Mortality of patients with mood disorders: follow-up over 34-38 years

BACKGROUND: All follow-up studies of causes of death in affective disordered patients have found they have markedly elevated suicide rates and a less reproducible increased mortality from other causes. The reported rates by gender, disorder type and treatment are more variable. METHODS: Hospitalised affective disordered patients (n=406) were followed prospectively for 22 years or more. Later, mortality was assessed for 99% of them at which time 76% had died. RESULTS: Standardised Mortality Rates (observed deaths/expected deaths) for patients were elevated especially for suicide and circulatory disorders in both men and women. Women actually had higher suicide rates but that did not take into account the twofold increase in general population rates for men. Unipolar patients had significantly higher rates of suicide than bipolar Is or IIs. In all groups long term medication treatment with antidepressants alone or with a neuroleptic, or with lithium in combination with antidepressants and/or neuroleptics significantly lowered suicide rates even though the treated were more severely ill. Although at the age of onset the suicide rates were most elevated, from ages 30 to 70 the rates were remarkably constant despite the different courses of illness. LIMITATIONS: The patients were identified as inpatients and followed prospectively. The treatments were uncontrolled and are not quantifiable but were documented during the follow-up. CONCLUSIONS: Men and women hospitalised for affective disorders have elevated mortality rates from suicide and circulatory disorders. Unipolars have higher suicide rates than bipolar Is or IIs. Long term medication treatment lowers the suicide rates, despite the fact that it was the more severely ill who were treated.     

Suicide mortality in patients on lithium maintenance therapy

Mood disorders are frequently recurrent and it has been shown that maintenance treatment can reduce long-term morbidity in this condition. It has also been shown that mood disorders carry an increased risk of suicide and that a significant proportion of individuals who commit suicide suffer from a mood disorder. This paper reports the results of a long term follow-up of a cohort of patients attending a specialist mood disorder clinic over a period of 18 years. Sixty-seven suffered from unipolar depression and 36 had bipolar or schizo-affective disorders In order to qualify for entry to the cohort the unipolar patients had to have had at least three episodes of depression and those with bipolar disorders had to have had at least three episodes – with at least one manic episode and one depressive episode. All patients were treated with lithium. The initial treatment refusal rate and drop our rates were low. The mortality from suicide in this group was compared with that reported in five recent studies – all of which involved patients who had not been given maintenance therapy. The standardised mortality ratio (SMR) for all causes for the whole group was 0.93. There were two suicides. In one case the patient had continued treatment with lithium until death and in the other the patient had discontinued treatment 12 months before death. The overall suicide rate was 1.3 per 1000 patient years. Amongst similar groups of patients who had not been given maintenance therapy suicide rates of about 5.5 per 1000 patient years have been reported. It is concluded that maintenance treatment of mood disorders reduces the suicide rate in this vulnerable group of patients.     

Suicides and parasuicides in a high-risk patient group on and off lithium long-term medication.

68 patients with affective disorders, and receiving lithium prophylaxis in a specialized lithium clinic were followed up for 8 years on average. Patients were selected for this study according to 2 criteria: They had been given lithium for at least 12 months, and they had attempted suicide at least once before onset of lithium prophylaxis. Outcome was analysed in terms of suicidal and parasuicidal behaviour. 55 patients took their lithium regularly, 13 discontinued or dropped the medication. One third of those patients having discontinued the medication died from suicide. Only one suicide occurred in patients with regular lithium intake and proven compliance during the last check before death. An impressive drop of parasuicides was observed in responders as well as in apparent non-responders. In total, 11 of 13 patients showed suicidal or parasuicidal behaviour 2 weeks-44 months after lithium discontinuation, which in about half of these cases took place on advice or with consent of the treating psychiatrist. It is concluded that lithium may have specific anti-suicidal properties, possibly related to its anti-aggressive effect, and that patients apparently not responding satisfactorily in terms of reduced number of episodes may still be protected against suicide or parasuicide.     

