Do SSRIs or antidepressants in general increase suicidality?

In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30–40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible ‘suicidal effects’ of antidepressants.

     

Do SSRIs or antidepressants in general increase suicidality? WPA Section on Pharmacopsychiatry: consensus statement

In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30-40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible 'suicidal effects' of antidepressants.     

Is there evidence for negative effects of antidepressants on suicidality in depressive patients?

The role of antidepressants in suicide prevention is a major public health question given the high prevalence of both depression and depression-related suicidality. Therefore all available means should be utilised to clarify the influence of antidepressants on suicidality, especially in view of the ongoing intensive debate about possible suicidality-inducing effects of antidepressants that may outweigh their traditionally hypothesised beneficial effects. This paper gives a systematic and comprehensive review of the empirical data which might indicate that antidepressants have negative effects on suicidality. First, principal methodological issues related to this research question are discussed. Thereafter, the results of controlled trials and epidemiological and cohort studies are presented. Altogether, there seems to be only a small amount of evidence from different research approaches that antidepressants, not only serotonin reuptake inhibitors (SSRIs), might induce, aggravate or increase the risk of suicidal ideation and suicide attempts. As to suicide, there are no hints in this direction. TCAs have a higher risk of fatal outcome in overdose compared to SSRIs, which, in case of mono-intoxication, carry almost no risk of lethal consequences. The ongoing discussion about suicidality-inducing effects should not prevent physicians from prescribing SSRIs and other antidepressants to their patients if they are clinically indicated. However, they should take into account potential risks and manage them by good clinical practice.     

Antidepressant drug use & the risk of suicide

There have been longstanding concerns about the propensity of antidepressants to precipitate suicidality in vulnerable individuals. To investigate this further, first we have analyzed all clinical trials, and in particular trials submitted to regulators for evidence on the relative risk of antidepressants versus placebo for this hazard. Second, we have compiled current epidemiological evidence germane to the issue. Third, we have constructed a model (Investigative Medication Routine; IMR) to shed light on the interactions between drug uptake, patient numbers on treatment and suicidal events. The clinical trial data gives rise to a relative risk of suicide on antidepressants over placebo of the order of a 2.0-2.5 times greater risk with treatment. These figures are supported by epidemiological findings. Investigative Medication Routine translates such findings into estimates of likely adverse outcomes, and explains why apparently increasing consumption of antidepressants would not be expected to lead to increased national suicide rates. From this data, we conclude that there is a clear signal that suicides and suicidal acts may be linked to antidepressant usage. It would seem likely that explicit warnings and monitoring in the early stages of treatment could greatly minimize these hazards.     

Antidepressant drug use & the risk of suicide

There have been longstanding concerns about the propensity of antidepressants to precipitate suicidality in vulnerable individuals. To investigate this further, first we have analyzed all clinical trials, and in particular trials submitted to regulators for evidence on the relative risk of antidepressants versus placebo for this hazard. Second, we have compiled current epidemiological evidence germane to the issue. Third, we have constructed a model (Investigative Medication Routine; IMR) to shed light on the interactions between drug uptake, patient numbers on treatment and suicidal events. The clinical trial data gives rise to a relative risk of suicide on antidepressants over placebo of the order of a 2.0–2.5 times greater risk with treatment. These figures are supported by epidemiological findings. Investigative Medication Routine translates such findings into estimates of likely adverse outcomes, and explains why apparently increasing consumption of antidepressants would not be expected to lead to increased national suicide rates. From this data, we conclude that there is a clear signal that suicides and suicidal acts may be linked to antidepressant usage. It would seem likely that explicit warnings and monitoring in the early stages of treatment could greatly minimize these hazards.     

Risk of Suicidality in Depression with Serotonergic Antidepressants

Since depression is a risk factor for suicidal thoughts and behaviors, and since suicidal behaviors are associated with low serotonin activity, are selective serotonin reuptake inhibitors (SSRIs) more effective than other antidepressants in treating suicidality in depressed patients? There is inconclusive evidence for and against this hypothesis. However, all studies suggest that antidepressants are effective treatments of suicidal ideations and behaviors, and SSRIs have been shown to have prophylactic effects in preventing suicidal behaviors. Although some reports suggest that SSRIs might increase suicidal ideations and behaviors, the results of large, double-blind studies do not suggest a causal relationship between pharmacotherapy and the emergence of suicidality. Undertreatment of depression and therapeutic failure are more significant problems with the use of antidepressants in suicidal patients than the risk of using antidepressants in overdose. Prescribing inadequate doses of antidepressants is therefore a source of overlooked risk.     

