Antidepressant medication prevents suicide in depression

Isacsson G, Reutfors J, Papadopoulos FC, Ösby U, Ahlner J. Antidepressant medication prevents suicide in depression. Objective: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. Method: Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992–2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. Results: The probability for the toxicological detection of an antidepressant was lowest in the non‐suicide controls, higher in suicides, and even higher in suicides that had been psychiatric in‐patients but excluding those who had been in‐patients for the treatment of depression. Conclusion: The finding that in‐patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.     

Suicide seasonality and antidepressants: a register‐based study in Sweden

Objective: Seasonality of completed suicides with a peak in spring and early summer is a well‐documented finding. The circannual serotonergic functioning is hypothesized to be central in this phenomenon. Antidepressant medications exert their pharmacological action mainly by regulating serotonin. Our aim is to study the amplitude of the seasonal effect among suicide victims positive for different classes of antidepressants or without any antidepressants at the time of death. Method: By using Swedish Registers, 12 448 suicides with forensic data for antidepressive medication and information on in‐patient‐treated mental disorder were identified during 1992–2003. Seasonality was estimated with a Poisson regression variant of the circular normal distribution of completed suicides. Results: Higher suicide seasonality was found for individuals treated with selective serotonin reuptake inhibitor (SSRIs) compared to those with other antidepressant treatment or without any antidepressant treatment. The finding is more evident for men and violent suicide methods and those without history of in‐patient treatment. Conclusion: Our results provide preliminary support for the serotonergic hypothesis of suicide seasonality and raise the question of a possible accentuation of the natural suicide seasonality in patients treated with SSRIs, a hypothesis that warrants further investigation.     

Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides

OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. METHOD: Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26,422 cases of deaths by accident or natural causes in Sweden 1992-2000. RESULTS: There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION: The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.     

Seasonal variation in suicide occurrence in Finland

The aim of this study was to investigate the age-, gender- and suicide method-related seasonality of suicide occurrence by using the largest database examined so far (n=21 279). The Chi-square test for multinomials was used as the overall measure of deviation. The monthly observed and expected numbers of suicides were calculated and classified by year, month, gender, age groups and suicide methods. To identify the statistically significant peak and trough months, the ratio of observed numbers of suicides to expected numbers with 95% confidence intervals was calculated. For males, there was a suicide peak from April to July, while for females the distribution was bimodal (with peaks in May and October). In elderly people there was a significant excess in the number of suicides in autumn, and the troughs were deeper in winter. For violent suicides there was a unimodal spring peak, but for non-violent suicides the distribution was bimodal. The results indicate that suicides among elderly subjects, as well as non-violent suicides, occur significantly more often during autumn than would be expected.     

CSF 5-HIAA, suicide intent and hopelessness in the prediction of early suicide in male high-risk suicide attempters

OBJECTIVE: To study the predictive value of the Beck Suicide Intent Scale (SIS), the Beck Hopelessness Scale (BHS) and of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid for future early suicide in a group of high-risk male suicide attempters. METHOD: Fifteen consecutive male suicide attempters admitted to a psychiatric ward at the Karolinska Hospital, who were not receiving any treatment with antidepressants were diagnosed according to DSM-III, assessed with SIS and BHS and submitted to lumbar puncture. All patients were followed up for cause of death. RESULTS: Five early suicides (within 2 years) were identified. Mean cerebrospinal fluid (CSF) 5-HIAA differed between suicides and survivors. Low CSF 5-HIAA was identified in those who committed early suicide. Neither the Suicide Intent Score nor the Hopelessness Score distinguished suicides from survivors. CONCLUSION: In high suicide risk hospitalized male psychiatric patients CSF 5-HIAA may be a better predictor of early suicide after attempted suicide than SIS or BHS.     

Ulcer, attempted suicide and suicide.

Attempted suicide and suicide have been investigated among 2,619 patients suffering from duodenal ulcer, gastric ulcer and ulcer dyspepsia without ulcer demonstrable by x-ray. There was no difference in the percentage of attempted suicides and suicides among the three ulcer groups or between the sexes. Within well-defined periods, there was a statistically significant greater excess of attempted suicides among patients operated on than among unoperated patients. The distribution according to psychiatric diagnosis was very similar to the one observed among persons in general in Copenhagen attempting suicide. The number of patients committing suicide exceeded the expected number significantly, for men as well as for women, but there was no difference between patients operated on and unoperated patients. The psychiatric diagnoses of those committing suicide were predominantly neuroses and psychopathy.     

