Can Selective Serotonin Reuptake Inhibitors (SSRIs) induce hypomania?

From the Guidelines

Hypomania is a potential side effect of selective serotonin reuptake inhibitors (SSRIs), and patients experiencing symptoms such as elevated mood, decreased need for sleep, and increased energy should contact their healthcare provider immediately. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, SSRIs can cause hypomania, particularly in individuals with undiagnosed bipolar disorder. The guideline notes that behavioral activation/agitation, which can be difficult to distinguish from hypomania, may occur early in SSRI treatment, with dose increases, or with concomitant administration of drugs that inhibit the metabolism of SSRIs.

Some key points to consider when managing SSRI-induced hypomania include:

• Reducing the SSRI dose or discontinuing it completely to alleviate symptoms 1
• Possibly adding a mood stabilizer like lithium, valproate, or an atypical antipsychotic to manage hypomania 1
• Careful screening for bipolar symptoms before starting antidepressants to minimize the risk of triggering hypomania 1
• Close monitoring for suicidality, especially in the first months of treatment and following dosage adjustments, as SSRIs have a boxed warning for suicidal thinking and behavior through age 24 years 1

It is essential to note that SSRIs can trigger hypomania because they increase serotonin levels in the brain, which can overstimulate mood regulation systems in susceptible individuals 1. Therefore, healthcare providers should be cautious when prescribing SSRIs, particularly in patients with a history of bipolar disorder or those who are at risk of developing hypomania. By prioritizing careful screening, close monitoring, and prompt management of hypomania, healthcare providers can minimize the risks associated with SSRI use and ensure the best possible outcomes for their patients.

From the Research

Hypomania Induced by SSRIs

• Hypomania can be induced by selective serotonin reuptake inhibitors (SSRIs) in patients with depressive disorders, as seen in a case study where sertraline and paroxetine induced hypomania in two patients with no family or personal history of bipolar disorder 2.
• The dose-response relationship of SSRI-induced hypomania suggests that hypomania may be a dose-dependent medication effect, as reducing the dose of sertraline and paroxetine resolved hypomanic symptoms in the patients 2.
• Another case report supports the idea that SSRI-induced hypomania can be a genuine side-effect of the medication, rather than a switch, as a patient with dissociative disorder experienced hypomanic symptoms after starting sertraline and recovered after stopping the medication 3.

Risk of Switching to Hypomania or Mania

• The risk of switching to hypomania or mania in patients with bipolar depression during treatment with antidepressants, including SSRIs, is a concern, as seen in a study where adjunctive treatment with antidepressants was associated with substantial risks of threshold switches to full-duration hypomania or mania 4.
• The study found that venlafaxine was associated with the highest relative risk of switching, while bupropion was associated with the lowest risk 4.
• Another study suggested that bupropion may be a safe and effective treatment for bipolar depression, with a lower risk of inducing switches to hypomania or mania, as seen in a sample of difficult-to-treat bipolar depressive patients 5.

Treatment of Mixed Mania/Hypomania

• The treatment of mixed mania/hypomania is challenging due to the need to treat both manic/hypomanic and depressive symptoms concurrently, and high-potency antipsychotics and antidepressants can potentially deteriorate symptoms of the opposite polarity 6.
• A review of the evidence suggests that aripiprazole, asenapine, carbamazepine, olanzapine, and ziprasidone may be effective in the acute-phase treatment of mixed mania/hypomania, while quetiapine and divalproex/valproate may also be efficacious 6.
• Combination therapies with atypical antipsychotics and mood stabilizers may be considered in severe cases, and olanzapine and quetiapine may be effective in maintenance treatment 6.