How have the selective serotonin reuptake inhibitor antidepressants affected suicide mortality?

OBJECTIVE: We review evidence on two claims that have been made about the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants; that they have: (i) decreased suicide rates in the population; and (ii) increased suicide rates in some individuals early in treatment. METHOD: We critically review evidence in the English-speaking peer-reviewed medical literature on: (i) meta-analyses of randomized controlled trials (RCTs) of SSRIs; (ii) observational studies of suicide risk in patients prescribed SSRIs and other antidepressants; and (iii) ecological studies of correlations between population use of SSRI use and population suicide rates. RESULTS: The largest and most recent meta-analyses of RCTs of SSRIs have found suggestive evidence that SSRIs increase suicidal ideation early in treatment compared with placebo. Observational studies have found an increased risk of self-harm within 9 days of an antidepressant drug being prescribed but the risk has been similar for the older tricyclic antidepressants and the SSRIs. Ecological studies in developed countries have found either that suicide rates have declined as SSRI use has increased, or have found no relationship between suicide rates and increased SSRI use. CONCLUSIONS: Meta-analyses of RCTs suggest that SSRIs increase suicide ideation compared with placebo but the observational studies suggest that SSRIs do not increase suicide risk more than older antidepressants. If SSRIs increase suicide risk in some patients, the number of additional deaths is very small because ecological studies have generally found that suicide mortality has declined (or at least not increased) as SSRI use has increased.     

Evidence for beneficial effects of antidepressants on suicidality in depressive patients

The role of antidepressants in suicide prevention is a major public health question, given the high prevalence of both depression and depression-related suicidality. Therefore all means available should be utilised to clarify the influence of antidepressants on suicidality. This paper gives a comprehensive overview of the positive effects of antidepressants on suicidality. In the first section, principal methodological issues related to suicidology in general as well as to clinical and epidemiological studies that investigate the influence of antidepressants on suicidality are discussed. In the second section, the results of controlled clinical studies on the efficacy of antidepressants in suicidality are presented. The third section reports on the results of other types of studies, especially epidemiological studies. Altogether, there seems to be reasonable evidence from different research approaches that antidepressants are able to reduce suicidal ideation and also suicidal behaviour in depressive patients. While the evidence for the beneficial effect on suicidal ideation comes from randomised control group studies, some of which used a placebo arm, the evidence for the prophylactic effect on suicidal behaviour, especially suicide, was primarily obtained from well-designed epidemiological studies.     

Lack of association between fluoxetine and suicidality in bulimia nervosa.

BACKGROUND: The coincidence of major depressive disorder in bulimia nervosa ranges from 35% to 80%. Because of this comorbidity and because suicidality (suicidal acts and ideation) is an inherent part of depression, assessment of the risk of suicide in patients with bulimia nervosa is of considerable interest. METHOD: Data from United States Investigational New Drug double-blind, placebo-controlled fluoxetine clinical trials in bulimia nervosa were analyzed comprehensively to assess the potential association between fluoxetine treatment and suicidality in 785 patients with DSM-III-R bulimia nervosa. Patients were predominantly women (98%), aged 17 to 63 years; of the randomly assigned patients, 16.9% exhibited 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 17 or greater at baseline (range, 0-31). Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred; 9 (1.15%) of 785 patients made nonfatal attempts; 24 (3.06%) experienced emergent (text-defined) suicidal ideation. No statistically significant increases in the incidence of suicidal acts or suicidal ideation were observed among fluoxetine-treated compared with placebo-treated patients. A smaller percentage of fluoxetine-treated (2.0%) than placebo-treated (3.8%) patients experienced emergence of substantial suicidal ideation (change in baseline HAM-D Item 3 [suicide item] score of 0 or 1 to 3 or 4 during therapy). A statistically significantly greater proportion of fluoxetine-treated than placebo-treated patients experienced improvement in suicidal ideation (decrease in HAM-D Item 3 score) from baseline to endpoint (p = .026). CONCLUSION: Analyses of the incidence of suicidal acts and suicidal ideation did not indicate an increased risk of suicidality in patients with bulimia nervosa treated with fluoxetine compared with those treated with placebo.     

