Post-stroke sleep disorder treated with the selective serotonin reuptake inhibitor citalopram—a case study

Even though stroke patients not uncommonly suffer from sleep disturbance, post-stroke sleep disorder is one of the least studied sequela of stroke. We present a case study providing polysomnographic evidence for the successful alleviation of persistent insomnia in a non-depressed stroke patient by treatment with the selective serotonin reuptake inhibitor citalopram. During open treatment with citalopram the patient's sleep efficiency index improved considerably, and REM latency gradually increased. Possible causes of post-stroke insomnia are discussed, and the suggestion is made that post-stroke sleep disorder might possibly be attributable to stroke-induced disruption of pathways involved in the neurophysiology of sleep, e.g. serotonergic neurotransmission.     

Autoreceptors remain functional after prolonged treatment with a serotonin reuptake inhibitor

Serotonin (5-hydroxytryptamine, 5-HT) autoreceptors may desensitize during prolonged administration of antidepressant drugs. If autoreceptors desensitize, their inhibitory influence on extracellular 5-HT should be attenuated. To test this hypothesis, the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg kg(-1), s.c., b.i.d.) or saline was administered for 14 days to rats. After a 24-h washout period, rats were anesthetized, and implanted with dialysis probes for determination of 5-HT in the frontal cortex (FCx) and dorsal hippocampus (DH). In response to citalopram (5 mg kg(-1), s.c.) challenge, there were moderate increases in 5-HT in the FCx and DH of both the chronic citalopram and saline pretreatment groups. After subsequent administration of the 5-HT(1A/1B) autoreceptor antagonist, (-)-penbutolol, there were further increases in 5-HT in the FCx and DH of the saline pretreatment group. Moreover, contrary to the expected effect if autoreceptors were desensitized, the potentiation produced by (-)-penbutolol was greater in the FCx and DH of the chronic citalopram group as compared to rats pretreated with saline. These results suggest that autoreceptors still restrain the increase in 5-HT produced by an SSRI after prolonged administration.     

Persistent blockade of potassium-evoked serotonin release from rat frontocortical terminals after fluoxetine administration

We examined 5-HT and 5-HIAA release from frontal cortex evoked by high potassium chloride concentrations in rats pretreated for 3 days with high doses of the 5-HT uptake blocker fluoxetine or of dexfenfluramine, which both releases 5-HT and blocks its reuptake. The standard fluoxetine dose (30 mg/kg i.p.) was about 4 times the drug's ED₅₀ in producing a serotonin-related behavioral effect, anorexia, while the dexfenfluramine dose (7.5 mg/kg i.p.) was about 6 times its ED₅₀. These high doses were chosen in order to elucidate the mechanism by which similar doses of fluoxetine and dexfenfluramine had been found to produce long-term changes in serotonin dynamics. Fluoxetine decreased the basal release of both compounds; dexfenfluramine decreased basal 5-HIAA efflux without affecting the release of 5-HT release. Potassium-evoked 5-HT release was unchanged after dexfenfluramine pretreatment but was suppressed by fluoxetine doses as low as 7.5 mg per kg per day. Basal release of 5-HT and 5-HIAA returned to normal after 7 days of fluoxetine pretreatment, but evoked relase continued to be suppressed. These data suggest that long-term changes in brain serotonin dynamics after high doses of dexfenfluramine or fluoxetine are related to the drug's mechanisms of action, specifically their blockade of 5-HT reuptake.     

