Decreased suicidal ideation in depressed patients with or without comorbid posttraumatic stress disorder treated with selective serotonin reuptake inhibitors: an open study

Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MDD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from the treatment.     

Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome

Objective

Chronic pain frequently coexists with psychiatric symptoms in patients diagnosed with complex regional pain syndrome (CRPS). Previous studies have shown a relationship between CRPS and the risk of suicide. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS.

Methods

Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD), and symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I, SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI).

Results

Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p=0.002), severity of pain (p=0.024), and low scores on the GAF (p=0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep.

Conclusion

Significant risk factors for suicidal ideation in patients with CRPS include severity of pain, depressive symptoms, and decreased functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.     

Specificity of symptoms of depression in Alzheimer disease: a longitudinal analysis.

OBJECTIVE: Authors examined the temporal stability of symptoms of major and minor depression and apathy in dementia. METHODS: A consecutive sample of 65 patients with Alzheimer disease (AD) and depression at baseline evaluation received a follow-up psychiatric assessment that included the Structured Clinical Interview for DSM-IV and the Hamilton Rating Scale for Depression an average of 17 months later. RESULTS: Half of the sample had no depression at follow-up, and showed a significant improvement in sadness, guilt, suicidal ideation, disruption in sleep, loss of interest, loss of energy, thoughts of death, social withdrawal, psychomotor changes, changes in appetite/weight, and symptoms of anxiety. No significant changes were found on scores of irritability or apathy. CONCLUSIONS: The study demonstrates the specificity of depressive symptoms in AD and suggests that apathy and depression are different behavioral domains.     

Characteristics of depression in Parkinson's disease: evaluating with Zung's Self-Rating Depression Scale

The purpose of the study was to elucidate characteristics of depression in Parkinson's disease (PD). Fifty-eight PD patients were evaluated with Zung's Self-Rating Depression Scale (SDS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Scores for "suicidal ideation" on the SDS correlated with posture and gait disturbances on the UPDRS. Twenty-six patients with spinocerebellar degeneration (SCD) were also evaluated with the SDS. SDS scores for "indecisiveness" and "constipation" were significantly higher in PD patients than SCD patients. Our results suggest that depression is common in disabled persons but PD patients might have a characteristic clinical presentation.     

No evidence for an association between serum cholesterol and the course of depression and suicidality

In a number of previous reports, an association of altered, in most cases lower, serum cholesterol levels with depression, suicidal ideation and current or past suicidal behavior has been suggested. In this investigation, the course of serum cholesterol concentrations was measured in depressed patients during treatment. Ninety-two inpatients with a major depressive episode were included. Serum lipid concentrations were assessed at admission, after 1 week and after 4 weeks of antidepressant treatment. Degrees of depression and suicidality were measured with the Hamilton Depression Rating Scale. Although there was a significant reduction in depression and suicidality scores, neither a significant change in serum cholesterol levels nor a correlation between cholesterol levels and clinical improvement was found. Further, there were no significant differences in lipid levels between patients with and without a history of attempted suicide. In patients who had used a violent method, there was a trend for lower total cholesterol levels compared to those who had poisoned themselves. The results of this study do not support the hypothesis of an association of serum cholesterol with the course of depression and suicidal ideation. Cholesterol levels do not appear to be an appropriate biological marker for suicidality during the first 4 weeks of treatment in patients with a major depressive episode.     

Depression in Kraepelinian schizophrenia

In order to improve our understanding of depression in chronic schizophrenia, depressive symptoms were assessed in institutionalized, so called Kraepelinian, patients with schizophrenia (N = 43). The patients had been ill and dependent on others for at least 5 years. Depressive symptoms as measured by the Hamilton Depression (HAM-D) scale were less prevalent in this population compared to published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients had a HAM-D score >/= 16. There was also a low prevalence of core depressive symptoms (depressed mood, suicidal ideation, and guilt). The relationship of depression to other dimensions of schizophrenia was explored. Depression had a modest positive correlation (r = 0.44) with general psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as measured by BPRS positive subscale or negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS). Depression also showed a modest positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian schizophrenia, depression is not prevalent, even though patients are severely ill both in symptom and functioning domains. The results of our analysis support that Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia. Finally, the low rate of depression observed revives the notion that preservation of core functional abilities is important for a depressive reaction to evolve in schizophrenia.     