The risk of acute suicidality in psychiatric inpatients increases with low plasma cholesterol

Several studies suggest that the reduction of total cholesterol in blood by lipid-lowering agents is accompanied by a decrease in the incidence of coronary heart disease, but not in total mortality. Likewise, epidemiological studies show that low total cholesterol concentrations appear to be associated with an increased risk of death from suicide and injuries. There is little information with respect to acute suicidality and cholesterol in psychiatric inpatients; therefore the aim of the present study was to examine exactly this relation between plasma cholesterol and acute suicidality. The study comprised 45 acutely suicidal psychiatric inpatients, 95 nonsuicidal inpatients with affective disorder, and 20 healthy subjects. Psychopathological measures (Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, Beck's Suicide Intent Scale) were established in these patients as well as the plasma concentrations of cholesterol in patients and healthy subjects. The most important finding of this study is that the risk of acute suicidality decreases with increasing total cholesterol levels irrespective of age, gender, and nutritional status (i.e., body mass index). Comparison of total cholesterol levels between age- and sex-matched suicidal and nonsuicidal patients with affective disorder supports this observation: Despite the slightly higher body mass index, suicidal patients have significantly lower cholesterol levels than nonsuicidal patients. Our findings support the notion that acute suicidality is associated with low plasma cholesterol; this observation needs to be further studied in the context of a biological marker for suicide risk.     

Suizidalität bei depressiven Kindern und Jugendlichen unter Behandlung mit selektiven Serotoninwiederaufnahmehemmern

Due to concerns that selective serotonin reuptake inhibitors (SSRI) might be associated with an increased risk of suicidal ideation and suicide attempts in depressive children and adolescents, treatment with these drugs is controversial. All available data from randomised controlled trials on SSRIs treating depression in these age groups were examined regarding efficacy and suicidality. Results suggest that fluoxetine and, less clearly, sertraline are effective in such treatment. A meta-analysis yielded no statistically significant difference between treatment with SSRI and placebo with regard to the occurrence of suicidal behavior. Following evidence-based criteria, the risk:benefit ratio is favourable for fluoxetine and sertraline. Their use in the pharmacotherapy of depressive children and adolescents is indicated.     

Antidepressants and suicidal behaviour in unipolar depression

OBJECTIVE: To compare the rates of suicidal behaviour during vs. after discontinuation of treatment with antidepressants, and to determine the comparative rates of suicidal behaviour for patients maintained on tricyclic (TCA) vs. selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD: Charts were reviewed for 521 patients with major depressive disorder and/or dysthymic disorder. Periods of active treatment or discontinuation with SSRIs or TCAs were determined. Rates of completed suicide, suicide attempts, and hospitalization for suicidality were analyzed. RESULTS: There was greater than a five-fold increase in risk for suicidal behaviour after discontinuation of antidepressant treatment (P < 0.0001). The rates of suicidal behavior during treatment with SSRIs or TCAs were similar. CONCLUSION: Suicidal behaviour in unipolar depressed patients treated with antidepressants increases substantially after medication discontinuation. This effect occurred in both patients who were maintained on SSRIs and TCAs. The findings support a possible protective effect on suicidal behaviour for both SSRIs and TCAs.     

