What is the efficacy and safety of fluoxetine (Selective Serotonin Reuptake Inhibitor - SSRI) in adolescents with suicidal ideation (SI)?

From the Guidelines

Fluoxetine is the preferred antidepressant for adolescents with suicidal ideation (SI), as it's the only SSRI with FDA approval for depression treatment in this age group, and it has been shown to be effective in reducing depressive symptoms and suicidal thoughts in adolescents 1. The recommended starting dose is 10mg daily for one week, then increasing to 20mg daily, with potential adjustments up to 60mg daily based on response and tolerability. Treatment should continue for at least 6-9 months after symptom resolution to prevent relapse, as studies have shown that longer medication continuation periods, possibly 1 year, may be necessary for relapse prevention 1. While fluoxetine can help reduce suicidal thoughts, it carries an FDA black box warning for potentially increasing suicidal thinking in the first few weeks of treatment. Therefore, close monitoring is essential during this period, with weekly check-ins for the first month, then biweekly for the second month, and monthly thereafter, as recommended by the guidelines for adolescent depression in primary care 1. Fluoxetine works by increasing serotonin levels in the brain, which helps regulate mood. Combining medication with cognitive behavioral therapy (CBT) or dialectical behavior therapy (DBT) is more effective than medication alone. Any adolescent with active suicidal ideation requires immediate safety assessment, consideration of hospitalization if at high risk, and implementation of a safety plan regardless of medication choice. Some studies have suggested that the risk of not prescribing antidepressant medication is significantly higher than the risk of prescribing, and that the reduction of antidepressant prescribing may be related to the increase in US youth suicides 1. However, it is essential to balance the potential benefits and risks of fluoxetine treatment in adolescents with suicidal ideation, and to closely monitor patients for any adverse events or changes in behavior. The guidelines for adolescent depression in primary care recommend that clinicians monitor for the emergence of adverse events during antidepressant treatment, including suicidal ideation, and that patients be assessed in person within 1 week of the initiation of treatment 1.

Key points to consider when prescribing fluoxetine to adolescents with suicidal ideation include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Monitoring closely for adverse events, including suicidal ideation, during the first few weeks of treatment
• Continuing treatment for at least 6-9 months after symptom resolution to prevent relapse
• Combining medication with cognitive behavioral therapy (CBT) or dialectical behavior therapy (DBT) for optimal effectiveness
• Implementing a safety plan and considering hospitalization if the patient is at high risk of suicide. It is crucial to weigh the potential benefits and risks of fluoxetine treatment in adolescents with suicidal ideation and to closely monitor patients for any adverse events or changes in behavior, as the risk of suicidal ideation and behavior is a significant concern in this population 1.

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

The efficacy of fluoxetine in adolescents with suicidal ideation (SI) is not established as the drug label does not provide direct information on its effectiveness in this specific population. The safety of fluoxetine in adolescents with suicidal ideation (SI) is a concern, as the drug label indicates that antidepressants, including SSRIs like fluoxetine, increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders 2. Key points to consider:

• Patients being treated with antidepressants should be monitored closely for clinical worsening, suicidality, and unusual changes in behavior.
• Symptoms such as anxiety, agitation, and impulsivity may represent precursors to emerging suicidality.
• Consideration should be given to changing the therapeutic regimen in patients whose depression is persistently worse or who are experiencing emergent suicidality.

From the Research

Efficacy of Fluoxetine in Adolescents with Suicidal Ideation

• The Treatment for Adolescents with Depression Study (TADS) 3, 4 found that fluoxetine, either alone or in combination with cognitive-behavioral therapy (CBT), was effective in reducing depression symptoms and suicidal ideation in adolescents.
• The study found that 27% of patients had at least minimal suicidal ideation at baseline, which reduced to 9% at the end of the treatment period 3.
• Another study found that fluoxetine with CBT showed the greatest reduction in suicidal ideation, with a significant improvement in 29% of the sample at baseline 4.
• A review of several trials found that fluoxetine was the only SSRI with consistent evidence of effectiveness in reducing depression symptoms in both children and adolescents, and 'response' to treatment 5.

Safety of Fluoxetine in Adolescents with Suicidal Ideation

• The TADS study 4 found that there were more suicide-related adverse events in patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223).
• Another study found that suicidal events were more common in patients receiving fluoxetine therapy (14.7%) than combination therapy (8.4%) or CBT (6.3%) 6.
• A review of several trials found that there was evidence of an increased risk of suicidal ideation and behavior for those prescribed SSRIs, including fluoxetine 5.
• However, the TADS study 4 and another study 6 found that adding CBT to medication enhanced the safety of medication and reduced the risk of suicidal events.

Combination Therapy with Fluoxetine and CBT

• The TADS study 4 found that the combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
• Another study found that combined treatment with fluoxetine and CBT was superior to either monotherapy as a treatment for major depression in adolescents, with a greater reduction in suicidal ideation and events 6.
• A review of several trials found that two controlled trials indicated that combination therapy had a more favorable benefit/risk balance than monotherapy in adolescent depression 7.