Suicide in current psychiatric in-patients: a case-control study The National Confidential Inquiry into Suicide and Homicide

BACKGROUND: Few controlled studies have investigated factors associated with suicide in current in-patients. We aimed to identify psychosocial, behavioural and clinical risk factors, including variations in care, for in-patient suicide. METHOD: We conducted a national population-based case-control study of people who died by suicide between 1 April 1999 and 31 December 2000 while in psychiatric in-patient care in England. Cases were 222 adult mental health in-patients who died by suicide matched on date of death with 222 living controls. RESULTS: Nearly a quarter of suicides took place within the first week of admission; most of these died on the ward or after absconding. After the first week, however, most suicides occurred away from the ward, the majority of patients having left the ward with staff agreement. Previous deliberate self-harm, recent adverse life events, symptoms of mental illness at last contact with staff and a co-morbid psychiatric disorder were associated with increased risk for suicide. Being off the ward without staff agreement was a particularly strong predictor. Those patients who were detained for compulsory treatment were less likely to die by suicide. Independent predictors of in-patient suicide were male sex, a primary diagnosis of affective disorder and a history of self-harm. Being unemployed or on long-term sick leave appeared to be independently protective. CONCLUSION: Prevention of in-patient suicide should emphasize adequate treatment of affective disorder, vigilance in the first week of admission and regular risk assessments during recovery and prior to granting leave. Use of compulsory treatment may reduce risk.     

Does lithium reduce the mortality of recurrent mood disorders?

Numerous follow-up studies have shown that patients with mood disorders who do not receive prophylactic medication are at increased risk of death, particularly from suicide. After 11 years follow-up we compared the mortality of 103 patients attending a lithium clinic with that expected on the basis of age/sex/year-specific rates for England and Wales. Only 10 patients died during the study, although the expected number of deaths was 18.31 (P = 0.052, two-tailed) and no deaths from suicide were observed. After correcting for the prevalence of mood disorder in the general population, the relative risk was 0.60 (95% CI 0.29-1.12) which suggests that lithium reverses the excess mortality associated with recurrent mood disorders, including that from suicide.     

Can ECT prevent premature death and suicide in ‘schizoaffective’ patients?

Mortality and suicide risks were higher in schizoaffective patients who had not received ECT compared to those having received ECT. The data are from a follow-up study of 74 schizoaffective patients admitted to University of Iowa Psychiatric Hospital between 1934 and 1944; these patients were traced in 1975. Even though the nature of schizoaffective disorder is still unknown, patients who present both schizophrenic and affective features, particularly with suicide risk, may benefit from ECT by lowering their mortality risk.     

Suicide attempts amongst elderly bipolar patients

BACKGROUND: Bipolar disorder is associated with high risk of suicide. In the elderly suicide rates are the highest of all age groups. There is a paucity of data regarding suicide amongst elderly bipolar patients. Mood stabilizers and particularly lithium are established as "antisuicide" compounds. OBJECTIVE: We aimed to evaluate the association between exposure to psychotropic drugs and suicide attempts in a cohort of elderly patients suffering from bipolar affective disorder (BAD). METHOD: This was a preliminary, retrospective, matched, case-controlled evaluation over a 10-year period. All records of admissions of patients with BAD (ICD-10) were assessed. The index group comprised all patients who had attempted suicide in the month prior to admission. The control group consisted of the next admission of a patient suffering from BAD, matched for sex and age who had not attempted suicide in the month prior to admission. RESULTS: The index group during the period 1995 to 2004 consisted of 16 patients, (8 men and 8 women.), mean age 74.8 +/- 1.3 years. The control group patients (N = 16) were matched for age (mean 74.3 +/- 1.5 years) and sex. The number of patients who had a history of a suicide attempt was significantly greater in the index group (7/16 vs., 2/16; p = 0.039). In the control group patients treated by both a mood stabilizer and an antidepressant were at a significantly lower risk for recent suicide attempt (p = 0.047). LIMITATIONS: Sample size is small, treatments were not standardized and data were collected retrospectively. CONCLUSION: Elderly BAD patients treated with mood stabilizers and antidepressants may be at reduced risk of attempting suicide. These findings need support from prospective randomized trials.     

