What are the risks of suicide in patients taking Selective Serotonin Reuptake Inhibitors (SSRIs) and what happens if they continue treatment?

From the Guidelines

SSRIs carry a small but significant risk of increased suicidal thoughts and behaviors, particularly during the first few weeks of treatment, especially in children, adolescents, and young adults under 25, but the risk typically decreases with continued treatment beyond the initial period. Medications like fluoxetine, sertraline, escitalopram, paroxetine, and citalopram all carry this risk 1. If patients continue treatment beyond this initial period, the beneficial effects of treating depression often outweigh the initial risks. Most patients experience improvement in depressive symptoms with continued treatment, usually requiring 4-6 weeks for full therapeutic effect.

Key Considerations

• Patients should be monitored closely during the first month of treatment with weekly follow-ups if possible, particularly watching for increased agitation, anxiety, insomnia, hostility, impulsivity, or panic attacks which may signal increased suicide risk 1.
• Abrupt discontinuation of SSRIs should be avoided as it can cause withdrawal symptoms and potentially worsen suicidal thoughts.
• The increased suicide risk occurs because SSRIs may initially increase energy and motivation before improving mood, potentially giving patients the energy to act on suicidal thoughts they previously couldn't act upon.
• Family members should be educated about warning signs and emergency resources should be provided to all patients starting SSRI treatment.

Monitoring and Treatment Adjustment

• Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 1.
• The U.S. Food and Drug Administration advises that all patients receiving antidepressants be closely monitored on a regular basis for increases in suicidal thoughts and behaviors, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases 1.
• If the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder, clinicians should modify treatment 1.

Long-Term Treatment

• Most studies suggest that medication maintenance after response is beneficial, with some studies indicating that longer medication continuation periods, possibly 1 year, may be necessary for relapse prevention 1.
• The best-fitting model for SSRI response may be a logarithmic model demonstrating statistically significant improvement in anxiety symptoms within 2 weeks of treatment initiation, clinically significant improvement by week 6, and maximal improvement by week 12 or later 1.

Conclusion is not allowed, so the response ends here.

From the FDA Drug Label

WARNINGS Clinical Worsening and Suicide Risk — Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs

Pooled analyses of short–term placebo–controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18–24) with major depressive disorder (MDD) and other psychiatric disorders

Short–term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric

Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Risks of Suicide with SSRIs:

• The risk of suicidal thinking and behavior is increased in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders.
• Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24.
• Adults aged 65 and older may experience a reduction in suicidality with antidepressants compared to placebo.
• Symptoms such as anxiety, agitation, and impulsivity may be precursors to emerging suicidality.

Continuing Treatment:

• Patients should be monitored closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment or at times of dose changes.
• Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or who are experiencing emergent suicidality.
• Medication should be tapered as rapidly as is feasible if the decision has been made to discontinue treatment, with recognition that abrupt discontinuation can be associated with certain symptoms 2.

Key Points:

• SSRIs may increase the risk of suicidal thinking and behavior in certain patients.
• Close monitoring is necessary, especially during the initial few months of treatment.
• Symptoms such as anxiety and agitation may be precursors to emerging suicidality.
• Consider changing the therapeutic regimen if the patient's depression is persistently worse or if they are experiencing emergent suicidality 3.

From the Research

Risks of Suicide in Patients Taking SSRIs

• The risk of suicide in patients taking Selective Serotonin Reuptake Inhibitors (SSRIs) has been studied extensively, with some studies suggesting a possible link between SSRIs and increased suicidal behavior 4, 5, 6.
• A meta-analysis of randomized controlled trials found no evidence that SSRIs increased the risk of suicide in adults, but did find weak evidence of an increased risk of self-harm 4.
• Another study found that only 5% of suicidal patients used their prescribed antidepressant to commit suicide, and that underprescription of antidepressants and failure of antidepressant therapy were of greater practical importance than the toxicity of individual compounds 5.

Effects of Continuing SSRI Treatment

• Continuing treatment with SSRIs may not increase the risk of suicide in adults, but may increase the risk of suicidal ideation and attempts in children, adolescents, and young adults 6, 7.
• A systematic literature search found that the benefits of antidepressant pharmacotherapy, including treatment with SSRIs, outweigh the risks of their use, but that agitation occasionally occurring at the beginning of treatment can intensify or trigger suicidal thoughts or impulses 7.
• A nested case-control study found little evidence that associations between SSRI use and non-fatal self-harm or suicide differed over time since starting or stopping treatment, but did find some evidence that risks of non-fatal self-harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group 8.

Age-Related Risks

• Children, adolescents, and young adults taking SSRIs may be at increased risk of suicidal ideation and attempts 6, 7, 8.
• One study found that the risk of non-fatal self-harm for current SSRI use among those aged 18 or younger was increased, but that no suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs 8.
• Adults taking SSRIs do not appear to be at increased risk of suicide or non-fatal self-harm compared with those taking tricyclic antidepressants 4, 8.