Platelet serotonin-2 receptor binding sites in depression and suicide

In order to examine the role of serotonin-2 (5HT2) receptors in depression and suicide, we determined 5HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the binding ligand in platelets obtained from 20 normal control and 23 drug-free depressed patients. Our results indicate significantly increased 125I-LSD binding sites (Bmax) in the platelets of depressed patients compared with normal control subjects. We also observed that a subgroup of depressed patients with a recent history of suicide attempts or suicidal ideation had significantly higher 5HT2 binding sites as compared with nonsuicidal depressed patients and normal controls. There were no significant differences in the apparent dissociation constant (Kd) values in the platelets of depressed patients compared with normal control subjects. To examine if the baseline 5HT2 receptors are related to either the severity of illness or treatment response, we determined the relationships of the baseline Bmax and Kd with baseline Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS) scores and change in scores after treatment. We found no significant correlation between baseline Bmax and Kd with the baseline HDRS or BPRS scores or change in these scores after psychoactive drug treatment. These results thus indicate increased platelet 5HT2 receptors in depression, but much more so in depressed patients with suicidal ideation or attempts.     

The prediction of suicidal intent in depressed patients

The aim of the present study was to examine the relationships between suicidal ideation or suicidal attempts and severity of depression, presence of personality disorders, and sociodemographic factors in a population of depressed in-patients. A total of 338 adult depressed psychiatric in-patients were examined and classified according to DSM-III criteria as having major depression with or without melancholic or psychotic features, adjustment disorder with depressed mood or dysthymic disorder. Scores on the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and Zung Self-Rating Depression and Anxiety Scales (SDS and SAS) were measured. We found that suicidal ideation was significantly related to severity of depression (according to the HDRS and all self-rating scales), a lower global assessment of functioning the year before hospitalization, and previous psychiatric hospitalizations. The items with the strongest predictive value for suicidal ideation were hopelessness, depressed mood, feelings of guilt, loss of interest and low self-esteem. These symptoms predicted 43% of the variance in suicidal ideation. None of the above predictors of suicidal ideation was related to suicidal attempts. Depressed patients with a personality disorder attempted significantly more suicidal attempts and showed more suicidal ideation than depressed patients without personality disorder. No significant correlations were found between suicidal ideation or suicide attempts and gender, marital status, employment status or psychosocial stressors during the previous 6 months.     

5-羟色胺和胆固醇水平对抑郁症患者再次自杀风险评估的研究

目的 探讨抑郁症患者血小板5-羟色胺（5-HT）和胆固醇水平与抑郁症患者再次自杀的关系.方法 对33例有自杀行为的抑郁症患者在接受治疗前测定血小板5-HT和胆固醇水平,评定汉密尔顿抑郁量表（HAMD-24）和Beck绝望量表（BHS）,然后进行2年的随访.结果 16例患者再次出现自杀行为,再次自杀组血小板5-HT及血清胆固醇水平显著低于无再次自杀组（P＜0.01）.5-HT和血清胆固醇水平与HAMD-24、BHS分及自杀次数、自杀严重程度均呈负相关（P＜0.01）,且5-HT与血清胆固醇水平呈正相关（P＜0.01）.多重回归分析显示血小板5-HT浓度、家族史是自杀次数的主要影响因素.结论 低血小板5-HT及血清胆固醇浓度是抑郁症自杀的危险因素,对抑郁症自杀行为可能具有一定的的预测作用.     

Diagnostic validity of assessment scales for depression in patients with schizophrenia

The aim of this study was to examine the diagnostic validity of four commonly used assessment scales for depression in schizophrenia. The study population consisted of 84 inpatients meeting the DSM-IV criteria for schizophrenia. Depression in the study subjects was defined by the DSM-IV criteria for major depressive episode. The Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Rating Scale (SARS) were used to differentiate depression from the negative and extrapyramidal symptom-related depressive phenomena in schizophrenia. The following four depression scales were assessed for their diagnostic validity as measures of depressive disorder in schizophrenia: the Calgary Depression Scale for Schizophrenia (CDSS), the Beck Depression Inventory (BDI), the Hamilton Rating Scale for Depression (HAM-D), and the depression subscale of the PANSS (PANSS-D). Of 84 patients with schizophrenia, 32 were diagnosed as having comorbid depressive disorder. The areas under the Receiver Operating Characteristic (ROC) curves of the CDSS, HAM-D, PANSS-D, and BDI were 0.94, 0.89, 0.90, and 0.81, respectively. The area under the ROC curve of the CDSS was significantly greater than that of the BDI and tended to be more favorable than those for the HAM-D and the PANSS-D. Our study suggests that the CDSS may provide the best assessment for depression in patients with schizophrenia.     

Mirtazapine in major depression with comorbid generalized anxiety disorder.

BACKGROUND: A high proportion of patients with generalized anxiety disorder (GAD) have comorbid depressive illness. The presence of anxiety in depression has significant prognostic implications. Because of mirtazapine's early anxiolytic effects, the present study was undertaken as a preliminary investigation in patients with a diagnosis of major depression with comorbid GAD. METHOD: Mirtazapine was administered to 10 patients with DSM-IV major depressive disorder and comorbid GAD in an 8-week open-label study. Mirtazapine was increased from an initial daily dose of 15 mg to a maximum daily dose of 45 mg. RESULTS: Patients were found to have significant reductions in Hamilton Rating Scale for Depression scores, Hamilton Rating Scale for Anxiety scores, and Beck Depression Inventory scores, with improvement noted after the first week of therapy and continuing improvement over the 8 weeks of study. CONCLUSION: These positive preliminary findings support the further investigation of mirtazapine's potential value as a treatment for generalized anxiety disorder in addition to its established efficacy as an antidepressant drug.     