Use of the selective serotonin reuptake inhibitor citalopram in treatment of trichotillomania

Previous trials of selective serotonin reuptake inhibitors (SSRIs) in the treatment of trichotillomania have provided conflicting data. Furthermore, the efficacy of citalopram, the most selective of the SSRIs, in trichotillomania has not previously been documented. Citalopram was used on an open-label naturalistic basis in 14 (1 male and 13 females) patients who presented with chronic hair pulling and met DSM-IV criteria for trichotillomania. Ratings were completed every 2 weeks for 12 weeks, during which time dosage was increased to a maximum of 60 mg daily (mean dose 36.2 ± 13.9 mg). One patient was unable to tolerate citalopram. In completers, ratings on each of the scales employed were significantly improved after treatment. Of completers 38.5% were responders (Clinical Global Impressions score of 2 or less) at week 12. Citalopram appears to be safe in trichotillomania, and it may be effective in a subset of patients. Given the relatively low response rate, however, a controlled trial is needed before this agent can be said to be more effective than placebo. The pharmacotherapy of trichotillomania deserves further study.     

Evaluation of [3H]paroxetine as an in vivo ligand for serotonin uptake sites: A quantitative autoradiographic study in the rat brain

Paroxetine, a selective inhibitor of serotonin uptake and an antidepressant, was used in conjunction with quantitative ex vivo autoradiography to study the feasibility of imaging serotonin terminals in the living brain. Tritiated paroxetine was injected in the rat tail vein, and the brain was processed for quantitative autoradiography 3 hours later. Animals received either [³H]paroxetine alone (100 μCi/animal) or a mixture of labeled paroxetine (100 μCi) and an excess of unlabeled drug (0.5 or 2 mg/kg intravenously [i.v.]). Computerized image analysis of the resulting autoradiograms revealed high densities of radioactivity in brain regions known to contain high densities of serotonergic terminals and high specific binding of [³H]paroxetine in vitro, such as the raphe nuclei, interpeduncular nucleus, basolateral amygdala, substantia nigra, and some hypothalamic nuclei. Radioactivity uptake in these brain regions was effectively blocked (50-72%) by coadministration of excess unlabeled paroxetine. However, cortical and hippocampal binding of paroxetine in vivo was moderately high, in contrast to the relatively sparse serotonergic innervation in these regions. Only a relatively small proportion of cortical and hippocampal binding (20-40%) could be blocked by excess unlabeled paroxetine, indicating that most of the radioactivity in these regions is not associated with serotonin terminals or uptake sites. The usefulness of [³H]paroxetine as an in vivo ligand for imaging serotonin terminals in the human brain is limited by these nonserotonergic binding sites. © 1993 Wiley-Liss, Inc.     

In vivo studies on the enhancement of serotonin reuptake by tianeptine

The present study investigates the in vivo effects of the serotonin uptake enhancer tianeptine. The serotonin metabolite, 5-hydroxy-indolacetic acid (5-HIAA) was measured by in vivo voltammetry and carbon fiber electrodes chronically implanted in different brain areas of freely moving rats. Tianeptine (10 mg/kg i.p.) increased extracellular 5-HIAA in the hippocampus and hypothalamus. The interaction between tianeptine and drugs known to interfere with the uptake or release of serotonin (sertraline, buspirone, D-norfenfluramine) was then studied and, to ascertain the in vivo pharmacological relevance of tianeptine's effects, its ability to reduce the serotoninergic syndrome was evaluated. Both the biochemical and behavioral data indicate that in vivo tianeptine's effects on the serotoninergic system are likely to be due to serotonin uptake enhancement.     

High-dose sildenafil citrate for selective serotonin reuptake inhibitor-associated ejaculatory delay: open clinical trial

