From the Guidelines
The singular risk of psychiatric side effects is highest with the use of SSRIs, particularly due to the risk of suicidal thinking and behavior, with a pooled absolute rate of 1% in youths treated with an antidepressant, as reported in the study by 1.
Psychiatric Side Effects of SSRIs
The use of SSRIs in children and adolescents is associated with various psychiatric side effects, including:
- Suicidal thinking and behavior, with a boxed warning for this risk through age 24 years
- Behavioral activation/agitation, which may occur early in treatment, with dose increases, or with concomitant administration of drugs that inhibit the metabolism of SSRIs
- Mania/hypomania, which can be difficult to distinguish from behavioral activation
- Sexual dysfunction, including erectile dysfunction, delayed ejaculation, and anorgasmia
Risk Factors and Monitoring
Patients with a personal or family history of psychiatric disorders are at higher risk for these side effects, and close monitoring is essential when starting SSRIs, particularly in the first months of treatment and following dosage adjustments, as recommended by the FDA and reported in the study by 1.
Management of Psychiatric Side Effects
Treatment of psychiatric side effects may involve slow up-titration of the SSRI dose, close monitoring, and education of parents/guardians and patients about the potential risks, as well as discontinuation of the medication if necessary, as discussed in the study by 1.
Comparison with Other Medications
While other medications, such as corticosteroids, interferon, isotretinoin, mefloquine, and levetiracetam, may also carry a risk of psychiatric side effects, the use of SSRIs is particularly notable due to the high risk of suicidal thinking and behavior, as reported in the study by 1.
From the FDA Drug Label
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 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 The singular risk of psychiatric side effects is suicidality, which may include worsening of depression, suicidal ideation, and behavior. Other psychiatric side effects that have been reported include:
- Anxiety
- Agitation
- Panic attacks
- Insomnia
- Irritability
- Hostility
- Aggressiveness
- Impulsivity
- Akathisia (psychomotor restlessness)
- Hypomania
- Mania 2 3
From the Research
Psychiatric Side Effects
The singular risk of psychiatric side effects is a complex issue, and research studies provide some insights:
- There is no single study that directly addresses the singular risk of psychiatric side effects, but several studies discuss the side effects of various treatments for psychiatric disorders 4, 5, 6, 7, 8.
- A study on the principles of conservative prescribing highlights the importance of being aware of adverse effects, including psychiatric side effects, when prescribing medications 4.
- Another study on the treatment of adolescent depression notes that selective serotonin reuptake inhibitors (SSRIs) can have side effects, including psychiatric side effects, and that combining medication with cognitive-behavioral therapy (CBT) may be beneficial in reducing these side effects 6.
- A study on the initial steps to inform selection of continuation cognitive therapy or fluoxetine for higher risk responders to cognitive therapy for recurrent major depressive disorder found that residual symptoms and negative temperament were moderators of the preventive effects of C-CT versus fluoxetine on relapse 7.
- A study on cognitive-behavioral therapy added to fluoxetine in major depressive disorder after 4 weeks of fluoxetine-treatment found that adjunctive treatment with CBT was effective in reducing symptoms of depression, but did not specifically address psychiatric side effects 8.
Key Findings
Key findings from the studies include:
- The importance of being aware of adverse effects, including psychiatric side effects, when prescribing medications 4.
- The potential benefits of combining medication with CBT in reducing psychiatric side effects 6.
- The need to consider individual patient characteristics, such as residual symptoms and negative temperament, when selecting continuation treatment for recurrent major depressive disorder 7.
- The effectiveness of adjunctive treatment with CBT in reducing symptoms of depression 8.