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.     

Hopelessness and suicidal ideation in outpatients with treatment-resistant depression: prevalence and impact on treatment outcome

Depression and hopelessness are risk factors for suicide. The purpose of this study was to examine the extent of suicidal ideation and hopelessness in outpatients with treatment-resistant depression (TRD) and to study the impact of suicidal ideation and hopelessness on treatment with nortriptyline (NT). The degree of suicidal ideation and hopelessness was assessed during the screen visit with the use of items #3 and #30 of the Hamilton Depression Rating Scale (HAM-D) in 89 patients with TRD who entered a 6-week open trial of NT. Forty of these patients also completed the Beck Hopelessness Index (BHI) during the screen visit. In separate logistic regressions, the scores from the BHI and the two HAM-D items were then tested as predictors of clinical response to the 6-week trial with NT, controlling for the severity of depression. More than half of patients reported thoughts or wishes of death to self and significant hopelessness. A greater degree of hopelessness before treatment in completers, reflected by the score on the HAM-D item #30, predicted response to NT. More than half of patients with prominent hopelessness who completed the trial responded. Patients with TRD are more likely than not to report prominent suicidal ideation and hopelessness. Furthermore, a full 6-week trial of NT, a relatively noradrenergic tricyclic antidepressant, may be particularly useful in patients who have failed to respond to several antidepressants and also report significant hopelessness.     

How does antiepileptic drug induce suicidality? A case associated with levitracetam use

New antiepileptic drugs have been known to increase the risk of suicide. Among them, levitracetam is a widely used antiepileptic drug approved as a monotherapy treatment for partial seizures or as an adjunctive therapy for partial, myoclonic and generalized tonic–clonic seizures. It has been reported that the incidence of suicidal ideation during treatment with levitracetam was about 0.5–0.7%, but an explanation regarding a mechanism by which it causes suicidality is lacking. We made a multifaceted approach using the Hamilton Depression Rating Score (HDRS), the Hamilton Anxiety Rating Score (HARS), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Beck Scale for Suicidal Ideation (BSS) ideation daily and the Sheehan Suicidality Tracking Scale (SSTS) weekly in a patient taking levitracetam who acutely developed suicidal ideation after starting the medication. Suicidal ideation disappeared within 5 days of levitracetam discontinuation. We found that decreasing HDRS and BHS scores were correlated with BSS and SSTS scores. On the other hand, HARS and BIS did not change from their baselines. Our findings suggest that suicidality induced by an antiepileptic drug may be related to depression rather than anxiety and impulsiveness.     

Platelet serotonin uptake in drug-naïve depressive patients before and after treatment with citalopram

We investigated the kinetic parameters of serotonin (5-HT) uptake into platelets in a group of 26 drug-na?ve patients suffering from major depression before and after 3-7 weeks of treatment with citalopram. The degree of depression was rated using the Hamilton Depression Rating Scale (HDRS). The 5-HT uptake characteristics in untreated depressive patients were not significantly different from those of normal subjects. The apparent Michaelis constant (K(M)) was significantly increased, the apparent maximal velocity (V(max)) was not different from baseline, and the uptake efficiency (V(max)/K(M)) was significantly decreased after citalopram treatment. A significantly positive correlation between K(M) and V(max) was found in all groups. There was a significantly lower V(max) and V(max)/K(M) in the female compared with the male depressed patients before citalopram treatment; a hypothesis was supported that lowered 5-HT uptake may reflect a gender-linked vulnerability to a serotonin-related depression. A significant negative correlation between 5-HT uptake efficiency and the initial HDRS score suggests that platelet 5-HT uptake can be used as a marker of effective depressive disorder pharmacotherapy. The initial severity of depression was significantly negatively correlated with V(max), which supported a hypothesis that the initial severity of depressive disorder could be related to the lower V(max).     

Association between AKT1 gene polymorphisms and depressive symptoms in the Chinese Han population with major depressive disorder

For this study, 461 Chinese Han patients with depressive disorder were recruited. The AKT1 genotype and allele distribution were determined by PCR amplification and direct sequencing. UNPHASED software was used to analyze associations between the 17-item Hamilton Depression Rating Scale, total score, four factors and the AKT1 rs2494746 and rs3001371 polymorphisms. The results indicate that there is a significant association between suicidal ideation and anxiety symptoms in depressed patients and the rs2494746 polymorphism. The other AKT1 polymorphism, rs3001371, was significantly associated with work and activities. Patients with the rs3001371-A allele had a significantly more severe illness compared to patients with the rs3001371-G allele. Thus, AKT1 polymorphisms appear to be associated with depression severity, anxiety symptoms, work and activities, and suicide attempts in patients with depressive disorder.     