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI)-induced ejaculatory delay is a common problem that has no treatment with established efficacy. Sildenafil citrate is effective for erectile dysfunction and appears to be safe at doses up to 200 mg. METHOD: We enrolled men who were in remission from depression according to DSM-IV criteria and who reported that they had developed new-onset ejaculatory delay in the setting of SSRI treatment. Enrolled patients were instructed to use 25 mg of sildenafil 1 hour prior to sexual activity on at least 2 occasions. If this was not effective for the ejaculatory delay, they were instructed to increase the dose progressively up to a maximum of 200 mg. We compared baseline sexual functioning to 2 phases of open treatment: low-dose phase (sildenafil 25-100 mg) and high-dose phase (sildenafil 150-200 mg). The primary outcome measure was a modified, self-report Clinical Global Impressions (CGI) scale that was specific for erectile (CGI-EF) and ejaculatory (CGI-EJF) aspects of sexual function. RESULTS: Twenty-one men (mean age = 56 years) with major depressive disorder (MDD) in remission and SSRI-associated ejaculatory delay enrolled in the study and received sildenafil. At baseline, 14 of 21(67%) had comorbid erectile dysfunction. At the low-dose phase follow-up assessment, 12 of 14 achieved full erectile dysfunction remission, and 4 of 21 achieved ejaculatory delay remission. Sixteen patients with persistent ejaculatory delay were eligible for the high-dose phase: 5 withdrew from the study, 4 increased to a maximum dose of 150 mg, and 6 increased to a maximum dose of 200 mg. The 1 patient who had clinically significant erectile dysfunction and ejaculatory delay reported improvement of both conditions after the high-dose phase. Of the 10 patients who had ejaculatory delay without significant erectile dysfunction and who chose to take high-dose sildenafil, 9 reported a significant clinical improvement in ejaculatory delay (CGI-EJF improvement score of 1 or 2) and 7 achieved full remission (CGI-EJF severity score of 1 or 2 and CGI-EJF improvement score of 1 or 2). CONCLUSION: In this open clinical trial with men who had SSRI-induced ejaculatory delay, high-dose sildenafil appeared to be effective in reducing ejaculatory latency.     

On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor

Antidepressant drugs are reported to be used as co-analgesics in clinical management of migraine and neuropathic pain. The mechanism through which they alleviate pain remains unknown. The present study explores the possible mechanism of a selective serotonin reuptake inhibitor (SSRI) fluoxetine-induced antinociception in animals. Acetic acid-induced writhing, hot plate and tail-flick test were used to assess fluoxetine-induced antinociception. Fluoxetine (5-20 mg kg(-1), i.p.) produced a significant and dose-dependent antinociceptive effect against acetic acid-induced writhing in mice. Fluoxetine (20 mg kg(-1)) also exhibited antinociceptive effect in tail flick as well as hot plate assays. Further, i.c.v. administration of fluoxetine showed significant antinociception against writhing test in rats. However, fluoxetine (1 microg/10 microl/rat, i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals. Further, pindolol (10 mg kg(-1), i.p.) enhanced fluoxetine-induced antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to blockade by naloxone (5 mg kg(-1), i.p.) and naltrexone (5 mg kg(-1), i.p.). These data suggest that fluoxetine-induced antinociception involves both central opioid and the serotoninergic pathways.     

Preclinical profiling and safety studies of ABT-769: a compound with potential for broad-spectrum antiepileptic activity

PURPOSE: The objective of this study was to characterize the antiseizure and safety profiles of ABT-769 [(R)-N-(2 amino-2-oxoethyl)spiro[2,5]octane-1-carboxamide]. METHODS: ABT-769 was tested for protection against maximal electroshock and pentylenetetrazol-induced seizures in the mouse and for suppression of electrically kindled amygdala seizures and spontaneous absence-like seizures in the rat. The central nervous system safety profile was evaluated by using tests of motor coordination and inhibitory avoidance. The potential for liver toxicity was assessed in vitro by using a mitochondrial fatty acid beta-oxidation assay. Teratogenic potential was assessed in the mouse. RESULTS: ABT-769 blocked maximal electroshock, subcutaneous pentylenetetrazol and intravenous pentylenetetrazol-induced seizures with median effective dose (ED50) values of 0.25, 0.38, and 0.11 mmol/kg, p.o., respectively. No tolerance was evident in the intravenous pentylenetetrazol test after twice-daily dosing of ABT-769 (0.3 mmol/kg, p.o.) for 4 days. ABT-769 blocked absence-like spike-wave discharge (ED50, 0.15 mmol/kg, p.o.) and shortened the cortical and amygdala afterdischarge duration of kindled seizures (1 and 3 mmol/kg, p.o.). The protective indices (ED50 rotorod impairment/ED50 seizure protection) were 4.8, 3.2, and 10.9 in the maximal electroshock, subcutaneous pentylenetetrazol and intravenous pentylenetetrazol seizure tests, respectively. ABT-769 did not affect inhibitory avoidance performance (0.1-1 mmol/kg, p.o.). ABT-769 did not affect mitochondrial fatty acid beta-oxidation or induce neural tube defects. CONCLUSIONS: ABT-769 is an efficacious antiseizure agent in animal models of convulsive and nonconvulsive epilepsy and has a favorable safety profile. ABT-769 has a broad-spectrum profile like that of valproic acid. Its profile is clearly different from those of carbamazepine, phenytoin, lamotrigine, topiramate, vigabatrin, and tiagabine.     

Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: a practical clinical trial

Clinical effectiveness of group cognitive-behavioral therapy (GCBT) versus fluoxetine in obsessive-compulsive disorder outpatients that could present additional psychiatric comorbidities was assessed. Patients (18-65 years; baseline Yale-Brown Obsessive-Compulsive-Scale [Y-BOCS] scores ≥ 16; potentially presenting additional psychiatric comorbidities) were sequentially allocated for treatment with GCBT (n=70) or fluoxetine (n=88). Mean Y-BOCS scores decreased by 23.13% in the GCBT and 21.54% in the SSRI groups (p=0.875). Patients presented a mean of 2.7 psychiatric comorbidities, and 81.4% showed at least one additional disorder. A reduction of at least 35% in baseline Y-BOCS scores and CGI ratings of 1 (much better) or 2 (better) was achieved by 33.3% of GCBT patients and 27.7% in the SSRI group (p=0.463). The Y-BOCS reduction was significantly lower in patients with one or more psychiatric comorbidities (21.15%, and 18.73%, respectively) than in those with pure OCD (34.62%; p=0.034). Being male, having comorbidity of Major Depression, Social Phobia, or Dysthymia predicted a worse response to both treatments. Response rates to both treatments were similar and lower than reported in the literature, probably due to the broad inclusion criteria and the resulting sample more similar to the real world population.     

A randomized controlled clinical trial of Citalopram versus Fluoxetine in children and adolescents with obsessive-compulsive disorder (OCD)

Objective  Several controlled trials have demonstrated the efficacy and safety of Fluoxetine in children and adolescents with Obsessive-Compulsive Disorder (OCD), but there is no controlled study on the effectiveness of Citalopram in this group. This report describes the use of Citalopram in comparison with Fluoxetine in childhood-onset OCD. Method  This study is a randomized, double blind, fixed-does (20mg) trial of Fluoxetine versus Citalopram in 29 children and adolescents (17 boys and 12 girls) with OCD, aged 7–18 years (mean 13.8 and SD 3.05). The length of study was 6 weeks. Obsessive-Compulsive symptom severity was measured by Yale–Brown Obsessive-Compulsive Scale (CY-BOCS) and Clinician’s Global Impression Scale (CGI). DICA (Diagnostic Interview of Children and Adolescents) was used to diagnose the psychiatric disorders. Results  Each group showed significant improvement over the baseline as measured by the CY-BOCS (p < 0.01) but not by CGI (p = NS). The Comparison between two groups showed no significant differences in efficacy and safety of the drugs. Most common adverse effects were headache for Citalopram and tremor for Fluoxetine. Conclusion  The results suggest that Citalopram is as safe and effective as Fluoxetine for children and adolescents with OCD. Further studies are needed to replicate our findings.     

