疗8周后HAMD-24评分及GAS评分差异均无统计学意义(P>0.05)。增效组治疗显效率为52%,换药组57%,组间差异无统计学意义(P>0.05)。2组不良反应均较轻微,总体发生率差异无统计学意义(P>0.05)。结论阿立哌唑增效与换用文拉法辛治疗对SSRI类药物治疗抵抗抑郁症均有一定疗效,2种方案的治疗效果及安全性基本相当。