Antidepressant drug use and suicide prevention

Depression has been identified as occurring in the majority of people who commit suicide. Effective antidepressant medications have been available for over half a century. It seems logical to conclude that treatment of depression with antidepressants would have a suicide preventive effect. This has been difficult to demonstrate due to the infrequency of suicide and methodological problems in prospectively testing the hypothesis. Pooled data from controlled clinical trials of antidepressants have not demonstrated a suicide preventive effect, but patient selection and the brief time of most trials limits the power of the data. Some reports from either long-term or very large databases have provided evidence that antidepressants prevent suicide. All but one study using aggregated data from naturalistic settings have shown inverse relationships between use of antidepressants and suicide rates in various populations. Definite conclusions cannot be drawn from naturalistic studies since unknown confounders cannot be excluded. The number of geographically widespread studies reporting positive results with varying methods leads us to conclude, however, that antidepressants do exert a suicide preventive effect.     

Antidepressant drug use and suicide prevention

Depression has been identified as occurring in the majority of people who commit suicide. Effective antidepressant medications have been available for over half a century. It seems logical to conclude that treatment of depression with antidepressants would have a suicide preventive effect. This has been difficult to demonstrate due to the infrequency of suicide and methodological problems in prospectively testing the hypothesis. Pooled data from controlled clinical trials of antidepressants have not demonstrated a suicide preventive effect, but patient selection and the brief time of most trials limits the power of the data. Some reports from either long-term or very large databases have provided evidence that antidepressants prevent suicide. All but one study using aggregated data from naturalistic settings have shown inverse relationships between use of antidepressants and suicide rates in various populations. Definite conclusions cannot be drawn from naturalistic studies since unknown confounders cannot be excluded. The number of geographically widespread studies reporting positive results with varying methods leads us to conclude, however, that antidepressants do exert a suicide preventive effect.     

Antidepressant prescribing and suicide rate in Northern Ireland.

PURPOSE: Although antidepressants are the most commonly used treatment for depressive illness, there is uncertainty if their use is associated with a reduction in suicide rate. Antidepressant prescribing in Northern Ireland has increased over fivefold in the decade 1989-1999. The authors sought to explore whether this increase was associated with a reduction in suicide rate taking into account social and political factors thought also to have an influence on suicide. MATERIALS AND METHODS: Factors that have been suggested to influence suicide were entered into a linear regression with frequency of suicide and undetermined deaths (referred to as suicide rate) as the dependent variable. The above factors were antidepressant prescribing, unemployment rate, household alcohol expenditure and persons charged with terrorist offences. The rise in younger suicides, in recent decades, suggests this analysis should be carried out separately for younger (less than 30 years) and older (30 years and above) suicides separately. The predictors in the two models are based on aggregate data for the total group. RESULT: In the younger group there was no association between antidepressant prescribing and suicide. For the older group increased antidepressant prescribing was associated with a reduction in suicide rate over the 10 years of the study. CONCLUSION: Increasing antidepressant prescribing appears to be an effective strategy for reducing suicide. This has been demonstrated in older individuals.     

Temporal changes in suicide rates for persons treated and not treated with antidepressants in Denmark during 1995-1999

OBJECTIVE: To compare the temporal changes in suicide rate among patients treated with antidepressants with the change in suicide rate among persons who have not been treated with antidepressants during 1995-1999. METHOD: In a historic prospective national pharmacoepidemiological register linkage study by using four Danish registers we included 438,625 patients who had purchased antidepressants, and compared them with 1,199,057 population based control persons. The annual rate of suicide was estimated using Poisson regression analyses. RESULTS: The suicide rate decreased for persons treated with antidepressants as well as for persons not treated with antidepressants. The proportion of persons, who committed suicide and who had not been treated with antidepressants decreased. The reduction in suicide rate was more pronounced among persons treated with SSRIs or older antidepressants than among persons not treated with antidepressants. CONCLUSION: Several factors contribute to the decreasing suicide rate. The most pronounced decrease in suicide rate was found among persons treated with antidepressants.     

Suicide prevention — a medical breakthrough?

OBJECTIVE: The author hypothesized, based on research until 1991, that a five-fold increase in the use of antidepressants might reduce Swedish suicide rates by 25%. A subsequent 3.5-fold increase in the use of antidepressants provided a 'natural experimental situation' for prospectively testing this hypothesis. METHOD: Swedish statistics on suicide, use of antidepressants, unemployment and alcohol consumption were obtained for 1978-96. Time-series of the latter variables were compared with suicide rates. Demographic subgroups regarding age, gender and county were analysed. Suicide rates were also compared with the use of antidepressants in Denmark, Norway and Finland. RESULTS: Suicide rates decreased in accordance with the a priori hypothesis. Alcohol consumption and unemployment rates did not correlate well with suicide rates. CONCLUSION: This naturalistic study is not conclusive. The increased use of antidepressants appears, however, to be one of the contributing factors to the decrease in the suicide rate. It is of great scientific and clinical importance that this be evaluated by further studies.     