文拉法辛对选择性5-羟色胺再摄取抑制剂治疗无效的抑郁症患者的疗效

目的研究文拉法辛对选择性5羟色胺再摄取抑制剂(SSRI)治疗无效的抑郁症患者的治疗效果。方法对经SSRI治疗8周而无明显疗效的34例抑郁症患者以文拉法辛治疗6周(研究组),剂量为(100±20)mg/d。在文拉法辛治疗前及治疗后第1,2,4,6周末评定汉密尔顿抑郁量表(17项,HAMD),并进行临床疗效评定,监测血压,记录不良反应。选择同期门诊34例年龄、诊断与研究组相匹配的患者作为对照组,给予文拉法辛治疗6周,剂量为(99±25)mg/d。结果两组患者的HAMD评分均从第1周末起明显下降(P<005或P<001),且一直持续至治疗第6周末。研究组治疗第6周末的有效率达68%(23/34),临床治愈率达53%(18/34);对照组分别为77%(26/34)和59%(20/34)。两组间的差异无统计学意义(P>005)。研究组口干、恶心、呕吐的发生率高于对照组,差异有统计学意义(P<005)。结论文拉法辛对SSRI治疗8周而无明显疗效的抑郁症患者有较好的疗效。     

Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy

Clinical research has demonstrated differential efficacy of selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which may relate to differential acute effects these medications have on emotional brain processes. Here we present findings from a Multi-Level Kernel Density Analysis meta-analysis that integrates and contrasts activations from disparate fMRI studies in order to examine whether single dose SSRIs and NRIs have different effects on emotion processing tasks in healthy participants. Seven SSRI and four NRI studies were eligible for inclusion. SSRIs decreased amygdala responses, suggesting reduced emotional reactivity to emotional stimuli, whereas NRIs increased frontal and medial activation, suggesting increased emotion regulation. As hypothesised, an interaction of antidepressant and task type was found, such that SSRIs modulated amygdaloid-hippocampal, medial and frontal activity during both the presentation of faces and pictures, whereas NRIs only modulated the activation in medial and frontal regions during the presentation of pictures. Findings are interpreted within a novel model of the differential effects of SSRIs and NRIs on emotion processing.     

Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors

We have previously shown that chronic treatment with selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and paroxetine, attenuated m-chlorophenylpiperazine (mCPP)-induced hypolocomotion in rats. The effect of these SSRIs on the response to mCPP is thought to be caused by the desensitization of 5-HT2C receptor function. In the present study, we investigated whether chronic administration of SSRI could reduce another pharmacological response to mCPP in rats, i.e., the induction of the secretion of corticosterone. The mCPP-induced increase in the serum concentration of corticosterone was not blocked by the 5-HT2C antagonist SB242084, but was blocked by the 5-HT2A antagonist ketanserin. Chronic treatment with fluvoxamine and paroxetine attenuated the response to mCPP, while these SSRIs had no effects in control rats. These results suggest that the desensitization of 5-HT2A receptor function occurs in the same way as that of 5-HT2C receptor function through chronic treatment with either fluvoxamine or paroxetine as a consequence of prolonged exposure to elevated levels of serotonin. The hypersensitivity of 5-HT2A receptors is observed in depressed patients, and chronic treatment with many antidepressants such as tricyclic antidepressants have been reported to reduce 5-HT2A receptor density and/or efficacy. The desensitization of 5-HT2A receptor function might contribute to the therapeutic mechanism of action of these SSRIs, as seen with other classes of antidepressants.     

In vivo autofluorescence spectrofluorometry of central serotonin

The autofluorescence properties of serotonin (5-HT) were investigated by light spectrofluorometry in in vitro, ex vivo and in vivo experiments. Ex vivo samples were prepared from rat brain regions containing serotonin (5-HT) i.e. cortex, striatum, hippocampus. Rats were untreated (controls) or previously submitted to chronic behavioural or pharmacological treatments known to affect endogenous 5-HT levels. Autofluorescence analysis (excitation: 366 nm) on hippocampus homogenates supplied with exogenous 5-HT revealed spectral alterations attributable to changes of endogenous 5-HT levels. In vivo, real time fluorescence studies were performed via a 50 microm diameter optic fiber probe stereotaxically implanted into selected brain areas of anaesthetised rats treated with fluoxetine or 5-OH-tryptophan. All autofluorescence data were consistent with those obtained in parallel experiments performed with ex vivo or in vivo voltammetry, confirming that auto-fluorescence spectroscopy is a suitable technique for the direct assessment of fluorescent neurotransmitters. This is a reliable evidence of the in vivo application of spectroscopy together with optic fiber probe for in vivo, in situ and real time measurement of 5-HT in discrete brain areas.     