Suicide and deliberate self-harm in personality disorders

PURPOSE OF REVIEW: This article reviews literature published over the period January 2004-May 2005 on suicidal behaviour and self-harm in personality disorders. RECENT FINDINGS: Studies have confirmed that personality disorders and their co-morbidity with other psychiatric conditions are risk factors for both fatal and nonfatal suicidal behaviours, and self-mutilation. Negative life events, childhood sexual abuse, difficulties in social functioning, deficits in future-directed thinking and time perception, as well as familial and neurocognitive factors may be related to increased suicide risk in individuals with borderline and other personality disorders. Findings seem to confirm that suicidality and self-injurious behaviour are efficient DSM-IV diagnostic criteria for borderline personality disorder. Out of several psychosocial and pharmacological interventions for treating suicidality in personality disorders, only one randomized, controlled study has recently been published. Medico-legal concerns related to the clinical management of chronically suicidal patients, including hospitalization and alternative treatment approaches, are also discussed. SUMMARY: Although recent studies have contributed to the theoretical knowledge and clinical practice, there are unsettled questions that should be addressed in the future. More randomized, controlled trials evaluating the efficacy of interventions in suicidal individuals with personality disorders should be conducted. As the majority of studies conducted to date have concentrated on borderline personality disorder and antisocial personality disorder, the prevalence and risk factors for suicidal behaviours and self-mutilation in other personality disorders require further clarification. The introduction of unified nomenclature related to suicidal behaviours and self-mutilation would facilitate comparability of results across studies.     

Pharmacotherapy of suicidal behavior in bipolar disorder.

Patients with Bipolar Disorder (BD) are at particularly high risk for both attempted and completed suicides. The period of highest risk for completed suicide is during the 2 years following discharge from a hospitalization. To date, pharmacological studies of suicidal behavior in BD have been quite limited. While strong evidence has been found regarding the anti-suicidal effects of lithium, evidence for such properties in other commonly prescribed medications for BD, including anticonvulsants, SSRIs and anti-psychotics, has been largely unexplored. Considering the high risk of suicidal acts in patients with BD, further research on the pharmacotherapy of suicidal behavior is crucial.     

Cholesterol, omega-3 fatty acids, and suicide risk: empirical evidence and pathophysiological hypotheses

Studies in psychiatric patients described an association between lower serum cholesterol concentrations, suicidality, depression, impulsivity, and aggression which is not entirely attributable to depression-related malnutrition and weight-loss. Several lines of evidence suggest that a serotonergic deficit in the prefrontal cortex may predispose vulnerable subjects to impulsive, autoaggressive, and suicidal behaviour in stressful life-events. In-vitro studies, animal experiments, and human in-vivo studies support the hypothesis that cholesterol reduction may contribute to the serotonergic abnormalities which have been postulated in suicidal subjects. Recently it was hypothesized that decreased consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, may be a risk factor for depression and suicide. Data from human studies in healthy volunteers suggest that increasing the dietary intake of omega-3 fatty acids may increase central serotonergic activity and reduce impulsive and aggressive behaviours. Earlier epidemiological studies showed an association between low cholesterol concentrations and increased suicide risk. Recent epidemiological studies with greater samples and longer follow-up periods, however, even showed a positive correlation between cholesterol concentrations and suicide risk after controlling for potential confounding variables. Large trials of statins (simvastatin, lovastatin, pravastatin) did not show an increase of suicide mortality.     

Kopfschmerzen und Migräne

Reanalyses of placebo-controlled trials reveal an increased risk of suicidal ideations or parasuicidal acts in children and adolescents under treatment with selective serotonin reuptake inhibitors (SSRI) or other antidepressants. Although no completed suicide was shown, these findings are the more important because, with the exception of fluoxetine, an evidence base for the efficacy of antidepressants is weak or lacking in this age group. For adults, there is no reason to doubt that antidepressants help to reduce suicides by shortening depressive episodes and preventing recurrence. A general and pronounced suicide-inducing effect of SSRI or other antidepressants can largely be excluded. On the other hand, in some vulnerable patients the risk of suicidal acts can increase, especially during the first days of antidepressant treatment. There is no evidence that this risk is higher with SSRI than with other antidepressants or nonpharmacological treatments. Safety in case of overdose is a strong argument favouring newer antidepressants over tri- and tetracyclic antidepressants in outpatients with unclear suicidality. The current widespread public discussions concering the risks of antidepressants is a risk in itself because confidence in treatment, compliance, and help seeking behaviour may get influenced negatively.     

Suicidality with selective serotonin reuptake inhibitors: Valid claim?