Suicide and other causes of mortality in bipolar disorder: a longitudinal study

BACKGROUND: The high risk of suicide in bipolar disorder is well recognized, but may have been overestimated. There is conflicting evidence about deaths from other causes and little known about risk factors for suicide. We aimed to estimate suicide and mortality rates in a cohort of bipolar patients and to identify risk factors for suicide. METHOD: All patients who presented for the first time with a DSM-IV diagnosis of bipolar I disorder in a defined area of southeast London over a 35-year period (1965-1999) were identified. Mortality rates were compared with those of the 1991 England and Wales population, indirectly standardized for age and gender. Univariate and multivariate analyses were used to test potential risk factors for suicide. RESULTS: Of the 239 patients in the cohort, 235 (98.3%) were traced. Forty-two died during the 4422 person-years of follow-up, eight from suicide. The standardized mortality ratio (SMR) for suicide was 9.77 [95% confidence interval (CI) 4.22-19.24], which, although significantly elevated compared to the general population, represented a lower case fatality than expected from previous literature. Deaths from all other causes were not excessive for the age groups studied in this cohort. Alcohol abuse [hazard ratio (HR) 6.81, 95% CI 1.69-27.36, p=0.007] and deterioration from pre-morbid level of functioning up to a year after onset (HR 5.20, 95% CI 1.24-21.89, p=0.024) were associated with increased risk of suicide. CONCLUSIONS: Suicide is significantly increased in unselected bipolar patients but actual case fatality is not as high as previously claimed. A history of alcohol abuse and deterioration in function predict suicide in bipolar disorder.     

Serious suicide attempts in affective patients.

A retrospective study was carried out including all patients who in the previous 6 years had required admission to our hospital for medical or surgical reasons following attempted suicide (n = 257). Those diagnosed as having affective disorder (n = 96), according to DSM-IIIR criteria, were compared with the other non-affective suicide attempters (n = 161). Affective patients were significantly different in that they were older, more often women, married or widowed, usually used non-violent methods, made more serious attempts and presented a higher incidence of concomitant physical illness. Affective patients with a history of previous attempts were more likely to be recurrent unipolar depressives or first episode unipolars with a concurrent diagnosis of personality disorder. Most of the depressed patients made the attempt within the first 12 months of the episode. Patients who attempted suicide in the first 12 months of the depression were more likely to use non-violent methods and to receive a diagnosis of bipolar or unipolar recurrent disorder.     

Mortality in affective disorders

BACKGROUND: To investigate the mortality rates in affective disorders due to unnatural and natural causes with respect to illness subtype and social-demographic features. METHODS: Mortality data were determined from a prospective study of 354 outpatients with affective disorders during a follow-up period of 5 years. Death from natural and unnatural causes was compared to sex- and age-specific expectations in the general population. Standardized mortality rates (SMR) in diagnostic subgroups and the influence of social-demographic features were investigated. RESULTS: The observed 30 deaths represented nearly three times (SMR, 2.9) the number expected on the basis of age- and sex-standardized reference population rates. Death from natural causes occurred with the same rate as expected (SMR, 1.0), death from unnatural causes was 28.8 times higher than expected. Women with affective disorders had a considerable high risk to die from unnatural causes (SMR, 47.1). A significant excess of unnatural death was found in all subtypes of affective disorders, particularly in recurrent major depressive episodes (SMR, 46.7). LIMITATIONS: The sample was restricted in size. Therefore subgroup differences and multiple relationships of risk factors could not be analyzed with high statistical power. CONCLUSIONS: The results corroborate earlier findings of excess mortality in major affective disorders and strengthen the view that suffering from recurrent major depression confers per se an important biological risk for suicide. Natural causes of death in affective disorders are comparable to expectations from reference populations. Social-demographic characteristics may contribute to an additional risk of premature death by suicide, particularly in women.     