Time-trends in method-specific suicide rates compared with the availability of specific compounds. The Danish experience

Restriction of means for suicide is an important part of suicide preventive strategies in different countries. All suicides in Denmark between 1970 and 2000 were examined with regard to method used for suicide. Overall suicide mortality and method-specific suicide mortality was compared with official information about availability of medical compounds (barbiturates, benzodiazepines, analgesics, antidepressants) and carbon monoxide in vehicle exhaust and household gas. Restrictions on the availability of carbon monoxide, barbiturates and dextropropoxyphen was associated with a decline in the number of suicides by self-poisoning with these compounds. Restricted access occurred concomittantly with a 55% decrease in suicide rate.     

Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort

BACKGROUND: It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide. OBJECTIVE: To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power. DESIGN AND SETTING: A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database. PARTICIPANTS: A total of 15 390 patients with a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES: The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment. RESULTS: In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P<.001), and this was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths (RR, 0.42; 95% CI, 0.24-0.71; P=.001). Among subjects who had ever used any antidepressant, the current use of medication was associated with a markedly increased risk of attempted suicide (39%, P<.001), but also with a markedly decreased risk of completed suicide (-32%, P=.002) and mortality (-49%, P<.001), when compared with no current use of medication. The results for subjects aged 10 to 19 years were basically the same as those in the total population, except for an increased risk of death with paroxetine hydrochloride use (RR, 5.44; 95% CI, 2.15-13.70; P<.001). CONCLUSIONS: Among suicidal subjects who had ever used antidepressants, the current use of any antidepressant was associated with a markedly increased risk of attempted suicide and, at the same time, with a markedly decreased risk of completed suicide and death. Lower mortality was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths during selective serotonin reuptake inhibitor use.     

Incidence and predictors of activation syndrome induced by antidepressants

Background: Activation syndrome is a side effect of antidepressants that is thought to carry a potentially increased risk of suicide. However, the incidence of activation syndrome has not been fully investigated and little has been reported on its predictors. The aim of this study was to survey the incidence of activation syndrome and clarify its predictors in a natural clinical setting. Methods: Among 2,521 new outpatients visiting between August 2003 and March 2005, we retrospectively surveyed the case records of 729 patients who had not taken any antidepressants during the 1 month before presentation and were prescribed antidepressants for 3 months after the initial visit. Patients were classified as developing activation syndrome if they experienced any symptom of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania during the first 3 months. Results: Of the 729 patients, 31 (4.3%) developed activation syndrome. The incidence was not significantly related to gender, age, class of antidepressant, combined use of benzodiazepine, or DSM‐IV‐TR diagnosis except for personality disorder. Diagnosis of personality disorder was significantly associated with the induction of activation syndrome (odds ratio=4.20, P=0.002). Conclusions: This study suggests that diagnosis of personality disorder may be a clinical predictor of activation syndrome. Depression and Anxiety, 2008. © 2008 Wiley‐Liss, Inc.     

Antidepressant drug consumption and public health indicators in Italy, 1955 to 2000

OBJECTIVE: This study investigated the impact of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer anti-depressants on the following public health indicators: (1) suicide rates, (2) proportion of completed suicides by poisoning with solid or liquid substances, and (3) hospital admissions for depression and proportion of admissions for depression that were first admissions. METHOD: Data collected by IMS Health on antidepressants dispensed in Italy from 1983 to 2000 were obtained from the Italian Ministry of Health, while data on suicide deaths from 1955 to 2000 were obtained from the Italian National Institute of Statistics. RESULTS: In Italy from 1983 to 2000, the use of tricyclic antidepressants remained substantially stable, and the use of SSRIs and newer agents dramatically increased. In contrast, suicide rates for males decreased from 1955 to 1974 and subsequently increased, reaching a peak in 1985 and then declining. In females, suicide rates remained substantially stable until 1978. A subsequent increase occurred up to 1985, followed by a steady decline. Suicide by poisoning using solids or liquids dropped by nearly 50% from 1986 to 2000. Admissions to the hospital for depression showed an erratic pattern; however, no decline was observed. No change was observed in the rate of first admissions for depression. CONCLUSION: Despite a reduction in suicides by poisoning using solids or liquids, the analysis of long-term trends in suicide did not suggest that increases in antidepressant prescribing lie behind recent reductions in population suicides. Furthermore, in Italy, newer antidepressants had no impact on the total number of admissions for depression or on the proportion of all admissions that were first admissions.