The red flags raised by the 1990 clinical reports of increased suicidality associated with treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine were followed by anecdotal reports of similar symptoms with other antidepressants of the same class. Recent discussions by Healy have argued in favour of a suicidogenic potential of the SSRIs. This paper reviews the relevant literature addressing the epidemiological data of Western populations and the data accumulated from clinical trial databases in several countries. The evidence currently available does not support the hypothesis that antidepressants or, more specifically, SSRIs cause increased suicidality in patients with depression, nor do they appear to do so in patients treated with these drugs for other reasons.     

Do Stroke Patients have an Increased Risk of Developing Suicidal Ideation or Dying by Suicide? An Overview of the Current Literature

Stroke is a leading cause of death that affects 15 million people worldwide each year. Increasing evidence suggests that stroke confers substantial risk for suicide and following a stroke, patients frequently develop poststroke depression, which is a well‐established risk factor for suicide. In this overview of the current literature, we examined the association between suffering a stroke and subsequent risk for suicide and suicidal ideation. We performed a careful MedLine, Excerpta Medica, PsycLit, PsycInfo, and Index Medicus search to identify all articles and book chapters in English. We initially selected 31 articles published between 1990 and 2011; however, only 16 studies were included in this review. All articles identified stroke as a significant risk factor for suicide, especially among depressed patients, providing further support for poststroke depression and suicidality. The results also indicated that there were differences between patients who developed acute‐onset suicidal plans and those who reported delayed‐onset plans, which occurred more frequently. Many of the stroke patients who died by suicide suffered from depression prior to their death, suggesting that being diagnosed with a mood disorder contributes to an increased risk of suicide in this population. Suffering from a stroke increases the risk of dying by suicide and developing suicidal ideation, particularly in young adults and women. The factors found to confer the most risk for suicidality were depression, previous mood disorder, prior history of stroke, and cognitive impairment.     

Differences in the Effectiveness of Psychosocial Interventions for Suicidal Ideation and Behaviour in Women and Men: A Systematic Review of Randomised Controlled Trials

The objective of this study was to explore outcomes of preventive programs and psychosocial treatments for suicidal ideation and behaviour in gender sub-groups in mixed gender studies and in studies limited to one gender. The method used was a systematic review of randomized controlled trials (RCTs) which included women or men only, or reported and/or examined outcomes of psychosocial interventions in mixed gender samples. A total of 27 (18%) of RCTs reported or examined differences in intervention outcomes. Of the mixed gender RCTs, 5 (33%) reported greater effectiveness for females than males. The review identified promising interventions in female-only samples. None of the trials reported greater effectiveness of the intervention in men. The majority of reviewed studies looking at treatment outcomes in gender sub-groups showed no differences between women and men or indicated that some psychosocial interventions are effective for women. There is a need for studies which look at gender effects and development of interventions more effective and appealing for men at risk of suicide.     

Prevalence and clinical correlates of self-harm and suicidality during admission of children in a mental health inpatient unit

BackgroundSelf-harm and suicidality are common presentations in children and adolescents requiring a mental health inpatient admission. Although there are several studies on adolescents, there is relatively limited research into childhood self-harm and suicidality during such admissions.MethodsA retrospective electronic file review was conducted on all children discharged from a national mental health inpatient children’s unit over a 6-year period. Several independent variables were compared between self-harm/suicidal and non-self-harm/non-suicidal children. Separate analyses investigated changes in self-harm/suicidality, functional outcomes, and risk assessment ratings between admission and discharge.ResultsA total of 105 children were included in this study. During admission, 65.7% of them reported self-harm thoughts, 61% engaged in self-harm, 50.5% expressed suicidal thoughts, and 14.3% engaged in suicidal behavior. Thoughts and acts of self-harm were associated with previous self-harm, longer admissions, and Attention Deficit Hyperactivity Disorder. Suicidality overlapped with self-harm and was strongly predicted by previous self-harm. The prevalence of self-harm and suicidal thoughts and acts significantly decreased during admission. Children in the non-self-harm group had marginally better functional outcomes upon discharge compared to those in the self-harm group. Children and parents/caregivers were similarly satisfied with treatment, irrespective of children’s self-harm/suicidality.ConclusionsSelf-harm and suicidality were widespread among children admitted to hospital. Better understanding of the mechanisms and factors related to self-harm and suicidality in this age group could help mitigate associated risks and improve existing safety strategies.