Family history of completed suicide and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study

BACKGROUND: Clinicians routinely ask patients with non-psychotic major depressive disorder (MDD) about their family history of suicide. It is unknown, however, whether patients with a family member who committed suicide differ from those without such a history. METHODS: Patients were recruited for the STAR*D multicenter trial. At baseline, patients were asked to report first-degree relatives who had died from suicide. Differences in demographic and clinical features for patients with and without a family history of suicide were assessed. RESULTS: Patients with a family history of suicide (n=142/4001; 3.5%) were more likely to have a family history of MDD, bipolar disorder, or any mood disorder, and familial substance abuse disorder, but not suicidal thoughts as compared to those without such a history. The group with familial suicide had a more pessimistic view of the future and an earlier age of onset of MDD. No other meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. CONCLUSIONS: A history of completed suicide in a family member was associated with minimal clinical differences in the cross-sectional presentation of outpatients with MDD. Limitations of the study include lack of information about family members who had attempted suicide and the age of the probands when their family member died. STAR*D assessments were limited to those needed to ascertain diagnosis and treatment response and did not include a broader range of psychological measures.     

Association study of p11 gene with major depressive disorder, suicidal behaviors and treatment response

The p11 protein (also called S100A10), which plays a pivotal role in the dynamic modulation of serotonergic 1B receptor function, has been implicated in the pathogenesis of major depressive disorder (MDD) and the therapeutic mechanisms of antidepressant action. Humans and mice with depression have lower central p11 levels, and treatment with antidepressant agents raises p11 levels in animals. Furthermore, brain p11 mRNA expression is lower in post mortem brains from patients who were suffering from depression and had committed suicide compared with control subjects who had died from other causes. From the above findings, the p11 gene may be considered a candidate gene for the investigation of MDD susceptibility, response to antidepressants or the likelihood of attempting suicide. Three p11 polymorphisms were genotyped in 470 patients with MDD and 447 normal controls. No significant association with MDD was discovered in single locus or haplotype analyses. The analysis for genotypic effects showed no significant association between any of the three p11 single nucleotide polymorphisms (SNPs) and MDD therapeutic response. With regard to the risk of suicide attempt, 51 of the 470 MDD patients were found to have attempted suicide in the depressive episode during which they were monitored. No significant association with suicide attempt was shown in both the alleles and genotypes of single loci or of haplotypes constructed from these three p11 polymorphisms. Our findings suggest that p11 genetic variants do not play a major role in the MDD susceptibility, antidepressant therapeutic response or the risk of suicide attempt in MDD.     

Malignancy of recurrent, early-onset major depression: a family study.

Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (> or = 2 episodes), early-onset (< or = 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members.     

Depression as a prognostic factor for breast cancer mortality

It is unclear if depression or depressive symptoms have an effect on mortality in breast cancer patients. In this population-based, nationwide, retrospective cohort study in Denmark, depression was defined as affective or anxiety disorders that necessitated psychiatric hospital admission. All the affective and anxiety disorders were divided and categorized into five ordinal diagnostic groups. Early-stage (N=10382) and late-stage (N=10211) breast cancer patients were analyzed separately with Cox's regression adjusted for well-documented somatic prognostic variables. The authors used survival analysis of data from three central registers and found that breast cancer patients with depression had a modestly but significantly higher risk of mortality depending on stage of breast cancer and time of depression. The same result was found after censoring unnatural causes of death such as accident, suicide, or homicide.     

Depression and cancer: a follow-up study

Thirty-nine male and 90 female patients aged 40 and over, who had been given a primary diagnosis of depression, were followed up for 2 1/3-4 years. During this period 9 male and 9 female patients died. Five male patients and 1 female died from cancer that had not been diagnosed at the time of their psychiatric admissions. The male cancer deaths are significantly higher than expected. The possible relationships of malignant neoplasm to affective disorder are discussed.     

