Differences in cytokines between non-suicidal patients and suicidal patients in major depression

Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamilton's depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.     

Reduced platelet BDNF level in patients with major depression

Serum and plasma brain-derived neurotrophic factor (BDNF) levels as well as brain BDNF have previously been shown to be decreased in patients with major depressive disorder (MDD). We explored whether platelet BDNF levels, circulating stored BDNF, would be lower in MDD patients than in normal controls. BDNF levels were examined in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in 20 hospitalized non-suicidal MDD patients, 20 recent-suicidal MDD patients, and 20 normal controls. Platelet BDNF content was calculated by subtracting PPP BDNF level from PRP BDNF level, and dividing the result by the total platelet count, and it was expressed as pg/10⁶ platelets. Individuals were evaluated using a Structured Clinical Interview for DSM-IV and a Hamilton Depression Rating Scale. Platelet BDNF contents were significantly lower in non-suicidal patients (3.09 ± 2.53 pg/10⁶ platelets) and recent-suicidal MDD patients (3.16 ± 1.99 pg/10⁶ platelets) than in healthy controls (6.17 ± 2.64 pg/10⁶ platelets) (p < 0.01). However, platelet BDNF contents had no significant differences between non-suicidal and recent-suicidal patients. PRP BDNF levels were also significantly lower in non-suicidal and suicidal MDD patients than in healthy controls (p = 0.029), while PPP BDNF had no significant difference between 3 groups (p = 0.971). Our findings suggest that there is a decrease in the platelet BDNF of patients with major depression. Reduced platelet BDNF contents as circulating stored BDNF could be associated with lower serum BDNF level in patients with major depression.     

TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression

Background

Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior.

Methods

One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by χ² statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype.

Results

There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the lethality of suicidal behavior in suicidal depressed patients according to the genotypes of three polymorphisms.

Conclusion

Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.     

Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients

BACKGROUND: Several studies have suggested that there is a substantial genetic contribution to suicidal behavior. Genes encoding proteins involved in serotonergic transmission are major candidates in association studies of suicidal behavior. In this study, we aimed to investigate the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for association with suicidal behavior in depressive patients. METHODS: Patients with major depression who had recently attempted suicide (n=191) and control subjects (n=193) were genotyped for 5HTR2A 102T/C, and TPH 218A/C. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured using the Hamilton Depression Rating Scale (HDRS). RESULTS: There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. CONCLUSIONS: We concluded that these polymorphisms may not be associated with susceptibility to suicidal behavior in our Korean population. Our results were in line with most previous studies. More work is needed to replicate these findings. Our future studies aim at identifying other genetic associations.     

Increased plasma nitric oxide level associated with suicide attempt in depressive patients

BACKGROUND: Nitric oxide (NO) is known to influence cerebral monoaminergic activity, including the activity of serotonin. We evaluated plasma NO metabolite (NO(x)) levels in depressive patients with and without a recent history of suicide attempt. METHOD: Plasma NO(x) levels were measured in 39 depressive patients who had recently attempted suicide, 44 non-suicidal depressed patients, and 70 normal controls. The severity of depression was measured with the Hamilton's Depression Rating Scale. The lethality of the suicide attempt was scored using Weisman and Worden's risk-rescue rating scale and Lethality Suicide Attempt Rating Scale. RESULTS: Plasma NO(x) levels were significantly higher in suicidal depressive patients than non-suicidal depressive patients or normal control subjects (Z=-2.472, p=0.013). However, higher plasma NO(x) levels in suicidal depressive patients were significantly related to a lower lethality of suicide attempts and lower severity of depression. CONCLUSIONS: Our study suggests that increased plasma NO(x) level is associated with suicide attempts in depressive patients. Moreover, higher plasma NO(x) level is related with suicide attempts in mild depressed patients. However, further studies are required to understand the role of NO system in depression and suicidal behavior.     

Cytokine levels in the blood may distinguish suicide attempters from depressed patients

Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressed patients, as well as healthy controls.Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS).We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication.These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.     