Pilot randomized clinical trial of an SSRI vs bupropion: effects on suicidal behavior, ideation, and mood in major depression

Randomized controlled trials in depressed patients selected for elevated suicidal risk are rare. The resultant lack of data leaves uncertainty about treatment in this population. This study compared a serotonin reuptake inhibitor with a noradrenergic/dopaminergic antidepressant in major depression with elevated suicidal risk factors. We conducted a double-blind, randomized, clinical pilot trial of paroxetine (N=36) or bupropion (N=38) in DSM IV major depression with a suicide attempt history or current suicidal ideation. The effects during acute (8 weeks) and continuation treatment (up to 16 weeks) were measured. Main outcomes were suicidal behavior and ideation. The secondary outcome was modified 17-item Hamilton Depression Rating Scale score subtracting the suicide item (mHDRS-17). Treatment was not associated with time to a suicidal event and no treatment main effect or treatment × time interaction on suicidal ideation or mHDRS-17 was found. Exploratory model selection showed modest advantages for paroxetine on: (1) mHDRS-17 (p=0.02); and (2) in a separate model adjusted for baseline depression, for suicidal ideation measured with the Beck Scale for Suicidal Ideation (p=0.03), with benefit increasing with baseline severity. Depressed patients with greater baseline suicidal ideation treated with paroxetine compared with bupropion appeared to experience greater acute improvement in suicidal ideation, after adjusting for global depression. Given the lack of evidence-based pharmacotherapy guidelines for suicidal, depressed patients-an important public health population-this preliminary finding merits further study.     

The functional neuroanatomy of mental pain in depression

This study aimed at determining the functional neuroanatomy of mental pain, a hitherto neglected symptom in the study of depression, which according to DSM-IV is stronglylinked with suicide. Mental pain (measured with the Orbach & Mikulincer Mental Pain Scale), suicidal ideation (measured using the Hamilton Rating Scale for Depression), hopelessness (measured using Beck's Hopelessness Scale), and regional cerebral blood flow as measured with single photon emission computed tomography were assessed in 39 depressed individuals. Levels of mental pain were significantly and positively associated with suicidal ideation and levels of hopelessness. When compared with patients with low levels of mental pain, those with high levels of mental pain showed relatively increased perfusion in the right dorsolateral prefrontal cortex, occipital cortex and inferior frontal gyrus and in the left inferior temporal gyrus, and relatively decreased perfusion at the medulla. The findings indicate that mental pain in depressed patients is associated with an increased risk of suicide and that high levels of mental pain are associated with changes in perfusion in brain areas that are involved in the regulation of emotions. Further study is warranted to understand whether this association reflects increased emotional processing or decreased cognitive control over mental pain in depressed individuals.     

社会支持对重性抑郁障碍患者自杀意念的影响

目的探讨社会支持对重性抑郁障碍(MDD)患者自杀意念的影响,为临床降低其自杀意念、减少自杀行为的发生提供参考。方法采用二阶段调查法,以在武汉市精神卫生中心门诊就诊的、符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准的1135例MDD患者为研究对象。采用患者健康问卷抑郁量表(PHQ-9)、社会支持评定量表(SSRS)进行调查,采用二元Logistic回归分析探讨MDD患者自杀意念的影响因素。结果1135例MDD患者中,有688例(60.62%)存在自杀意念,有自杀意念者PHQ-9评分高于无自杀意念者,差异有统计学意义[(14.18±5.02)分vs.(11.07±4.61)分,t=10.497,P<0.01]。有自杀意念者的主观支持、对支持的利用度及SSRS总评分均低于无自杀意念者,差异均有统计学意义(P均<0.01)。以自杀意念为因变量,以客观支持、主观支持、对支持利用度及PHQ-9评分为自变量的二元Logistic回归模型为logit(P)=-0.286+0.026X1-0.035X2-0.063X3+0.128X4,其中主观支持和抑郁均对自杀意念有预测作用(B=-0.035、0.128,P<0.05或0.01)。结论存在抑郁症状及缺乏社会支持(尤其是主观支持)可能是MDD患者出现自杀意念的危险因素。     

Diagnosis of major depression in cancer patients according to four sets of criteria

Diagnoses of major depression in 152 cancer patients differed as much as 13% depending on the diagnostic system used. The Beck Depression Inventory and the Hamilton Rating Scale for Depression were useful tools for screening patients with depressive symptoms but frequently misclassified those who had no major depression according to one or more of the criteria-based diagnostic systems.