Mortality among patients with schizophrenia and reduced psychiatric hospital care

BACKGROUND: There are suggestions that mortality, especially that due to suicide, increases among schizophrenia patients during a period of declining psychiatric beds. We investigated the mortality of schizophrenia patients in the general population of Finland during the reduction of psychiatric beds during 1980-1996. METHOD: Patients hospitalized for schizophrenia before 31 December 1996, and alive on 1 January 1980 (n = 58761) were identified via the National Hospital Discharge Register. General population data came from the National Population Register, and mortality data from the National Causes of Death Register. We calculated relative risks (RR) for total mortality, mortality due to natural causes (cancer, ischaemic heart disease, respiratory disease), unnatural causes (accident, homicide, suicide), and suicide. RESULTS: Patients with schizophrenia had an increased mortality both from natural causes (RR 2.59, 95% CI 2.55-2.63) and from suicide (RR 9.9, 95% CI 9.43-10.30). The RR for both natural and unnatural deaths was highest among patients with < 5 years since onset of schizophrenia. Among them all-cause mortality rose in the 1990s, but decreased among patients with > 10 years from onset. Otherwise no major changes or linear trends were found in mortality during deinstitutionalization. CONCLUSIONS: Reduction of psychiatric beds did not generally increase the mortality of patients with schizophrenia. However, patients in their early years of illness experienced increased mortality after the steepest bed reduction. Improved recognition and treatment of somatic illness would benefit patients with schizophrenia.     

Mortality in offspring of mothers with psychotic disorder

BACKGROUND: Previous studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders. METHOD: The Helsinki High-Risk Study follows up offspring (n=337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population. RESULTS: Within the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24, p=0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p<0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p<0.0001). CONCLUSIONS: Offspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.     

Plasma GABA levels in psychiatric illness

In two separate studies, we have obtained plasma levels of GABA in 134 psychiatric patients and 22 normal controls. Patients with a unipolar affective disorder had levels significantly lower than control (n = 58) as did patients with alcoholism (n = 10). Patients with a bipolar affective disorder had levels significantly higher than control when manic (n = 28) and also when euthymic on lithium prophylaxis (n = 17), but levels in the control range when depressed (n = 4). Patients with schizophrenia demonstrated a high degree of variability in their levels of plasma GABA but were not statistically different from control (n = 36). Patients with unipolar depression who received a dexamethasone suppression test had no correlation between nonsuppression of cortisol secretion and plasma levels of GABA. Diagnostic and research implication of plasma GABA in psychiatric illness are discussed.     

住院精神病人死亡案例分析

目的探讨降低精神病人住院死亡率及医疗纠纷的措施。方法对我科1998年至2007年共10年期间住院死亡的精神病人病案进行回顾性调查,内容包括死亡原因及相关因素。结果研究期间总住院7682人次,住院期间死亡12例,死亡率0.16%;死亡原因：自杀4例,躯体疾病死亡3例,中毒3例,猝死及多脏器衰竭各1例;死亡案例中,有6例发生医疗纠纷。结论自杀是我科住院精神病人死亡的主要原因,其次为躯体疾病致死、中毒死亡;对风险较大的患者,从各个环节采取相应措施,更有利于降低精神病人住院死亡率及医疗纠纷。     

Lithium,anticonvulsants and suicidal behavior in bipolar disorder

BACKGROUND: Lithium has been found to be effective in reducing suicide rates during long term treatment of patients with bipolar disorders. Data on the efficacy of anticonvulsant mood stabilizers in reducing suicide risk are sparse. METHOD: Charts of 140 bipolar patients treated continuously for a minimum of 6 months during a 23-year period of private practice by the senior author were extracted from nearly 4000 patient records. Data extracted from the charts were incidence of completed suicide, number of suicide attempts, and number of hospitalizations for suicidal ideation or behavior per 100 patient-years of either 'on' or 'off' lithium or anticonvulsant mood stabilizer monotherapy. RESULTS: Only one completed suicide (during a period off of lithium) occurred in the patients studied. Incidence of non-lethal suicidal behavior was not different during treatment with lithium, compared with anticonvulsants. Being on a mood stabilizer significantly protected against suicidal behavior. The relative protective effect was more modest than in reports from other treatment settings. LIMITATIONS: This was a retrospective chart review study of naturalistically treated patients. CONCLUSIONS: Treatment of patients with bipolar disorder with either lithium or anticonvulsant mood stabilizers was associated with reduced risk of suicidal behavior. This study did not find evidence for a difference in the protective effect of the two types of mood stabilizing medications against non-lethal suicidal behavior in the naturalistic setting of private practice.