抑郁发作自杀未遂患者脑源性神经营养因子水平及其相关因素研究

目的 探讨脑源性神经营养因子(BDNF)在抑郁发作自杀未遂者中的可能作用.方法 对抑郁发作自杀未遂患者(自杀未遂组,23例)和抑郁发作无自杀行为患者(无自杀组,24例)采用汉密尔顿抑郁量表(24项,HAMD24)、Beck绝望量表(BHS)和自杀意念自评量表(SIOSS)评定抑郁严重程度、绝望程度及自杀意图的强烈程度;采用酶联免疫吸附法测定其血清BDNF浓度,并与正常对照者(对照组,30名)比较;对自杀未遂组的血清BDNF浓度与各相关因素进行Pearson相关分析.结果 (1)自杀未遂组的HAMD24[(37.8±8.7)分]、BHS[(13.0±3.8)分]及SIOSS评分[(18.1±3.9)分]均高于无自杀组[分别为(26.0±6.0)分、(7.5±4.3)分、(12.0±4.0)分;P<0.01].(2)自杀未遂组的BDNF平均浓度[(57 ±16)ng/L]低于无自杀组[(75 ±28)ng/L;P<0.05],无自杀组的BDNF平均浓度亦低于正常对照组[(111±39)ng/L;P<0.01].(3)自杀未遂组的血清BDNF浓度与抑郁发作的病程(r=-0.541)、BHS总分(r=-0.494)、SIOSS总分(r=-0.754)呈负相关(P<0.01-0.05).结论 低水平的BDNF可能是抑郁发作自杀未遂的一个危险因素.     

Suicidal status during antidepressant treatment in 789 Sardinian patients with major affective disorder

Objective: Relationships between antidepressant treatment and suicidality remain uncertain in major depressive disorder (MDD), and rarely evaluated in bipolar disorder (BPD). Method: We evaluated changes in suicidality ratings (Hamilton Depression Rating Scale item‐3) at the start and after 3.59 ± 2.57 months of sustained antidepressant treatment in a systematically assessed clinical sample (n = 789) of 605 patients with MDD, 103 patients with BPD‐II and 81 patients with BPD‐I (based on DSM‐IV; 68.1% women; aged 44.3 ± 16.1 years), comparing suicidal vs. non‐suicidal and recovered vs. unrecovered initially suicidal patients. Results: Suicidal patients (103/789, 16.5%; BPD/MDD risk: 2.2) were more depressed and were ill longer. During treatment, 81.5% of suicidal patients became non‐suicidal; 0.46% of 656 initially non‐suicidal patients reported new suicidal thoughts, with no new attempts. Becoming non‐suicidal was associated with greater depression severity and greater improvement. Conclusion: Suicidal ideation was prevalent in patients with depressed major affective disorder, but most of the initially suicidal patients became non‐suicidal with antidepressant treatment, independent of diagnosis, treatment type or dose.     

抑郁症自杀未遂患者血清脑源性神经营养因子水平的变化

目的探讨血清脑源性神经营养因子（BDNF）水平与抑郁症患者自杀行为的关系。方法采用酶联免疫分析实验测定抑郁症自杀未遂患者（36例）、无自杀行为患者（55例）及36名正常对照血清BDNF水平,对抑郁症患者以汉密尔顿抑郁量表（HAMD）评定抑郁症状,以自杀意念自评量表（SIOSS）评定自杀意念的强烈程度。结果抑郁症患者组血清BDNF水平低于正常对照组（P〈0．01）。自杀未遂组血清BDNF水平低于无自杀组及正常对照组（P〈0．01）。自杀未遂组HAMD总分和SIOSS总分高于无自杀组。抑郁症患者血清BDNF水平与SIOSS总分呈负相关。结论抑郁症患者存在血清BDNF降低,BDNF水平可能是自杀倾向行为的生物学标志。     

Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants

Numerous studies have demonstrated that depression is associated with a decreased expression of brain-derived neurotrophic factor (BDNF). BDNF shows antidepressant-like effects in animal models. Therefore, we tested the hypothesis that BDNF might be a peripheral marker for the mechanism of action of antidepressant agents in humans. Thirty-two patients meeting the DSM-IV criteria for major depressive disorder and 50 normal control subjects were recruited for this study. Plasma BDNF levels and Hamilton Depression Rating Scales were measured at baseline and 6 weeks after antidepressant administration. At baseline, the mean plasma BDNF level was lower in the depressive patients (698.1 +/- 537.7 pg/ml) than in the control subjects (830.7 +/- 624.8 pg/ml), although the difference was not statistically significant (p = 0.33). The plasma BDNF levels in depressive patients significantly increased from 698.1 +/- 537.7 to 1,028.9 +/- 744.5 after 6 weeks of antidepressant treatment (p = 0.01). Moreover, plasma BDNF levels were significantly increased after 6 weeks of treatment in the responder group, while there was no statistically significant change in the unresponsive group. These results suggest that the therapeutic response after antidepressant administration might be attributable to the increase in BDNF levels. BDNF may play a critical role in the action mechanism of antidepressant drugs. Further studies with a larger number of subjects are needed to verify these findings.     

抑郁症患者自杀行为与血清脑源性神经营养因子水平的关系

目的:探讨血清脑源性神经营养因子(BDNF)水平与抑郁症患者自杀行为之间的关系.方法:采用酶联吸附反应方法对有自杀行为的21例抑郁症患者(自杀组)、无自杀行为的52例抑郁症患者(非自杀组)以及80例正常人(对照组)血清的BDNF进行检测,应用汉密尔顿抑郁量表(HAMD)对抑郁症患者的抑郁症状进行评定. 结果:抑郁症患者...     

Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression

Although many studies have examined the neurobiological aspects of suicide, the molecular mechanisms and pathophysiologic mechanisms associated with suicide remain unclear. In this study, it is aimed to investigate whether there is a difference in serum brain-derived neurotrophic factor (BDNF) levels among suicide attempters without a major psychiatric disorder, compared to major depressive disorder patients and healthy subjects. It was undertaken with the hypothesis that suicide per se lowers serum BDNF levels, since it is a source of stress. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Ten suicide attempters, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. All subjects were asked to give their written consent. Blood samples were collected at the baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA kit (Promega; Madison, Wisc., USA) after dilution with the block and sample solution provided with the kit. The data were subjected to the Kruskal-Wallis test for nonparametric analysis of variance. Mean serum BDNF levels were significantly lower in the suicide group (21.2 +/- 12.4 ng/ml) and the major depressive disorder group (21.2 +/- 11.3 ng/ml) than the control group (31.4 +/- 8.8 ng/ml; p = 0.004). These results suggest that BDNF may play an important role in the neurobiology of suicidal behavior. BDNF levels may be a biological marker for suicidal behavior. To investigate the role of BDNF in suicide, further studies with a wider sample size and a variety of psychiatric diagnoses accompanying suicide attempt are needed.     

Serum lipid levels and suicidality among male patients with schizoaffective disorder

Suicidal behavior in schizoaffective disorder is a serious problem and suicide risk during lifetime ranges between 5%-10%. Neurobiology of suicidal behavior has not been studied sufficiently, and a high number of studies are oriented toward lipid investigation. The aim of our study was to investigate whether there were differences in the level of lipids (cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) in hospitalized suicidal (n=20) and non-suicidal (n=20) patients with schizoaffective disorder. The study also included male healthy control subjects (n=20). Hamilton Depression Rating Scale (HDRS-17), and Positive and Negative Syndrome Scale (PANSS) were used to confirm the level of psychopathology in patients with schizoaffective disorder. Severity of suicidality was measured by Scale for Suicide Ideation (SSI) at time of admission. Results of the study indicated significantly lower concentrations of cholesterol (p<0.001), LDL-cholesterol (p<0.01) and HDL-cholesterol (p<0.01). There were no differences in the number of previous hospitalization and previous suicide attempts between suicidal and non-suicidal patients (p>0.05). Duration of the illness was significantly (p<0.05) shorter in suicidal patients. Suicidal patients also had a significantly higher score on HDRS-17 (p<0.001) and PANSS (p<0.01) compared to non-suicidal patients.     

Citalopram and suicidality in adult major depression and anxiety disorders

The suicide-related data on citalopram from controlled clinical trials in depression and anxiety disorders were analysed. Safety data from placebo-controlled and relapse prevention citalopram trials in depression/major depressive disorder (MDD) and anxiety were searched for specific events relating to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item 10, suicidal thoughts, on the Montgomery–Åsberg Depression Rating Scale [MADRS]) were also analysed. In the clinical trial database, the number of adverse events (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during the first 2?weeks of treatment and during the full treatment period, with no statistically significant differences between citalopram and placebo. There was one fatal suicide during treatment (after 12?weeks of double-blind treatment in a relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%; rate: 0.010) and none on placebo. Citalopram was significantly more efficacious than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item 10). There was no indication from this review of clinical trial data that citalopram may increase the risk of suicide in patients with MDD or anxiety. However, the patients in these clinical trials represent a selected group, as those patients with a significant risk of suicide were excluded at trial onset.     

CSF-hypocretin-1 levels in patients with major depressive disorder compared to healthy controls

Depressive patients exhibit symptoms of impaired regulation of wakefulness with hyperarousal and agitation as well as difficulties to falling asleep and preserving sleep continuity. Changes in hypocretin (hcrt) levels as polypeptides with impact on arousal and sleep-wake-regulation have been discussed in affective disorders but have not been investigated in patients with solely unipolar depression in comparison to healthy controls. In the present study, cerebrospinal fluid (CSF) levels of hcrt-1 for the first time were analyzed in patients with major depressive disorder (MDD) without psychiatric comorbidities and compared with levels in healthy controls. In 17 inpatients with MDD (mean Hamilton Depression Rating Scale 13.9 ± 7.4) and 10 healthy controls, CSF-hcrt-1 levels were measured using a fluorescence immunoassay (FIA). The mean hcrt-1 CSF levels in patients with MDD (74.3 ± 17.8pg/ml) did not differ compared to that of healthy controls (82.8 ± 22.1pg/ml). Hcrt-1 levels did not correlate with the severity of depressive episode, the symptoms of depression or the number of episodes. Although autonomic and neurohumoral signs of hyperarousal are common in MDD, hcrt-1 levels in CSF were not found to be altered in MDD compared to healthy controls. Whether hcrt-1 levels are altered in depressive patients exhibiting impaired vigilance regulation has to be investigated in further studies combining measures of CSF-hcrt-1 with electroencephalography.     

Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder

Objective

The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD).

Methods

Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal controls. Hamilton''s 17-item Depression Rating Scale (HDRS), the Risk-Rescue rating system (RRR) and the Lethality Suicide Attempt Rating Scale updated (LSARS-II) were assessed for the depressed patients.

Results

Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. Comparing allele frequency, those with a 10 allele or 10 allele carriers were higher in suicidal subjects than in control subjects. No difference was noted in 5-HTTLPR genotypes and haplotype distribution between the suicidal subjects and control subjects. The RRR scores in subjects with the 10/10 5-HTTVNTR genotype or 10 5-HTTVNTR allele were significantly lower than those in subjects with other genotypes.

Conclusion

These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.     

Suicidal Behavior and Insight into Illness Among Patients with Schizophrenia Spectrum Disorders

The purpose of the present study was to explore the relationship between suicidal behavior and socio-demographic and clinical factors, including insight into illness, in patients with schizophrenia spectrum disorders. We evaluated 104 inpatients using the Self-Appraisal of Illness Questionnaire (SAIQ) for insight assessment, several Beck-related symptoms rating scales, and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. These patients were also evaluated for suicidal behavior and risk using the critical items of the Scale for Suicide Ideation (SSI) and lifetime suicide attempts. Patients with suicidal behavior generally had greater insight into illness than those who were non-suicidal. After controlling for depressive symptoms, the association of insight into illness with current suicidal ideation remained significant, whereas the association between insight and lifetime suicide attempts was no longer significant. As predicted, the regression analyses revealed that those with greater suicide risk had significantly higher levels of depressive symptoms and hopelessness and more lifetime suicide attempts. Moreover, greater insight into illness appeared to have a close, independent connection to suicidal behavior. Our findings suggest that depression, hopelessness, and greater insight into illness are major risk factors for suicide in patients with schizophrenia. It is plausible that depression mediates the relationship between greater insight into illness and suicidal behavior. Aggressive improvement of insight without the risk of deteriorating depressive symptoms may be warranted to reduce the risk of suicide.     

Gender effect of catechol-O-methyltransferase Val158Met polymorphism on suicidal behavior

Genetic factors and catecholaminergic dysfunction have been suggested as the etiology of suicide. The catechol-O-methyltransferase (COMT) 158Val/Met polymorphism affects COMT activity; that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. We aimed to identify the role of the COMT Val158Met polymorphism in suicidal attempt behavior. The COMT 158Val/Met polymorphisms were analyzed in 197 suicide attempters (male/female: 70/127), 170 control subjects (male/female: 85/85). All subjects were ethnic Korean. The Lethality Suicide Attempt Rating Scale (LSARS) and risk-rescue rating (RRR) system were explored. For the male subjects, there was a significant difference in genotype distributions and allele frequencies between control subjects and suicide attempters. That is, Val/Val genotype and Val carriers were more frequent in suicide attempters than in control subjects. For the female subjects, however, no significant difference was shown in genotype distributions and allele frequencies between control subjects and suicide attempters. There were no significant differences in LSARS and RRR according to the genotypes. The distribution of the COMT 158Val/Met polymorphism showed a biologically meaningful difference between control subjects and suicide attempters among the male subjects although selection bias should be considered.     

Citalopram and suicidality in adult major depression and anxiety disorders

The suicide-related data on citalopram from controlled clinical trials in depression and anxiety disorders were analysed. Safety data from placebo-controlled and relapse prevention citalopram trials in depression/major depressive disorder (MDD) and anxiety were searched for specific events relating to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item 10, suicidal thoughts, on the Montgomery-Asberg Depression Rating Scale [MADRS]) were also analysed. In the clinical trial database, the number of adverse events (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during the first 2 weeks of treatment and during the full treatment period, with no statistically significant differences between citalopram and placebo. There was one fatal suicide during treatment (after 12 weeks of double-blind treatment in a relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%; rate: 0.010) and none on placebo. Citalopram was significantly more efficacious than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item 10). There was no indication from this review of clinical trial data that citalopram may increase the risk of suicide in patients with MDD or anxiety. However, the patients in these clinical trials represent a selected group, as those patients with a significant risk of suicide were excluded at trial onset.