选择性5-羟色胺再摄取抑制剂对抑郁症患者快动眼睡眠肌电活动的影响

目的 观察选择性5-羟色胺再摄取抑制剂(SSRIs)对抑郁症患者的快动眼(REM)睡眠肌张力的影响.方法 选择年龄和性别匹配的接受SSRIs治疗的抑郁患者(治疗组,21例)、未接受SSRIs治疗的抑郁患者(未治疗组,21例)和正常对照组(21例),根据Lapierre和Montplaisir的标准重新评估每组患者每个REM睡眠包含的张力性和位相性肌电活动.结果 (1)REM睡眠张力性:治疗组[(10.1±9.4)%]与未治疗组[(3.3±3.7)%]和正常对照组[(2.8±3.4)%]比较,REM睡眠张力性增加,差异有统计学意义(P＜0.001).(2)位相性肌电活动:治疗组[(11.5±6.8)%]与未治疗组[(6.3±4.1)%]和正常对照组[(5.0±3.7)%]比较,颌肌位相性肌电活动增加,差异有统计学意义(P＜0.05);治疗组[(18.8±13.2)%]与未治疗组[(10.3±7.2)%]和正常对照组[(9.8±5.5)%]比较,胫骨前肌位相性肌电活动增加,差异有统计学意义(P＜0.05).(3)治疗组REM睡眠的张力性和位相性肌电活动均与REM潜伏期呈正相关(γ=4.475,γ=0.397,γ=0.402),与REM比例呈负相关(γ=-0.353,γ=-0.511,γ=-0.463).结论 SSRIs阻碍了抑郁症患者REM睡眠肌张力消失.     

Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.     

Occupancy of the serotonin transporter by fluoxetine,paroxetine, and sertraline: In vivo studies with [125i]rti-55

[¹²⁵I]RTI-55 was used in tracer doses to label serotonin (5-HT) transporters in vivo in the mouse brain. Fluoxetine, paroxetine, and sertraline, potent antidepressants and selective inhibitors of serotonin transporter sites, were administered in various doses and at various times. The doses and times that result in significant binding of the drugs to transporters correspond to doses and times where they are reported to have physiological effects. Estimates of occupancy rate and duration of binding to serotonin transporters were made. The rate of occupancy of the 5-HT transporter site was fastest for sertraline, intermediate for paroxetine and slowest for fluoxetine. Similarly, the duration of occupancy was significantly shorter for sertraline and paroxetine (approximately 10 h) than for fluoxetine (approximately 50 h). The results indicate that in competition studies, [¹²⁵I]RTI-55 can be used to identify doses of drugs that are physiologically effective, to determine their relative rate of occupancy, and most importantly, to measure the residency time on the central serotonin transporter in vivo. © 1994 Wiley-Liss, Inc.     

Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder

Patients with major depressive disorder (MDD) usually suffer from altered cognitive functions of episodic memory, working memory, mental processing speed and motor response. Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD. The aim of this work is to study the effects of serotonergic reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments to improve the performance on memory tasks and mental processing speed in MDD. Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery. The subjects were medicated with escitalopram (n = 36) or duloxetine (n = 37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same neuropsychological battery used prior to the treatment. Both treatments improved importantly the episodic memory and to a lesser extent, working memory, mental processing speed and motor performance. Our results suggest that cognition is partially independent from improvement in clinical symptoms. Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment, but SNRI was superior to SSRI at improving episodic and working memory. Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinically relevant.